ABSTRACT
Appropriate DNA end synapsis, regulated by core components of the synaptic complex including KU70-KU80, LIG4, XRCC4, and XLF, is central to non-homologous end joining (NHEJ) repair of chromatinized DNA double-strand breaks (DSBs). However, it remains enigmatic whether chromatin modifications can influence the formation of NHEJ synaptic complex at DNA ends, and if so, how this is achieved. Here, we report that the mitotic deacetylase complex (MiDAC) serves as a key regulator of DNA end synapsis during NHEJ repair in mammalian cells. Mechanistically, MiDAC removes combinatorial acetyl marks on histone H2A (H2AK5acK9ac) around DSB-proximal chromatin, suppressing hyperaccumulation of bromodomain-containing protein BRD4 that would otherwise undergo liquid-liquid phase separation with KU80 and prevent the proper installation of LIG4-XRCC4-XLF onto DSB ends. This study provides mechanistic insight into the control of NHEJ synaptic complex assembly by a specific chromatin signature and highlights the critical role of H2A hypoacetylation in restraining unscheduled compartmentalization of DNA repair machinery.
Subject(s)
Chromatin , Nuclear Proteins , Animals , Chromatin/genetics , Nuclear Proteins/metabolism , Transcription Factors/metabolism , DNA/genetics , DNA End-Joining Repair , Histones/genetics , Histones/metabolism , Chromosome Pairing , Ku Autoantigen/genetics , Ku Autoantigen/metabolism , Mammals/metabolismABSTRACT
Homologous recombination (HR) plays a key role in maintaining genomic stability, and the efficiency of the HR system is closely associated with tumor response to chemotherapy. Our previous work reported that CK2 kinase phosphorylates HIV Tat-specific factor 1 (HTATSF1) Ser748 to facilitate HTATSF1 interaction with TOPBP1, which in turn, promotes RAD51 recruitment and HR repair. However, the clinical implication of the CK2-HTATSF1-TOPBP1 pathway in tumorigenesis and chemotherapeutic response remains to be elucidated. Here, we report that the CK2-HTATSF1-TOPBP1 axis is generally hyperactivated in multiple malignancies and renders breast tumors less responsive to chemotherapy. In contrast, deletion mutations of each gene in this axis, which also occur in breast and lung tumor samples, predict higher HR deficiency scores, and tumor cells bearing a loss-of-function mutation of HTATSF1 are vulnerable to poly(ADP-ribose) polymerase inhibitors or platinum drugs. Taken together, our study suggests that the integrity of the CK2-HTATSF1-TOPBP1 axis is closely linked to tumorigenesis and serves as an indicator of tumor HR status and modulates chemotherapy response.
Subject(s)
Carrier Proteins , Casein Kinase II , DNA-Binding Proteins , Signal Transduction , Humans , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Signal Transduction/drug effects , Casein Kinase II/metabolism , Casein Kinase II/genetics , Carrier Proteins/metabolism , Carrier Proteins/genetics , Animals , Female , Mice , Cell Line, Tumor , Nuclear Proteins/metabolism , Nuclear Proteins/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Neoplasms/metabolism , Neoplasms/drug therapy , Neoplasms/genetics , Neoplasms/pathologyABSTRACT
BACKGROUND: Abdominal aortic aneurysm (AAA) is a potentially life-threatening vascular condition, but approved medical therapies to prevent AAA progression and rupture are currently lacking. Sphingolipid metabolism disorders are associated with the occurrence and development of AAA. It has been discovered that ganglioside GM3, a sialic acid-containing type of glycosphingolipid, plays a protective role in atherosclerosis, which is an important risk factor for AAA; however, the potential contribution of GM3 to AAA development has not been investigated. METHODS: We performed a metabolomics study to evaluated GM3 level in plasma of human patients with AAA. We profiled GM3 synthase (ST3GAL5) expression in the mouse model of aneurysm and human AAA tissues through Western blotting and immunofluorescence staining. RNA sequencing, affinity purification and mass spectrometry, proteomic analysis, surface plasmon resonance analysis, and functional studies were used to dissect the molecular mechanism of GM3-regulating ferroptosis. We conditionally deleted and overexpressed St3gal5 in smooth muscle cells (SMCs) in vivo to investigate its role in AAA. RESULTS: We found significantly reduced plasma levels of GM3 in human patients with AAA. GM3 content and ST3GAL5 expression were decreased in abdominal aortic vascular SMCs in patients with AAA and an AAA mouse model. RNA sequencing analysis showed that ST3GAL5 silencing in human aortic SMCs induced ferroptosis. We showed that GM3 interacted directly with the extracellular domain of TFR1 (transferrin receptor 1), a cell membrane protein critical for cellular iron uptake, and disrupted its interaction with holo-transferrin. SMC-specific St3gal5 knockout exacerbated iron accumulation at lesion sites and significantly promoted AAA development in mice, whereas GM3 supplementation suppressed lipid peroxidation, reduced iron deposition in aortic vascular SMCs, and markedly decreased AAA incidence. CONCLUSIONS: Together, these results suggest that GM3 dysregulation promotes ferroptosis of vascular SMCs in AAA. Furthermore, GM3 may constitute a new therapeutic target for AAA.
