Single-dose methamphetamine administration impairs ORM retrieval in mice via excessive DA-mediated inhibition of PrLGlu activity.

Methamphetamine (METH), an abused psychostimulant, impairs cognition through prolonged or even single-dose exposure, but animal experiments have shown contradictory effects on memory deficits. In this study we investigated the effects and underlying mechanisms of single-dose METH administration on the retrieval of object recognition memory (ORM) in mice. We showed that single-dose METH administration (2 mg/kg, i.p.) significantly impaired ORM retrieval in mice. Fiber photometry recording in METH-treated mice revealed that the activity of prelimbic cortex glutamatergic neurons (PrLGlu) was significantly reduced during ORM retrieval. Chemogenetic activation of PrLGlu or glutamatergic projections from ventral CA1 to PrL (vCA1Glu-PrL) rescued ORM retrieval impairment. Fiber photometry recording revealed that dopamine (DA) levels in PrL of METH-treated mice were significantly increased, and micro-infusion of the D2 receptor (D2R) antagonist sulpiride (0.25 µg/side) into PrL rescued ORM retrieval impairment. Whole-cell recordings in brain slices containing the PrL revealed that PrLGlu intrinsic excitability and basal glutamatergic synaptic transmission were significantly reduced in METH-treated mice, and the decrease in intrinsic excitability was reversed by micro-infusion of Sulpiride into PrL in METH-treated mice. Thus, the impaired ORM retrieval caused by single-dose METH administration may be attributed to reduced PrLGlu activity, possibly due to excessive DA activity on D2R. Selective activation of PrLGlu or vCA1Glu-PrL may serve as a potential therapeutic strategy for METH-induced cognitive dysfunction.

Polystyrene microplastics exposure reduces meat quality and disturbs skeletal muscle angiogenesis via thrombospondin 1.

Microplastics (MPs) pose a significant threat to livestock health. Yet, the roles of polystyrene MPs (PS-MPs) on meat quality and skeletal muscle development in pigs have not been fully determined. To investigate the effect of PS-MPs on skeletal muscle, piglets were given diets supplementation with 0 mg/kg (CON group), 75 mg/kg (75 mg/kg PS-MPs group), and 150 mg/kg PS-MPs (150 mg/kg PS-MPs group), respectively. The results indicated that the average daily gain (ADG) of piglets in the 150 mg/kg PS-MPs group was significantly lower than that in the CON group. No significant differences were observed in the final body weight and ADG between the CON group and the 75 mg/kg PS-MPs group. Piglets in the 150 mg/kg PS-MPs group exhibited decreased meat redness index and type I muscle fiber density. Metabolomic analysis revealed that the contents of meat flavor compounds carnosine, beta-alanine, palmitic acid, and niacinamide in muscle were lower in the 150 mg/kg PS-MPs group than in the CON group. Additionally, piglets subjected to 150 mg/kg PS-MPs exhibited impaired muscle angiogenesis. Further analysis indicated that PS-MPs exposure up-regulated thrombospondin 1 (THBS1) expression by inhibiting THBS1 mRNA and protein degradation, thereby disrupting skeletal muscle angiogenesis. These findings indicate that PS-MPs exposure adversely affects meat quality and hinders skeletal muscle angiogenesis in pigs, providing deeper insights into the detrimental effects of PS-MPs on meat quality and skeletal muscle development.

Effects of High-Concentrate-Induced SARA on Antioxidant Capacity, Immune Levels and Rumen Microbiota and Function in Goats.

