Farnesoid X Receptor Protects Murine Lung against IL-6-promoted Ferroptosis Induced by Polyriboinosinic-Polyribocytidylic Acid.

Various infections trigger a storm of proinflammatory cytokines in which IL-6 acts as a major contributor and leads to diffuse alveolar damage in patients. However, the metabolic regulatory mechanisms of IL-6 in lung injury remain unclear. Polyriboinosinic-polyribocytidylic acid [poly(I:C)] activates pattern recognition receptors involved in viral sensing and is widely used in alternative animal models of RNA virus-infected lung injury. In this study, intratracheal instillation of poly(I:C) with or without an IL-6-neutralizing antibody model was combined with metabonomics, transcriptomics, and so forth to explore the underlying molecular mechanisms of IL-6-exacerbated lung injury. We found that poly(I:C) increased the IL-6 concentration, and the upregulated IL-6 further induced lung ferroptosis, especially in alveolar epithelial type II cells. Meanwhile, lung regeneration was impaired. Mechanistically, metabolomic analysis showed that poly(I:C) significantly decreased glycolytic metabolites and increased bile acid intermediate metabolites that inhibited the bile acid nuclear receptor farnesoid X receptor (FXR), which could be reversed by IL-6-neutralizing antibody. In the ferroptosis microenvironment, IL-6 receptor monoclonal antibody tocilizumab increased FXR expression and subsequently increased the Yes-associated protein (YAP) concentration by enhancing PKM2 in A549 cells. FXR agonist GW4064 and liquiritin, a potential natural herbal ingredient as an FXR regulator, significantly attenuated lung tissue inflammation and ferroptosis while promoting pulmonary regeneration. Together, the findings of the present study provide the evidence that IL-6 promotes ferroptosis and impairs regeneration of alveolar epithelial type II cells during poly(I:C)-induced murine lung injury by regulating the FXR-PKM2-YAP axis. Targeting FXR represents a promising therapeutic strategy for IL-6-associated inflammatory lung injury.

Effect of Mn2+ on RO membrane organic fouling: Insights into the complexation and interfacial interaction.

RO process is commonly used to treat and reuse manganese-containing industrial wastewater. Nevertheless, even after undergoing multi-stage treatment, the secondary biochemical effluent still exhibits a high concentration of Mn2+ coupled with organics entering the RO system, leading to membrane fouling. In this work, we systematically analyze the RO membrane organic fouling processes and mechanisms, considering the coexistence of Mn2+ with humic acid (HA), sodium alginate (SA), bovine serum albumin (BSA) and their mixtures (HBS). The impact of Mn2+ on membrane fouling was HBS > SA > HA > BSA, controlling polysaccharide pollutant concentrations should be a priority for mitigating membrane fouling. In the presence of Mn2+ with HA, SA, or HBS, membrane fouling is primarily attributed to the complexation of organics and Mn2+ and the facilitation of interfacial interaction energy. RO membrane BSA fouling was not directly affected by Mn2+, the addition of Mn2+ induced a salting-out effect, leading to the deposition of BSA in a single molecular on the membrane. Simultaneously, adhesion energy hinders the deposition of BSA on the membrane, resulting in milder membrane fouling. This study provided the theoretical basis and suggestions for RO membrane organic fouling control in the presence of Mn2+.

Enhanced nitrogen removal of the anaerobic ammonia oxidation process by coupling with an efficient nitrate reducing bacterium (Bacillus velezensis M3-1).

Bacillus velezensis M3-1 strain isolated from the sediment of Myriophyllum aquatium constructed wetlands was found to efficiently convert NO3--N to NO2--N, and the requirements for carbon source addition were not very rigorous. This work demonstrates, for the first time, the feasibility of using the synergy of anammox and Bacillus velezensis M3-1 microorganisms for nitrogen removal. In this study, the possibility of M3-1 that converted NO3--N produced by anammox to NO2--N was verified in an anaerobic reactor. The NO3--N reduction ability of M3-1 and denitrifying bacteria in coupling system was investigated under different C/N conditions, and it was found that M3-1 used carbon sources preferentially over denitrifying bacteria. By adjusting the ratio of NH4+-N to NO2--N, it was found that the NO2--N converted from NO3--N by M3-1 participated in the original anammox.The nitrogen removal efficacy (NRE) of the coupled system was increased by 12.1%, compared to the control group anammox system at C/N = 2:1. Functional gene indicated that it might be a nitrate reducing bacterium.This study shows that the nitrate reduction rate achieved by the Bacillus velezensis M3-1 can be high enough for removing nitrate produced by anammox process, which would enable improve nitrogen removal from wastewater.