Subject(s)
Aortic Aneurysm, Abdominal , Ferroptosis , Humans , Mice , Animals , G(M3) Ganglioside/metabolism , Proteomics , Muscle, Smooth, Vascular/metabolism , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/prevention & control , Aortic Aneurysm, Abdominal/metabolism , Iron , Myocytes, Smooth Muscle/metabolism , Disease Models, AnimalABSTRACT
Unscheduled R-loops are a major source of replication stress and DNA damage. R-loop-induced replication defects are sensed and suppressed by ATR kinase, whereas it is not known whether R-loop itself is actively involved in ATR activation and, if so, how this is achieved. Here, we report that the nuclear form of RNA-editing enzyme ADAR1 promotes ATR activation and resolves genome-wide R-loops, a process that requires its double-stranded RNA-binding domains. Mechanistically, ADAR1 interacts with TOPBP1 and facilitates its loading on perturbed replication forks by enhancing the association of TOPBP1 with RAD9 of the 9-1-1 complex. When replication is inhibited, DNA-RNA hybrid competes with TOPBP1 for ADAR1 binding to promote the translocation of ADAR1 from damaged fork to accumulate at R-loop region. There, ADAR1 recruits RNA helicases DHX9 and DDX21 to unwind R-loops, simultaneously allowing TOPBP1 to stimulate ATR more efficiently. Collectively, we propose that the tempo-spatially regulated assembly of ADAR1-nucleated protein complexes link R-loop clearance and ATR activation, while R-loops crosstalk with blocked replication forks by transposing ADAR1 to finetune ATR activity and safeguard the genome.
Subject(s)
DNA-Binding Proteins , R-Loop Structures , Ataxia Telangiectasia Mutated Proteins/genetics , Ataxia Telangiectasia Mutated Proteins/metabolism , Cell Cycle Proteins/metabolism , DNA Replication , DNA-Binding Proteins/genetics , RNA/genetics , Humans , Animals , MiceABSTRACT
Hydrogen energy and biomass energy are green and sustainable forms that can solve the energy crisis all over the world. Electrocatalytic water splitting is a marvelous way to produce hydrogen and biomass platform molecules can be added into the electrolyte to reduce the overpotential and meanwhile are converted into some useful organics, but the key point is the design of electrocatalyst. Herein, ultralow noble metal Ru is doped into NiS2 to form RuO2@NiS2 heterojunction. Amongst them, the 0.06 RuO2@NiS2 has low overpotentials of 363 mV for OER and 71 mV for HER in 1 m KOH, which are superior to the RuO2 and Pt/C. Besides, the 0.06 RuO2@NiS2 shows a low overpotential of 173 mV in 1 m KOH+0.1 m glycerol, and the glycerol is oxidized to glyceraldehyde and formic acid via the high Faraday efficiency GlyOR process, and the splitting voltage is only 1.17 V. In addition, the 0.06 RuO2@NiS2 has a low overpotential of 206 mV in 1 m KOH+0.1 m glucose, and the glucose is converted to glucaric acid, lactic acid, and formic acid. This work has a "one stone three birds" effect for the production of hydrogen, low splitting voltage, and high-value-added biomass chemicals.
