Complete mitochondrial genome and phylogenetic analysis of Cirriformia tentaculata (Annelida, Polychaeta, Cirratulidae) from Weihai, Shandong, China.

Cirriformia species usually inhabit intertidal zones and deep-sea sediments. Their accurate identification has proven to be challenging. Here, we present the complete mitochondrial genome of one Cirriformia tentaculata_Montagu 1808 specimen collected from China. The total length of the complete mitochondrial sequence of C. tentaculata is 15,516 bp and consists of 13 protein-coding genes (PCGs), 23 tRNA genes, two rRNA genes, and an A + T rich region (64.20%). All PCGs begin with the typical ATN start codon, except for cox1, which uses TTG. TAA or TAG serve as termination codons for twelve PCGs, while nad5 terminates with an incomplete codon, T. The phylogenetic tree revealed a close relationship between C. tentaculata in this study, and Cirriformia cf. tentaculata and Timarete posteria from Korea. The information will assist in the future identification and understanding of this species and offers a novel point of reference for identifying Cirriformia species, and phylogenetic studies.

Metabolic transformation of cyclopiazonic acid in liver microsomes from different species based on UPLC-Q/TOF-MS.

To investigate the metabolic transformation of cyclopiazonic acid (CPA) in the liver of different species and to supplement accurate risk assessment information, the metabolism of CPA in liver microsomes from four animals and humans was studied using the ultra-high-performance liquid chromatography-quadrupole/time-of-flight method. The results showed that a total of four metabolites were obtained, and dehydrogenation, hydroxylation, methylation, and glucuronidation were identified as the main metabolic pathways of CPA. Rat liver microsomes exhibited the highest metabolic capacity for CPA, with dehydrogenated (C20H18N2O3) and glucuronic acid-conjugated (C26H28N2O10) metabolites identified in all liver microsomes except chicken, indicating significant species metabolic differences. Moreover, C20H18N2O3 was only detected in the incubation system with cytochromes P450 3A4 (CYP3A4). The hydroxylated (C20H20N2O4) and methylated (C21H22N2O3) metabolites were detected in all incubation systems except for the CYP2C9, with CYP3A4 demonstrating the strongest metabolic capacity. The "cocktail" probe drug method showed that CPA exhibited a moderate inhibitory effect on the CYP3A4 (IC50 value = 8.658 µM), indicating that the substrate had a negative effect on enzyme activity. Our results provide new insights to understand the biotransformation profile of CPA in animals and humans.

Epidemiological Surveillance of Respiratory Diseases in Urban Stray Cats in Shanghai.

Urban stray cats are cats without owners that survive in the wild for extended periods of time. They are one of the most common stray animals in cities, and as such, monitoring the pathogens carried by urban stray cats is an important component of urban epidemiological surveillance. In order to understand the prevalence of respiratory diseases in urban stray cats in Shanghai and provide scientific evidence for the development of targeted prevention and control strategies for respiratory diseases in stray cats, we collected 374 ocular, nasal, and oropharyngeal swabs from urban stray cats in Shanghai from January 2022 to December 2022. After RNA extraction, we used real-time PCR to detect six respiratory pathogens, including influenza A virus, feline calicivirus, feline herpesvirus type 1, Mycoplasma, Chlamydia, and Bordetella bronchiseptica. The results showed that among the 374 samples, 146 tested positive, with a positivity rate of 39.04%. The highest positivity rate was observed for Mycoplasma felis at 18.72% (70/374), followed by Chlamydia felis at 11.76% (44/374), feline calicivirus at 3.74% (14/374), feline herpesvirus 1 at 3.48% (13/374), Bordetella bronchiseptica at 1.34% (5/374), and influenza A virus was not detected. The highest positivity rate for Mycoplasma felis was in Minhang District at 31.94% (23/72), while Chlamydia felis and Bordetella bronchiseptica had the highest positivity rates in Jiading District at 23.53% (8/34) and 5.88% (2/34), respectively. The highest positivity rates for feline calicivirus and feline herpesvirus 1 were both observed in Qingpu District, at 14.46% (12/83) and 9.64% (8/83), respectively. A total of 36 samples showed mixed infections with two or more pathogens, with Mycoplasma felis being involved in 32 of these mixed infections, with the highest number of mixed infections being with Chlamydia felis at 25 samples. Respiratory pathogen positivity was detected throughout the year, with peak detection rates in summer and winter. The positivity rates of cat respiratory pathogens in different seasons showed statistical differences (χ2 = 27.73, p < 0.01). There was no statistical difference in the positivity rates of respiratory pathogens between cats of different genders (χ2 = 0.92, p > 0.05). The positivity rates of respiratory pathogens in cats of different age groups showed statistical differences (χ2 = 44.41, p < 0.01). Mycoplasma felis and Chlamydia felis were the main pathogens causing respiratory infections in stray cats, with Mycoplasma felis showing a much higher positivity rate than other respiratory pathogens and often co-infecting with Chlamydia felis and feline calicivirus. The positivity rate of Mycoplasma felis was high in summer, autumn, and winter, with no statistical difference between seasons. These results indicate a serious overall prevalence of respiratory pathogens in urban stray cats in the Shanghai area, showing seasonal trends and mixed infections with other pathogens. These findings suggest the need for comprehensive prevention and control measures to address respiratory pathogen infections in urban stray cats in the Shanghai area.

