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ABSTRACT: Selenium-enriched Saccharomyces cerevisiae (SSC) as organic selenium (Se) has been shown to have better advantages and is approved for use in animal feed rather than inorganic Se, however, there is little available data on the toxic effects of SSC on poultry. The present study was conducted to investigate the effects of high-dose SSC on growth performance, antioxidant status, tissue fat content and Se concentration, and selenoenzyme mRNA expression in chicks. A total of 500, 1-day-old SPF chicks were randomly divided into 5 groups with 10 replicates of 10 chicks each. Group 1 served as a control and was fed a basal diet supplemented with 0.15 mg/kg Se from sodium selenite (SS), group 2 was fed the basic diet supplemented with 1.5 mg/kg Se from SS, while groups 3, 4, and 5 were fed the basal diet supplemented with 1.5, 5 and 10 mg/kg Se from SSC, respectively. The results showed that SS and SSC supplementation significantly affected the average daily feed intake (ADFI), feed/gain ratio (FCR), glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities, total antioxidant capacity (T-AOC), malondialdehyde (MDA) content, tissue fat content and Se concentration, and GPx1 and GPx4 mRNA levels compared with the control group (P < 0.05). Compared with group 2, group 3 exhibited higher GPx and SOD activities, tissue Se concentration, and lower MDA content on d 30, and higher Se concentration, GPx1 mRNA levels in liver and breast muscle and GPx4 mRNA levels in liver and thigh muscle, and lower MDA content on d 60 (P < 0.05). The results of correlation analysis showed that high-dose SSC supplementation was positively correlated with AFDI, FCR, MDA content, and tissue Se concentration, and negatively correlated with GPx and SOD activities, T-AOC, GPx1 and GPx4 mRNA levels in tissues. In conclusion, up to 1.5 mg/kg Se from SSC in diet may be a safe concentration for chicks that exhibited better biological effects than SS, the toxic effects of high-dose SSC supplementation mainly exhibited growth decrease, peroxidation and lipid metabolism disturbance, and became stronger with the increase of dietary Se levels.

Cadmium (Cd) has adverse effects on organisms. Serine is an essential nutritional factor and its nutritional value is extremely high for body. To explore the effects of serine on spleen toxicity induced by Cd in mice, cadmium chloride (CdCl2, 50 mg/L) and serine (50 g/L) were individually administered or co-administrated in drinking water of mice for 18 weeks. Results demonstrated that Cd exposure induced splenic toxicity and serine against the toxicity damage caused by Cd in mice. Under Cd stress, trace element homeostasis was disturbed, the mice's body weight and spleen index were increased, and splenic morphology and ultrastructure were altered. Furthermore, Cd exposure led to the cell populations disorder, which in turn triggers cell death. Notably, Cd treatment induced oxidative stress and inflammation, increased M1/M2 (iNOS, CD68) and Th1/Th2 (T-bet, CD4) levels, decreased M1/M2 (Arg1) and Th1/Th2 (GATA3) levels, while disrupted the macrophages and lymphocytes homeostasis, which trigged apoptosis and pyroptosis in spleen. In contrast, serine supplementation changed the levels of Cd and other elements, weakened Cd-induced tissue damage and inflammation, enhanced antioxidant capacity, significantly restored cell homeostasis, and effectively inhibited Cd-induced apoptosis and pyroptosis in the spleen. Shortly, the results verified that serine had an ameliorating toxicity effect and restored the M1/M2 and Th1/Th2 balance, restrained apoptosis and pyroptosis induced by Cd.

Intervertebral disc degeneration (IDD) is one of the major leading causes of back pain affecting the patient's quality of life. However, the roles of circular RNA (circRNA) in IDD remains unclear. This study aimed to explore the function and underlying mechanism of circ_0036763 in IDD. In this study, expressions of circ_0036763, U2 small nuclear RNA auxiliary factor 2 (U2AF2), miR-583 and aggrecan (ACAN) in primary human nucleus pulposus cells (HNPCs) derived from IDD patients and healthy controls were detected by quantitative real-time reverse transcription-PCR (qRT-PCR) or Western blot (WB). The relationship between pre-circ_0036763 and U2AF2, circ_0036763 and miR-583, miR-583 and ACAN mRNA was determined by bioinformatic analysis, miRNA pull down or RNA immunoprecipitation (RIP) assay. The expressions of Collagen I and Collagen II were evaluated by WB. Co-culture of bone marrow mesenchymal stem cells (bMSCs) or bMSCs-derived exosomes and HNPCs were performed to identify the effect of U2AF2 on the mature of circ_0036763 and ACAN. Results indicated that circ_0036763, U2AF2 and ACAN were downregulated while miR-583 was upregulated in HNPCs derived from IDD patients compared with that in normal HNPCs. Besides, overexpression of circ_0036763 elevated the expressions of ACAN and Collagen II whereas reduced Collagen I expression in HNPCs. Moreover, U2AF2 promoted the mature of circ_0036763, and circ_0036763 positively regulated ACAN by directly sponging miR-583. Furthermore, exosomal U2AF2 derived from bMSCs could increase U2AF2 levels in HNPCs and subsequently regulate the expression of ACAN by circ_0036763/miR-583 axis. In summary, circ_0036763 modified by exosomal U2AF2 derived from bMSCs alleviated IDD through regulating miR-583/ACAN axis in HNPCs. Thus, this study might provide novel therapeutic targets for IDD.