Fast start-up of anammox process: Effects of extracellular polymeric substances addition on performance, granule properties, and bacterial community structure.

The slow startup is the major obstacle to the application of anaerobic ammonium oxidation (anammox) process in mainstream wastewater treatment. Extracellular polymeric substances (EPS) are one potential resource for stable anammox reactor operation. Response surface analysis was used to optimize the specific anammox activity (SAA) with the addition of EPS; SAA was maximum at a temperature of 35 °C and the EPS concentration of 4 mg/L. By comparing the nitrogen removal of anammox reactors with no EPS (R0), immobilized EPS (EPS-alginate beads) (R1), and liquid EPS (R2), we found that EPS-alginate beads significantly speed up the startup of anammox process and enable the start time to be shortened from 31 to 19 days. As a result of the higher MLVSS content, higher zeta potential, and lower SVI30, anammox granules of R1 exhibited a stronger capacity to aggregate. Moreover, EPS extracted from R1 had higher flocculation efficiencies than EPS derived from R0 and R2. Phylogenetic analysis of 16S rRNA genes revealed that the main anammox species in R1 is Kuenenia taxon. To clarify the relative significance of stochastic vs deterministic processes in the anammox community, neutral model and network analysis are employed. In R1, community assembly became more deterministic and stable than in other cultures. Our results show that EPS might inhibit heterotrophic denitrification and thereby promote anammox activity. This study suggested a quick start-up strategy for the anammox process based on resource recovery, which is helpful for environmentally sustainable and energy-efficient wastewater treatment.

Microbial community structure analyses and cultivable denitrifier isolation of Myriophyllum aquaticum constructed wetland under low C/N ratio.

With the rapid expansion of livestock production, the amount of livestock wastewater accumulated rapidly. Lack of biodegradable organic matter makes denitrification of livestock wastewater after anaerobic digestion more difficult. In this study, Myriophyllum aquaticum constructed wetlands (CWs) with efficient nitrogen removal performance were established under different carbon/nitrogen (C/N) ratios. Analysis of community composition reveals the change of M. aquaticum CWs in microbial community structure with C/N ratios. The proportion of Proteobacteria which is one of the dominant phyla among denitrifier communities increased significantly under low C/N ratio conditions. Besides, to obtain cultivable denitrifier that could be added into CWs in situ, 33 strains belonging to phylum Proteobacteria were isolated from efficient M. aquaticum CWs, while the best-performing denitrification strain M3-1 was identified as Bacillus velezensis JT3-1 (GenBank No. CP032506.1). Redundancy analysis and quadratic models showed that C/N ratio had significant effects on disposal of nitrate (NO3--N) and the strains isolated could perform well in denitrification when C/N ratio is relatively low. In addition, they have relatively wide ranges of carbon sources, temperature and a high NO3- removal rate of 9.12 mg/(L·hr) at elevated concentrations of 800 mg/L nitrate. Thus, strains isolated from M. aquaticum CWs with low C/N ratio have a practical application value in the treatment of nitrate-containing wastewater. These denitrifying bacteria could be added to CWs to enhance nitrogen removal efficiency of CWs for livestock wastewater with low C/N ratio in the future.

Novosphingobium aureum sp. nov., a marine bacterium isolated from salt flat sediment.

