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Inflammation is much more intrinsic to hernia then is what is generally appreciated. The occurrence of hernias is associated with swelling, stress and inflammation. Surgery remains an important intervention to treat hernias and for many years, post-surgical levels of inflammatory cytokines have been evaluated to compare the different strategies for their comparative advantages. All surgical procedures elicit some sort of inflammatory response and moreover the meshes used for hernia repair are also associated with elevated inflammatory response, although some favor predominantly a pro-inflammatory response while the other meshes favor anti-inflammatory response. An estimated more than 90% of hernia repairs involve some meshes with polypropylene considered as the gold standard. Efforts are underway to modulate polypropylene meshes associated inflammation through use of alternative materials as well as modifications to polypropylene meshes themselves. In the last one decade, miRNAs have entered hernia research and the data on a role of miRNAs in different hernias is slowly emerging, providing the first evidence of epigenetics in hernia. Some reports are connecting miRNAs with inflammation in hernia. All these aspects, such as, surgery-related to mesh-related inflammation as well as miRNA-related inflammation, are discussed in this article to present an up-to-date information on the topic. [ABSTRACT FROM AUTHOR]

Background: Previous studies, predominantly in Western individuals, have reported weight gain or weight loss are related to the increased depressive symptoms at all ages, but no study of depressive symptoms has examined its relation to actual (not just self-reported) weight changes in the middle-aged and older adults. Evidence of the relationship in older Asian individuals remains sparse. The study aimed to examine the relationship between weight changes and incidence of depressive symptoms in a nationally representative sample of community-dwelling older Asians. Method: Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS), which included 17,284 adults aged 45 years. Participants were followed every two years using a face-to-face, computer-aided personal interview (CAPI) and structured questionnaire. We excluded participants with no follow-up data. The numbers of individuals who completed both the baseline and follow-up surveys were 3118 for the short-term (two years from 2011–2013) and the long-term (four years from 2011–2015). Additionally, to associate weight change with subsequent depressive symptoms, we also included 2472 participants without depressive symptom in 2013 and observed the incidence of depressive symptom in 2015 (subsequent term from 2013–2015). Finally, weight changes were classified as loss > -3%, stable-3–3%, gain3-6%, gain6-9%, and gain > 9%. Multivariable-adjusted cox regression in the study were used to assess the hazard ratios (HRs) of each weight change category. Results: The incidence of depressive symptoms was 20.72% in the 2011–2013, 27.04% in the 2011–2015, and 23.02% in 2013–2015. Weight loss > 3% for all intervals was associated with higher depressive symptoms than stable weight during the 2011–2013 [1.305(1.031,1.651)] among the total populations. When stratified by sex, the results in males and females were different from those in the total population [females:1.389(0.997, 1.935); males:1.263(0.902, 1.767)]. Weight loss > 3% for intervals was associated with higher depressive symptoms than stable weight during the 2013–2015[1.643(1.140, 2.368)] among the males and its effect was also stronger for the total in 2011–2013. Moreover, there was no significant association between weight gain and incident depressive symptom, and no significant interaction effect in terms of the sex*weight changes. Conclusion: Our findings could inform health promotion interventions to body-weight management aimed at improving the health of the middle-aged and older adults, particularly in the total people with short-term weight loss and males with subsequent term weight loss. [ABSTRACT FROM AUTHOR]

Chiral materials with circularly polarized luminescence (CPL) are currently attracting great attention for their wide applications in bioresponsive imaging, 3D displays, and storage of information. Herein, CPL‐active enantiomorphic hybrids (R)‐ and (S)‐C6H15Cl2NO⋅SbCl5 are obtained by self‐assembling chiral R/S‐(3‐chloro‐2‐hydroxypropyl)trimethylammonium chloride with antimony(III) chloride, giving a 0D structure with SbCl5 pyramids isolated by (3‐chloro‐2‐hydroxypropyl)trimethylammonium chloride cations. The formed enantiomers exhibit brilliant orange emission peaked at 604 nm with photoluminescence quantum yield as high as 71.2%, originating from the self‐trapped exciton emission demonstrated by photophysical characterization. Due to the existence of chiral organic cations, the enantiomers exhibit strong chiral‐optical properties with mirror‐image circular dichroism signals in ground state and obvious CPL activity with the dissymmetry factor glum of 2.5 × 10−4 and −1.6 × 10−4 for R‐type and S‐type, respectively. It should be mentioned that these are the first reported 0D hybrids with CPL‐activity. This work paves an avenue for developing eco‐friendly CPL materials with highly ‐efficient luminescence. [ABSTRACT FROM AUTHOR]

As low‐dimensional lead‐free hybrids with higher stability and lower toxicity than those of three‐dimensional lead perovskites, organic antimony(III) halides show great application potential in opt‐electronic field owing to diverse topologies along with exceptional optical properties. We report herein an antimony(III) hybrid (MePPh3)2SbCl5 with a zero‐dimensional (0D) structure, which exhibits brilliant orange emission peaked at 593 nm with near‐unity photoluminescent quantum yield (99.4 %). The characterization of photophysical properties demonstrates that the broadband emission with a microsecond lifetime (3.24 μs) arises from self‐trapped emission (STE). Electrically driven organic light‐emitting diodes (OLEDs) based on neat and doped films of (MePPh3)2SbCl5 were fabricated. The doped devices show significant improvement in comparison to non‐doped OLEDs. Owing to the much improved surface morphology and balanced carrier transport in light‐emitting layers of doped devices, the peak luminance, current efficiency (CE) and external quantum efficiency (EQE) are boosted from 82 cd m−2 to 3500 cd m−2, 1.1 cd A−1 to 6.8 cd A−1, and 0.7 % to 3.1 % relative to non‐doped devices, respectively. [ABSTRACT FROM AUTHOR]

As low‐dimensional lead‐free hybrids with higher stability and lower toxicity than those of three‐dimensional lead perovskites, organic antimony(III) halides show great application potential in opt‐electronic field owing to diverse topologies along with exceptional optical properties. We report herein an antimony(III) hybrid (MePPh3)2SbCl5 with a zero‐dimensional (0D) structure, which exhibits brilliant orange emission peaked at 593 nm with near‐unity photoluminescent quantum yield (99.4 %). The characterization of photophysical properties demonstrates that the broadband emission with a microsecond lifetime (3.24 μs) arises from self‐trapped emission (STE). Electrically driven organic light‐emitting diodes (OLEDs) based on neat and doped films of (MePPh3)2SbCl5 were fabricated. The doped devices show significant improvement in comparison to non‐doped OLEDs. Owing to the much improved surface morphology and balanced carrier transport in light‐emitting layers of doped devices, the peak luminance, current efficiency (CE) and external quantum efficiency (EQE) are boosted from 82 cd m−2 to 3500 cd m−2, 1.1 cd A−1 to 6.8 cd A−1, and 0.7 % to 3.1 % relative to non‐doped devices, respectively. [ABSTRACT FROM AUTHOR]

Triazole polycarboxylic acid ligands are widely employed in the construction of MOFs due to their strong coordination ability and flexible coordination modes. In this work, three novel complexes (Pb(MCTCA)(H2O) (1), Co(HMCTCA)2(H2O)2 (2) and Cu(HMCTCA)2(H2O)2 (3)) based on the H2MCTCA ligand (5-methyl-1-(4-carboxyl)-1H-1,2,3-triazole-4-carboxylic acid) were successfully synthesized under hydrothermal conditions, respectively. X-ray single crystal structure analysis shows that complex 1 is a 3D network structure, where the central metal Pb(II) is six coordinated to form deformed triangular prism geometry. The complexes 2 and 3 are both 2D layer supramolecular structures connected through intermolecular hydrogen, where the central metals (Co/Cu) are six coordinated to form octahedral configuration geometry. Based on functional properties, it is found that complex 1 exhibits excellent detection ability for small-molecule drugs (azithromycin, colchicine and balsalazide disodium) and actinide cations (Th4+ and UO22+) within a lower concentration range without interference from other components. In particular, the detection limits of three small-molecule drugs are all lower than 0.30 μM. In addition, complexes 2 and 3 exhibited excellent catalytic reduction performance toward p-nitrophenol (PNP), with a reduction efficiency exceeding 98%. These experimental results evidence that complexes 1–3 have potential application prospects in fluorescence sensing and catalytic reduction. [ABSTRACT FROM AUTHOR]