This study aims to explore the antioxidant, immune, and enzyme metabolism aspects in goats experiencing subacute ruminal acidosis (SARA). Furthermore, we seek to elucidate the relationship between the symbiotic microbiota of goats and their metabolic function. Sixteen goats were equally divided into two groups and fed a normal-concentrate diet (NC, 55% concentrate) or a high-concentrate diet (HC, 90% concentrate) for five weeks. We found that the HC diet reduced the total antioxidant capacity (T-AOC) (p = 0.022) and increased interleukin-1ß (IL-1ß) (p = 0.015), interleukin-4 (IL-4) (p = 0.008) and interleukin-6 (IL-6) (p = 0.002) concentration of goats. Simultaneously, the HC diet significantly increased the concentrations of alkaline phosphatase (ALP) and amylase (AMY) in the blood and rumen fluid of goats (p < 0.05). Microbial analysis in the rumen of goats revealed that the HC diet decreased bacterial richness and diversity, as evidenced by the changed observed species, Chao 1, PD whole tree and Shannon when compared to the NC diet (p < 0.01). The proportion of Proteobacteria increased while that of Spirochaetes and Fibrobacteres significantly decreased with the HC diet (p < 0.05). The Christensenellaceae_R-7_group and Ruminococcaceae_UCG-010 in rumen was notably decreased when a diet was switched from 55% concentrate diet to 90% concentrate diet (p < 0.05). Additionally, microbial functional potentials deduced that the HC diet significantly increased the abundance of the citrate cycle (TCA cycle) (ko00020) associated with carbohydrate metabolism (p = 0.028). Furthermore, the HC diet significantly increased the glutathione metabolism (ko00480) associated with the metabolism of other amino acids (p = 0.008). Our findings suggested that SARA reduced the total antioxidant capacity and increased levels of inflammatory factors in goats, as well as decreased rumen bacterial species and abundance.

Systemic lupus erythematosus is associated with lower risk of hepatitis B virus infection: A multivariable Mendelian randomization study in East Asian population.

The relationship between systemic lupus erythematosus (SLE) and hepatitis B virus (HBV) infection is still unclear. We conducted a two-sample Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies for SLE and HBV infection in individuals of East Asian ancestry. The inverse-variance weighted (IVW) method, weighted median (WM) method, and MR-Egger method were used to estimate the causal effect of SLE on HBV infection. Additionally, we performed a multivariable MR analysis adjusting for the effects of body mass index and rheumatoid arthritis. This MR study included a total of 225 106 individuals of East Asian ancestry, comprising 5616 cases and 219 490 controls. The IVW method (OR: 0.79, p = 3.34E-08) and the WM method (OR: 0.79, p = 9.09E-06) revealed a causal relationship between genetically predicted SLE and a low risk of HBV infection. The multivariable MR analysis still suggested a low risk of HBV infection associated with SLE (OR: 0.83, p = 2.89E-06). Our MR analysis supports a causal relationship between SLE and a low risk of HBV infection in individuals of East Asian ancestry.

Causal associations between human gut microbiota and cholelithiasis: a mendelian randomization study.

Background: There was some evidence that gut microbiota was closely related to cholelithiasis, but the causal relationship between them remained unclear. In this study, we try to use Two-sample Mendelian randomization (MR) to clarify the potential causal relationship between gut microbiota and cholelithiasis. Methods: Summary Genome-Wide Association Studies (GWAS) statistical data for gut microbiota was obtained from MiBioGen, and the data of cholelithiasis was obtained from UK Biobank (UKB). Two-sample MR analyses were performed to assess causalities between gut microbiota and cholelithiasis mainly using the inverse-variance weighted (IVW) method. Sensitivity analyses were used to determine the robustness of the MR results. Reverse MR analyses were performed to examine the reverse causal association. Results: Our research results, based primarily on the IVW method, support the existence of a causal relationship between nine gut microbial taxa and cholelithiasis. We observed a positive association between Genus Butyrivibrio (p=0.032), Genus Lachnospiraceae_UCG_001 (p=0.015), Genus Ruminococcaceae_NK4A214_group (p=0.003), Genus Ruminococcaceae_UCG_011 (p=0.010) and cholelithiasis, while Order Rhodospirillales (p=0.031), Genus Actinomyces (p=0.010), Genus Phascolarctobacterium (p=0.036), Genus Rikenellaceae_RC9_gutgroup (p=0.023), Genus Ruminococcaceae_UCG_013 (p=0.022) may be associated with a reduced risk of cholelithiasis. We did not find a reverse causal relationship between cholelithiasis and 9 specific gut microbial taxa. Conclusions: This is the first mendelian randomization study to explore the causalities between specific gut microbiota taxa and cholelithiasis, which may provide new ideas and a theoretical basis for the prevention and treatment of cholelithiasis in the future.