A Gram-stain-negative, aerobic, pale yellow-coloured, rod-shaped marine bacterium designated strain YJ-S2-02T was isolated from salt flat sediment sampled in Yongyu-do, Republic of Korea. Strain YJ-S2-02T grew at pH 6.0-9.0 (optimum, pH 7.0), 10-40 °C (optimum, 30 °C) and with optimum 1 % (w/v) NaCl. The 16S rRNA gene sequence analysis indicated that strain YJ-S2-02T was closely related to Novosphingobium naphthalenivorans NBRC 102051T (97.8 %) followed by Novosphingobium mathurense SM117T (97.5 %), Novosphingobium indicum H25T (97.3 %), Novosphingobium pentaromativorans US6-1T (96.8 %), Novosphingobium fontis STM-14T (96.6 %), Novosphingobium endophyticum EGI60015T (96.5 %), Novosphingobium naphthae D39T (96.5 %) and Novosphingobium malaysiense MUSC 273T (95.9 %). The average nucleotide identity and estimated DNA-DNA hybridization values between YJ-S2-02T and related type strains were 77.0-77.9 % and 19.1-24.0 %. Strain YJ-S2-02T was characterized as having Q-10 as the predominant respiratory quinone and the principal fatty acids (>10 %) were summed feature 8 (C18 : 1 ω6c/ω7c, 20.7 %), C18 : 3 ω6c (16.3 %) and C17 : 1 ω6c (11.8 %). The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, sphingolipids and two unidentified lipids. The DNA G+C content of strain YJ-S2-02T was 65.6 mol%. On the basis of the polyphasic taxonomic evidence presented in this study, YJ-S2-02T should be classified as representing a novel species within the genus Novosphingobium, for which name Novosphingobium aureum is proposed, with the type strain YJ-S2-02T (=KACC 21677T =KCTC 72891T=JCM 33996T).

Altererythrobacter lutimaris sp. nov., a marine bacterium isolated from a tidal flat and reclassification of Altererythrobacter deserti, Altererythrobacter estronivorus and Altererythrobacter muriae as Tsuneonella deserti comb. nov., Croceicoccus estronivorus comb. nov. and Alteripontixanthobacter muriae comb. nov.

A yellow-coloured bacterium, designated strain JGD-16T, was isolated from a tidal flat in Janggu-do, Garorim Bay, Taean-gun, Chungcheongbuk-do, Republic of Korea. Cells were Gram-stain-negative, aerobic, non-flagellated and short ovoid to coccoid-shaped. Growth was observed at 10-37 °C (optimum, 30 °C), pH 6.0-9.0 (pH 8.0) and with 1-5% (w/v) NaCl (2%). Results of 16S rRNA gene sequence analysis indicated that strain JGD-16T was closely related to Altererythrobacter xiamenensis LY02T (97.1 %), Altererythrobacter aurantiacus O30T (96.3 %), Altererythrobacter ishigakiensis JPCCMB0017T (95.8 %), Altererythrobacter epoxidivorans JCS350T (95.7 %) and Altererythrobacter insulae BPTF-M16T (95.3%). Phylogenomic analysis using the maximum-likelihood algorithm showed that strain JGD-16T formed a clade with the genus Altererythrobacter. The genomic DNA G+C content was 57.8 mol%. The predominant respiratory quinone was ubiquinone-10. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, a sphingoglycolipid, an unidentified glycolipid and an unidentified lipid. The major fatty acids were C18:1 ω7c (31.5 %) and C18:3 ω6c (19.6 %). On the basis of its phylogenomic, physiological and chemotaxonomical characteristics, strain JGD-16T represents a novel species within the genus Altererythrobacter, for which the name Altererythrobacter lutimaris JGD-16Tsp. nov. is proposed. The type strain is JGD-16T (=KCTC 72632T=KACC 21405T=JCM 33750T). We also propose the reclassification of Altererythrobacter deserti as Tsuneonella deserti comb. nov., Altererythrobacter estronivorus as Croceicoccus estronivorus comb. nov. and Altererythrobacter muriae as Alteripontixanthobacter muriae comb. nov.

Muricauda ochracea sp. nov., isolated from a tidal flat in the Republic of Korea.