A new insight into fluoride induces cardiotoxicity in chickens: Involving the regulation of PERK/IRE1/ATF6 pathway and heat shock proteins.

Fluorosis poses a significant threat to human and animal health and is an urgent public safety concern in various countries. Subchronic exposure to fluoride has the potential to result in pathological damage to the heart, but its potential mechanism requires further investigation. This study investigated the effects of long-term exposure to sodium fluoride (0, 500, 1000, and 2000 mg/kg) on the hearts of chickens were investigated. The results showed that an elevated exposure dose of sodium fluoride led to congested cardiac tissue and disrupted myofiber organisation. Sodium fluoride exposure activated the ERS pathways of PERK, IRE1, and ATF6, increasing HSP60 and HSP70 and decreasing HSP90. The NF-κB pathway and the activation of TNF-α and iNOS elicited an inflammatory response. BAX, cytc, and cleaved-caspase3 were increased, triggering apoptosis and leading to cardiac injury. The abnormal expression of HSP90 and HSP70 affected the stability and function of RIPK1, RIPK3, and MLKL, which are crucial necroptosis markers. HSPs inhibited TNF-α-mediated necroptosis and apoptosis of the death receptor pathway. Sodium fluoride resulted in heart injury in chickens because of the ERS and variations in HSPs, inducing inflammation and apoptosis. Cardiac-adapted HSPs impeded the activation of necroptosis. This paper may provide a reference for examining the potential cardiotoxic effects of sodium fluoride.

Zinc attenuates arsenic overdose-induced brain damage via PERK/ATF6 and TLR/MyD88/NF-κB pathways.

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-1ß 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.

Effects of environmentally relevant cypermethrin and sulfamethoxazole on intestinal health, microbiome, and liver metabolism in grass carp.

The incorrect use of antibiotics and pesticides poses significant risks of biological toxicity. Their simultaneous exposure could jeopardize fish health and hinder sustainable aquaculture. Here, we subjected grass carp to waterborne cypermethrin (0.65 µg/L) or/and sulfamethoxazole (0.30 µg/L) treatments for a duration of 6 weeks. We closely monitored the effects on intestinal function, the intestinal microbiome, and the liver metabolome. The results revealed that exposure to waterborne cypermethrin or/and sulfamethoxazole compromised intestinal barrier function and decreased the expression of intestinal tight junction proteins. Additionally, heightened levels of pro-inflammatory cytokines in the intestines and reduced antioxidant levels indicated systemic inflammation and oxidative stress, with more severe effects observed in the combined exposure group. 16S rRNA sequencing of intestinal tissues suggested Firmicutes play a key role in the intestinal microbiota. GC/MS metabolomics of the liver showed more differential metabolites (56) in the co-exposure group compared to cypermethrin (45) or sulfamethoxazole (32) alone, indicating greater toxicological effects with combined exposure. Our analyses also suggest that ATP-binding cassette transporters could serve as a novel endpoint for assessing the risk of pesticide and antibiotic mixtures in grass carp. In summary, this study underscores the potential ecological risks posed by antibiotics and pesticides to aquatic environments and products. It emphasizes the importance of the gut-liver axis as a comprehensive pathway for assessing the toxicity in fish exposed to environmental contaminants.

The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer's Disease in AppNL-G-F Knock-In Mice.