High-power, multi-junction, 905†nm vertical-cavity surface-emitting laser with an AlGaAsSb electron-blocking layer.

We report high-power multi-junction vertical-cavity surface-emitting lasers (VCSELs) with a significantly suppressed carrier leakage issue under high injection current and temperature. By carefully optimizing the energy band structure of quaternary AlGaAsSb, we obtained a 12-nm-thick AlGaAsSb electron-blocking layer (EBL) with a high effective barrier height (∼122 meV), a low compressive strain (∼0.99%), and a reduced electronic leakage current. The resulting three-junction (3J) 905 nm VCSEL with the proposed EBL exhibits an improved maximum output power (∼46.4 mW) and power conversion efficiency (PCE; ∼55.4%) during room-temperature operation. Also, it was found from thermal simulation that the optimized device shows more advantages over the original device during high-temperature operation. The type-II AlGaAsSb EBL provided an excellent electron-blocking effect and would be a promising strategy for multi-junction VCSELs to realize high-power applications.

Systemic lupus erythematosus is causally associated with hypothyroidism, but not hyperthyroidism: A Mendelian randomization study.

Background: The relationship between systemic lupus erythematosus (SLE) and thyroid diseases is still controversial. Due to confounders and reverse causation, previous studies were not convincing. We aimed to investigate the relationship between SLE and hyperthyroidism or hypothyroidism by Mendelian randomization (MR) analysis. Methods: We performed a two-step analysis using bidirectional two-sample univariable and multivariable MR (MVMR) to explore the causality of SLE and hyperthyroidism or hypothyroidism in three genome-wide association studies (GWAS) datasets, including 402,195 samples and 39,831,813 single-nucleotide polymorphisms (SNPs). In the first step analysis, with SLE as exposure and thyroid diseases as outcomes, 38 and 37 independent SNPs strongly (P < 5*10-8) associated with SLE on hyperthyroidism or SLE on hypothyroidism were extracted as valid instrumental variables (IVs). In the second step analysis, with thyroid diseases as exposures and SLE as outcome, 5 and 37 independent SNPs strongly associated with hyperthyroidism on SLE or hypothyroidism on SLE were extracted as valid IVs. In addition, MVMR analysis was performed in the second step analysis to eliminate the interference of SNPs that were strongly associated with both hyperthyroidism and hypothyroidism. 2 and 35 valid IVs for hyperthyroidism on SLE and hypothyroidism on SLE were obtained in MVMR analysis. MR results of two steps analysis were estimated respectively by multiplicative random effects-inverse variance weighted (MRE-IVW), simple mode (SM), weighted median (WME) and MR-Egger regression methods. Sensitivity analysis and visualization of MR results were performed by heterogeneity test, pleiotropy test, leave-one-out test, scatter plots, forest plots and funnel plots. Results: The MRE-IVW method in the first step of MR analysis revealed that SLE was causally associated with hypothyroidism (OR = 1.049, 95% CI = 1.020-1.079, P < 0.001), but not causally associated with hyperthyroidism (OR = 1.045, 95% CI = 0.987-1.107, P = 0.130). In the inverse MR analysis, the MRE-IVW method revealed that both hyperthyroidism (OR = 1.920, 95% CI = 1.310-2.814, P < 0.001) and hypothyroidism (OR = 1.630, 95% CI = 1.125-2.362, P = 0.010) were causally associated with SLE. Results from other MR methods were consistent with MRE-IVW. However, when MVMR analysis was performed, there was no longer a causal relationship of hyperthyroidism on SLE (OR = 1.395, 95% CI = 0.984-1.978, P = 0.061), nor was there a causal relationship of hypothyroidism on SLE (OR = 1.290, 95% CI = 0.823-2.022, P = 0.266). The stability and reliability of the results were confirmed by sensitivity analysis and visualization. Conclusions: Our univariable and multivariable MR analysis revealed that systemic lupus erythematosus was causally associated with hypothyroidism, but did not provided evidence to support a causal relationship of hypothyroidism on SLE or between SLE and hyperthyroidism.