A yellowish-brown-coloured bacterium, designated strain JGD-17T, was isolated from a tidal flat of Janggu-do, Garorim bay, Taean-gun, Chungcheongbuk-do, Republic of Korea. Cells were Gram-stain-negative, aerobic, non-flagellated and long-rod-shaped. Growth was observed at 20-45 °C (optimum, 25-30 °C), at pH 6.0-10.0 (9.0) and with 1-5 % (w/v) NaCl (1-3 %). Results of 16S rRNA gene sequence analysis indicated that strain JGD-17T was closely related to Muricauda nanhaiensis SM1704T (96.1 %), Muricauda olearia CL-SS4T (95.0 %), Muricauda beolgyonensis BB-My12T (94.9 %), Muricauda marina H19-56T (94.7 %) and Muricauda indica 3PC125-7T (94.5 %). The ranges of values for the average nucleotide identity and digital DNA-DNA hybridization analyses with related strains were 71.3-74.1 % and 16.9-18.2 %. The genomic DNA G+C content was 41.1 mol%. Phylogenetic analysis using the neighbour-joining method showed that strain JGD-17T formed a clade with Muricauda nanhaiensis SM1704T, Muricauda lutaonensis CC-HSB-11T, Muricauda lutea CSW06T and Muricauda pacifica SM027T. The major fatty acids were iso-C15 : 0 (26.9 %), iso-C15 : 1 G (19.5 %) and iso-C17 : 0 3-OH (12.7 %). The predominant respiratory quinone was menaquinone-6. The polar lipids were phosphatidylethanolamine, an unidentified aminolipid, an unidentified phospholipid and two unidentified lipids. On the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, strain JGD-17T represents a novel species within the genus Muricauda, for which the name Muricauda ochracea sp. nov. is proposed. The type strain is JGD-17T (=KCTC 72732T=KACC 21486T=JCM 33817T).

Targeted traction of impacted teeth with C-tube miniplates.

Orthodontic traction of impacted teeth has typically been performed using full fixed appliance as anchorage against the traction force. This conventional approach can be difficult to apply in the mixed dentition if the partial fixed appliance offers an insufficient anchor unit. In addition, full fixed appliance can induce unwanted movement of adjacent teeth. This clinical report presents 3 cases where impacted teeth were recovered in the mixed or transitional dentition with skeletal anchorage on the opposite arch without full fixed appliance. Instead, intermaxillary traction was used to bring the impacted teeth into position. With this approach, side effects on teeth and periodontal tissues adjacent to the impaction were minimized.

Achieving partial nitrification by sludge treatment using sulfide: Optimal conditions determination, long-term stability evaluation and microbial mechanism exploration.

This study proposes an innovative strategy for achieving PN in synthetic domestic wastewater by side-stream sludge treatment using sulfide as the sole control factor. By conducting controllable batch experiments and response surface analysis, optimal sulfide treatment conditions were firstly determined as 90 mg/L of sulfide, 7.5 of pH, 100 rpm of rotation and 12 h of treatment time. After treatment, half of ammonia oxidizing bacteria (AOB) activity remained, but nitrite oxidizing bacteria (NOB) activity was barely detected. Nitrite accumulation rate of long-term running PN steadily reached 83.9 % with 99.1 % of ammonia removal efficiency. Sulfide treatment increased community diversity and facilitated stability of microbiota functioning with PN phenotype, which might be sustained by the positive correlation between ammonia oxidation gene (amoA) and sulfur oxidation gene (soxB). Correspondingly, the network analysis identified the keystone microbial taxa of persistent PN microbiota as Nitrosomonas, Thauera, Truepera, Defluviimonas and Sulitalea in the later stage of long-term reactor.

Rapid start-up of an innovative pilot-scale staged PN/A continuous process for enhanced nitrogen removal from mature landfill leachate via robust NOB elimination and efficient biomass retention.