Three MM-MOFs based on the reaction of H 6 TTHA ligand, Ln(NO 3) 3 ·6H 2 O (Ln=Eu, Sm, Dy) and Zn(NO 3) 2 ·6H 2 O under hydrothermal conditions. Complex 1 had the fluorescence sensing abilities for metal ions, anions, and organic nitro compounds. It was worth noting that complex 1 showed prominent sensitivity for TNP, the detection limit was as low as 1.14 μM. [Display omitted] Metal-organic frameworks composed of two metals in the structure are called mixed-metal metal organic frameworks (MM-MOFs). In this work, we constructed three MM-MOFs, namely [Zn 3 Eu 2 (TTHA) 2 (H 2 O) 6 ]·6H 2 O (1), [Zn 3 Sm 2 (TTHA) 2 (H 2 O) 6 ]·2H 2 O (2) and [ZnDy(HTTHA)(H 2 O) 4 ]·2H 2 O (3) by the reaction of H 6 TTHA ligand (H 6 TTHA = 1, 3, 5-triazine-2, 4, 6-triamine hexaacetic acid), Ln(NO 3) 3 ·6H 2 O (Ln = Eu, Sm, Dy) and Zn(NO 3) 2 ·6H 2 O under hydrothermal conditions. The complexes 1 – 2 were a 3D microporous structure and complex 3 formed a 3D network structure. Furthermore, complex 1 exhibited excellent fluorescence properties. We explored the fluorescence sensing abilities of complex 1 for metal ions, anions, and organic nitro compounds. The experimental results showed that complex 1 could sensitively and efficiently detect Fe3+, Cr 2 O 7 2- ions and 2,4,6-trinitrophenol (TNP). It was worth noting that complex 1 showed prominent sensitivity for TNP, the detection limit was as low as 1.14 μM. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV) is an acute infectious disease characterized by neurological and respiratory symptoms. In order to have a better understanding of the current prevalence of PRV in northeastern China, a strain of PRV was isolated by us. Then, protein structure analysis and pathogenicity testing of the virus were performed to give insight into the characterization of the isolated PRV strains. In this study, the PRV strain named CH/HLJPRVJ/2023 was isolated and identified. Genome-wide phylogenetic analysis shows CH/HLJPRVJ/2023 and HeN1 have higher homology. The CH/HLJPRVJ/2023 strain had the highest homology with HeN1 strain (97.3%) and the lowest homology with Bartha-K61 (89.2%). Recombinant evolution analysis shows CH/HLJPRVJ/2023 shows many variants in OBP, AN, UL21, UL17, VP11/12, and VP1/2 fragments, which predict its unique genetically. VP1/2, an effector protein of capsid transport and neuroinvasion, has mutations and deletions in its amino acids, which cause changes in the protein conformation of CH/HLJPRVJ/2023. Besides the typical neurologic and respiratory lesions, infection with highly pathogenic CH/HLJPRVJ/2023 can lead to damage to the colonic villi and colonic barrier in piglets. This study will provide a basis for knowledge about the prevalence, genetic evolution, and vaccine optimization of endemic PRV strains in northeastern China. [ABSTRACT FROM AUTHOR]

Geomagnetically induced currents (GICs) generated by geomagnetic disturbances (GMD) during strong magnetic storms may trigger chain failures in power systems. In this paper, a critical node identification method based on the improved LeaderRank algorithm considering the effects of geomagnetic storms is proposed. A chain fault identification process based on the fragility theory of complex systems is proposed to determine the initial fault line by critical nodes and simulate the fault development process to obtain the accident chain set. The effectiveness of the method is verified by using the IEEE RTS79 node system as an example. The research results show that the method can reflect the critical nodes and accident chain set of power systems under different geomagnetic storm effects, and the research results can provide a reference for geomagnetic storm disaster quantification, assessment, and prevention. [ABSTRACT FROM AUTHOR]

Stress-induced intestinal epithelial injury (IEI) and a delay in repair in infancy are predisposing factors for refractory gut diseases in adulthood, such as irritable bowel syndrome (IBS). Hence, it is necessary to develop appropriate mitigation methods for mammals when experiencing early-life stress (ELS). Weaning, as we all know, is a vital procedure that all mammalian newborns, including humans, must go through. Maternal separation (MS) stress in infancy (regarded as weaning stress in animal science) is a commonly used ELS paradigm. Drinking silicon-rich alkaline mineral water (AMW) has a therapeutic effect on enteric disease, but the specific mechanisms involved have not been reported. Herein, we discover the molecular mechanism by which silicon-rich AMW repairs ELS-induced IEI by maintaining intestinal stem cell (ISC) proliferation and differentiation through the glucagon-like peptide (GLP)2–Wnt1 axis. Mechanistic study showed that silicon-rich AMW activates GLP2-dependent Wnt1/β-catenin pathway, and drives ISC proliferation and differentiation by stimulating Lgr5+ ISC cell cycle passage through the G1–S-phase checkpoint, thereby maintaining intestinal epithelial regeneration and IEI repair. Using GLP2 antagonists (GLP23−33) and small interfering RNA (SiWnt1) in vitro, we found that the GLP2–Wnt1 axis is the target of silicon-rich AMW to promote intestinal epithelium regeneration. Therefore, silicon-rich AMW maintains intestinal epithelium regeneration through the GLP2–Wnt1 axis in piglets under ELS. Our research contributes to understanding the mechanism of silicon-rich AMW promoting gut epithelial regeneration and provides a new strategy for the alleviation of ELS-induced IEI. [ABSTRACT FROM AUTHOR]

The present study found that drinking alkaline mineral water confers diarrhea resistance in maternally separated piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis. The improvement in gut microbiota composition and function maintains intestinal epithelial regeneration by activating Wnt/β-catenin signaling to repair damaged intestinal mucosa and interrupted ISC differentiation. This study provides a potential prevention strategy for young mammals at risk of diarrhea. [Display omitted] • Drinking AMC water confers diarrhea resistance in piglets under weaning stress. • Brain-microbe-gut axis is the target of AMC water for diarrhea therapy. • Drinking AMC water alleviates weaning-induced intestinal injury in MS piglets. • Drinking AMC water maintains intestinal epithelial regeneration in MS piglets. • Gut microbe is a key factor in stimulating intestinal stem cell differentiation. Diarrhea has the fourth-highest mortality rate of all diseases and causes a large number of infant deaths each year. The maternally separated (MS) piglet (newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infants. Drinking alkaline mineral water has the potential to be therapeutic in gastrointestinal disorders, particularly diarrhea, but the supporting evidence from system studies and the mechanisms involved have yet to be reported. This study aims to determine whether drinking alkaline mineral water confers diarrhea resistance in MS piglets under weaning stress and what the fundamental mechanisms involved are. MS piglets were used to create a stress-induced intestinal disorder-diarrhea susceptibility model. A total of 240 MS piglets were randomly divided into two groups (6 pens/group and 20 piglets/pen). IPEC-J2 cell line was used for in vitro evaluation. An alkaline mineral complex (AMC) water was employed, and its effect on the hypothalamus-pituitary-adrenocortical (HPA) axis, gut microbes, gut morphology, and intestinal epithelial cell (IEC) proliferation and differentiation were investigated using a variety of experimental methodology. AMC water reduced diarrhea rate in MS piglets by inhibiting the HPA axis, ameliorating gut microbiota structure, and stimulating IEC proliferation and differentiation. Apparently, the brain-microbe-gut axis is linked with AMC water conferring diarrhea resistance in piglets. Mechanistically, AMC water decreased stress hormones (COR and Hpt) secretion by suppressing HPA axis, which then increased the abundance of beneficial gut microbes; accordingly, maintained the proliferation of IEC and promoted the differentiation of intestinal stem cells (ISC) into goblet cell and Paneth cell by activating the Wnt/β-catenin signaling pathway. In the absence of gut microbiota (in vitro), AMC activated the LPS-induced Wnt/β-catenin signaling inhibition in IPEC-J2 cells and significantly increased the number of Lgr5 + cells, whereas had no effect on IPEC-J2 differentiation. Drinking alkaline mineral water confers diarrhea resistance in MS piglets by maintaining intestinal epithelial regeneration via the brain-microbe-gut axis; thus, this study provides a potential prevention strategy for young mammals at risk of diarrhea. [ABSTRACT FROM AUTHOR]