BACKGROUND: The endocannabinoid system (ECS) and associated lipid transmitter-based signaling systems play an important role in modulating brain neuroinflammation. ECS is affected in neurodegenerative disorders, such as Alzheimer's disease (AD). Here we have evaluated the non-psychotropic endocannabinoid receptor type 2 (CB2) and lysophosphatidylinositol G-protein-coupled receptor 55 (GPR55) localization and expression during Aß-pathology progression. METHODS: Hippocampal gene expression of CB2 and GPR55 was explored by qPCR analysis, and brain distribution was evaluated by immunofluorescence in the wild type (WT) and APP knock-in AppNL-G-F AD mouse model. Furthermore, the effects of Aß42 on CB2 and GPR55 expression were assessed in primary cell cultures. RESULTS: CB2 and GPR55 mRNA levels were significantly upregulated in AppNL-G-F mice at 6 and 12 months of age, compared to WT. CB2 was highly expressed in the microglia and astrocytes surrounding the Aß plaques. Differently, GPR55 staining was mainly detected in neurons and microglia but not in astrocytes. In vitro, Aß42 treatment enhanced CB2 receptor expression mainly in astrocytes and microglia cells, whereas GPR55 expression was enhanced primarily in neurons. CONCLUSIONS: These data show that Aß pathology progression, particularly Aß42, plays a crucial role in increasing the expression of CB2 and GPR55 receptors, supporting CB2 and GPR55 implications in AD.

Fluoride induces neutrophil extracellular traps and aggravates brain inflammation by disrupting neutrophil calcium homeostasis and causing ferroptosis.

Endemic fluorosis (EF) has been listed as one of the serious public health problems in many countries. Long-term exposure to high fluoride can lead to severe neuropathological damage to the brain. Although long-term research has revealed the mechanism of some brain inflammation caused by excessive fluoride, the role of intercellular interactions, especially immune cells, in brain damage is still unclear. Fluoride can induce ferroptosis and inflammation in the brain in our study. A co-culture system of neutrophil extranets and primary neuronal cells showed that fluoride can aggravate neuronal cell inflammation by causing neutrophil extranets (NETs). In terms of the mechanism of action, we found that fluoride leads to the opening of calcium ion channels by causing neutrophil calcium imbalance, which in turn leads to the opening of L-type calcium ion channels (LTCC). Extracellular free iron enters the cell from the open LTCC, leading to neutrophil ferroptosis, which releases NETs. Blocking LTCC (nifedipine) rescued neutrophil ferroptosis and reduced the generation of NETs. Inhibition of ferroptosis (Fer-1) did not block cellular calcium imbalance. In summary, our study explores the role of NETs in fluoride-induced brain inflammation and suggests that blocking calcium channels may be one of the possibilities to rescue fluoride-induced ferroptosis.

Polystyrene microplastics promote liver inflammation by inducing the formation of macrophages extracellular traps.

Microplastics (MPs), a new and increasing environmental pollutant, can cause ongoing damage to organisms. Although recent studies have revealed mechanisms of action for some of the hepatotoxicity caused by MPs, the role-played by cellular interactions, particularly immune cells, in the process of liver injury has not been elucidated. In the present study, 5-µm polystyrene microplastics (PS-MPs) induced liver inflammation as well as the formation of Macrophage extracellular traps (METs). Macrophage and LMH cell co-culture systems confirmed that PS-MPs-induced METs promote inflammation in hepatocytes. Mechanistically, macrophages actively phagocytose particles after 4 h of exposure to PS-MPs. Subsequently PS-MPs elevated ROS levels and disrupt mitochondrial kinetic homeostasis. Further activation of mitochondrial autophagy and lysosomes. After phagocytosis of PS-MPs by macrophages for 12 h, continued autophagy and lysosome activation eventually lead to lysosome rupture and release of calcium ions to induce the formation of METs. Blocking ROS (NAC) and autophagy (3MA) partially alleviated mitochondrial and lysosomal damage and thus inhibited the formation of METs induced by PS-MPs. NAC also delayed the onset of respiratory burst to alleviate METs formation. In conclusion, our study reveals the mechanism of METs formation in liver inflammation induced by PS-MPs exposure and suggests that lysosomal damage may be one of the key players in the formation of METs induced by PS-MPs.

Novel pathways of fluoride-induced hepatotoxicity: P53-dependent ferroptosis induced by the SIRT1/FOXOs pathway and Nrf2/HO-1 pathway.

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.

Nonenzymatic Glucose Sensor Based on Porous Co3O4 Nanoneedles.

