Nitrite Production Research Articles

The Summary of Nitritation Process in Mainstream Wastewater Treatment

The application of the mainstream partial nitritation/anammox (PN/A) process is promising due to the huge cost reduction compared to traditional biological nitrogen removal. However, the nitrite production rate (NPR) of a biological nitritation pre-treatment process is relatively lower than the nitrite consumption rate in a pure anammox reactor with a high nitrogen loading rate (NLR). Thus, the NPR is the rate-limiting step for operating the PN/A process with a higher NLR. Various studies have attempted to improve mainstream NPR. A comprehensive review of these processes is needed for the actual application of the PN/A process. This study focuses on: (1) various nitrite production processes that have emerged in recent years; (2) the main microbial species and characteristics involved in biological nitritation; (3) the existing problems and the N2O emission problem of these processes; and (4) a proposed novel and promising PN/A process facilitated with photocatalyst oxidation. This review is expected to provide references and a basis for the research on the nitritation step of the application of the mainstream PN/A process.

Potential causes of partial-denitrification (PD) granular sludge breakdown under high nitrate loading rates

The granule instability has been frequently reported during the operation of high loading rates. While, there no research was performed on the recently developed anoxic partial-denitrification (PD) granules, a novel pathway in producing nitrite from nitrate for anammox process. Herein, this work, for the first time, investigated the influence of nitrate loading rates on the instability of PD granules and identified the key causes. Two lab-scale sequencing batch reactors (SBRs) were operated with nitrate loading rates (NLR) increased from 0.48 to 3.84 kg N/m3/d (R1, 8 cycles/d), and 0.96 to 7.68 kg N/m3/d (R2, 16 cycles/d) by gradually elevating the influent nitrate concentration. Results showed that nitrite production rates increased with the NLRs, with a maximal value of 5.26 kg N/m3/d obtained. However, the compact regular PD granules were not stable and broke down when NLR was above 3.84 kg N/m3/d, which resulted in serious sludge washing out from SBR. The high NLRs led to the extracellular polymeric substances (EPS) transformation in terms of its composition and structure, which the protein content in the EPS and the tightly bound EPS (T-EPS) fraction was significantly decreased, this was supposed to be the major reason causing the breakdown of PD granules. Besides, it was found the PD granule in R2 was more deteriorated than that in R1 under the same high NLR, suggesting the short starvation (idle) times in SBR cycle was likely another reason impairing the stability of PD granules. Overall, this research provides useful information in development of granule-based PD systems and sheds light on achieving high-rate nitrite production in SBR with great stability.

Use of wood and cork in biofilters for the simultaneous removal of nitrates and pesticides from groundwater

About 13% and 7% of monitored groundwater stations in Europe exceed the permitted levels of nitrates (50 mg NO3− L−1) or pesticides (0.1 μg L−1), respectively. Although slow sand filtration can remove nitrates via denitrification when oxygen is limited, it requires an organic carbon source. The present study evaluates the performance of the use of wood pellets and granulated cork as carbon sources in bench-scale biofilters operated under water-saturated and water-unsaturated conditions for more than 400 days. The biofilters were monitored for nitrate (200 mg L−1) and pesticide (mecoprop, diuron, atrazine, and bromacil, each at a concentration of 5 μg L−1) attenuation, as well as for the formation of nitrite and pesticide transformation products. Microbiological characterization of each biofilter was also performed. The water-saturated wood biofilter achieved the best nitrate removal (>99%), while the cork biofilters lost all denitrification power over time (from 38% to no removal). The unsaturated biofilter columns were not effective for removing nitrates (20–30% removal). As for pesticides, all the biofilters achieved high removal rates of mecoprop and diuron (>99% and >75%, respectively). Atrazine removal was better in the wood-pellet biofilters than the cork ones (68–96% vs. 31–38%). Bromacil was only removed in the water-unsaturated cork biofilter (67%). However, a bromacil transformation product was formed there. The water-saturated wood biofilter contained the highest number of denitrifying microorganisms, with Methyloversatilis as the characteristic genus. Microbial composition could explain the high removal of pesticides and nitrates achieved in the wood-pellet biofilter. Overall, the results indicate that wood-pellet biofilters operated under water-saturated conditions are a good solution for treating groundwater contaminated with nitrates and pesticides.