BACKGROUND: Cadmium (Cd), known as a vital contaminant in the environment, penetrates the blood–brain barrier and accumulates in the cerebrum. Acute toxicosis of Cd, which leads to lethal cerebral edema, intracellular accumulation and cellular dysfunction, remains to be illuminated with regard to the exact molecular mechanism of cerebral toxicity. Resveratrol (RES), present in the edible portions of numerous plants, is a simply acquirable and correspondingly less toxic natural compound with neuroprotective potential, which provides some theoretical bases for antagonizing Cd‐induced cerebral toxicity. RESULTS: This work was executed to research the protective effects of RES against Cd‐induced toxicity in chicken cerebrum. Markedly, these lesions were increased in the Cd group, which also exhibited a thinner cortex, reduced granule cells, vacuolar degeneration, and an enlarged medullary space in the cerebrum. Furthermore, Cd induced CYP450 enzyme metabolism disorders by disrupting the nuclear xenobiotic receptor response (NXRs), enabling the cerebrum to reduce the ability to metabolize exogenous substances, eventually leading to Cd accumulation. Meanwhile, accumulated Cd promoted oxidative damage and synergistically promoted the damage to neurons and glial cells. CONCLUSION: RES initiated NXRs (especially for aromatic receptor and pregnancy alkane X receptor), decreasing the expression of CYP450 genes, changing the content of CYP450, maintaining CYP450 enzyme normal activities, and exerting antagonistic action against the Cd‐induced abnormal response of nuclear receptors. These results suggest that the cerebrum toxicity caused by Cd was reduced by pretreatment with RES. © 2023 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

The present study identified a critical role of Cx43 in LYC maintaining BTB integrity, which is a prerequisite for normal spermatogenesis. This study reveals the role of Cx43 in LYC preventing phthalate-induced spermatogenic disorders, and Cx43 regulation may provide the basis for future therapeutic male infertility. [Display omitted] • Phthalate induced spermatogenic disorders and destroyed BTB integrity. • Phthalate caused cell migration capacity decline and cytoskeletal disorganization. • LYC alleviated DEHP-induced disruption of intercellular junctions in mouse testes. • LYC improved DEHP-induced spermatogenic disorders by regulating BTB integrity. • LYC ameliorated DEHP-induced BTB disruption by modulating Cx43 expression. Male infertility is a multifactorial pathological condition and may be a harbinger of future health. Phthalates are ubiquitous environmental contaminants that have been implicated in the global decline in male fertility. Among them, di-(2-ethylhexyl) phthalate (DEHP) is the most prevalently used. Lycopene (LYC) is a possible preventive and therapeutic agent for male infertility owing to its antioxidant properties. The blood-testis barrier (BTB) is formed between Sertoli cells where it creates a unique microenvironment for spermatogenesis. We hypothesize that phthalate caused male infertility and LYC plays an important role in phthalate-induced male fertility disorders. Hematoxylin-eosin (H&E) staining, ultrastructure observation, and fluorescence microscopy were used to examine the morphological changes. RNA-Seq, and western blotting were conducted to detect gene and protein levels. Routine testing for sperm morphology and sperm-egg binding assay were conducted to examine the morphological structure and function of sperm. Cell scratch assay and transepithelial electrical resistance (TER) were used to detect cell migration capacity and barrier integrity. In vivo experiments, we showed that LYC prevented DEHP-induced impairment of BTB integrity, which provided a guarantee for the smooth progress of spermatogenesis. LYC improved DEHP-induced change in sperm parameters and fertilization ability. Subsequent in vitro experiments, LYC alleviated MEHP-induced disruption of intercellular junctions in mouse Spermatogonia cells (GC-1 cells) and mouse Sertoli cells (TM4 cells). In MEHP-induced BTB impairment models of Sertoli cells, treatment with LYC or overexpressing connexin-43 (Cx43) promoted cell migration capacity and normalized BTB integrity. Cx43 knockdown inhibited cell migration capacity and perturbed BTB reassembly in LYC preventing DEHP-induced BTB impairment. Our study provides evidence for the role of LYC in phthalates-induced spermatogenic disorders and points to Cx43 as a potential target for male fertility. [ABSTRACT FROM AUTHOR]

The continuous challenge of existing vaccine systems by porcine epidemic diarrhea virus (PEDV) variant strains in recent years, it caused significant economic losses in the global swine industry. A PEDV virulent strain CH/HLJBQL/2022 was successfully isolated in China in this study. A genome-wide based phylogenetic analysis suggests that CH/HLJBQL/2022 belongs to the GII subtype, and 96.3%–99.6% homology existed in the whole genomes of other strains. For the first time, simultaneous mutations of four amino acids were found in the highly conserved membrane (M) and nucleocapsid (N) proteins, as well as five amino acid mutations that differed from the vast majority of strains in the spike (S) protein. Mutations in the M and S proteins were found to produce coils with different angles by building 2D and 3D structural models. Epitope analysis indicated that the isolates produced specific changes and that the transmembrane function of the M protein had not been affected. In addition, typing markers exist during strain evolution, but isolates are using the fusion of specific amino acids from multiple variant strains to add additional features, as also demonstrated by protein alignments and 3D models of numerous subtype strains. These results suggest that aa mutations in the M and S proteins may have changed the structure and antigenic epitope of the isolates and PEDV is evolving again on the basis of variants that have been found to counteract the immune network of the new vaccine. [ABSTRACT FROM AUTHOR]