In China, the Liaodong Peninsula is an important growing area for blueberries because of the high organic matter content in the soil, the abundance of light, and the large temperature difference between day and night. However, the low temperature and relative humidity of the air during the winter and early spring in the Liaodong Peninsula are the main reasons for the damage to blueberry plants. Here, we documented the transcriptome and proteome dynamics in response to cold stress in three blueberry cultivars (‘Northland’, ‘Bluecrop’, and ‘Berkeley’). Functional enrichment analysis indicated that many differentially expressed genes (DEGs) and differentially abundant proteins (DAPs) were mainly involved in the pathways of protein processing in the endoplasmic reticulum, the glutathione metabolism pathway, and ribosomes. We identified 12,747 transcription factors (TFs) distributed in 20 families. Based on our findings, we speculated that cold tolerance development was caused by the expression of calcium-related genes (CDPKs and CMLs), glutathione proteins, and TFs (NAC, WRKY, and ERF). Our investigation found that three cultivars experienced cold damage when exposed to temperatures between −9 °C and −15 °C in the field. Therefore, the cold resistance of blueberries during overwintering should not only resist the influence of low temperatures but also complex environmental factors such as strong winds and low relative humidity in the air. The order of cold resistance strength in the three blueberry cultivars was ‘Berkeley’, ‘Bluecrop’, and ‘Northland’. These results provide a comprehensive profile of the response to cold stress, which has the potential to be used as a selection marker for programs to improve cold tolerance in blueberries.

Subway tunnel flooding is one of the typical scenarios in urban waterlogging. When the emergency decision-making is untimely and inaccurate, it can lead to serious casualties. However, it is expected that through some responsive monitoring methods, an intelligent system can be constructed to achieve the real-time perception of the underground flood situation and to predict the process and intensity of the disaster. This study is based on a scale model experiment of flooding in straight subway tunnels. Firstly, it classified the basic patterns of the flood process. Some fitting formulas were respectively established for water depth and kinematic parameters. A calculation method for quickly predicting the flood inundation process was constructed. Secondly, this paper proposed a mode for the monitoring and early warning system. Based on the flood patterns and characteristic variables in subway tunnel flooding, the system can quickly determine the flow rate and entry position of flood and deduce the flood trend in the future at a relatively low cost. The system workflow was divided into three phases, and the mechanism for each phase of the system was sorted out. It could help to provide scientific and reliable information for emergency decision-making and gain time for the emergency response.

Chickens are a major source of meat and eggs in human food and have significant economic value. Cadmium (Cd) is a common environmental pollutant that can contaminate feed and drinking water, leading to kidney injury in livestock and poultry, primarily by inducing the generation of free radicals. It is necessary to develop potential medicines to prevent and treat Cd-induced nephrotoxicity in poultry. Luteolin (Lut) is a natural flavonoid compound mainly extracted from peanut shells and has a variety of biological functions to defend against oxidative damage. In this study, we aimed to demonstrate whether Lut can alleviate kidney injury under Cd exposure and elucidate the underlying molecular mechanisms. Renal histopathology and cell morphology were observed. The indicators of renal function, oxidative stress, DNA damage and repair, NAD+ content, SIRT1 activity, and autophagy were analyzed. In vitro data showed that Cd exposure increased ROS levels and induced oxidative DNA damage and repair, as indicated by increased 8-OHdG content, increased γ-H2AX protein expression, and the over-activation of the DNA repair enzyme PARP-1. Cd exposure decreased NAD+ content and SIRT1 activity and increased LC3 II, ATG5, and particularly p62 protein expression. In addition, Cd-induced oxidative DNA damage resulted in PARP-1 over-activation, reduced SIRT1 activity, and autophagic flux blockade, as evidenced by reactive oxygen species scavenger NAC application. The inhibition of PARP-1 activation with the pharmacological inhibitor PJ34 restored NAD+ content and SIRT1 activity. The activation of SIRT1 with the pharmacological activator RSV reversed Cd-induced autophagic flux blockade and cell injury. In vivo data demonstrated that Cd treatment caused the microstructural disruption of renal tissues, reduced creatinine, and urea nitrogen clearance, raised MDA content, and decreased the activities or contents of antioxidants (GSH, T-SOD, CAT, and T-AOC). Cd treatment caused oxidative DNA damage and PARP-1 activation, decreased NAD+ content, decreased SIRT1 activity, and impaired autophagic flux. Notably, the dietary Lut supplement observably alleviated these alterations in chicken kidney tissues induced by Cd. In conclusion, the dietary Lut supplement alleviated Cd-induced chicken kidney injury through its potent antioxidant properties by relieving the oxidative DNA damage-activated PARP-1-mediated reduction in SIRT1 activity and repairing autophagic flux blockade.

