Antagonistic effect of selenium on mercuric chloride in the central immune organs of chickens: The role of microRNA-183/135b-FOXO1/TXNIP/NLRP3 inflammasome axis.

Mercury (Hg) is a persistent environmental and industrial pollutant that accumulated in the body and induces oxidative stress and inflammation damage. Selenium (Se) has been reported to antagonize immune organs damage caused by heavy metals. Here, we aimed to investigate the prevent effect of Se on mercuric chloride (HgCl2 )-induced thymus and bursa of Fabricius (BF) damage in chickens. The results showed that HgCl2 caused immunosuppression by reducing the relative weight, cortical area of the thymus and BF, and the number of peripheral blood lymphocytes. Meanwhile, HgCl2 induced oxidative stress and imbalance in cytokines expression in the thymus and BF. Further, we found that thioredoxin-interacting protein (TXNIP) and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome mediated HgCl2 -induced oxidative stress and inflammation. Mechanically, the targeting and inhibitory effect of microRNA (miR)-135b/183 on forkhead box O1 (FOXO1) were an upstream event for HgCl2 -activated TXNIP/NLRP3 inflammasome pathway. Most importantly, Se effectively attenuated the aforementioned damage in the thymus and BF caused by HgCl2 and inhibited the TXNIP/NLRP3 inflammasome pathway by reversing the expression of FOXO1 through inhibiting miR-135b/183. In conclusion, the miR-135b/183-FOXO1/TXNIP/NLRP3 inflammasome axis might be a novel mechanism for Se to antagonize HgCl2 -induced oxidative stress and inflammation in the central immune organs of chickens.

Selenium alleviates mercury chloride-induced liver injury by regulating mitochondrial dynamics to inhibit the crosstalk between energy metabolism disorder and NF-κB/NLRP3 inflammasome-mediated inflammation.

Mercury (Hg) is a persistent heavy metal contaminant with definite hepatotoxicity. Selenium (Se) has been shown to alleviate liver damage induced by heavy metals. Therefore, the present study aimed to explore the mechanism of the antagonistic effect of Se on mercury chloride (HgCl2)-induced hepatotoxicity in chickens. Firstly, we confirmed that Se alleviated HgCl2-induced liver injury through histopathological observation and liver function analyzation. The results also showed that Se prevented HgCl2-induced liver lipid accumulation and dyslipidemia by regulating the gene expression related to lipid as well as glucose metabolism. Moreover, Se blocked the nuclear factor kappa B (NF-κB)/NLR family pyrin domain containing 3 (NLRP3) inflammasome signaling pathway, which was the key to alleviate the inflammation caused by HgCl2. Mechanically, Se inhibited immoderate mitochondrial division, fusion, and biogenesis caused by HgCl2, and also improved mitochondrial respiration, which were essential for preventing energy metabolism disorder and inflammation. In conclusion, our results suggested that Se inhibited energy metabolism disorder and inflammation by regulating mitochondrial dynamics, thereby alleviating HgCl2-induced liver injury in chickens. These results are expected to provide potential intervention and therapeutic targets for diseases caused by inorganic mercury poisoning.

Built-in Electric Field Triggered Interfacial Accumulation Effect for Efficient Nitrate Removal at Ultra-Low Concentration and Electroreduction to Ammonia.

A built-in electric field in electrocatalyst can significantly accumulate higher concentration of NO3 - ions near electrocatalyst surface region, thus facilitating mass transfer for efficient nitrate removal at ultra-low concentration and electroreduction reaction (NO3 RR). A model electrocatalyst is created by stacking CuCl (111) and rutile TiO2 (110) layers together, in which a built-in electric field induced from the electron transfer from TiO2 to CuCl (CuCl_BEF) is successfully formed . This built-in electric field effectively triggers interfacial accumulation of NO3 - ions around the electrocatalyst. The electric field also raises the energy of key reaction intermediate *NO to lower the energy barrier of the rate determining step. A NH3 product selectivity of 98.6 %, a low NO2 - production of <0.6 %, and mass-specific ammonia production rate of 64.4 h-1 is achieved, which are all the best among studies reported at 100 mg L-1 of nitrate concentration to date.

Dietary Iron Overload Triggers Hepatic Metabolic Disorders and Inflammation in Laying Hen.