Background: Porcine epidemic diarrhea virus (PEDV) variant strains cause great economic losses to the global swine industry. However, vaccines do not provide sufficient protection against currently circulating strains due to viral mutations. This study traced the molecular characteristics of the most recent isolates in China and aimed to provide a basis for the prevention and treatment of PEDV. Methods: We obtained samples from a Chinese diarrheal swine farm in 2022. Reverse transcription polymerase chain reaction and immunofluorescence were used to determine the etiology, and the full-length PEDV genome was sequenced. Nucleotide similarity was calculated using MEGA to construct a phylogenetic tree and DNASTAR. Mutant amino acids were aligned using DNAMAN and modeled by SWISS-MODEL, Phyre2 and FirstGlance in JMOL for protein tertiary structure simulation. Additionally, TMHMM was used for protein function prediction. Results: A PEDV virulent strain CH/HLJJS/2022 was successfully isolated in China. A genome-wide based phylogenetic analysis suggests that it belongs to the GII subtype, and 96.1–98.9% homology existed in the whole genomes of other strains. For the first time, simultaneous mutations of four amino acids were found in the highly conserved membrane (M) and nucleocapsid (N) proteins, as well as eight amino acid mutations that differed from the vast majority of strains in the spike (S) protein. Three of the mutations alter the S-protein spatial structure. In addition, typing markers exist during strain evolution, but isolates are using the fusion of specific amino acids from multiple variant strains to add additional features, as also demonstrated by protein alignments and 3D models of numerous subtype strains. Conclusion: The newly isolated prevalent strain CH/HLJJS/2022 belonged to the GII subtype, and thirteen mutations different from other strains were found, including mutations in the highly conserved m and N proteins, and in the S1° and COE neutralizing epitopes of the S protein. PEDV is breaking through original cognitions and moving on a more complex path. Surveillance for PEDV now and in the future and improvements derived from mutant strain vaccines are highly warranted. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a toxic environmental contaminant, which bio-accumulate in animals through the food chain. Cerebellum is one of the primary target organs for Cd exposure. In this study, we established a chronic Cd exposure model; 60 chickens were treated with Cd (0 mg/kg, 35 mg/kg, 70 mg/kg) for 90 days. Clinical manifestations indicated that the chicken was depressed and has unstable gait under Cd exposure. Histopathological results indicated that Cd induced neuronal shrunken and indistinct nucleoli, and the number of Purkinje cells decreased significantly. Cerebellar metal contents were analyzed by ICP-MS. We found that Cd caused Cd and Cu accumulation and decreased the content of Se, Fe, and Zn, suggesting that Cd disturbed metal homeostasis. Besides, Cd treatment group also showed high levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) content and inhibited selenoprotein transcriptome, suggesting that Cd exposure resulted in oxidative stress. Notably, low-dose Cd exposure activated MTF1 mRNA and protein expression and its target metal-responsive genes, including MT1, MT2, DMT1, ZIP8, ZIP10, TF, and ATP7B which indicate cellular adaptive response against Cd-induced damage. On the other hand, 70 mg/kg Cd downregulated MTF1-mediated metal response, which was involved in Cd-induced cerebellar injury in chicken. In conclusion, our data demonstrated that molecular mechanisms are associated with Cd-induced cerebellar injury due to disturbing MTF1-mediated metal response. This study indicated that the cerebellum is one of the target organs of Cd-induced toxicity. Additionally, Cd exposure induced metal dyshomeostasis in chicken's cerebellum, whereas this study found that lower level of Cd dose triggered the activation of the cytoprotective mechanism through activating the expression of MTF1 which regulate MT1, MT2, DMT1, ZIP8, ZIP10, TF, and ATP7B expressions in cerebellum. However, MTF1-mediated metal response was inhibited under the exposure of high dose of Cd, which ultimately caused cerebellar injury. The present study provides a new insight that Cd through disturbed MTF1-mediated metal response disrupts metal homeostasis that induced cerebellar injury. [ABSTRACT FROM AUTHOR]

In the modern poultry industry, newly hatched chicks are unavoidably transported from the hatching to the rearing foster. Stress caused by multiple physical and psychological stressors during transportation is particularly harmful to the liver. Astragalus polysaccharide (APS) possesses multiple benefits against hepatic metabolic disorders. Given that transport stress could disturb hepatic glucolipid metabolism and the role of APS in metabolic regulation, we speculated that APS could antagonize transport stress-induced disorder of hepatic glucolipid metabolism. Firstly, newly hatched chicks were transported for 0, 2, 4, and 8 h, respectively. Subsequently, to further investigate the effects of APS on transport stress-induced hepatic glucolipid metabolism disturbance, chicks were pretreated with water or APS and then subjected to transport treatment. Our study suggested that APS could relieve transport stress-induced lipid deposition in liver. Meanwhile, transport stress also induced disturbances in glucose metabolism, reflected by augmented mRNA expression of key molecules in gluconeogenesis and glycogenolysis. Surprisingly, APS could simultaneously alleviate these alterations via peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α)/Sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway. Moreover, APS treatment regulated the level of peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ), thereby alleviating transport stress-induced alterations of VLDL synthesis, cholesterol metabolism, lipid oxidation, synthesis, and transport-related molecules. These findings indicated that APS could prevent the potential against transport stress-induced hepatic glucolipid metabolism disorders via PGC-1α/SIRT1/AMPK/PPARα/PPARγ signaling system. [ABSTRACT FROM AUTHOR]

Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread. • Matrine inhibits PEDV attachment and entry to cells. • Matrine has virucidal effect on PEDV. • Matrine shows antiviral effects by targeting to Spike protein. • The carbonyl oxygen of Matrine is the main pharmacophore binding to Spike protein. • Matrine inhibits PEDV infection via promoting PEDV-induced apoptosis by activating MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is widely used worldwide as a commercial herbicide, Diaminochlorotriazine (DACT) is the main metabolite of ATR in the organism. Both of them disrupt the production of steroids and induce abnormal reproductive development. The granulosa cells (GC s) are important for growth and reproduction of animals. However, the toxicity of ATR on the GCs of birds is not well clarified. To evaluate the effect of the environmental pollutant ATR on bird GCs. The quail GCs were allotted into 7 groups, C (The medium of M199), A20 (20 µM ATR), A100 (100 µM ATR), A250 (250 µM ATR), D20 (20 µM DACT), D100 (100 µM DACT) and D200 (200 µM DACT). The results demonstrated that ATR reduced the viability of GCs, disrupted mitochondrial structure (including mitochondrial cristae fragmentation and the mitochondrial morphology disappearance) and decreased mitochondrial membrane potential. Meanwhile, ATR interfered with the expression of key factors in the steroid synthesis pathway, inducing the secretion of the sex hormones E 2 and P in GCs. which in turn induced apoptosis. Furthermore, the Nrf2/ARE pathway as a potential target to ameliorate ATR-induced endocrine disruption in GCs for proper reproductive functions. Our research provides a new perspective for understanding the effects of ATR on reproductive functions in birds. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a well-known testis toxicant. The blood-testis barrier (BTB) is a crucial component of the testis. Cd can disrupt the integrity of the BTB and reproductive function. However, the mechanism of Cd-induced disruption of BTB and testicular damage has not been fully elucidated. Here, our study investigates the effects of Cd on BTB integrity and testicular dysfunction. 80 (aged 1 day) Hy-Line white variety chickens were randomly designed into 4 groups and treated for 90 days, as follows: control group (essential diet), 35 Cd, 70 Cd and 140 Cd groups (35, 70 and 140 mg/kg Cd). The results found that Cd exposure diminished volume of the testes and induced histopathological lesions in the testes. Exposure to Cd induced an inflammatory response, disrupted the structure and function of the FAK/occludin/ZO-1 protein complex and disrupted the tight junction and adherens junction in the BTB. In addition, Cd exposure reduced the expression of steroid-related proteins and inhibited testosterone synthesis. Taken together, these data elucidate that Cd disrupts the integrity of the BTB and further inhibits spermatogenesis by dissociating the FAK/occludin/ZO-1 complex, which provides a basis for further investigation into the mechanisms of Cd-induced impairment of male reproductive function and pharmacological protection. [Display omitted] • Cd caused testicular injury in the testes. • Cd induced dissociation and redistribution of the FAK/occludin/ZO-1 complexes. • Cd destroyed the integrity of the BTB in the chicken testes. • Cd led to steroid hormone disorders in the testes. [ABSTRACT FROM AUTHOR]