ABSTRACT Understanding the mechanisms of microbiome assembly during host development is crucial for successful modulation of the gut microbiome to improve host health and growth. However, results from previous microbial intervention studies to improve swine growth have largely been inconsistent due to the constantly changing nature of the gut microbiota and limited longitudinal sampling. Detailed characterization of the swine gut microbiota through meta-analysis allows us to understand the dynamics of microbial community succession, as well as the transient and natural variations between time points and animals. A total of 3,313 fecal microbial communities from over 349 pigs covering 60 time points (from birth to market age) from 14 publications were included in this meta-analysis. Despite differences in animal breeds and management, generalizable patterns of community assembly were identified. Alpha diversity continuously increased during early stages of animal growth and more slowly in the later stages. Beta regression analysis revealed that more microbial taxa were enriched, while fewer were excluded by the gut microbiota. The microbial community structure also changed significantly between days at early ages and became more similar as pigs aged, as revealed by dissimilarity and distance metrics. Dirichlet multinomial mixtures analysis supported gradient microbial clustering in longitudinal pig fecal samples, and we found that the early samples spread to more clusters than those from older pigs. Random forest regression identified 30 operational taxonomic units as potential microbial biomarkers for modeling swine gut microbiota development. External validation showed this model could be generalized to future microbiome studies conducted in suckling and weaning pigs and adds to the toolkit to quantify community succession. IMPORTANCE The swine gut microbiome undergoes an age-dependent assembly pattern with a developmental phase at early ages and a stabilization phase at later ages. Shorter time intervals and a wider range of data sources provided a clearer understanding of the gut microbiota colonization and succession and their associations with pig growth and development. The rapidly changing microbiota of suckling and weaning pigs implies potential time targets for growth and health regulation through gut microbiota manipulation. Since swine gut microbiota development is predictable, swine microbiota age can be calculated and compared between animal treatment groups rather than relying only on static time-matched comparisons.

Abstract Background The livestock industry is striving to identify antibiotic alternatives to reduce the need to use antibiotics. Postbiotics, such as Saccharomyces cerevisiae fermentation product (SCFP), have been studied and proposed as potential non-antibiotic growth promoters due to their effects on animal growth and the rumen microbiome; however, little is known of their effects on the hind-gut microbiome during the early life of calves. The objective of this study was to measure the effect of in-feed SCFP on the fecal microbiome of Holstein bull calves through 4 months of age. Calves (n = 60) were separated into two treatments: CON (no SCFP added) or SCFP (SmartCare®, Diamond V, Cedar Rapids, IA, in milk replacer and NutriTek®, Diamond V, Cedar Rapids, IA, incorporated into feed), and were blocked by body weight and serum total protein. Fecal samples were collected on d 0, 28, 56, 84, and 112 of the study to characterize the fecal microbiome community. Data were analyzed as a completely randomized block design with repeated measures when applicable. A random-forest regression method was implemented to more fully understand community succession in the calf fecal microbiome of the two treatment groups. Results Richness and evenness of the fecal microbiota increased over time (P