ABSTRACT
Proton exchange membrane water electrolysis (PEMWE) is considered an ideal green hydrogen production technology with promising application prospects. However, the development of efficient and stable acid electroanalytic oxygen electrocatalysts is still a challenging bottleneck. This progress is achieved by adopting a strategic approach with the introduction of the high valence metal Ta to regulate the electronic configuration of RuO2 by manipulating its local microenvironment to optimize the stability and activity of the electrocatalysts. The Ta-RuO2 catalysts are notable for their excellent electrocatalytic activity, as evidenced by an overpotential of only 202 mV at 10 mA cm-2, which significantly exceeds that of homemade RuO2 and commercial RuO2. Furthermore, the Ta-RuO2 catalyst exhibits exceptional stability with negligible potential reduction observed after 50 h of electrolysis. Theoretical calculations show that the asymmetric configuration of Ru-O-Ta breaks the thermodynamic activity limitations usually associated with adsorption evolution, weakening the energy barrier for the formation of the OOH* formation. The strategic approach presented in this study provides an important reference for the development of a stable active center for acid water splitting.
ABSTRACT
Location-based application services and location privacy protection solutions are often required for the storage, management, and efficient retrieval of large amounts of geolocation data for specific locations or location intervals. We design a hierarchical tree-like organization structure, GL-Tree, which enables the storage, management, and retrieval of massive location data and satisfies the user's location-hiding requirements. We first use Geohash encoding to convert the two-dimensional geospatial coordinates of locations into one-dimensional strings and construct the GL-Tree based on the Geohash encoding principle. We gradually reduce the location intervals by extending the length of the Geohash code to achieve geospatial grid division and spatial approximation of user locations. The hierarchical tree structure of GL-Tree reflects the correspondence between Geohash codes and geographic intervals. Users and their location relationships are recorded in the leaf nodes at each level of the hierarchical GL-Tree. In top-down order, along the GL-Tree, efficient storage and retrieval of location sets for specified locations and specified intervals can be achieved. We conducted experimental tests on the Gowalla public dataset and compared the performance of the B+ tree, R tree, and GL-Tree in terms of time consumption in three aspects: tree construction, location insertion, and location retrieval, and the results show that GL-Tree has good performance in terms of time consumption.
ABSTRACT
Single-atom catalysts anchored to oxide or carbonaceous substances are typically tightly coordinated by oxygen or heteroatoms, which certainly impact their electronic structure and coordination environment, thereby affecting their catalytic activity. In this study, we prepared a stable oxygen evolution reaction (OER) catalyst on tungsten carbide using a simple pyrolysis method. The unique structure of tungsten carbide allows the atomic RuNi catalytic site to weakly bond to the surface W and C atoms. XRD patterns and HRTEM images of the WCx-RuNi showed the characteristics of phase-pure WC and W2C, and the absence of nanoparticles. Combined with XPS, the atomic dispersion of Ru/Ni in the catalyst was confirmed. The catalyst exhibits excellent catalytic ability, with a low overpotential of 330 mV at 50 mA/cm2 in 1 m KOH solutions, and demonstrates high long-term stability. This high OER activity is ascribed to the synergistic action of metal Ru/Ni atoms with double monomers. The addition of Ni increases the state density of WCx-RuNi near the Fermi level, promoting the adsorption of oxygen-containing intermediates and enhancing electron exchange. The larger proximity of the d band center to the Fermi level suggests a strong interaction between the d electrons and the valence or conduction band, facilitating charge transfer. Our research offers a promising avenue for reasonable utilization of inexpensive and durable WCx carrier-supported metal single-atom catalysts for electrochemical catalysis.