Transport stress (TS) not only weakens poultry performance but also affects animal welfare. Additionally, TS can evoke cardiac damage by triggering sterile inflammation in chicks, but the underlying mechanism is not fully understood. Here, we aimed to elucidate how TS induces sterile inflammation and heart injury and to clarify the antagonism effect of astragalus polysaccharides (APS). We randomly divided 60 chicks (one-day-old female) into 5 groups (n = 12): Control_0h (Con_0h) group (chicks were slaughtered at initiation), Control group (stress-free control), TS group (simulated TS exposure for 8 h), TS plus water (TS+W) group, and TS plus APS (TS+APS) group. Before simulation transport, the chicks of TS+W and TS+APS groups were, respectively, dietary with 100 μL of water or APS (250 μg/mL). H&E staining was employed for cardiac histopathological observation. ELISA assay was used to measure oxidative stress marker levels (GSH, GPX, GST, and MDA). A commercial kit was used to isolate the mitochondrial portion, and qRT-PCR was employed to measure the mitochondrial DNA (mtDNA) levels. Furthermore, we evaluated the activity of mtDNA-mediated NF-κB, NLRP3 inflammasome, and cGAS-STING inflammatory pathways and the expression of downstream inflammatory factors by Western Blotting or qRT-PCR. Our findings revealed that APS notably relieved TS-induced myocardial histopathological lesions and infiltrations. Likewise, the decrease in proinflammatory factors (TNF-α, IL-1β, and IL-6) and IFN-β by APS further supported this result. Meanwhile, TS caused severe oxidative stress in the chick heart, as evidenced by decreased antioxidant enzymes and increased MDA. Importantly, APS prevented mtDNA stress and leakage by reducing oxidative stress. Interestingly, TS-induced mtDNA leakage caused a series of inflammation events via mtDNA-PRRs pathways, including TLR21-NF-κB, NLRP3 inflammasome, and cGAS-STING signaling. Encouragingly, all these adverse changes related to inflammation events induced by mtDNA-PRRs activation were all relieved by APS treatment. In summary, our findings provide the first evidence that inhibition of mtDNA-PRRs pathway-mediated sterile inflammation by APS could protect against TS-induced cardiac damage in chicks. [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is easily found in the environment. Excessive daily exposure of it may lead to an increased risk of cardiovascular disease (CVD). Lycopene (LYC), as a natural carotenoid, has been shown to have the potential to prevent CVD. However, the mechanism of LYC on cardiotoxicity caused by DEHP exposure is unknown. The research was aimed to investigate the chemoprotection of LYC on the cardiotoxicity caused by DEHP exposure. Mice were treated with DEHP (500 mg/kg or 1,000 mg/kg) and/or LYC (5 mg/kg) for 28 d by intragastric administration, and the heart was subjected to histopathology and biochemistry analysis. The results indicated that DEHP caused cardiac histological alterations and enhanced the activity of cardiac injury indicators, and interfered with mitochondrial function and activating mitophagy. Notably, LYC supplementation could inhibit DEHP-induced oxidative stress. The mitochondrial dysfunction and emotional disorder caused by DEHP exposure were significantly improved through the protective effect of LYC. We concluded that LYC enhances mitochondrial function by regulating mitochondrial biogenesis and dynamics to antagonize DEHP-induced cardiac mitophagy and oxidative stress. DEHP exposure can cause heart damage and destroy the pathophysiological integrity of the mouse heart. LYC can alleviate this phenomenon. LYC can alleviate the heart oxidative stress damage induced by the imbalance of mitochondrial biogenesis and mitochondrial dynamics disorder DEHP. This study provides new insights and shows that LYC can prevent DEHP-induced heart damage by activating mitophagy, which may be the target molecule of DEHP toxicity and LYC effect mechanism in the future. [Display omitted] [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a commercially available herbicide that is used worldwide. The intensive use of ATR poses potential risks to animals' and humans' health. Lycopene (LYC) is an anti-oxidative phytochemical that normalizes health hazards triggered by environmental factors. In this study, we aimed to investigate the toxic effects of ATR on the hippocampus and its amelioration by LYC. Male mice were exposed to ATR (50 mg/kg/day or 200 mg/kg/d) and/or LYC (5 mg/kg/d) for 21 days. The results showed that ATR exposure induced hippocampus-dependent learning and memory impairments. ATR-induced ferroptosis in hippocampal cells affects the homeostasis of lipid metabolism, whereas LYC ameliorates the neurotoxic effects of ATR in the hippocampus. LYC inhibited ATR-induced ferroptosis by increasing the expression of HO-1, Nrf2 and SLC7A11. Therefore, this study established that LYC ameliorates ATR-induced spatial learning and memory impairments by inhibiting ferroptosis in the hippocampus and also provides a novel approach for the treatment in contradiction of environmental pollutants. ATR is a kind of herbicide that spreads throughout the environment. Because of its biological activity, particularly antioxidant properties, LYC has attracted a lot of interest. According to our findings, LYC ameliorates ATR-induced spatial learning and memory impairments by inhibiting ferroptosis in the hippocampus of mice. This research may lead to a plausible molecular mechanism for LYC therapy of ATR-induced neurological damage. [Display omitted] • ATR caused spatial learning and memory impairments. • ATR induced ferroptosis in the hippocampus. • LYC can prevent ferroptosis and promote nerve cell repair. • LYC mitigated ATR-induced spatial learning and memory impairments. [ABSTRACT FROM AUTHOR]

Di (2-ethylhexyl) phthalate (DEHP) is commonly used as a plasticizer in plastic products, and due to its unique chemical composition, it frequently dissolves and enters the environment. Lycopene as a natural carotenoid has been shown to have powerful antioxidant capacity and strong kidney protection. This study aimed to investigate the role of the interplay between oxidative stress and the classical pyroptosis pathway in LYC alleviating DEHP-induced renal injury. ICR mice were given DEHP (500 mg/kg/d or 1000 mg/kg/d) and/or LYC (5 mg/kg/d) for 28 days to explore the underlying mechanisms of this hypothesis. Our results indicated that DEHP caused the shedding of renal tubular epithelial cells, increased the content of kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) in the tissue, the decrease of antioxidant activity markers and the increase of oxidative stress indexes. It is gratifying that LYC alleviates DEHP-induced renal injury. The expression of nuclear factor erythrocyte 2-related factor 2 (Nrf2) and its downstream target genes is improved in DEHP induced renal injury through LYC mediated protection. Meanwhile, LYC supplementation can inhibit DEHP-induced Caspase-1/NLRP3-dependent pyroptosis and inflammatory responses. Taken together, DEHP administration resulted in nephrotoxicity, but these changes ameliorated by LYC may through crosstalk between the Nrf2/Keap-1/NLRP3/Caspase-1 pathway. Our study provides new evidence that LYC protects against kidney injury caused by DEHP. [Display omitted] [ABSTRACT FROM AUTHOR]

Di-(2-ethylhexyl) phthalate (DEHP) is an environmental toxicant that is widely used in the whole world as a plasticizer that can enhance plastic properties. A number of reserarches have demonstrated that DEHP could cause varying degrees of damage to the normal function of nerve. The research aimed to investigate the mechanism of DEHP-induced cerebellar toxicity. In present study, we set DEHP-caused cerebellar injury models of quail and implied that DEHP induced cerebellar dysplasia by abnormity of Purkinje cell and reduction of cerebellar granule cell. Furthermore, the mitochondrial damage was confirmed by the swelling, cristae reduction, membrane rupture of mitochondria or even the occurrence of autophagic vacuole. To clarified DEHP-induced mitochondrial damage in cerebellum, we examined the relevant genes of mitochondrial biogenesis, mitochondrial dynamics, oxidative damage, the pathways related to Nrf2 and PINK1/Parkin in cerebellum. Based on data, it appeared that DEHP treatment had a damaging effect on the cerebellum and led to mitophagy as well as oxidative stress. In conclusion, the research indicated that DEHP-actuated mitochondrial injury has a directly relationship with mitophagy. DEHP-actuated reduced mitochondrial biogenesis and dysregulation of mitochondrial dynamics. The increase of oxidative stress damaged mitochondria, and the redundant ROS in damaged mitochondria that gave rise to cerebellar harm. [Display omitted] • DEHP leads to a block in Sirt1-PGC-1α-mediated mitochondrial biogenesis. • DEHP leads to mitochondrial dynamics unbalance. • DEHP stimulates PINK1/parking-mediated mitophagy leading to cerebellar injury. • DEHP induces the reinforcement of oxidative stress. [ABSTRACT FROM AUTHOR]