Magnetic activation of TREK1 triggers stress signalling and regulates neuronal branching in SH-SY5Y cells.

TWIK-related K+ 1 (TREK1) is a potassium channel expressed in the nervous system with multiple functions including neurotransmission and is a prime pharmacological target for neurological disorders. TREK1 gating is controlled by a wide range of external stimuli including mechanical forces. Previous work has demonstrated that TREK1 can be mechano-activated using magnetic nanoparticles (MNP) functionalised with antibodies targeted to TREK1 channels. Once the MNP are bound, external dynamic magnetic fields are used to generate forces on the TREK channel. This approach has been shown to drive cell differentiation in cells from multiple tissues. In this work we investigated the effect of MNP-mediated TREK1 mechano-activation on early stress response pathways along with the differentiation and connectivity of neuronal cells using the model neuronal cell line SH-SY5Y. Results showed that TREK1 is well expressed in SH-SY5Y and that TREK1-MNP initiate c-Myc/NF-κB stress response pathways as well as Nitrite production after magnetic stimulation, indicative of the cellular response to mechanical cues. Results also showed that TREK1 mechano-activation had no overall effect on neuronal morphology or expression of the neuronal marker βIII-Tubulin in Retinoic Acid (RA)/Brain-derived Neurotrophic factor (BDNF) differentiated SH-SY5Y but did increase neurite number. These results suggest that TREK1 is involved in cellular stress response signalling in neuronal cells, which leads to increased neurite production, but is not involved in regulating RA/BDNF mediated neuronal differentiation.

Anti-inflammatory activity of Kyungok-go on Lipopolysaccharide-Stimulated BV-2 Microglia Cells

Objectives: Kyungok-go (KOG) is a traditional multi-herbal medicine commonly used for enforcing weakened immunity for long time. Recently, there are several reports that KOG has anti-inflammatory and immuno-stimulatory activities in many experimental models. However, the protective effects of KOG on neuronal inflammation are still undiscovered. Thus, we investigated the neuro-protective activity of KOG on lipopolysaccharide (LPS)-stimulated mouse microglia cells. To find out KOG’s anti-neuroinflammatory effects on microglial cells, we examined the production of nitrite using griess assay, and mRNA expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and interleukin (IL)-1<i>β</i>, IL-6, tumor necrosis factor (TNF)-<i>α</i> using real time RT-PCR. In addition, to examine the regulating mechanisms of KOG, we investigated the protein expression of mitogen-activated protein kinases (MAPKs) and I<i>κ</i>-B<i>α</i> by western blot. KOG inhibited the elevation of nitrite, iNOS and COX-2 on LPS-stimulated BV2 cells. Also, KOG significantly inhibited the pro-inflammatory cytokines such as IL-1<i>β</i>, IL-6, and TNF-<i>α</i> on LPS-stimulated BV2 microglial cells. Moreover, KOG inhibited the activation of c-Jun N-terminal kinase (JNK), P38 and degradation of I<i>κ</i>-B<i>α</i> but not the activation of extracellular signal regulated kinase (ERK) on LPS-stimulated BV2 microglial cells. These results showed KOG has the anti-inflammatory effects through the inhibition on nitrite, iNOS, COX-2, IL-1<i>β</i>, IL-6, and TNF-<i>α</i> via the deactivation of JNK, p38 and nuclear factor (NF)-<i>κ</i>B on LPS-stimulated BV2 microglial cells. Thereby, KOG could offer the new and promising treatment for neurodegenerative disease related to neuroinflammation.

Molecular Hybridization Strategy on the Design, Synthesis, and Structural Characterization of Ferrocene-N-acyl Hydrazones as Immunomodulatory Agents.