Dysregulation of innate cell types in the hepatic immune microenvironment of alcoholic liver cirrhosis.

Introduction: The risk of alcoholic cirrhosis increases in a dose- and time-dependent manner with alcohol consumption and ethanol metabolism in the liver. Currently, no effective antifibrotic therapies are available. We aimed to obtain a better understanding of the cellular and molecular mechanisms involved in the pathogenesis of liver cirrhosis. Methods: We performed single-cell RNA-sequencing to analyze immune cells from the liver tissue and peripheral blood form patients with alcoholic cirrhosis and healthy controls to profile the transcriptomes of more than 100,000 single human cells and yield molecular definitions for non-parenchymal cell types. In addition, we performed single-cell RNA-sequencing analysis to reveal the immune microenvironment related to alcoholic liver cirrhosis. Hematoxylin and eosin, Immunofluorescence staining and Flow cytometric analysis were employed to study the difference between tissues and cells with or without alcoholic cirrhosis. Results: We identified a fibrosis-associated M1 subpopulation of macrophages that expands in liver fibrosis, differentiates from circulating monocytes, and is pro-fibrogenic. We also define mucosal-associated invariant T (MAIT) cells that expand in alcoholic cirrhosis and are topographically restricted to the fibrotic niche. Multilineage modeling of ligand and receptor interactions between the fibrosis-associated macrophages, MAIT, and NK cells revealed the intra-fibrotic activity of several pro-fibrogenic pathways, including responses to cytokines and antigen processing and presentation, natural killer cell-mediated cytotoxicity, cell adhesion molecules, Th1/Th2/Th17 cell differentiation, IL-17 signaling pathway, and Toll-like receptor signaling pathway. Discussion: Our work dissects unanticipated aspects of the cellular and molecular basis of human organ alcoholic fibrosis at the single-cell level and provides a conceptual framework for the discovery of rational therapeutic targets in liver alcoholic cirrhosis.

Benign gallbladder disease is a risk factor for colorectal cancer, but cholecystectomy is not: A propensity score matching analysis.

Background: Previous studies reported controversial results on the relationship between cholecystectomy (CHE) and colorectal cancer (CRC). We hypothesized that gallbladder disease (GBD), instead of cholecystectomy, increased the risk of CRC. We aimed to investigate the incidence of benign gallbladder disease (BGBD) and CHE in CRC patients and local adults undergoing annual health examination by analyzing large data from a tertiary hospital in southwest China. Methods: A propensity score matching (PSM) analyzed, retrospective study from January 1, 2013, to August 31, 2020, including 7,471 pathologically confirmed CRC patients and 860,160 local annual health examination adults in the First Affiliated Hospital of Chongqing Medical University, was conducted. The prevalence of BGBD and the CHE rate were analyzed before and after a 1:1 PSM. Results: Of the 7,471 CRC patients, 7,160 were eligible for the case group. In addition, 860,160 local health examination adults were included for comparison. The incidence of BGBD was higher in the CRC patients than in the local adults (19.2% vs. 11.3%, P < 0.001), but no significant difference in CHE rate existed between the case group and the control group (5.0% vs. 4.8%, P = 0.340). In the subgroup analysis, patients with BGBD had a higher risk of colon cancer than rectal cancer (20.4% vs. 18.2%, P = 0.024) and more significantly in the right colon (P = 0.037). A weakly positive correlation between CHE and right colon cancer was observed before PSM but no longer existed after PSM (P = 0.168). Conclusions: Benign gallbladder disease was positively correlated with colorectal cancer, especially right colon cancer. Cholecystectomy did not increase the risk of colorectal cancer.