Phthalates are extensively used in the production of plastics products and have been verified to induce lung injury. Lycopene (LYC) has proved an effective preventive and can be utilized to prevent phthalates-induced toxicity. However, the role of phthalate in pathogenesis of lung injury remain poorly researched, and little work has been devoted whether LYC could alleviate phthalate-induced lung toxicity via modulating nuclear xenobiotic receptors (NXRs) response. Here, di (2-ethylhexyl) phthalate (DEHP) is used as the representative of phthalates for further studies on toxicity of phthalates and the antagonistic role of LYC in phthalates-induced lung injury. We found that DEHP exposure caused alveoli destruction and alveolar epithelial cells type II damage. Mechanistically, DEHP exposure increased nuclear accumulation of aryl hydrocarbon receptor (AHR) and its downstream genes level, including cytochrome P450-dependent monooxygenase (CYP) 1A1 and CYP1B1. Constitutive androstane receptor (CAR) and their downstream gene level, including CYP2E1 are also increased after phthalates exposure. Significantly, LYC supplementation relieves lung injury from DEHP exposure by inhibiting the activation of NXRs. We confirm that NXRs plays a key role in phthalates-induced lung injury. Our study showed that LYC may have a positive role in alleviating the toxicity effects of phthalates, which provides an effective strategy for revising phthalates-induced injury. DEHP activates xenobiotic-sensing nuclear receptors AHR and CAR signaling pathway, and thereby resulted in lung injury. LYC supplementation is a potential therapeutic strategy to attenuates phthalates-induced lung injury (By Figdraw). [Display omitted] • DEHP causes lung injury via activating AHR/CAR signaling pathway. • DEHP increases the nuclear accumulation of AHR and CAR. • DEHP causes vacuolization and electron density reduced of lamellar bodies. • AHR and CAR can be used as targets for LYC to attenuate DEHP-induced lung injury. [ABSTRACT FROM AUTHOR]

Stress or stress-induced intestinal disturbances, especially diarrhea, are the main triggers for inflammatory bowel disease and irritable bowel syndrome. Diarrhea and intestinal inflammatory disease afflict patients around the world, and it has become a huge burden on the global health care system. Drinking sodium metasilicate-based alkaline mineral water (SM-based AMW) exerts a potential therapeutic effect in gastrointestinal disorders, including gut inflammation, and diarrhea, but the supportive evidence on animal studies and mechanism involved remain unreported. The maternally separated (MS) piglet (Newly weaned piglet) is an excellent model to investigate the treatment of diarrhea in infant. This study aims to determine whether drinking SM-based AMW confers diarrhea resistance in maternally separated (MS) piglets under weaning stress and what the underlying mechanisms are involved. 240 newly weaned piglets were randomly divided into the Control group and the sodium metasilicate pentahydrate (SMP) group. A decreased diarrhea incidence was observed in SMP treatment piglets. The intestine injury and activated stress hormones (COR and ACTH) induced by weaning was alleviated by SM-based AMW. This may be related to the improvement of intestinal microflora structure and function by SMP, especially the increase of s_copri abundance. Meanwhile, SMP maintained the integrity of the duodenal mucus barrier in MS piglets. Importantly, by targeting NF-κB inhibition via the microbiota-gut interaction, SM-based AMW alleviated intestinal inflammation, maintained fluid homeostasis by modulating aquaporins and fluid transporter expression, and enhanced barrier integrity by suppressing MLCK/p-MLC signaling. Therefore, drinking metasilicate-based alkaline mineral water confers diarrhea resistance in MS piglets via the microbiota-gut interaction. [Display omitted] • Drinking SM-based AMW confers diarrhea resistance in MS piglets under weaning stress. • Drinking SM-based AMW alleviates intestinal injury in MS piglets. • Drinking SM-based AMW improves the structure of gut microbiota in MS piglets. • Anti-diarrhea effect of SM-based AMW is related to microbiota-gut interaction. • s_copri is the key community of SM-based AMW mediated microbiota-gut interaction. [ABSTRACT FROM AUTHOR]

Atrazine (ATR) is a widely used herbicide with biologically toxic effects that can lead to neurotoxicity. Lycopene (LYC) is an antioxidant with chemoprotective properties. However, little know about the mechanisms of preventative interventions about LYC alleviated ATR-induced neurotoxicity. Male mice were treated with distilled water (C), 5 mg/kg BW/day LYC (L), 50 and 200 mg/kg BW/day ATR (A1, A2), respectively and LYC + ATR (A1+L, A2+L). ATR promoted oxidative stress and inflammatory damage, as showed by the effects on MDA, H 2 O 2 , IL-6 and TNF-α accumulation, and IL-10, SOD, CAT and GSH depletion, which caused neuronal swelling and mitochondrial vacuolar degeneration. ATR disrupted the CYP450s balance via increasing contents of CYP450 and cytochrome B5, enhancing activities of NCR and ERND and activating NXRs and NXRs-related transcription factors. However, all these effects were reversed by LYC pretreatment. Collectively, these data indicated that LYC inhibited ATR-induced oxidative damage through modulating xenobiotic-sensing nuclear receptors and CYP450s. [Display omitted] • LYC inhibits ATR exposure-induces neurotoxicity. • LYC alleviates ATR exposure-induces AHR/PXR/CAR pathway responses. • LYC alleviates ATR-induces the CYP450 homeostasis disorders and CYPs transcription. • LYC alleviates ATR exposure triggers oxidative stress and inflammatory response. [ABSTRACT FROM AUTHOR]

As one of the most used phthalates, Di (2-ethylhexyl) phthalate (DEHP) is a widespread environmental contaminant. Extremely persistent plastic can enter the food chain of animals through the aquatic environment, affect metabolic pathways and cause damage to the digestive system. But the molecular mechanism of its toxic effects on the duodenum in birds has not been elucidated. To investigate the toxicity of phthalates in the duodenum, quails were gavaged with 250, 500, and 750 mg/kg doses of DEHP for 45 days, and water and oil control groups were retained. This study revealed that subchronic exposure to DEHP could lead to duodenal barrier defect in quail. The damage to duodenum was reflected in a reduction in V/C and tight junction proteins. Moreover, DEHP also led to a breakdown of antimicrobial defenses through the flora derangement, which acted as a biological barrier. The massive presence of Lipopolysaccharide (LPS) led to the activation of TLR4 receptors. In addition, DEHP activated oxidative stress, which synergized the inflammatory response induced by the TLR4-NFκB pathway, and further promoted duodenum damage. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction. DEHP (a commonly used phthalate) induced duodenal barrier defect and flora derangement of quail, which is sensitive to environmental pollutants. This study provides a base for the further effect of phthalates on the microbiota-barrier-immune interaction. [Display omitted] • Duodenal barrier defect disrupts microbiota-barrier-immune interaction. • DEHP causes duodenal flora derangement and dysbiosis of antimicrobial function. • Duodenal Proteobacteria increased most significantly after DEHP treatment. • DEHP induces duodenum damage and decreases V/C in quail. • DEHP activates duodenal oxidative stress and inflammation in quail. DEHP (a commonly used phthalate) is ubiquitous in the environment due to overuse. This study could warn of the health risks to animals exposed to phthalates and even humans. [ABSTRACT FROM AUTHOR]

As a plasticizer, di-2-ethylhexyl phthalate (DEHP) has been listed as a potential endocrine disruptor by The World Health Organization. The toxicity of DEHP has been widely studied, but its toxicity on the digestive tract of birds has not been clarified. Female quail were treated by gavage with DEHP (250, 500, 750 mg/kg), with the blank and vehicle control groups reserved. The result showed that DEHP raised the damage severity grade, and decreased the ratio of villus length to crypt depth. The content and activity of cytochrome P450 system (CYP450s) were increased by DEHP. DEHP interfered with the transcription of nuclear xenobiotic receptors (NXRs), CYP isoforms, and the nuclear factor-E2-related factor 2 (Nrf2) signaling pathway. This study revealed DEHP could cause the imbalance in CYP450s mediated by NXRs, and then promote Nrf2 mediated antioxidant defense. This study provided new evidence about the mechanisms of DEHP-induced toxic effects on digestive tract. [Display omitted] • DEHP increases the damage severity grade and decreases the villus length/crypt depth. • DEHP-induced jejunal toxicity is associated with oxidative stress in quail. • DEHP destroys the steady state of the NXR and CYP response in the quail jejunum. • DEHP activates Nrf2-mediated antioxidant defense in the quail jejunum. [ABSTRACT FROM AUTHOR]