Immunomodulatory agents are widely used for the treatment of immune-mediated diseases, but the range of side effects of the available drugs makes necessary the search for new immunomodulatory drugs. Here, we investigated the immunomodulatory activity of new ferrocenyl-N-acyl hydrazones derivatives (SintMed(141−156). The evaluated N-acyl hydrazones did not show cytotoxicity at the tested concentrations, presenting CC50 values greater than 50 µM. In addition, all ferrocenyl-N-acyl hydrazones modulated nitrite production in immortalized macrophages, showing inhibition values between 14.4% and 74.2%. By presenting a better activity profile, the ferrocenyl-N-acyl hydrazones SintMed149 and SintMed150 also had their cytotoxicity and anti-inflammatory effect evaluated in cultures of peritoneal macrophages. The molecules were not cytotoxic at any of the concentrations tested in peritoneal macrophages and were able to significantly reduce (p < 0.05) the production of nitrite, TNF-α, and IL-1β. Interestingly, both molecules significantly reduced the production of IL-2 and IFN-γ in cultured splenocytes activated with concanavalin A. Moreover, SintMed150 did not show signs of acute toxicity in animals treated with 50 or 100 mg/kg. Finally, we observed that ferrocenyl-N-acyl hydrazone SintMed150 at 100 mg/kg reduced the migration of neutrophils (44.6%) in an acute peritonitis model and increased animal survival by 20% in an LPS-induced endotoxic shock model. These findings suggest that such compounds have therapeutic potential to be used to treat diseases of inflammatory origin.

New models of Parkinson's like neuroinflammation in human microglia clone 3: Activation profiles induced by INF-γ plus high glucose and mitochondrial inhibitors.

Microglia activation and neuroinflammation have been extensively studied in murine models of neurodegenerative diseases; however, to overcome the genetic differences between species, a human cell model of microglia able to recapitulate the activation profiles described in patients is needed. Here we developed human models of Parkinson's like neuroinflammation by using the human microglia clone 3 (HMC3) cells, whose activation profile in response to classic inflammatory stimuli has been controversial and reported only at mRNA levels so far. In fact, we showed the increased expression of the pro-inflammatory markers iNOS, Caspase 1, IL-1β, in response to IFN-γ plus high glucose, a non-specific disease stimulus that emphasized the dynamic polarization and heterogenicity of the microglial population. More specifically, we demonstrated the polarization of HMC3 cells through the upregulation of iNOS expression and nitrite production in response to the Parkinson's like stimuli, 6-hydroxidopamine (6-OHDA) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), the latter depending on the NF-κB pathway. Furthermore, we identified inflammatory mediators that promote the pro-inflammatory activation of human microglia as function of different pathways that can simulate the phenotypic transition according to the stage of the pathology. In conclusion, we established and characterized different systems of HMC3 cells activation as in vitro models of Parkinson's like neuroinflammation.

Nitrite Quantification by Second Derivative Chemometric Models Mitigates Natural Organic Matter Interferences under Chloraminated Drinking Water Distribution System Conditions

Nitrite (NO2−) production in chloraminated drinking water distribution systems (CDWDSs) is among the first bulk water indicators of a nitrification event and is typically quantified using ion chromatography (IC) or colorimetric techniques. NO2− can also be quantified using chemometric models (CMs) formulated using molar absorptivity (Ɛ) and/or ultraviolet absorbance (UVA) spectra, but concerns exist regarding their accuracy and generalizability because of varying source water natural organic matter (NOM), monochloramine (NH2Cl), bromide (Br−), and other species in CDWDSs. We demonstrate that the impact of NOM was mitigated in the second derivative molar absorptivity (Ɛ″) and UVA spectra (UVA″) between 200–300 nm and developed a generalizable CM for NO2− quantification. The Ɛ″+UVA″ CM was calibrated with daily NO2− measurements by IC from five biofilm annular reactor (BAR) tests with feedwater from Fayetteville, Arkansas, USA (FAY1, n = 275) and validated with eight BAR tests (n = 376) with another Fayetteville water (FAY2) and two waters from Dallas, Texas, USA (DAL1 and DAL2). The Ɛ″+UVA″ CM used Ɛ″ for NO2−, nitrate (NO3−), Br−, and NH2Cl at wavelengths of 213-, 225-, 229- and 253 nm, had an adjusted R2 of 0.992 for FAY1 and 0.987 for the other waters, and had a method detection limit (MDL) of 0.050 mg·L−1-N. NO2− challenge samples with three reconstituted NOM types and Br− indicated the Ɛ″+UVA″ CM was generalizable at NOM concentrations like those in the BAR tests (≤ 2.5 mg·L−1-C). The Ɛ″+UVA″ CM accurately simulated NO2− in field tests from two CDWDSs undergoing nitrification, including one with NOM at 3.5 mg·L−1-C, illustrating a practical application of the CM for identifying biological ammonia oxidation.