ABSTRACT
PEDOT-Ag/AgCl is a highly promising material with dual functions of hydrogen evolution reaction (HER) and supercapacitors. In this study, a simple low-temperature stirring and light irradiation method was used to synthesize PEDOT-Ag/AgCl on the surface. Then, PEDOT-Ag/AgCl was analyzed using X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, and transmission electron microscopy. PEDOT-Ag/AgCl reacted in 1 M KOH alkaline electrolyte with an overpotential of 157 mV at 20 mA·cm-2 and a Tafel slope of 66.95 mv·dec-1. Owing to the synergistic effect of PEDOT and Ag/AgCl, this material had a small resistance (1.7 Ω) and a large specific capacitance (978 F·g-1 at current density of 0.5 A·g-1). The synthesis method can prepare nanostructured PEDOT with uniformly-distributed Ag nanoparticles and rod-shaped AgCl on the surface, which can be used as both HER electrocatalysts and supercapacitor electrodes.
ABSTRACT
With the development of mobile applications, location-based services (LBSs) have been incorporated into people's daily lives and created huge commercial revenues. However, when using these services, people also face the risk of personal privacy breaches due to the release of location and query content. Many existing location privacy protection schemes with centralized architectures assume that anonymous servers are secure and trustworthy. This assumption is difficult to guarantee in real applications. To solve the problem of relying on the security and trustworthiness of anonymous servers, we propose a Geohash-based location privacy protection scheme for snapshot queries. It is named GLPS. On the user side, GLPS uses Geohash encoding technology to convert the user's location coordinates into a string code representing a rectangular geographic area. GLPS uses the code as the privacy location to send check-ins and queries to the anonymous server and to avoid the anonymous server gaining the user's exact location. On the anonymous server side, the scheme takes advantage of Geohash codes' geospatial gridding capabilities and GL-Tree's effective location retrieval performance to generate a k-anonymous query set based on user-defined minimum and maximum hidden cells, making it harder for adversaries to pinpoint the user's location. We experimentally tested the performance of GLPS and compared it with three schemes: Casper, GCasper, and DLS. The experimental results and analyses demonstrate that GLPS has a good performance and privacy protection capability, which resolves the reliance on the security and trustworthiness of anonymous servers. It also resists attacks involving background knowledge, regional centers, homogenization, distribution density, and identity association.
ABSTRACT
Autothermal thermophilic aerobic digestion (ATAD) is a promising biological process that will produce an effluent satisfying the Class A requirements on pathogen control and land application. The thermophilic temperature in an ATAD reactor is one of the critical factors that can affect the satisfactory operation of the ATAD process. This paper established a thermal equilibrium model to predict the effect of variables on the auto-rising temperature in an ATAD system. The reactors with volumes smaller than 10 m(3) could not achieve temperatures higher than 45 °C under ambient temperature of -5 °C. The results showed that for small reactors, the reactor volume played a key role in promoting auto-rising temperature in the winter. Thermophilic temperature achieved in small ATAD reactors did not entirely depend on the heat release from biological activities during degrading organic matters in sludges, but was related to the ambient temperature. The ratios of surface area-to-effective volume less than 2.0 had less impact on the auto-rising temperature of an ATAD reactor. The influence of ambient temperature on the auto-rising reactor temperature decreased with increasing reactor volumes. High oxygen transfer efficiency had a significant influence on the internal temperature rise in an ATAD system, indicating that improving the oxygen transfer efficiency of aeration devices was a key factor to achieve a higher removal rate of volatile solids (VS) during the ATAD process operation. Compared with aeration using cold air, hot air demonstrated a significant effect on maintaining the internal temperature (usually 4-5 °C higher).
Subject(s)
Bioreactors , Energy Transfer , Hot Temperature , Models, Theoretical , Thermodynamics , Waste Disposal, Fluid/methods , Aerobiosis , SewageABSTRACT
DNA methylation plays a critical role in hematopoietic differentiation. Epimutation is a stochastic variation in DNA methylation that induces epigenetic heterogeneity. However, the effects of epimutations on normal hematopoiesis and hematopoietic diseases remain unclear. In this study, we developed a Julia package called EpiMut that enabled rapid and accurate quantification of epimutations. EpiMut was used to evaluate and provide an epimutation landscape in steady-state hematopoietic differentiation involving 13 types of blood cells ranging from hematopoietic stem/progenitor cells to mature cells. We showed that substantial genomic regions exhibited epigenetic variations rather than significant differences in DNA methylation levels between the myeloid and lymphoid lineages. Stepwise dynamics of epimutations were observed during the differentiation of each lineage. Importantly, we found that epimutation significantly enriched signals associated with lineage differentiation. Furthermore, epimutations in hematopoietic stem cells (HSCs) derived from various sources and acute myeloid leukemia were related to the function of HSCs and malignant cell disorders. Taken together, our study comprehensively documented an epimutation map and uncovered its important roles in human hematopoiesis, thereby offering insights into hematopoietic regulation.