Male infertility is an attracting growing concern owing to decline in sperm quality of men worldwide. Phthalates, in particular to di (2-ethylhexyl) phthalate (DEHP) or its main metabolite mono-2-ethylhexyl phthalate (MEHP), affect male reproductive development and function, which mainly accounts for reduction in male fertility. Lycopene (LYC) is a natural antioxidant agent that has been recognized as a possible therapeutic option for treating male infertility. Testosterone (T)/androgen receptor (AR) signaling pathway is involved in maintaining spermatogenesis and male fertility. How DEHP causes spermatogenesis disturbance and whether LYC could prevent DEHP-induced male reproductive toxicity have remained unclear. Using in vivo and vitro approaches, we demonstrated that DEHP caused T biosynthesis reduction in Leydig cell and secretory function disorder in Sertoli cell, and thereby resulted in spermatogenic impairment. Results also showed that MEHP caused mitochondrial damage and oxidative damage, which imposes a serious threat to the progress of spermatogenesis. However, LYC supplement reversed these changes. Mechanistically, DEHP contributed to male infertility via perturbing T/AR signaling pathway during spermatogenesis. Overall, our study reveals critical role for T/AR signal transduction in male fertility and provides promising insights into the protective role of LYC in phthalate-induced male reproductive disorders. [Display omitted] • DEHP caused testosterone synthesis decline in Leydig cells. • DEHP resulted in secretory function disorder in Sertoli cells. • DEHP led to spermatogenic disorders by disrupting testosterone/androgen pathway. • LYC prevented DEHP-induced sperm parameters decline and spermiogenesis impairment. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is an omnipresent environmental pollutant. It has been determined that DEHP is involved in multiple health disorders. Lycopene (Lyc) is a natural carotenoid pigment, with anti-inflammatory and antioxidant properties. However, it is not clear whether Lyc can protect the spleen from DEHP-induced oxidative damage. A total of 140 mice were randomly divided into seven groups (n = 20) and continuously gavaged with corn oil, distilled water, DEHP (500 or 1000 mg/kg BW/day) and/or Lyc (5 mg/kg BW/day) for 28 days. Histopathological and ultrastructural results showed a DEHP-induced inflammatory response and mitochondrial injuries. Moreover, DEHP exposure induced redox imbalance, which resulted in the up-regulation of ROS activity and MDA content, and the down-regulation of T-AOC, T-SOD and CAT in the DEHP groups. Simultaneously, our results also demonstrated that DEHP-induced kelch-like ECH-associated protein 1 (Keap1) expression was downregulated, and the expression levels of P62, nuclear factor erythroid 2-related factor (NRF2) and their downstream target genes were up-regulated. However, the supplementary Lyc reverted these changes to normal levels. Together, Lyc prevented DEHP-induced splenic injuries by regulating the P62-Keap1-NRF2 signaling pathway. Hence, the protective effects of Lyc might be a therapeutic strategy to ameliorate DEHP-induced splenic damage. Exposure to persistent environmental pollutants such as di(2-ethylhexyl) phthalate (DEHP) has been involved in multiple health disorders, including splenic diseases. In this study, we clarified the potential protective effect of lycopene on DEHP-induced splenic injury. The results showed that Lyc inhibited DEHP induced oxidative damage by regulating the P62-Keap1-NRF2 signaling pathway, indicating that Lyc could alleviate the toxic effects of DEHP and may be helpful in reducing spleen injury. [Display omitted] • Lyc alleviated DEHP exposure-induced splenic injury. • Lyc alleviated the DEHP exposure-induced redox imbalance. • Lyc mitigated the inhibition of P62-Keap1-NRF2 pathway induced by DEHP exposure. • Lyc alleviated the splenic cell mitochondrial injuries induced by DEHP exposure. [ABSTRACT FROM AUTHOR]

Transport stress (TS) not only affects animal welfare but also eventually leads to higher morbidity and mortality. Moreover, TS could induce heart injury in animals, but the possible mechanism has yet to be fully explored. Astragalus polysaccharide (APS) is a main active component of Radix Astragali , which has an extensive anti-stress effect. However, the effect of APS on TS-induced heart injury has not yet been elucidated. In this study, a chick model of simulated TS was used. 240 newly hatched chicks were arranged into 4 groups: Control (Con), Transport group (T), Transport + water group (TW), and Transport + APS group (TA). Before transport, the chicks of the TW and TA groups were treated with deionized water and APS (0.25 mg/mL, 100 µL) by oral drops respectively. The histopathological analysis of myocardial tissue was assessed by hematoxylin and eosin staining. qRT-PCR and Western Blotting assays were employed to measure the expression of genes and proteins. Semiquantitative PCR was performed for the X box-binding protein-1 (XBP-1) mRNA splicing assay. The results indicated that APS significantly reduced TS-induced myocardial histopathological changes. Meanwhile, TS induced endoplasmic reticulum stress (ERS), evidenced by an activation of the unfolded protein response (UPR) signaling pathway and up-regulation of ERS-markers (P < 0.05). Moreover, TS markedly triggered autophagy induction by activating AMP-activated protein kinase (AMPK), reflected by augmented LC3-II/LC3-I, AMPK phosphorylation and autophagy-related genes (ATGs) expression (P < 0.05). Importantly, our study manifested that treatment of APS could reduce TS-induced ERS and AMPK-activated autophagy, accordingly alleviating heart injury of transported chicks. In summary, these findings indicate that TS induces heart injury in chicks via an ERS-UPR-autophagy-dependent pathway, and APS as an effective therapeutic method to alleviate it. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is a widely used heavy metal which is reported to exert extensive harm to the environment and human health. Owing to Cd being an element it is continuously enriched in the environment. The mechanism of splenic toxicity by Cd, however, is not yet clear. In order to explore the toxic mechanism of Cd exposure to the spleen, we added 0, 35, 70 and 140 mg/kg of Cd to the diet of chicken and fed them this diet for 90 days. Analysis of histopathological sections showed that Cd exposure damaged the spleen structure, the spleen red pulp, the white pulp boundary disappeared and the number of lymphocytes decreased significantly, suggesting that Cd exposure leads to organ injury to the spleen. Particularly, Cd-induced anoikis - a special form of programmed cell death caused by the loss of contact between cells and extracellular matrix and other cells - is associated with integrin-related cell detachment and activation of apoptotic signaling pathways. Moreover, Cd exposure leads to an increase in free radicals content and affects the activity of antioxidant enzymes resulting in oxidative stress. Simultaneously, Cd activated the body's antioxidant defense system mediated by the Nuclear factor related factor 2 (Nrf2) signaling pathway. Based on our results Cd-induced splenic lymphocytes anoikis is not mitigated by Nrf2-mediated antioxidative defense response. Cd exposure induced the toxic effects on spleen and triggered anoikis through changing the expression of Integrin and apoptotic factor in the spleen. Cd can activate Nuclear factor related factor 2 (Nrf2) signaling pathway and to a certain extent inhibit oxidative stress. [Display omitted] • Cd exposure induces the spleen injury. • Cd exposure causes splenic lymphocyte anoikis. • Nuclear factor related factor 2(Nrf2)can be activated by Cd. • Cd reduces oxidative stress injury by triggered the Nrf2 signaling pathway. • Cd induced anoikis is not mitigated by activating Nrf2 pathway. [ABSTRACT FROM AUTHOR]