PH-Dependent Hydrogenotrophic Denitratation Based on Self-Alkalization.

Producing stable nitrite is a necessity for anaerobic ammonium oxidation (anammox) but remains a huge challenge. Here, we describe the design and operation of a hydrogenotrophic denitratation system that stably reduced >90% nitrate to nitrite under self-alkaline conditions of pH up to 10.80. Manually lowering the pH to a range of 9.00-10.00 dramatically decreased the nitrate-to-nitrite transformation ratio to <20%, showing a significant role of high pH in denitratation. Metagenomics combined with metatranscriptomics indicated that six microorganisms, including a Thauera member, dominated the community and encoded the various genes responsible for hydrogen oxidation and the complete denitrification process. During denitratation at high pH, transcription of periplasmic genes napA, nirS, and nirK, whose products perform nitrate and nitrite reduction, decreased sharply compared to that under neutral conditions, while narG, encoding a membrane-associated nitrate reductase, remained transcriptionally active, as were genes involved in intracellular proton homeostasis. Together with no reduction in only nitrite-amended samples, these results disproved the electron competition between reductions of nitrate and nitrite but highlighted a lack of protons outside cells constraining biological nitrite reduction. Overall, our study presents a stably efficient strategy for nitrite production and provides a major advance in the understanding of denitratation.

IMMU-22. REPROGRAMMING OF MICROGLIA/MACROPHAGES IN GLIOBLASTOMA IMPROVES ANTI-TUMOR T CELL RESPONSES

Abstract Glioma-infiltrating myeloid cells such microglia and macrophages (GAM) are a major component of the immunosuppressive tumor microenvironment in glioblastoma (GBM). Especially their anti-inflammatory M2-like activation state might counteract efficacy of immunotherapeutic interventions by impairing effector T cell infiltration and function. Therefore, we studied the ability of the small molecule inhibitors (SMI) PLX3397, BLZ945, and GW2580 that target the M2-associated colony stimulating factor-1 receptor (CSF1R) to shape GAM phenotype towards a pro-inflammatory M1-like phenotype and how this affects the T cell compartment.Upon treatment of freshly isolated CD11b-sorted GBM patient-derived GAMs (n = 15) a decreased expression of CD163 (M2-like) and an increased expression of HLA-DR (M1-like) as well as an increased nitrite production as an indirect measure for iNOS activation (M1-like) was observed which was most pronounced for BLZ945, and GW2580. Transcriptome analysis of treated vs. untreated GAMs supported a reprogramming towards a pro-inflammatory phenotype. In addition, treatment of GAMs in a GBM patient-derived tumor organoid model confirmed a substantial decrease of CD163+ M2-polarized GAM together with a reduced number of proliferating tumor cells. Finally, treatment of patient-derived GAMs led to an increased T cell transmigration through a dense barrier of autologous tumor-derived endothelial cells and increased the ability of T cells to kill autologous tumor cells. Our results support CSF1R blockade is able to reduce the immunosuppressive and pro-tumorigenic functions of GAM substantially and thereby could enhance the effectiveness of T cell-based immunotherapy.

Aqueous extract of bay leaf (Laurus nobilis) ameliorates testicular toxicity induced by aluminum chloride in rats.