Herein, porous Co3O4 nanoneedle arrays were synthesized on nickel (Ni) foam (Co3O4 NNs/NF) by one-step hydrothermal method. Some electrochemical methods were used to investigate its nonenzymatic glucose sensing performance in alkaline solution. The results show that the sensitivity of Co3O4 NNs/NF electrode to glucose is 4570 µA mM-1 cm-2. The linear range is 1 µM-0.337 mM, and the detection limit is 0.91 µM (S/N = 3). It also displays good selectivity and repeatability for glucose. The good electrochemical sensing performance of Co3O4 NNs/NF based sensor for glucose can be attributed to interconnected porous structure and large specific surface area of Co3O4.

Secondary brain injury after polystyrene microplastic-induced intracerebral hemorrhage is associated with inflammation and pyroptosis.

Unlike regular environmental pollutants, microplastics cannot dissolve in liquids. Physical contact of microplastic (MPs) with tissue can damage tissue structure, and it is unclear how this physical secondary injury affects brain tissue. Through CTD database analysis, it was determined that cerebral ischemia may be one of the main ways of brain tissue damage caused by MPs, and inflammatory response may play a key role in it. In the present study, PS-MPs (L-PS group:1 mg/L, M - PS group:10 mg/L, H-PS group: 100 mg/L in water) were assessed to brain tissue damage in chicken after six weeks of continuous exposure. Exposure to PS-MPs caused cerebral hemorrhage as well as generation of microthrombi and loss of Purkinje cells. Intracerebral hemorrhage caused a strong infiltration of inflammatory cells and activated the ASC-NLRP3-GSDMD signaling pathway to induce pyroptosis. Disruption of mitochondrial dynamics by PS-MPs exposure disrupts mitochondrial function and activates AMPK signaling. In conclusion, this study explored the mechanism regulation of subsequent brain injury from the perspective of physical injury (cerebral hemorrhage) of PS-MPs. To provide a reference for elucidating the neurotoxicity induced by microplastic exposure.

Polystyrene microplastics induce apoptosis in chicken testis via crosstalk between NF-κB and Nrf2 pathways.

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.

Polystyrene microplastics induced oxidative stress, inflammation and necroptosis via NF-κB and RIP1/RIP3/MLKL pathway in chicken kidney.

Microplastics (MPs) are a novel environment pollutant widespread among the natural environment, also causing damage to aquatic animals and mammals. However, their effects on the kidney of poultry are still unclear. In this study, chickens were exposure to the different doses of PS-MPs (1, 10, 100 mg/L) for six weeks, with 1 mg/L being the environmental concentration. The effects of PS-MPs on renal tissue damage in chicken were analyzed. Our results suggested that MPs exposure causes mitochondrial morphology and dysbiosis (MFN1/2, OPA1, Drp1), mitochondrial structural damage by triggering imbalance in mitochondrial dynamics. Antioxidant enzyme (SOD, CAT, MDA, GSH, T-AOC) activity was significantly altered, which in turn caused oxidative stress. H&E staining results showed damage and inflammation of chicken kidney. Mechanistically, the inflammation featured by activated NF-κB P65 and increased expression of pro-inflammatory factors (TNFα, iNOs, IL-1ß and IL-6). Moreover, PS-MPs intake induced necroptosis through activated RIP1/RIP3/MLKL signaling pathway. In conclusion, our study was the first to show that oral intake of PS-MPs induced inflammation and necroptosis in chicken kidney and the differences in damage were linked to the concentration of PS-MPs. The purpose of this study provided theoretical support for the environmental risk assessment of PS-MPs.

Endoplasmic reticulum stress-controlled autophagic pathway promotes polystyrene microplastics-induced myocardial dysplasia in birds.

In complex ecosystems, birds are generally long-lived and occupy high trophic positions, making them good bioindicators for monitoring environmental contaminants. The effects of microplastics (MPs) on myocardial development in bird is currently unknown. Chicks, as a high trophic level terrestrial bird, may be more affected by MPs exposure and. Therefore, we established an in vivo model of chicks exposed to different concentrations of polystyrene microplastics (PS-MPs) and selected 12-day-old chicken embryos in vitro to extract primary cardiomyocytes to further investigate the potential molecular mechanisms of the effect of PS-MPs on myocardial development in birds. Histopathological observations revealed that the PS-MPs treated exhibited loose and irregular myocardial arrangement, large cell gaps and broken myocardial fiber bundles. More mechanistically, TnnT2, Nkx2-5, Gata4, TBX5 and ACTN2 were down-regulated, endoplasmic reticulum (ER) stress markers GRP78, PERK, eIF2α, IRE1, ATF4, ATF6 and CHOP were overexpressed, autophagy-related genes LC3, ATG5, Beclin1 and P62 were down-expressed after PS-MPs exposure, and the addition of 4PBA effectively deregulated the above aberrant expression. Hence, our report indicated that PS-MPs induced myocardial dysplasia in birds is mainly attributed to the ER stress-mediated autophagic pathway. This provided data supporting the protection of birds from the health risks of MPs pollution. More critically, the study of cardiac developmental toxicity in birds may help to better explain or solve the problem of MPs pollution in complex ecosystems.