Cadmium (Cd) is a heavy metal pollutant in the environment, and the kidney is one of the target organs after Cd exposure. Previous studies have shown that apoptosis and autophagy disorders are the main mechanisms of Cd-induced nephrotoxicity in rats. As a transcription factor that balances cell survival and death, nuclear factor-kappaB (NF-κB) protein plays dual regulatory effects on apoptosis and autophagy in multiple renal diseases. However, the regulatory mechanisms of NF-κB in Cd-induced kidney injury remain unclear. Therefore, the normal rat kidney cell line (NRK-52E cells) was applied to investigate the above questions in this study. Here, we found that Cd promotes the nuclear translocation and activation of NF-κB in a concentration-dependent manner, and activated NF-κB mediates NRK-52E cells survival after Cd exposure. Next, our study elaborated the mechanisms of NF-κB in antagonizing Cd-induced renal cytotoxicity. Inhibition of NF-κB by inhibitor BAY 11-7082 (BAY) and NF-κB p65 siRNA (siNF-κB p65) exacerbate Cd-induced apoptosis and autophagy inhibition, and then aggravate Cd-induced NRK-52E cells injury. Activation of NF-κB by activator phorbol-12-myristate-13-acetate (PMA) alleviates Cd-induced apoptosis and autophagy inhibition, and then attenuates Cd-induced NRK-52E cells injury. In conclusion, Cd exposure promotes the activation of NF-κB, and activated NF-κB mediates the survival of NRK-52E cells after Cd exposure via promoting autophagy and inhibiting apoptosis.

The primary determinants of apple (Malus) tree architecture include plant height and internode length, which are the significant criteria for evaluating apple dwarf rootstocks. Plant height and internode length are predominantly governed by phytohormones. In this study, we aimed to assess the mechanisms underlying dwarfism in a mutant of Malus baccata. M. baccata dwarf mutant (Dwf) was previously obtained through natural mutation. It has considerably reduced plant height and internode length. A comparative transcriptome analysis of wild-type (WT) and Dwf mutant was performed to identify and annotate the differentially expressed genes responsible for the Dwf phenotype using RNA-seq and GO and KEGG pathway enrichment analyses. Multiple DEGs involved in hormone signaling pathways, particularly auxin signaling pathways, were identified. Moreover, the levels of endogenous indole-3-acetic acid (IAA) were lower in Dwf mutant than in WT. The Aux/IAA transcription factor gene MbIAA19 was downregulated in Dwf mutant due to a single nucleotide sequence change in its promoter. Genetic transformation assay demonstrated strong association between MbIAA19 and the dwarf phenotype. RNAi-IAA19 lines clearly exhibited reduced plant height, internode length, and endogenous IAA levels. Our study revealed that MbIAA19 plays a role in the regulation of dwarfism and endogenous IAA levels in M. baccata.

Melatonin is an indoleamine produced in the pineal gland and has many physiological roles. There is increasing evidence that melatonin ameliorates cadmium (Cd)-induced nephrotoxicity. The potential protective impact of melatonin against Cd-induced nephrotoxicity and the mechanisms behind this protection are unknown. The relevance of mitochondrial dynamics in Cd-induced nephrotoxicity and the putative mechanism of melatonin-mediated protection were examined in this study. We show that melatonin prevents Cd-induced nephrotoxicity by inhibiting dynamin‐related protein 1 (Drp1)- and mitochondrial fission protein 1 (Fis1)-mediated mitochondrial fission. Melatonin treatment attenuated cytotoxicity, suppressed oxidative stress, restored mitochondrial membrane potential, and increased mitochondrial mass in response to Cd exposure. Consistent with this finding, melatonin treatment increased Cd-inhibited sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) expression and inhibited Drp1- and Fis1-mediated mitochondrial fission. Like melatonin, SIRT1 overexpression via resveratrol attenuated Drp1- and Fis1-mediated mitochondrial fission and other Cd-induced mitochondrial oxidative injuries effectively. Melatonin has significant pharmacological potential for protecting against Cd-induced nephrotoxicity by preventing excessive mitochondrial fission.

Japanese quail is a highly economically valuable bird due to its commercial production for meat and eggs. Although studies have reported Cadmium (Cd) is a ubiquitous heavy metal that can cause injury to various organs, the molecular mechanisms of Cd on quail kidney injury remain largely unknown. It has been reported that Honokiol (HKL), a highly functional antioxidant, can protect cells against oxidative stress effectively. This study was conducted to investigate the effects of Cd on quail kidneys injury and the protective effect of HKL on Cd-induced nephrotoxicity. A total of 40 Japanese quails were randomly divided into four groups: the control group, Cd treatment group, Co-treatment group and HKL treatment group. The results showed that Cd resulted in significant changes in growth performance, kidney histopathology and kidney biochemical status, antioxidant enzymes and oxidative stress parameters, and ultrastructure of renal tubular epithelial cells, compared with controls. Cd increased the expression of autophagy-related and apoptosis-related genes, but decreased expression of lysosomal function-related and UPRmt-related genes. The co-treatment group ameliorated Cd-induced nephrotoxicity by alleviating oxidative stress, inhibiting apoptosis, repairing autophagy dysfunction and UPRmt disorder. In conclusion, dietary supplementation of HKL showed beneficial effects on Japanese quail kidney injury caused by Cd.