ABSTRACT
Although, superkiller complex protein 8 (SKI8), previously known as WDR61 has been identified and mapped in breast tumor, little is currently known about its function. This study aims to elucidate the role of WDR61 in breast tumor development and its potential as a therapeutic target. Here, we show that tamoxifen-induced knockout of Wdr61 reduces the risk of breast tumors, resulting in smaller tumor size and weight, and improved overall survival. Furthermore, we show that knockdown of WDR61 compromises the proliferation of breast tumor cells with reduced colony-forming capacity. Further investigations demonstrate that the protective effect of WDR61 loss on breast tumor development is due to genomic instability. Mechanistic studies reveal that WDR61 interacts with the R-loop, and loss of WDR61 leads to R-loops accumulation in breast tumor cells, causing DNA damage and subsequent inhibition of cell proliferation. In summary, this study highlights the critical dependence of breast tumors on WDR61, which suppresses R-loop and counteracts endogenous DNA damage in tumor cells.
Subject(s)
Breast Neoplasms , Cell Proliferation , DNA Damage , Breast Neoplasms/pathology , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Female , Humans , Animals , Mice , Genomic Instability , Disease Progression , Cell Line, Tumor , Gene Expression Regulation, NeoplasticABSTRACT
Macleaya cordata was a kind of traditional herbal medicine, which may a potential substitute for antibiotics. However, the effects of Macleaya cordata on neonatal piglets have rarely been reported. In this study, three groups were designed, including normal saline (Control group, CON), 8â¯mg/mL Macleaya cordata extract (MCE group, MCE) and 5â¯mg/mL Chlortetracycline Hydrochloride (CCH group, CCH), to investigate the effects of MCE on growth performance, blood parameters, inflammatory cytokines, regenerating islet-derived 3â¯gamma (REG3γ) expression and the transcriptomes of neonatal piglets. The results showed that, compared with the control group, MCE significantly increased the average daily gain (p < 0.01); spleen index (p < 0.05) contents of IL-10, TGF-ß, IgG in serum and sIgA in the ileum mucus of neonatal piglets at 7 d and 21 d (p < 0.01). The diarrhoea incidence and serum TNF-α and IFN-γ contents of neonatal piglets at 7 d and 21 d were significantly decreased (p < 0.01). In addition, MCE significantly increased the mRNA expression of TGF-ß, IL-10, and REG3γ (p < 0.01) and significantly decreased the mRNA expression of IL-33, TNF-α and IFN-γ in the ileal mucosa of neonatal piglets at 21 d (p < 0.01). The differentially expressed genes and the signal pathways, related to cytokine generation and regulation, immunoregulation and inflammation were identified. In conclusion, MCE can significantly improve growth performance, reduce diarrhoea incidence, relieve inflammation, improve immune function, and improve disease resistance in neonatal piglets. MCE can be used as a potential substitute for antibiotics in neonatal piglets.