The start-up and stable operation of partial nitritation-anammox (PN/A) treatment of mature landfill leachate (MLL) still face challenges. This study developed an innovative staged pilot-scale PN/A system to enhance nitrogen removal from MLL. The staged process included a PN unit, an anammox upflow enhanced internal circulation biofilm (UEICB) reactor, and a post-biofilm unit. Rapid start-up of the continuous flow PN process (full-concentration MLL) was achieved within 35 days by controlling dissolved oxygen and leveraging free ammonia and free nitrous acid to selectively suppress nitrite-oxidizing bacteria (NOB). The UEICB was equipped with an annular flow agitator combined with the enhanced internal circulation device of the guide tube, which achieved an efficient enrichment of Candidatus Kuenenia in the biofilm (relative abundance of 33.4 %). The nitrogen removal alliance formed by the salt-tolerant anammox bacterium (Candidatus Kuenenia) and denitrifying bacteria (unclassified SBR1031 and Denitratisoma) achieved efficient nitrogen removal of UEICB (total nitrogen removal percentage: 90.8 %) and at the same time effective treatment of the refractory organic matter (ROM). The dual membrane process of UEICB fixed biofilm combined with post-biofilm is effective in sludge retention, and can stably control the effluent suspended solids (SS) at a level of less than 5 mg/L. The post-biofilm unit ensured that effluent total nitrogen (TN) remained below the 40 mg/L discharge standard (98.5 % removal efficiency). Compared with conventional nitrification-denitrification systems, the staged PN/A process substantially reduced oxygen consumption, sludge production, CO2 emissions and carbon consumption by 22.8 %, 67.1 %, 87.1 % and 87.1 %, respectively. The 195-day stable operation marks the effective implementation of the innovative pilot-scale PN/A process in treating actual MLL. This study provides insights into strategies for rapid start-up, robust NOB suppression, and anammox biomass retention to advance the application of PN/A in high-ammonia low-carbon wastewater.

The effects, mechanisms, and applications of sulfide as both an inhibitor and electron donor in novel biological nitrogen removal process.

The impacts of sulfide on biological nitrogen removal have been investigated repeatedly, but the impacts in terms of the removal technologies have not been systematically organized and discussed yet. This review recapped the dual character of sulfide in novel biological nitrogen removal and proposed the coupling mechanisms of nitrogen removal and sulfide interaction. The dual character of sulfide was basically divided into the advantage as electron donors and the disadvantage as cytotoxic agent to wide bacteria. The positive character of sulfide has been utilized for improving the performances of denitrification and anaerobic ammonium oxidation in laboratory and polit scales. Intriguingly, the sulfide cytotoxicity was feasibly turned into the profit which was to trigger the partial nitrification by selectively inhibiting ammonia oxidizing bacteria and nitrite oxidizing bacteria. Thus, this productive conversion dramatically promoted the importance of sulfide in sewage treatment. In order to maximize the favorable aspect of sulfide utilization, it was crucial to manage the sulfide concentration for fear of the side reactions with untargeted substances. Furthermore, S/N ratio in sewage may be the keystone that decides if sulfide benefits biological nitrogen removal. In sum, our work can facilitate the dialectical development of effective strategies for sulfide utilization in biological nitrogen removal.

B cell-derived anti-beta 2 glycoprotein I antibody mediates hyperhomocysteinemia-aggravated hypertensive glomerular lesions by triggering ferroptosis.

Hyperhomocysteinemia (HHcy) is a risk factor for chronic kidney diseases (CKDs) that affects about 85% CKD patients. HHcy stimulates B cells to secrete pathological antibodies, although it is unknown whether this pathway mediates kidney injury. In HHcy-treated 2-kidney, 1-clip (2K1C) hypertensive murine model, HHcy-activated B cells secreted anti-beta 2 glycoprotein I (ß2GPI) antibodies that deposited in glomerular endothelial cells (GECs), exacerbating glomerulosclerosis and reducing renal function. Mechanistically, HHcy 2K1C mice increased phosphatidylethanolamine (PE) (18:0/20:4, 18:0/22:6, 16:0/20:4) in kidney tissue, as determined by lipidomics. GECs oxidative lipidomics validated the increase of oxidized phospholipids upon Hcy-activated B cells culture medium (Hcy-B CM) treatment, including PE (18:0/20:4 + 3[O], PE (18:0a/22:4 + 1[O], PE (18:0/22:4 + 2[O] and PE (18:0/22:4 + 3[O]). PE synthases ethanolamine kinase 2 (etnk2) and ethanolamine-phosphate cytidylyltransferase 2 (pcyt2) were increased in the kidney GECs of HHcy 2K1C mice and facilitated polyunsaturated PE synthesis to act as lipid peroxidation substrates. In HHcy 2K1C mice and Hcy-B CM-treated GECs, the oxidative environment induced by iron accumulation and the insufficient clearance of lipid peroxides caused by transferrin receptor (TFR) elevation and down-regulation of SLC7A11/glutathione peroxidase 4 (GPX4) contributed to GECs ferroptosis of the kidneys. In vivo, pharmacological depletion of B cells or inhibition of ferroptosis mitigated the HHcy-aggravated hypertensive renal injury. Consequently, our findings uncovered a novel mechanism by which B cell-derived pathogenic anti-ß2GPI IgG generated by HHcy exacerbated hypertensive kidney damage by inducing GECs ferroptosis. Targeting B cells or ferroptosis may be viable therapeutic strategies for ameliorating lipid peroxidative renal injury in HHcy patients with hypertensive nephropathy.