Polystyrene microplastics-induced cardiotoxicity in chickens via the ROS-driven NF-κB-NLRP3-GSDMD and AMPK-PGC-1α axes.

Microplastics (MPs) pollution is getting increasingly prominent, and its dangers have attracted widespread attention. The heart is the central hub of the organism's survival, and the mechanism of MPs-induced heart injury in chickens is unknown. Here, we investigated the effects of 5 µm polystyrene microplastics (PS-MPs) on the heart and primary cardiomyocytes of chickens at varied concentrations. We observed that PS-MPs caused severe pathological damage and ultrastructural changes in heart, induced myocardial pyroptosis, inflammatory cell infiltration and mitochondrial lesions. PS-MPs evoked abnormal antioxidant enzyme content and ROS overproduction. Detailed mechanistic investigation indicated that PS-MPs triggered pyroptosis via NF-κB-NLRP3-GSDMD axis and exacerbated myocardial inflammation (NLRP3, Caspase-1, IL-1ß, IL-18, ASC, GSDMD, NF-κB, COX-2, iNOS and IL-6 overexpression). Additionally, PS-MPs induced mitochondrial damage (TFAM, OPA1, MFN1 and MFN2 down-expression, DRP1 and Fis1 overexpression) and energy metabolism disorders (HK2, PKM2, PDHX and LDH up-regulation) by inhibiting AMPK-PGC-1α pathway. Interestingly, NAC alleviated these aberrant manifestations in vitro. We suggested that PS-MPs driven alterations in NF-κB-NLRP3-GSDMD and AMPK-PGC-1α pathways via ROS overload, which in turn triggered oxidative stress, myocardial pyroptosis, inflammation, mitochondrial and energy metabolism dysfunction. This provided theoretical bases for protecting chickens from toxic injury by MPs.

High hemoglobin fluctuation was a protective factor for cardiovascular-related death in peritoneal dialysis (PD) patients: A retrospective analysis of 232 patients with PD.

OBJECTIVES: This study aimed to investigate the effect of hemoglobin (Hb) fluctuation after dialysis on the prognosis of cardiovascular-related and all-cause deaths in peritoneal dialysis (PD). METHODS: According to the Hb fluctuation, patients were divided into low fluctuation group, moderate fluctuation group, and high fluctuation group, and then, the effects of Hb fluctuation after dialysis on the prognosis of cardiovascular-related and all-cause death in PD were analyzed by regression analysis. RESULTS: A total of 232 patients were selected in this study. Compared with the low Hb fluctuation group, the moderate and high fluctuation groups had lower body mass index (BMI), estimated glomerular filtration rate (eGFR), and baseline Hb, and the moderate fluctuation group had less erythropoietin (EPO) and dialysis dose. Compared with survivors, patients with cardiovascular-related and all-cause deaths had lower mean Hb and Hb fluctuation (all p < 0.05). Cox regression analysis showed that before and after adjusting for confounding factors, Hb fluctuation was still independently correlated with cardiovascular prognosis, and higher Hb fluctuation was still a protective factor for cardiovascular-related death in the Hb-substandard group, but there was no significant correlation between Hb fluctuation and all-cause death. Multivariate linear regression analysis revealed that Hb fluctuation was positively correlated with Kt/V and EPO dosage, but negatively correlated with the baseline Hb. CONCLUSION: High Hb fluctuation was a protective factor for cardiovascular-related death in PD with substandard Hb. Compared with Hb fluctuation, correction of anemia timely and making Hb reaches the standard level had a greater impact on reducing cardiovascular-related death in PD.

Polystyrene microplastics up-regulates liver glutamine and glutamate synthesis and promotes autophagy-dependent ferroptosis and apoptosis in the cerebellum through the liver-brain axis.