Subject(s)
Animals, Newborn , Anti-Inflammatory Agents , Cytokines , Plant Extracts , Animals , Swine , Plant Extracts/pharmacology , Anti-Inflammatory Agents/pharmacology , Cytokines/genetics , Cytokines/metabolism , Papaveraceae/chemistry , Swine Diseases/immunology , Diarrhea/veterinary , Diarrhea/drug therapyABSTRACT
Rosemary (Rosmarinus officinalis L.) is a natural spice plant with an aromatic flavor and antioxidant properties that can help enhance the flavor and texture of food, as well as be used as an antioxidant source in pet feed. This study explored the effect of rosemary on the growth performance and antioxidant capacity of broiler chickens. In total, 144 healthy 1-day-old Arbor Acres broilers were randomly divided into four groups: The control group was fed a basic diet, while the positive control group was fed a basic diet supplemented with 30 mg/kg kitasamycin, and the treatment groups were fed a basic diet supplemental with 0.5% rosemary, or 2% rosemary. The average daily feed intake of broilers fed with 0.5% and 2% rosemary in 1-42 days was higher than that in the basal diet group (p < 0.05). The pH was lower in the rosemary groups than in the 30 mg/kg kitasamycin group as measured in the thigh muscle tissue (p < 0.05), and the monounsaturated fatty acid C17:1 heptadecanoic acid content of the 2% rosemary group was higher than that of the other groups (p < 0.05). With 0.5% rosemary supplementation, the activities of the serum and liver antioxidant enzymes catalase (CAT) activity and total antioxidant capacity (T-AOC) increased (p < 0.05); malondialdehyde content decreased (p < 0.05). The serum activities of CAT, total superoxide dismutase, and T-AOC increased with 2% rosemary supplementation (p < 0.05). The relative expression of liver antioxidant genes, the nuclear factor E2-related factor 2, glutathione catalase 1, and superoxide dismutase 1 increased (p < 0.05) with 0.5% rosemary supplementation. The addition of rosemary resulted in higher intestinal lactobacilli counts and lower E. coli counts. In summary, adding 0.5% or 2% rosemary to the diet improved the growth performance of Arbor Acres broilers and increased the number of intestinal probiotics, and supplementing with 0.5% rosemary yielded better results than adding 2% rosemary. This study provides valuable insights into the broader application of plant-derived antioxidants in promoting sustainable and health-focused animal farming practices.
ABSTRACT
To improve the reproductive performance of sows and the iron nutrition of newborn piglets, we studied the effects of dietary iron on reproductive performance in pregnant sows as well as antioxidant capacity and the visceral iron content of sows and newborn piglets. Forty pregnant sows were divided into four groups, the iron deficiency group (Id group) was fed a basic diet while sows in the treatment groups were fed diets supplemented with 200 mg/kg lactoferrin (LF group), 0.8% heme-iron (Heme-Fe group), or 500 mg/kg iron-glycine complex (Fe-Gly group). The results indicated that (1) different sources of iron had no significant effect on litter size, live litter size, and litter weight of sows; (2) the three additives improved iron nutrition in newborn piglets, with LF and Heme-Fe having better improvement effects; and (3) the addition of different iron sources improved the level of serum antioxidant biochemical indexes of sows and newborn piglets, and it can have an effect on gene level, among which lactoferrin has the best effect. Thus, adding LF, Heme-iron, or Fe-Gly to the diet of sows during the second and third trimester of gestation can improve the antioxidant capacity of the sows. The supplementation of LF in pregnant sow diets can also improve the antioxidant capacity and the iron nutrition of newborn piglets, with better additive effects than in Heme-Fe and Fe-Gly.
ABSTRACT
Developing multifunctional catalysts applied in diversiform modes via advanced oxidation processes (AOPs) is a promising and attractive approach for organic pollution degradation. Herein, a novel hollow bamboo-like structural cobalt/nitrogen-doped carbonized material (CoC/N) was employed as a catalyst for AOPs, in which CoC/N was prepared in situ through calcining a Co-based coordination polymer. When CoC/N was utilized as a peroxymonosulfate (PMS) activator, the catalyst stood out prominent activities for effective CA oxidation. Furthermore, a five-level central composite rotatable design (CCRD) model describing CA decay as a function of PMS concentration, CoC/N dosage, and solution pH value was successfully constructed and engaged to explore the optimal operating conditions. Finally, the possible degradation mechanism of CA in CoC/N-PMS system was proposed by quantum chemistry calculation and LC/MS analysis. This work shed light on the structural morphology of the catalyst and its PMS synergy degradation pathway, which promotes its applications in miscellaneous pollutant degradation. A new Co/N-doped material was used to degrade unconventionality organic pollutant creatinine (CA) for the first time, in which the scientific approaches of five-level central composite rotatable design (CCRD) model, response surface methodology (RSM) and density function theory (DFT) were employed to evaluate the material performance and CA degradation pathway. The toxicity evaluation, statistical modeling and mechanisms study have been investigated meticulously.
