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Exposure to arsenic (As), a widespread non-metallic toxicant in nature, often results in neurotoxicity, although the exact mechanism is unknown. Zinc (Zn) is a powerful nutrient often thought to be beneficial for growth, development and immunity. Whether Zn can rescue brain damage caused by As contamination remains to be demonstrated. Therefore, in this study, a 30-day model of As poisoning (2.83 mg/L) in carp was established and treated with Zn (1 mg/L) to investigate the detoxification mechanism involved. Histological observations showed that As induced the loosening of the molecular layer structure of the cerebellum and the dissolution or even disappearance of nuclei, accompanied by the occurrence of microthrombi in the granular layer, and the addition of Zn attenuated such As-induced damage. Further mechanistic studies indicated that Zn ameliorated As exposure-induced abnormalities in antioxidant capacity (decreased CAT and Cu/Zn-SOD), activation of the Nrf2/keap1 pathway and endoplasmic reticulum stress (ERs), which is a key factor in As-induced brain damage. ERs (high expression of PERK, ATF6, CHOP, eiF2α and GRP78) and inflammation (overexpression of TLR2, TLR4, MyD88, IKK, NF-κB, IL-1β and IL-6 and low expression of IκBα and IL-10). We suggest that Zn can alleviate excessive As-induced brain damage by attenuating As-induced oxidative stress, PERK/ATF6 and TLR/MyD88/NF-κB pathways. The present study fills in the preventive mechanism of As injury in fish and provides the possibility of prevention and control of As pollution-induced brain tissue injury by Zn rescue., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Fluoride (F) is an environmental pollutant that continues to threaten human health. Long-term or excessive fluoride exposure can cause a series of acute or chronic systemic and organ-specific diseases. The liver is considered to be one of the important target organs of fluoride poisoning, however, the specific cause of liver damage caused by fluoride is still unclear. In the present study, we identified ferroptosis as a key mechanism of fluoride-induced liver injury. Under fluorosis conditions, lipid peroxidation levels in the liver are significantly increased and iron overload is induced. Combined transcriptomic and metabolomic analysis revealed that activation of the SIRT1/FOXOs pathway is one of the main causes of fluorosis-induced liver damage. Further analysis by in vitro experiments showed that the SIRT1/FOXOs pathway can cause the activation of the Nrf2/HO-1 pathway under the condition of fluorosis, and can activate the P53-dependent ferroptosis pathway, leading to the occurrence of lipid peroxidation and iron accumulation, ultimately leading to ferroptosis. Our study provides insight into the mechanism of fluoride-induced liver injury, and our results also provide strategies for treatment to alleviate liver injury caused by fluorosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Microplastics (MPs) are a new type of pollutants that are widespread in nature, and their toxic effects on humans or animals are receiving attention. Birds are in a higher ecological niche in nature, and MPs may have potential bioaccumulation and biomagnification risks to birds. The mechanisms underlying the reproductive toxicity of MPs to birds are mainly unknown. To study the reproductive toxicity of MPs to birds, we randomly divided chickens into six groups and exposed polystyrene microplastics (PS-MPs) through drinking water (0, 1, and 100 mg/L) for 28 and 42 days. We found that PS-MPs caused testicular inflammatory infiltration and interstitial hemorrhage, resulting in testicular tissue damage; the expression of Claudin3 and Occludin in the blood-testis barrier (BTB) decreased and may damage the integrity of the BTB. PS-MPs exposure inhibited the expression of the Nrf2-Keap1 pathway, which in turn reduced HO-1 and NQO1, simultaneous GSH and T-AOC were also reduced, resulting in an imbalance of the redox system; in addition, the NF-κB signaling pathway was activated, increasing the expression of TNF-α, COX-2 and iNOS. Under redox system imbalance and inflammatory stress, exposure to PS-MPs led to decreased expression of Bcl-2 and increased Bax, cytc, caspase-8, and caspase-3, etc., activating apoptosis, and ultimately causing testicular damage. These results suggested that PS-MPs exposure led to an imbalance of the redox system and an inflammatory response, inducing both endogenous and exogenous apoptosis, resulting in testicular tissue damage. Our study provides a theoretical basis for reproductive injury mechanisms in chicken., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

As a group of cytokines, interferons are the first line of defense in the antiviral immunity. In this study, Siberian tiger IFN-β (PtIFN-β) and IFN-γ (PtIFN-γ) were successfully amplified, and the two were fused (PtIFN-γ) by overlap extension polymerase chain reaction (SOE-PCR). Bioinformatics analysis disclosed that PtIFN-β and PtIFN-γ have species-specificity and conservation in the course of evolution. After being expressed in prokaryotes, the antiviral activities and physicochemical properties of PtIFN-β, PtIFN-γ and PtIFNβ-γ were analyzed. In Feline kidney cells (F81), PtIFNβ-γ showed more active antiviral activity than PtIFN-β and PtIFN-γ, which has more stable physicochemical properties (acid and alkali resistance, high temperature resistance). In addition, PtIFN-β, PtIFN-γ and PtIFN-γ activated the JAK-STAT pathway and induced the transcription and expression of interferon-stimulated genes (ISGs). Janus kinase (JAK) 1 inhibitor inhibited ISGs expression induced by PtIFN-β, PtIFN-γ and PtIFN-γ. Overall, this research clarified that PtIFN-β, PtIFN-γ and PtIFNβ-γ have the ability to inhibit viral replication and send signals through the JAK-STAT pathway. These findings may facilitate further study on the role of PtIFN in the antiviral immune response, and help to develop approaches for the prophylactic and therapeutic of viral diseases based on fusion interferon., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