CD34+ cell-derived fibroblast-macrophage cross-talk drives limb ischemia recovery through the OSM-ANGPTL signaling axis.

CD34+ cells improve the perfusion and function of ischemic limbs in humans and mice. However, there is no direct evidence of the differentiation potential and functional role of these cells in the ischemic muscle microenvironment. Here, we combined the single-cell RNA sequencing and genetic lineage tracing technology, then provided exact single-cell atlases of normal and ischemic limb tissues in human and mouse, and consequently found that bone marrow (BM)-derived macrophages with antigen-presenting function migrated to the ischemic site, while resident macrophages underwent apoptosis. The macrophage oncostatin M (OSM) regulatory pathway was specifically turned on by ischemia. Simultaneously, BM CD34+-derived proregenerative fibroblasts were recruited to the ischemia niche, where they received macrophage-released OSM and promoted angiopoietin-like protein-associated angiogenesis. These findings provided mechanisms on the cellular events and cell-cell communications during tissue ischemia and regeneration and provided evidence that CD34+ cells serve as fibroblast progenitors promoting tissue regeneration.

Partial nitrification in free nitrous acid-treated sediment planting Myriophyllum aquaticum constructed wetland strengthens the treatment of black-odor water.

Black-odor water pollution in rural areas, especially swine wastewater, can lead to the deterioration of water quality and thus seriously affect the daily life of people in the area. However, there is a lack of effective treatment measures with simultaneous attention to carbon, nitrogen and sulfur pollution in rural black-odor water bodies. This study evaluated the feasibility of an in-situ pilot-scale constructed wetland (CW) for the synchronous removal of COD, ammonium, and sulfur compounds in the swine wastewater. In this study, the operation strategy of CW sediment pretreated with free nitrous acid (FNA) and Myriophyllum aquaticum plantation was established. Throughout the 114-day operation, the total removal efficiencies of COD and ammonium nitrogen in experimental groups were 81.2 ± 4.2 % and 72.8 ± 1.8 %, respectively, which were significantly higher than CW without any treatment. Removal efficiencies of Sulfur compounds, i.e. sulfide, sulfate, thiosulfate, and sulfite, were 92.3 ± 1.9 % (61.2 % higher than the no-treatment group), 42.1 ± 3.8 %, 97.9 ± 1.7 %, and 42.7 ± 4.5 % respectively. High-throughput sequencing and qPCR revealed that experimental group significantly increased denitrification genes (nirK, nosZ) and sulfur oxidation genes (soxB, fccAB) and enriched the corresponding microbial taxa (Bacillus, Conexibacter and Clostridium sensu stricto). Moreover, metabolic pathways related to nitrogen and sulfur and the degradation of organic matter were up-regulated. These results indicated that partial nitrification in CW planted with M. aquaticum promoted sulfur oxidation denitrification and heterotrophic denitrification. Overall, the in-situ pilot-scale study revealed that the cultivation of M. aquaticum in FNA-treated CW can be a sustainable approach to treat black-odor water bodies.

T lymphocyte-derived extracellular vesicles aggravate abdominal aortic aneurysm by promoting macrophage lipid peroxidation and migration via pyruvate kinase muscle isozyme 2.