Subject(s)
Cobalt , Environmental Pollutants , Cobalt/chemistry , Creatinine , Nitrogen , Peroxides/chemistryABSTRACT
The immune function of the intestinal mucosa plays a crucial role in the intestinal health of hosts. As signaling molecules and precursors of metabolic reactions, intestinal chyme metabolites are instrumental in maintaining host immune homeostasis. Saba (SB) pigs, a unique local pig species in central Yunnan Province, China. However, research on jejunal metabolites in this species is limited. Here, we used immunohistochemistry and untargeted metabolomics by liquid chromatography mass spectrometry (LC-MS/MS) to study differences in jejunal immunophenotypes and metabolites between six Landrace (LA) and six SB piglets (35 days old). The results showed that the levels of the anti-inflammatory factor interleukin 10 (IL-10) were markedly higher in SB piglets than in LA piglets (P < 0.01), while the levels of the proinflammatory factors IL-6, IL-1ß, and Toll-like receptor 2 (TLR-2) were markedly lower (P < 0.01). Furthermore, the levels of mucin 2 (MUC2) and zona occludens (ZO-1), which are related to mucosal barrier function, were significantly higher in SB piglets than in LA piglets (P < 0.01), as were villus height, villus height/crypt depth ratio, and goblet cell number (P < 0.05). Differences in jejunal chyme metabolic patterns were observed between the two piglets. In the negative ion mode, cholic acid metabolites ranked in the top 20 and represented 25% of the total. Taurodeoxycholic acid (TDCA) content was significantly higher in SB piglets than in LA piglets (P < 0.01). TDCA positively correlated with ZO-1, villus height, villus height/crypt depth ratio, and goblet cell number. These results suggest that SB pigs have a strong jejunal immune function and that TDCA was positively regulates jejunal immunity and mucosal barrier function. Our findings provide a reference for understanding intestinal immune function in different pig breeds and for the discovery of potential biomarkers to help solve health issues related to pig production.
ABSTRACT
The atomically-dispersed and nitrogen-coordinated iron (FeNC) on a carbon catalyst is a potential non-noble metal catalyst that can replace precious metal electrocatalysts. However, its activity is often unsatisfactory owing to the symmetric charge distribution around the iron matrix. In this study, atomically- dispersed Fe-N4 and Fe nanoclusters loaded with N-doped porous carbon (FeNCs/FeSAs-NC-Z8@34) were rationally fabricated by introducing homologous metal clusters and increasing the N content of the support. FeNCs/FeSAs-NC-Z8@34 exhibited a half-wave potential of 0.918 V, which exceeded that of the commercial benchmark Pt/C catalyst. Theoretical calculations verified that introducing Fe nanoclusters can break the symmetric electronic structure of Fe-N4, thus inducing charge redistribution. Furthermore, it can optimize a part of Fe 3d occupancy orbitals and accelerate OO fracture in OOH* (rate-determining step), thus significantly improving oxygen reduction reaction activity. This work provides a reasonably advanced pathway to modulate the electronic structure of the single-atom center and optimize the catalytic activity of single-atom catalysts.
ABSTRACT
Anodic oxidation with boron-doped diamond (BDD) has been regarded as outstanding option for wastewater treatment. However, in the presence of halide, the extreme promise of the technology may be hampered by the formation of toxic halogenated by-products. While the behaviors of chloride are relatively understood, little is currently known about the role of bromide and its effect on the generation of brominated transformation by-products (BTPs). Herein, we reported for the first time the bromide-mediated electrochemical mineralization of bisphenol A with BDD anodes. Firstly, we employed statistical methodology to determine the impacts of the main operating variables on the mineralization performance, and the novel and peculiar roles of bromides during the electrolytic oxidations were identified. Next, LC/MS analysis was used to identify the reaction intermediates, and plenty of BTPs (including oligomers of complex structures) were thus detected. Detailed transformation mechanisms responsible for the BTPs were also proposed. Lastly, we used ECOSAR program to determine the ecological toxicity of all detected by-products, and the structure-toxicity relation involved was discussed. Overall, the above results are of particular interest to understand BTPs formation mechanism in electrochemical oxidation processes, which as well provide guidelines to minimize potential risks of BDD technology for phenolic wastewater treatment.