Iron, an essential trace element, is involved in various physiological processes; however, consumption of excessive iron possesses detrimental effects. In practical feed production, the iron content added to feeds often far exceeds the actual demand, resulting in an excess of iron in the body. The liver as a central regulator of iron homeostasis is susceptible to damage caused by disorders in iron metabolism. A model of hepatic iron overload in laying hens was developed in this study by incorporating iron into their diet, and the specific mechanisms underlying iron overload-induced hepatic injury were investigated. Firstly, this study revealed that a high-iron diet resulted in hepatic iron overload, accompanied by impaired liver function. Next, assessment of oxidative stress markers indicated a decrease in activities of T-SOD and CAT, coupled with an increase in MDA content, pointing to the iron-overloaded liver oxidative stress. Thirdly, the impact of iron overload on hepatic glycolipid and bile acid metabolism-related gene expressions were explored, including PPAR-α, GLUT2, and CYP7A1, highlighting disruptions in hepatic metabolism. Subsequently, analyses of inflammation-related genes such as iNOS and IL-1ß at both protein and mRNA levels demonstrated the presence of inflammation in the liver under conditions of dietary iron overload. Overall, this study provided comprehensive evidence that dietary iron overload contributed to disorders in glycolipid and bile acid metabolism, accompanied by inflammatory responses in laying hens. Further detailing the specific pathways involved and the implications of these findings could offer valuable insights for future research and practical applications in poultry nutrition.

Substrate-controlled [4+1] and [3+2] annulations of ninhydrin-derived Morita-Baylis-Hillman carbonates to access polysubstituted furans and cyclopentenes.

The effective and mild [4+1] annulation of ninhydrin-derived MBH carbonates with α,ß-unsaturated ketones has been developed, providing a wide range of multisubstituted furans in high yields (up to 90%) with excellent ß-regioselectivities. In contrast, the polysubstituted cyclopentenes bearing dispiro-bisindanedione motifs were obtained via classical [3+2] annulations by employing ninhydrin-derived MBH carbonates with 2-arylidene-1,3-indandiones under the same catalytic conditions. Furthermore, the structures of two kinds of cycloadducts were straightforwardly confirmed through X-ray diffraction analysis.

Bimetallic Cu-Fe catalysts on MXene for synergistically electrocatalytic conversion of nitrate to ammonia.

NO3- is a common water pollutant that can serve as a potential nitrogen source for electrocatalytic NH3 production. However, an efficient and complete removal of low NO3- concentrations remains a challenge. Fe1Cu2@MXene bimetallic catalysts were constructed on two-dimensional Ti3C2Tx MXene carriers via a simple solution-based synthetic method and used for the electrocatalytic reduction of NO3-. The combination of the rich functional groups, high electronic conductivity on the MXene surface, and the synergistic effect between the Cu and Fe sites enabled the composite to effectively catalyse NH3 synthesis, with a 98% conversion of NO3- in 8 h and a selectivity for NH3 of up to 99.6%. In addition, Fe1Cu2@MXene showed excellent environmental and cyclic stability at various pH values and temperatures over multiple (14) cycles. Semiconductor analysis techniques and electrochemical impedance spectroscopy confirmed that the synergistic effect provided by the dual active sites of the bimetallic catalyst enabled fast electron transport. This study provides new insights into the synergistic promotion of NO3- reduction reactions using bimetals.

Mercuric chloride induces sequential activation of ferroptosis and necroptosis in chicken embryo kidney cells by triggering ferritinophagy.

Mercuric chloride (HgCl2) is an environmental pollutant with serious nephrotoxic effects, but the underlying mechanism of HgCl2 nephrotoxicity is not well understood. Ferroptosis and necroptosis are two programmed cell death (PCD) modalities that have been reported singly in heavy metal-induced kidney injury. However, the interaction between ferroptosis and necroptosis in HgCl2-induced kidney injury is unclear. Here, we established a model of HgCl2-exposed chicken embryo kidney (CEK) cells to dissect the progresses and mechanisms of these two PCDs. We found that ferroptosis was initially activated in CEK cells after HgCl2 exposure for 12 h, and necroptosis was activated subsequently at 24 h. Importantly, further study indicated that the shift from ferroptosis to necroptosis was driven by ROS, which was produced by iron-dependent Fenton reaction, and the iron chelation by DFO prevented the sequential activation of both ferroptosis and necroptosis. To investigate the source of intracellular iron, the regulation of iron homeostasis was first explored and demonstrated a tendency for intracellular iron overload in CEK cells. Interestingly, the cellular ferritin, a free iron depository, decreased in a time-dependent manner. Further studies revealed that the degradation of ferritin was attributed to the activation of selective cargo receptor nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy, and the inhibition of ferritinophagy by CQ prevented the HgCl2-induced cell death. In conclusion, our study demonstrated that HgCl2 released excess free iron via ferritinophagy, led to a sustained accumulation of ROS and ultimately activated ferroptosis and necroptosis sequentially. These findings provide a new understanding for the nephrotoxic mechanism of HgCl2.

Protective mechanism of selenium on mercuric chloride-induced testis injury in chicken via p38 MAPK/ATF2/iNOS signaling pathway.