Human exposure to aluminum is inevitable, and one of the most adverse health effects of aluminum is a decrease in male fertility rates. Therefore, this study investigated the ameliorative effects of an aqueous extract from Laurus nobilis-bay leaf (BL) on aluminum chloride (AlCl3)-induced testicular toxicity in rats. Twenty-four Wistar rats were divided into four groups (n = 6, each group): The control (group 1) received normal saline; Group 2 animals were intraperitoneally administered with 30 mg/kg body weight (BW) AlCl3; and Groups 3 and 4 were co-administered AlCl3 with 125 or 250 mg/kg BW of BL extract, respectively, for 21 days. Testes, epididymis, and blood samples were collected. Testicular plasma enzyme activity was measured using a spectrophotometric assay, while concentrations of inflammatory biomarkers were determined using enzyme-linked immunosorbent assay kits. There was a significant increase (p < 0.05) in testicular enzyme activity in the group treated with AlCl3. However, there was no significant (p > 0.05) difference in testicular enzyme activity in groups co-administered AlCl3 and BL extract as compared with that in control. There was a significant (p < 0.05) increase in testicular nitrite concentration in the AlCl3-treated group, whereas the administration of BL extract significantly (p < 0.05) decreased nitrite concentration in Groups 3 and 4. Furthermore, the administration of BL extracts increased sperm count and improved the morphology of the testes in AlCl3-treated rats. Flavonoids, phenolic compounds, alkaloids, tannin, glycosides, saponin, anthraquinones, and steroids were identified in BL extract, with alkaloids and glycosides being the most abundant. Aqueous extract from BL ameliorated the toxic effect of AlCl3 and exhibited anti-inflammatory properties by inhibiting nitrite production while improving sperm count and morphology in AlCl3-treated rats. The bioactivity of the extract may be attributed to the presence of a wide range of phytochemicals. Therefore, BL aqueous extract could be a promising source of novel compounds with male fertility-promoting and anti-inflammatory properties.

Boosted photocatalytic efficiency of GQDs sensitized (BiO)2CO3/β-Bi2O3 heterojunction via enhanced interfacial charge transfer

The NO gas is easily oxidized to form toxic by-products (NO2) during the oxidation process, which are adsorbed on the catalyst surface and inhibit the subsequent reaction. For photocatalytic NO removal, a significant challenge is to achieve catalytic stability while maintaining high conversion efficiency. Here, we fabricated a (BiO)2CO3/β-Bi2O3 heterostructure that enables efficient charge transfer and promotes the NO removal. We propose that the catalytic stability depends on the heterojunction structure, which is able to generate interfacial charge transfer channels. In addition, we further introduce graphene quantum dots on the heterojunction structure, which further strengthens the interfacial charge transfer dynamics and finally realizes that the NO2 byproduct could gain electrons and convert to the final product (nitrite or nitrate). This composite structure not only exhibits high activity for NO removal but also maintains long-term stability under visible light.

Secondary metabolites from Gentiana cruciata L. and their anti-inflammatory and analgesic activities

A previously unreported secoiridoid glycoside, cruciatoside (1) was isolated from the aerial parts of Gentiana cruciata L. along with ten known compounds eustomoside (2), eustomorusside (3), gentiopicroside (4), 6'-O-β-D-glucopyranosyl gentiopicroside (5), loganic acid (6), isoorientin (7), isovitexin (8), isovitexin 2''-(E)-ferulate (9), mangiferin (10), and 2-methyl-inositol (11). The chemical structures of the isolates were elucidated based on extensive 1 D and 2 D NMR experiments as well as HRMS analysis. All isolates were evaluated for their in vitro anti-inflammatory and analgesic activities. Compounds 9, 4, and 7 (200 µM) showed moderate anti-inflammatory activity by inhibiting nitrite production from LPS-induced RAW 264.7 macrophage cells, with the inhibition rates of 39.5%, 25.8% and 22.9% respectively without exhibiting substantial cytotoxicity. Besides, 1, 2, 4, and 7 exerted the highest decrease in IL-6 levels. Moreover, compound 4 showed in vitro analgesic activity by decreasing the PGE2 level comparable to the reference drugs.

Arginine metabolism and the role of arginine deiminase-producing microorganisms in kimchi fermentation

In this study, we evaluated the correlation between the arginine deiminase (ADI) pathway and nitrogen cycle during cabbage kimchi fermentation. Nitrite used as a food additive can be converted to carcinogenic N-nitroso compounds via reactions with secondary amines under specific conditions; thus, high nitrate- and nitrite-containing foods present a potential risk to human health. We monitored the bacterial community, levels of ADI metabolites, and nitrogen compounds present in kimchi that contained bacteria that showed low ADI activity during fermentation. The dominant growth of microorganisms with weak ADI activity reduced arginine degradation and ornithine production. Furthermore, nitrite production in kimchi samples was affected by ADI activity. The ornithine and nitrite contents in the control kimchi were 1.7- and 2.6-fold higher at week 2 than at week 1. These results suggest that ADI-associated metabolism is correlated with the nitrogen cycle in kimchi and that the addition of bacteria with weak ADI activity may reduce nitrite production in kimchi.