Anthocyanins are important pigments in peach fruit and are beneficial to human health. Sugars are both energy-storing and signaling molecules and their roles in inducing anthocyanin biosynthesis have received a great deal of research attention. However, the mechanism by which sugars induce anthocyanin biosynthesis in peach fruit is unknown. In order to understand this induction mechanism, comprehensive transcriptome and metabolome were performed in fruit flesh treated with four different sugars for 12 and 24 h, respectively. Here, we found that cyanidin-3-O-(6-O-p-coumaroyl) glucosides accumulated in fruit flesh treated with glucose, sucrose, sorbitol, and fructose in vitro. Two key structural genes of the anthocyanin biosynthesis pathway, namely, PpDFR and PpUFGT, were upregulated in the flesh of sugar-treated peach fruit. By contrast, the two main transcription factors (TFs) PpMYB10.1 and PpBL regulating anthocyanin biosynthetic genes in peach fruit were not upregulated accordingly. Interestingly, two MYB family genes (PpMYB6 and PpMYB44-like) and three bHLH family genes (PpbHLH35, PpbHLH51, and PpbHLH36-like) were upregulated. A dual luciferase assay revealed that PpMYB6 strongly activated the PpUFGT promoter when it was co-infiltrated with PpbHLH35, PpbHLH51, and PpbHLH36-like. When PpMYB44-like was co-infiltrated with PpbHLH35, it also potently activated the PpUFGT promoter. The results of this study help clarify the molecular mechanisms by which glucose, sucrose, sorbitol, and fructose regulate anthocyanin accumulation in peach fruit.

Weaning is one of the most stressful events for piglets, due to diet change from sow milk to grainbased feed. This diet change causes turnover of the gut microbial which can allow proliferation of pathogens leading to diarrhea. Antibiotics are administered to treat or prevent post-weaning diarrhea (PWD). Increased occurrence of antimicrobial resistance has increased incentives to develop viable antibiotic alternatives. Previous studies have shown that fecal microbiota transplant (FMT) reduced diarrhea incidence and improved body weight gain in piglets. However, one barrier to FMT adoption in swine production is that FMT are generally given via oral gavage, which is difficult and labor intensive for large swine operations. For FMT to be a viable option in swine management, a simple method is needed to administer the transplant. The objective of this study was to determine the effect of three methods of FMT administration (oral, rectal and lyophilized in-feed) on growth performance, diarrhea incidence and gut microbiome. We hypothesize that FMT (in-feed and rectal) will increase colonization efficiency, improve growth performance and reduce diarrhea incidence compared with control. Weaned male piglets (n = 40) were allotted to 4 treatments at 10 piglets per treatment (no FMT - Control, Oral gavage - FMT1, rectal gavage - FMT2 and lyophilized in-feed - FMT3). Feces from 12-week-old pigs, screened for pathogens, was donor material. The study lasted nine days and FMT was for five days. Diarrhea incidences and body weight were observed for the first week. Fecal samples were collected on days 0, 2, 5 and 7. Five piglets per group were sacrificed on day 4 and the remaining on day 8. Cecal and colon contents were collected from the sacrificed piglets. DNA was extracted from fecal and digesta samples and 16S rRNA gene libraries (V4 region) were prepared for bacterial community analysis. Data were analyzed with one-way ANOVA in R. All FMT groups had significantly greater body weight on day 3 (P < 0.05) and average daily gain between day 0 - 3 (P < 0.05) compared with control but there was no difference between FMT groups. There was no effect of FMT on average daily feed intake and diarrhea incidence. Only FMT3 had greater alpha diversity (Observed features and Faith's phylogenetic diversity) on day 5 (P < 0.05) compared with control, but there was no difference in beta diversity between FMT groups. There was decreased abundance of 27 ASVs (amplicon sequence variant) and increased abundance of 30 ASVs in increased in FMT3 compared with control on day 5. In conclusion, the three FMT groups has similar colonization pattern but there was no difference in diarrhea incidence. FMT3 (lyophilized in-feed) altered overall community structure of piglets and modulated individual taxa. [ABSTRACT FROM AUTHOR]