Mercuric chloride (HgCl2) is a well-known toxic heavy metal contaminant, which causes male reproductive function defects. Selenium (Se) has been recognized as an effective antioxidant against heavy metals-induced male reproductive toxicity. The aim of present study was to explore the potentially protective mechanism of Se on HgCl2-induced testis injury in chicken. Firstly, the results showed that Se mitigated HgCl2-induced testicular injury through increasing the blood-testis barrier (BTB) cell-junction proteins expression of occludin, zonula occludens-1 (ZO-1), connexin 43 (Cx43), and N-cadherin. Secondly, Se alleviated HgCl2-induced oxidative stress through decreasing the malondialdehyde (MDA) content and increasing the superoxidase dismutase (SOD), glutathione peroxidase (GSH-Px) activities as well as the total antioxidant capacity (T-AOC) level. Thirdly, Se inhibited the activation of p38 MAPK signaling through decreasing the proteins expression of phosphorylated-p38 (p-p38) and phosphorylated-ATF2 (p-ATF2), and alleviated inflammation response through decreasing the proteins expression of inducible nitric oxide synthase (iNOS), nuclear factor kappa B (NF-κB), tissue necrosis factor-alpha (TNF-α), and cyclooxygenase 2 (COX2). Collectively, these results demonstrated that Se effectively alleviated HgCl2-induced testes injury via improving antioxidant capacity to reduce inflammation mediated by p38 MAPK/ATF2/iNOS signaling pathway in chicken. Our data shed a new light on potential mechanisms of Se antagonized HgCl2-induced male reproductive toxicity.

Selenium ameliorates mercuric chloride-induced brain damage through activating BDNF/TrKB/PI3K/AKT and inhibiting NF-κB signaling pathways.

Mercuric chloride (HgCl2), a heavy metal compound, causes neurotoxicity of animals and humans. Selenium (Se) antagonizes heavy metal-induced organ damage with the properties of anti-oxidation and anti-inflammation. Nevertheless, the molecular mechanism underlying the protective effects of sodium selenite (Na2SeO3) against HgCl2-induced neurotoxicity remains obscure. Therefore, the present study aimed to explore the protective mechanism of Na2SeO3 on HgCl2-induced brain damage in chickens. Morphological observations showed that Na2SeO3 alleviated HgCl2-induced brain tissues damage. The results also showed that Na2SeO3 decreased the protein expression of S100 calcium binding protein B (S100B), and increased the levels of nerve growth factors (NGF), doublecortin domain containing 2 (DCDC2), as well as neurotransmitter to reverse HgCl2-induced brain dysfunction. Further, Na2SeO3 attenuated HgCl2-induced oxidative stress by decreasing the level of malondialdehyde (MDA) and increasing the activities of total superoxide dismutase (T-SOD), glutathione peroxidase (GSH-Px), and total antioxidant capacity (T-AOC). Mechanistically, Na2SeO3 activated the brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor type B (TrKB)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and suppressed the nuclear factor kappa B (NF-κB) signaling pathway to inhibit apoptosis and inflammation caused by HgCl2 exposure. In summary, Na2SeO3 ameliorated HgCl2-induced brain injury via inhibiting apoptosis and inflammation through activating BDNF/TrKB/PI3K/AKT and suppressing NF-κB pathways.

Aberrant Gene Expression of Selenoproteins in Chicken Spleen Lymphocytes Induced by Mercuric Chloride.

Mercury (Hg) is a heavy metal widely distributed in ecological environment, poisoning the immune system of humans and animals. Selenium (Se) is an essential microelement and selenoproteins involved in the procedure of Se antagonizing organ toxicity induced by heavy metals. The aim of this research was to investigate the changes of gene expression profile of selenoproteins induced by mercuric chloride (HgCl2) in chicken spleen lymphocytes. We established cytotoxicity model of chicken spleen lymphocytes by HgCl2 exposure, the messenger RNA (mRNA) expression levels of 25 selenoproteins in spleen lymphocytes were analyzed by real-time quantitative PCR (qPCR), and the gene expression pattern of selenoproteins was revealed by principal component analysis (PCA). The results showed that the mRNA expression levels of 13 selenoproteins (GPX3, GPX4, TXNRD2, TXNRD3, DIO2, SELENOS, SELENON, SELENOT, SELENOO, SELENOP, SELENOP2, MSRB1, and SEPHS2) were decreased in HgCl2 treatment group, and there was strong positive correlation between these selenoproteins and component 1 as well as component 2 of the PCA. At the same time, the protein expression levels of GPX4, TXNRD1, TXNRD2, SELENOM, SELENOS, and SELENON were detected by Western blotting, which were consistent with the changes of gene expression. The results showed that the expression levels of selenoproteins were aberrant in response to HgCl2 toxicity. The information presented in this study provided clues for further research on the interaction between HgCl2 and selenoproteins, and the possible mechanism of immune organ toxicity induced by HgCl2.