Microplastics (MPs), which are emerging environmental pollutants, remain uncertainties in their toxic mechanism. MPs have been linked to severe liver metabolic disorders and neurotoxicity, but it is still unknown whether the abnormal metabolites induced by MPs can affect brain tissue through the liver-brain axis. Exposed to MPs of chickens results in liver metabolic disorders and increased glutamine and glutamate synthesis. The relative expression of glutamine in the C group was -0.862, the L-PS group was 0.271, and the H-PS group was 0.592. The expression of tight junction proteins in the blood-brain barrier (BBB) was reduced by PS-MPs. Occludin protein expression decreased by 35.8%-41.2%. Claudin 3 decreased by 19.6%-42.3%, and ZO-1 decreased by 28.3%-44.6%. Excessive glutamine and glutamate cooperated with PS-MPs to inhibit the Nrf2-Keap1-HO-1/NQO1 signaling pathway and triggered autophagy-dependent ferroptosis and apoptosis. GPX protein expression decreased by 30.9%-38%. LC3II/LC3I increased by 54%, and Caspase 3 increased by 45%. Eventually, the number of Purkinje cells was reduced, causing neurological dysfunction. In conclusion, this study provides new insights for revealing the mechanism of nervous system damaged caused by PS-MPs exposed in chickens.

Lycopene attenuates oxidative stress, inflammation, and apoptosis by modulating Nrf2/NF-κB balance in sulfamethoxazole-induced neurotoxicity in grass carp (Ctenopharyngodon Idella).

All drugs that can penetrate the blood-brain barrier (BBB) may lead to mental state changes, including the widely used anti-infective drug sulfamethoxazole (SMZ). Herein, we investigated whether lycopene (LYC) could ameliorate SMZ-induced brain injury and the postulated mechanisms involved. A total of 120 grass carps were exposed under SMZ (0.3 µg/L, waterborne) or LYC (10 mg/kg fish weight, diet) or their combination for 30 days. Firstly, brain injury induced by SMZ exposure was suggested by the damage of BBB (decreases of Claudins, Occludin and Zonula Occludens), and the decrease of neurotransmitter activity (AChE). Through inducing oxidative stress (elevations of malondialdehyde and 8-hydroxy-2 deoxyguanosine, inhibition of glutathione), SMZ increased the intra-nuclear level of NF-κB and its target genes (TNF-α and interleukins), creating an inflammatory microenvironment. As a positive feed-back mechanism, apoptosis begins with activation of pro-death proteins (Bax/Bcl-2) and activation of caspases (caspase-9 and caspase-3). Meanwhile, a compensatory upregulation of constitutive Nrf2 and its downstream antioxidative gene expression (NAD(P)H Quinone Dehydrogenase 1 and Heme oxygenase 1) and accelerated autophagy (increases of autophagy-related genes and p62 inhibition) were activated as a defense mechanism. Intriguingly, under SMZ stress, LYC co-administration decreased NF-κB/apoptosis cascades and restored Nrf2/autophagy levels. The neuroprotective roles of LYC make this natural compound a valuable agent for prevention SMZ stress in environment. This study suggests that LYC might be developed as a potential candidate for alleviating environmental SMZ stress in aquaculture.

Oxidative stress is involved in the activation of NF-κB signal pathway and immune inflammatory response in grass carp gill induced by cypermethrin and/or sulfamethoxazole.

At present, the concentration of environmental pollutants, such as pesticides and antibiotics exposed in environment, especially in aquatic environment is increasing. Research on environmental pollutants has exploded in the last few years. However, studies on the combined effects of pesticides and antibiotics on fish are rare, especially the toxic damage to gill tissue is vague. In this paper, cypermethrin (CMN) and sulfamethoxazole (SMZ) were analyzed and found that there was a strong correlation between the pathways affected by the first 30 genes regulated by CMN and SMZ, respectively. Therefore, the toxic effects of CMN (0.651 µg L-1) and/or SMZ (0.3 µg L-1) on grass carp gill were studied in this paper. Histopathology, quantitative real-time PCR, and other methods were used to detect the tissue morphology, oxidative stress level, inflammation, and apoptosis-related indicators of the fish gills after exposure of 42 days. It was found that compared with the single exposure (CMN/SMZ) group, the combined exposure (MIX) group had a more pronounced oxidative stress index imbalance. At the same time, nuclear factor-κB (NF-κB) signal pathway was activated and immuno-inflammatory reaction appeared in MIX group. The expression of tumor necrosis factor (TNF-α) in the rising range is 2.94 times that of the C group, while the expression of interleukin 8 (IL-8) is as high as 32.67 times. This study reveals the harm of CMN and SMZ to fish, and provides a reference and basis for the rational use of pesticides and antibiotics.