Anti-Inflammatory and Antimicrobial Activities of Portuguese Prunus avium L. (Sweet Cherry) By-Products Extracts.

The bioactivity of natural by-products in food and pharmaceutical applications is the subject of numerous studies. Cherry production and processing generates large amounts of biowaste, most of which is not used. The recovery of these by-products is essential for promoting the circular economy and to improving sustainability in the food industry. In this work, we explored the anti-inflammatory and antimicrobial potential of two different extracts from stems, leaves, and flowers of Portuguese cherries. The anti-inflammatory potential was studied on lipopolysaccharide (LPS)-stimulated mouse macrophages (RAW 264.7) by evaluating the effect of by-products on cellular viability and nitric oxide (NO) production. Disc diffusion and minimum inhibitory concentration (MIC) were used to determine antimicrobial activity. The cherry by-products had no cytotoxic effect on RAW 264.7 cells, and were able to inhibit nitrite production in a dose-dependent manner. Moreover, all aqueous infusions showed good antioxidant activity against NO radicals. Moreover, leaf extracts showed the best activity against most of the strains studied. The results revealed, for the first time, interesting anti-inflammatory and antimicrobial properties of cherry by-products. This could potentially be of interest for their therapeutic use in the treatment of inflammation-related diseases or in controlling the growth of microorganisms.

Metagenomics-based interpretation of selective bioaugmentation promoting partial-denitrification coupling with anammox process reactivation in suspended sludge system

The partial-denitrification coupled to anammox process (PD/A) has been emerging as a potential alternative for cost-efficient nitrogen removal from wastewater. Although there has been intensive study on startup and optimization, efficient reactivation and controlling strategy after disturbance of this process still lack essential information. Here, a selective bioaugmentation strategy with low dosage for stepwise recovery of PD and anammox activity were proposed and demonstrated for the first time, and the mechanism of coupling process reactivation was revealed based on metagenomic analysis. A significant increase in nitrite (NO2-N) production was obtained after introducing PD inoculum by weight ratio of 7.7 %, with nitrate (NO3−-N)-to-NO2−-N transformation ratio (NTR) increasing from 15.7 % to 45.0 %, while anammox activity stayed at a relatively low level. The ammonia (NH4+-N) removal rate significantly increased by 4.0 times after supplying PD/A biomass by only 1.2 % due to sufficient substrate NO2−-N for anammox. Consequently, nitrogen removal efficiency was remarkably improved to 99.2 % and kept stable with low-strength wastewater. Metagenomics analysis revealed that the abundances of genes nar and nap encoding NO3−-N reductase were kept at much higher level than nir for NO2−-N reductase. Significantly, higher diversity and abundance of genes responsible for carbon metabolism could accelerate the electron generation and transfer to PD, thus stimulating anammox activity, which was the key reason for the rapid reactivation of PD/A process. Furthermore, the substate ratio, nitrogen loading rates and morphological characteristics of sludge have crucial influence on the recovery of biomass activity. The dominant genus Thauera responsible for PD and Candidatus Brocadia for anammox coexisted stably after bioaugmentation. These results provide a comprehensive understanding of reactivating and regulating a novel PD/A process towards application and microbial interaction.

Reactive Uptake of Gas-Phase NO2 by Urban Road Dust in the Dark.

Road dust constitutes a prominent source of anthropogenic particulate matter, making its heterogeneous interactions with common atmospheric gas-phase compounds important. Here, we show that three distinct samples of urban road dust-including dust samples collected from city streets in summer and winter, and an urban park in summer-react with NO2 in the dark, forming NO and surface nitrite. The loss of NO2 ranged from ∼2 to 13% of its gas-phase concentration and scaled with its concentration as well as with the mass of the road dust sample. The uptake of NO2 by the winter dust was ∼4 times greater than that seen from summer street dust, which was in turn greater than that by the park dust. The conversion ratio of NO2 → NO ranged from 0.06 to 0.8 NO produced per NO2 lost and was greatest for the summer park dust. Exposure of the summer road dust to NO2 roughly doubles the concentration of inorganic nitrite anion in the dust but does not produce nitrate. The formation of NO and photolabile nitrite products means that heterogeneous NO x reactions occurring on the surface of road dust in the dark could have wide implications for the oxidative potential of urban areas.