The regulation of interferon-α signaling pathways is essential to protect the host from infection with a broad range of viruses. However, information regarding antiviral response and the specific molecular mechanism of Columba livia interferon-α (CoIFN-α) has not been reported to date. In this study, we cloned a 723bp complete ORF of CoIFN-α gene. The specific antiviral activity of CoIFN-α in VSV (TCID 50  = 10 -5.87 /100 μL)-infected CEFs reached 5.5 × 10 5 U/mg. Moreover, our result indicated that the anti-VSV efficient of CoIFN-α might depend on the expression of NF-κB. CoIFN-α also showed high sensitivity to trypsin and relatively stable after acid, alkali or heat treatment. Moreover, CoIFN-α activated STAT/Jak signaling and autophagy to inhibit VSV-induced apoptosis. Although the expression of p53 was further increased, apoptosis was not involved in CoIFN-α against VSV. Notably, although STAT signaling was efficiently activated, knockdown p53 did inhibit the antiviral activity of the CoIFN-α via decreasing the expression of Mx1 but not weakened Jak phosphorylation. Moreover, VSV aggravated the apoptosis and the expression of cleaved Mdm2 in knockdown p53 under preincubated CoIFN-α. Taken together, p53 might as a highly interconnected regulator in IFN-α antiviral response and cleaved Mdm2 might as a dominant-negative regulator by competing with full length Mdm2 for p53 binding in virus infection. Overall, our research not only enriches CoIFN-α antiviral features but also helps explain that p53 enhance the CoIFN-α antiviral response against pigeon viral diseases., (Copyright © 2018. Published by Elsevier Ltd.)

Arsenic and copper, two common environmental contaminants, presented potentially harmful to the immune system. In order to examine whether simultaneous exposure to arsenic and copper has the potential effects on immunity and inflammatory response in chicken thymus, 30 mg/kg arsenic trioxide and/or 300 mg/kg copper sulfate were added to chicken basal diet, respectively. After 12 weeks of administrations, we observed significantly decreased thymus weight and thymus index, inflammatory cell infiltration and hyperemia visible to the unaided eye. Concurrent administration arsenic and copper markedly increased levels of NF-κB, COX-2, iNOS and PTGEs and pro-inflammatory cytokines in concomitant with a tendency of Th1 bias immune response. Additionally, heat shock proteins levels were noticeably elevated in all treated groups. Above mentioned indicators were more pronounced among co-administrated groups. Collectively, arsenic and/or copper exposure engendered immunotoxicity of chicken thymus, resulting in inflammatory responses and imbalance of the immune response. Concurrent exposure of arsenic and copper was likely to potentiate the toxicity of chicken thymus and detailed mechanisms required further exploration. Heat shock proteins may play protective roles in thymus damage, and HSP60 combines with the IL-17/IL-10 ratio may be potential predictive marker of arsenic and/or copper-subchronic toxicity in chicken thymus., (Copyright © 2018. Published by Elsevier B.V.)

Arsenic and copper, two ubiquitous pollutants, can be oxidative stress inducers when organisms are heavy or chronically exposed, causing adverse effects on digestion and absorption function, resulting in potential losses to poultry husbandry. The present study examined the effects of arsenic trioxide (30 mg/kg)- and copper sulfate (300 mg/kg)-mixed foods, administered alone or in combination for 12 weeks, on various biochemical indices of oxidative stress and immunity in the small intestines of Hy-line chickens. The results showed that for the first four weeks of exposure, both the redox and immune systems were unaffected. Subsequently, exposure to arsenic or copper significantly increased the level of lipid peroxidation (malondialdehyde and ability of anti-hydroxy radical) concomitant with a collapse of the antioxidant system (catalase and glutathione peroxidase), in a time-dependent manner. An increase in the mRNA and protein levels of pro-inflammatory indicators (nuclear factor kappa B, cyclooxygenases-2, tumor necrosis factor-α and prostaglandin E2 synthases) with a definite tendency toward Th1 (Th, helper T cell) cytokines was observed in both arsenic and copper treated chickens. Histologically, the destruction of the biofilm structure and inflammatory infiltrates was observed. Thus, in the intestine, heat shock proteins play protective roles against tissue damage. In some cases, we observed that the tissues of the small intestine were more sensitive to arsenic than to copper. Moreover, co-exposure induced more serious intestinal toxicity than single treatment group, and this mechanism needs further exploration., (Copyright © 2018. Published by Elsevier B.V.)

Interferon has a broad-spectrum of antiviral effects and represents an ideal choice for the development of antiviral drugs. Nonetheless, information about alpha interferon (IFN-α) is vacant in Amur tiger (Panthera tigris altaica), an endangered species and indigenous to northeast Asia. Herein, 11 PtIFN-αs genes, which encoded proteins of 164-165 amino acids, were amplified. Afterwards, expression and purification were conducted in Escherichia coli. In physicochemical analysis, PtIFN-αs were shown to be highly sensitive to trypsin and remained stable despite changes in pH and temperature. In feline kidney cells (F81)/vesicular stomatitis virus (VSV)/canine distemper virus (CDV)/avian influenza virus (AIV) systems, PtIFN-αs were demonstrated to have distinct antiviral activities, some of them (PtIFN-α and PtIFN-α9) inhibited viral transcription levels more effectively than the other subtypes including Felis catus IFN-α, an effective therapeutic agent used for viral infections clinically. Additionally, PtIFN-α and PtIFN-α9 can up-regulate the transcription and expression of p53, a tumor suppressor factor, which could promote apoptosis of virus-infected cells. In conclusion, we cloned and expressed 11 subtypes of PtIFN-α for the first time. Furthermore, PtIFN-α and PtIFN-α9 were likely to be more efficient against both chronic viral infections and neoplastic diseases that affect the Amur tiger population. It will be of significant importance for further studies to protect this endangered species., (Copyright © 2017. Published by Elsevier Ltd.)