Selenium (Se), a nutritionally essential mineral for humans and animals, has a significant antagonistic effect on heavy metal cadmium (Cd) biotoxicity. Still, the impact of different Se sources on alleviating Cd toxicity has received only limited attention. Therefore, the purpose of the current study was to assess the mitigation level of Cd-induced cardiotoxicity by different sources such as nanoparticles of Se, Se-rich yeast, and sodium selenite (SS). The results evidenced that the presence of Cd led to a significant increase in biochemical parameters such as lactate dehydrogenase and creatine kinase, as well as histopathological lesions in the heart of chickens. Cd exposure also resulted in more extensive effects on phase I metabolism enzymes and transcript cytochrome P450 isoforms, elevated the levels of malondialdehyde (MDA), glutathione (GSH), and hydrogen peroxide (H2O2) and depressed total superoxide dismutase (T-SOD), copper-zinc SOD (Cu-Zn SOD), total antioxidant capacity (T-AOC) and catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-S-transferase (GST) activities. The expression of nuclear receptors, aryl hydrocarbon receptor (AHR), constitutive androstane receptor (CAR), and pregnane X receptor (PXR) was declined, down-regulated nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream targets in the Cd-treat group. Notably, Se sources application alleviated Cd toxicity by triggering AHR/CAR/PXR/Nrf2 signaling pathway to promote restoring antioxidant defense system and phase I metabolism enzymes system. However, when compared to the effectiveness of antagonism, the nanoparticles of Se were superior in relieving Cd-induced cardiotoxicity via AHR/CAR/PXR/Nrf2 pathway activation than other Se-sources. [ABSTRACT FROM AUTHOR]

Di-2-ethylhexyl phthalate (DEHP) has been widely used in many fields (agricultural products, medical instruments, and food packing). As an environmental contaminant, DEHP has a negative impact on human and animal health, and thus toxicity caused by DEHP is increasingly serious health concern. Nevertheless, DEHP-induced liver damage in quail remains unclear. To investigate the mechanism of liver damage caused by DEHP, male quail were treated with DEHP (250, 500, and 750 mg/kg) by gavage. Notably, DEHP exposure results in increased blood lipids and the accumulation of triglycerides (TG), total cholesterol (TC), and non-esterified fatty acid (NEFA) in the liver. Histopathological analysis showed that steatosis and inflammatory cell infiltration were observed in the liver tissue of quails exposed to DEHP. The results of Oil Red O staining displayed that DEHP induced lipid storage in the liver. Moreover, DEHP induced lipid metabolism disorders by activating the LXR / SREBP-1c and PPARα / γ signaling pathway. DEHP exposure obviously caused the up-regulation of pro-inflammatory cytokines (NF-κB , IL-6 , IL-8 , IL-1β , and TNF-a). This study showed that DEHP could induce lipid metabolism disorders and inflammatory response via LXR / SREBP-1c / PPARα / γ and NF-κB signaling pathways. This research showed that DEHP could induce lipid metabolism disorder and inflammatory response via LXR / SREBP-1c / PPARα / γ / NF-κB signal pathways. This study provides new evidence for the mechanisms of DEHP-induced hepatotoxicity. [Display omitted] • DEHP exposure caused hepatotoxicity. • DEHP induced lipid metabolism disorders in liver. • DEHP disrupted lipid metabolism to induce lipotoxicity in liver. • DEHP exposure caused inflammation response in liver. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer widely used in agricultural and industrial plastic products. Many researchers have demonstrated that DEHP can cause varying degrees of harm to the heart. This research investigated the mechanism by which DEHP causes heart damage in quail. The quail were treated with DEHP (250 mg/kg BW/day, 500 mg/kg BW/day or 750 mg/kg BW/day) for 45 days. The present study suggested that DEHP could cause varying levels of heart damage, including disordered myocardial fiber arrangements, myocardial fiber breakage and myocardial cell swelling. The results showed that DEHP induced mitochondrial damage, such as cavitation lesions and mitochondrial crest breakage. DEHP damaged mitochondria and inhibited nuclear respiratory factor 1 (Nrf1)-mediated mitochondrial biogenesis, which led to mitochondrial damage. DEHP caused oxidative stress in the heart and activated the defense mechanism of the nuclear factor red blood cell 2 related factor 2 (Nrf2) system. DEHP-induced mitophagy was related to a decline in mitochondrial biogenesis and disordered mitochondrial dynamics. The data indicated that DEHP exposure damaged cardiac mitochondria and caused mitophagy and cardiotoxicity. Of note, this study showed that DEHP-induced mitophagy and mitochondrial damage are associated with the dysregulation of mitochondrial biogenesis. This study showed that DEHP exposure can cause cardiotoxicity, which was closely related to mitochondrial damage. DEHP inhibited Nrf1-mediated mitochondrial biogenesis and caused an imbalance in mitochondrial dynamics. DEHP exposure increased the level of Nrf2 because it induced oxidative stress and activated the Nrf2 signaling pathway. DEHP-induced mitochondrial damage leads to the occurrence of mitophagy, which ultimately leads to cardiotoxicity. This study provided new evidence for the effect of DEHP on the cardiotoxicity of quail. [Display omitted] • DEHP caused an Nrf1-mediated decline in mitochondrial biogenesis. • DEHP-induced cardiac oxidative stress damage activates the Nrf2 signaling pathway. • DEHP caused disordered mitochondrial dynamics in the heart of quail. • DEHP-induced mitophagy was associated with reduced mitochondrial biogenesis. [ABSTRACT FROM AUTHOR]

Cadmium (Cd) is one of the toxic environmental heavy metals that poses health hazard to animals due to its toxicity. Nano-Selenium (Nano-Se) is a Nano-composite form of Se, which has emerged as a promising therapeutic agent for its protective roles against heavy metals-induced toxicity. Heat shock proteins (HSPs) play a critical role in cellular homeostasis. However, the potential protective effects of Nano-Se against Cd-induced cerebellar toxicity remain to be illustrated. To investigate the toxic effects of Cd on chicken's cerebellum, and the protective effects of Nano-Se against Cd-induced cerebellar toxicity, a total of 80 male chicks were divided into four groups and treated as follows: (A) 0 mg/kg Cd, (B) 1 mg/kg Nano-Se (C) 140 mg/kg Cd + 1 mg/kg Nano-Se (D) 140 mg/kg Cd for 90 days. We tested heat shock protein pathway-related factors including heat shock factors (HSFs) HSF1, HSF2, HSF3 and heat shock proteins (HSPs) HSP10, HSP25, HSP27, HSP40, HSP60, HSP70 and HSP90 expressions. Histopathological results showed that Cd treatment caused degradation of Purkinje cells. In addition, HSFs and HSPs expression decreased significantly in the Cd group. Nano-Se co-treatment with Cd enhanced the expression of HSFs and HSPs. In summary, our findings explicated a potential protective effect of Nano-Se against Cd-induced cerebellar injury in chicken, suggesting that Nano-Se is a promising therapeutic agent for the treatment of Cd toxicity. Cd can be absorbed to chickens through the food chain, eventually caused cerebellar injury. However, Nano-Se attenuated cerebellar injury induced by Cd. This study indicated that the cerebellum is the target organ of Cd-induced cerebellar injury. Chronic and high-dose Cd treatment caused blurring nucleolus and degradation of Purkinje cell. In addition, HSFs and HSPs expression were decreased significantly, However, supplementation of Nano-Se exerts protective function against chronic Cd-induced cerebellar injury through activating heat shock protein pathway. [Display omitted] • Cerebellum is the target organ of Cd toxicity. • Cd inhibited heat shock protein pathway in cerebellum. • Nano-Se activated the heat shock protein pathway that alleviated cerebellar injury. • Nano-Se is a promising candidate for the treatment of Cd toxicity. [ABSTRACT FROM AUTHOR]