Predictive Theoretical Model for the Selective Electroreduction of Nitrate to Ammonia.

The electrochemical reduction of nitrate (eNO3RR) emerges as a promising route for decentralized ammonia synthesis. However, the competitive production of nitrite at low overpotentials is a challenging issue. Herein, using the combination of density functional theory and microkinetic modeling, we show that the selectivity for NH3 surpasses that of NO2- at -0.66 VRHE, which nicely reproduced the experimental value on titania. NH2OH* → NH2* is the kinetically controlling step at a low overpotential for NH3 generation, while NO2* → HNO2 has the highest barrier to producing nitrite. Based on these mechanistic insights, we suggest that ΔG1 (NH2OH* → NH2*) - ΔG2 (NO2* → HNO2) can serve as a descriptor to predict the S(NO2-)/S(NH3) crossover potential. Such a model is verified by the experimental results on Ag, Cu, TiO2-x, Fe3O4, and Fe-MoS2 and can be extended to the Au catalyst. Thus, this work sheds light on the rational design of catalysts that are simultaneously energy-efficient and selective to NH3.

Oxidative stress and iron metabolism in human sperm

Infertility is a global problem in couples. The decrease in sperm quality and function might be related to intrinsic and extrinsic factors, which ultimately converge on inducing oxidative stress (OS) in male gametes. Seminal plasma (SP) contains a large amount of antioxidants which protect sperm against OS. The iron in semen has a great influence on male fertility. Its transport, celluar uptake and storage depend on Transferrin (Tf), the cell membrane receptor for Transferrin (RTf) and Ferritin (FN), respectively. An isoform found in SP, testicular transferrin (TfT), is essential for spermatogenesis. The objective was to evaluate the antioxidant capacity of metalloproteins in SP involved in iron metabolism. A total of 328 semen samples from patients from the Urology Service of Eva Perón School Hospital (Granadero Baigorria) and Centenario Hospital (Rosario) (n=166) and healthy volunteers (n=162) were studied. Of these participants, 204 met the inclusion criteria. Semen samples were analyzed according to WHO criteria (2010-2021). Measurement of Fe and total proteins was carried out by colorimetric method, FN was measured by immunoturbidimetric method. ELISA technique was used for measuring the Tf concentration in SP. To measure OS we used 3 techniques: MOST test, (TBARs) technique and determination of total nitrite production by colorimetric method. Concentration of nitrites vs TfT showed an inverse relationship (R2=0,921; M= -0,7057; p<0,05). For abnormal MOST values (less than or equal to 0.39), the seminal Tf values were mostly below the mean value found in our population (5 mg/dL). An inverse relationship was seen between lipid peroxidation and TfT. (R2=0,4869; M=-0,0028). Our data suggest that TfT may fulfill an antioxidant role in the testis. It is necessary to study a greater number of patients and discriminate them by pathology in order to conclude which OS measurement technique is the most appropriate to assess male reproductive function.

Thionated aminofluorophthalimides reduce classical markers of cellular inflammation in LPS-challenged RAW 264.7 cells

Herein, we present the synthesis of several fluorinated pomalidomide derivatives and their thionated counterparts with subsequent biological evaluation against classical markers of cellular inflammation. Treatment in LPS-challenged cells effected varying reductions in levels of secreted TNF-α and nitrite relative to basal amounts. While arene fluorination and thioamidation had marginal and sporadic effects on TNF-α production, specific 7-position fluorination combined with subsequent increases in carbonyl thionation produced compounds 11, 14, and 15 which demonstrated corresponding and escalating anti-nitrite activities concurrent with minimal cellular toxicity. In this regard, compound 15 displayed roughly 96 % cell viability combined with a 65 % drop in nitrite production when supplied to RAW cells challenged with 60 ng/mL LPS. When a focused family of fluorinated isomers were directly compared, the analogous 5-fluorinated isomer 17 displayed comparable minimal toxicity but markedly less anti-nitrite activity versus 15 in RAW cells challenged with 70 ng/mL LPS. Compound 15 was subsequently screened in human liver microsomes for preliminary Phase 1 analysis where it demonstrated heightened stability relative to its non-fluorinated counterpart 3,6′-dithiopomalidomide 4, a result in line with the expected metabolic fortitude provided by fluorination at the sensitive pomalidomide 7-position.