T lymphocyte and macrophage infiltration in the aortic wall is critical for abdominal aortic aneurysm (AAA). However, how T lymphocytes interact with macrophages in the pathogenesis of AAA remains largely uncharacterized. In an elastase-induced murine AAA model, we first found that the expression of pyruvate kinase muscle isozyme 2 (PKM2), the last rate-limiting enzyme in glycolysis, was increased in infiltrated T lymphocytes of vascular lesions. T lymphocyte-specific PKM2 deficiency in mice (LckCrePKM2fl/fl) or intraperitoneal administration of the sphingomyelinase inhibitor GW4869 caused a significant attenuation of the elastase-increased aortic diameter, AAA incidence, elastic fiber disruption, matrix metalloproteinases (MMPs) expression, and macrophage infiltration in the vascular adventitia compared with those in PKM2fl/fl mice. Mechanistically, extracellular vesicles (EVs) derived from PKM2-activated T lymphocytes elevated macrophage iron accumulation, lipid peroxidation, and migration in vitro, while macrophages treated with EVs from PKM2-null T lymphocytes or pretreated with the lipid peroxidation inhibitors ferrostatin-1 (Fer-1), liproxstatin-1 (Lip-1), or the iron chelating agent deferoxamine mesylate (DFOM) reversed these effects. In vascular lesions of elastase-induced LckCrePKM2fl/fl mice with AAA, the oxidant system weakened, with downregulated 4-hydroxynonenal (4-HNE) levels and strengthened antioxidant defense systems with upregulated glutathione peroxidase 4 (GPX4) and cystine/glutamate antiporter solute carrier family 7 member 11 (Slc7a11) expressions in macrophages. High-throughput metabolomics showed that EVs derived from PKM2-activated T lymphocytes contained increased levels of polyunsaturated fatty acid (PUFA)-containing phospholipids, which may provide abundant substrates for lipid peroxidation in target macrophages. More importantly, upregulated T lymphocyte PKM2 expression was also found in clinical AAA subjects, and EVs isolated from AAA patient plasma enhanced macrophage iron accumulation, lipid peroxidation, and migration ex vivo. Therefore, from cell-cell crosstalk and metabolic perspectives, the present study shows that PKM2-activated T lymphocyte-derived EVs may drive AAA progression by promoting macrophage redox imbalance and migration, and targeting the T lymphocyte-EV-macrophage axis may be a potential strategy for early warning and treating AAA.

Gut microbiota and the prevalence and incidence of renal stones.

The role of the gut microbiome in the development of renal stone diseases has not been well characterized. This study focused on the taxonomic and functional profiles of gut microbiomes according to the prevalence and incidence of nephrolithiasis. Stool samples from 915 Korean adults were collected at baseline. Participants were followed for a median of 4.0 years. We evaluated the biodiversity of the gut microbiota and taxonomic profiles associated with nephrolithiasis status, using 16S rRNA gene sequencing. Nephrolithiasis status was categorized into three groups: control (no-stone at both baseline and follow-up visits), incidental nephrolithiasis, and prevalent nephrolithiasis. Compared to the control and incidental nephrolithiasis, the prevalent nephrolithiasis showed a reduced evenness in alpha diversity. Nephrolithiasis was associated with a reduced abundance of some key taxa involved in short-chain fatty acid production. Moreover, the abundance of Bifidobacterium, which possess oxalate-degrading ability, was higher in the control. Conversely, there was no significant difference in the bacterial composition between the incidental and prevalent nephrolithiasis. In our study with repeated nephrolithiasis measurements, prevalent renal stones were associated with an altered gut microbiota composition compared to the control. Besides the known oxalate degradation pathway, other functional pathways inferred in this study require further investigation.

Gut Microbiota Composition across Normal Range Prostate-Specific Antigen Levels.

Animal studies have shown the interaction between androgens and the gut microbiome directly and indirectly; however, limited evidence from human studies is available. To evaluate the association between prostate-specific antigen (PSA) levels within the normal range, reflective of androgen receptor activity, and the gut microbiota composition, a cross-sectional analysis was performed in 759 Korean men aged between 25 and 78 years with normal PSA levels of ≤4.0 ng/mL. We evaluated the biodiversity of gut microbiota as well as the taxonomic and functional signatures associated with PSA levels using 16S rRNA gene sequencing data. PSA levels within the normal range were categorized into three groups: lowest quartile (G1), interquartile range (G2, reference), and highest quartile (G3). The G3 group had higher microbial richness than the G2 group, although it was dominated by a few bacteria. An increase in Escherichia/Shigella abundance and a reduction in Megamonas abundance in the G3 group were also detected. A U-shaped relationship was observed between the three groups across most analyses, including biodiversity, taxonomic composition, and inferred pathways in the gut microbiota. This study showed different microbiota patterns across PSA levels within the normal range. Further studies are required to elucidate the role of microbiota in regulating PSA levels.

Enhancing nitrogen removal from anaerobically-digested swine wastewater through integration of Myriophyllum aquaticum and free nitrous acid-based technology in a constructed wetland.

Despite of low operation costs and convenient maintenance, the application of natural systems for swine wastewater treatment has been limited by large construction area and unsatisfactory effluent quality. Introducing ammonium high uptake aquatic plants and shifting nitrogen removal pathway from nitrate to nitrite in constructed wetlands (CWs) has been regarded as promising approach to promote their performances. This study aimed to establish nitrite pathway and enhance N removal via free nitrous acid (FNA)-sediment treatment and Myriophyllum aquaticum vegetation in the CWs treating anaerobically digested swine wastewater. Nitrite pathway was successfully and stably achieved in the M. aquaticum CW with FNA-treated sediment. The overall removal efficiencies of ammonium nitrogen and total nitrogen were 42.3 ± 10.2% and 37.7 ± 9.3% in the planted CWs with FNA-treated sediment, which were 76.3% and 65.4% higher than those in the conventional oxidation pond system, respectively. Microbial community analysis (qPCR and metagenomics) suggested that the nitrite pathway established through FNA-sediment treatment was based on the inactivation of nitrite oxidizing bacteria (lower nxrA gene abundance) and the reduction of relative abundances of NOB (especially Nitrobacter and Nitrospira). During the denitrification processes, the integration of M. aquaticum vegetation with FNA-sediment treatment can lower the nitrate reduction by decreasing narG gene abundances and decreasing the relative abundances of napA affiliated bacteria (especially Bradyrhizobium), while strengthening reduction of nitrite and nitrous oxide by increasing nirK and nosZ gene abundances and enriching the corresponding affiliated microbial taxa, Mycobacterium and Bacillus, respectively. Our findings suggest that applying FNA-based technology in CW systems is technically and economically feasible, which holds promise for upgrading current CW systems treating swine wastewater to meet future water quality requirements.

Chronologic trends of cancer-related lymph node research in PubMed: informetrics analysis.

PURPOSE: Given the long history of investigation into cancer and its relevance to the lymph node (LN), it would be meaningful to plot the trends of research on cancer-related LN. METHODS: Queries such as "cancer," "lymph node," and "cancer and lymph node" were submitted to PubMed to collect articles on cancer and LN published between 1945 and 2017. The collected articles were then extracted by an automatic web crawler and examined through informetrics and linguistic analysis. RESULTS: The number of articles related to cancer was 2,795,476 and 127,897 articles (4.6%) were found to be relevant to LN. With regard to cancer types, breast cancer was the most studied (37%), followed by gastric cancer (17%). With regard to the subjects in which the surgeon is interested, LN metastasis (57%) was found to be the topic most discussed, followed by LN dissection (22%) and sentinel LN (17%). Publications on LN metastasis gradually increased over time from 1988 to 2017 although those on sentinel LN and LN dissection have stagnated since the early 2000s. CONCLUSION: Although research on cancer was abundant, only a small portion was dedicated to investigating its relevance to LN. Western countries had led the research on cancer-related LN, but Asian countries began to participate as major players, expanding their contributions. While LN metastasis, one of the major cancer-related LN topics, showed a steady increase, those involved in oncologic surgery such as LN dissection and sentinel LN did not.