Protective effect of nano-selenium on mercury-induced prehierarchical follicular atresia in laying hens.

This study investigated the effect of nano-selenium (nano-Se) in protecting laying hens from mercury (Hg)-induced prehierarchical follicular atresia. Furthermore, the endoplasmic reticulum stress (ERS) was explored to reveal the molecular mechanism. In vivo, 720 Hyline-Brown laying hens were treated with Hg and nano-Se alone or in combination. In vitro, the prehierarchical follicles were treated with Hg, nano-Se and 4-phenyl butyric acid (4-PBA) alone or in combination (Control, 25 µM Hg group, 10 µM nano-Se group, 20 µM nano-Se group, 25 µM Hg + 10 µM nano-Se group, 25 µM Hg + 20 µM nano-Se group, 25 µM Hg + 4-PBA group, and 25 µM Hg + 20 µM nano-Se + 4-PBA group). The GCs were treated with Hg and nano-Se alone or in combination (Control, 15 µM Hg group, 6 µM nano-Se group, 12 µM nano-Se group, 15 µM Hg + 6 µM nano-Se group, 15 µM Hg + 12 µM nano-Se group). The results revealed that dietary Hg significantly reduced laying performance (P < 0.05) and egg quality (P < 0.05), whereas nano-Se addition prevented these reductions (P < 0.05). Hg exposure significantly induced the accumulation of Hg in PHFs (P < 0.05), prehierarchical follicular atresia (P < 0.05) and apoptosis in PHFs, whereas nano-Se addition significantly prevented these effects (P < 0.05). The levels of sex hormones (P < 0.05) were significantly decreased after Hg exposure in vivo and in vitro, while nano-Se addition prevented the reductions. Furthermore, the RNA-Seq results showed that the key factors of the ERS presented differential expression, including C/EBP homologous protein, protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcription factor 6 (ATF6) in GCs. Hg exposure significantly increased the key gene expression of endoplasmic reticulum stress in GCs, whereas nano-Se addition prevented the induction of expression of these genes. In addition, the protein levels of PERK, inositol requiring protein 1α (IRE1α) and ATF6 were significantly increased, whereas nano-Se addition prevented the enhancements of protein expression in GCs. In conclusion, this study shows that Hg exposure can reduce induce prehierarchical follicular atresia, whereas nano-Se can prevent these effects. Our results also elucidate a key role of ERS in these protective effects of nano-Se in laying hens.

Federated learning with workload-aware client scheduling in heterogeneous systems.

Federated Learning (FL) is a novel distributed machine learning, which allows thousands of edge devices to train models locally without uploading data to the central server. Since devices in real federated settings are resource-constrained, FL encounters systems heterogeneity, which causes considerable stragglers and incurs significant accuracy degradation. To tackle the challenges of systems heterogeneity and improve the robustness of the global model, we propose a novel adaptive federated framework in this paper. Specifically, we propose FedSAE that leverages the workload completion history of clients to adaptively predict the affordable training workload for each device. Consequently, FedSAE can significantly reduce stragglers in highly heterogeneous systems. We incorporate Active Learning into FedSAE to dynamically schedule participants. The server evaluates the devices' training value based on their training loss in each round, and larger-value clients are selected with a higher probability. As a result, the model convergence is accelerated. Furthermore, we propose q-FedSAE that combines FedSAE and q-FFL to improve global fairness in highly heterogeneous systems. The evaluations conducted in a highly heterogeneous system demonstrate that both FedSAE and q-FedSAE converge faster than FedAvg. In particular, FedSAE outperforms FedAvg across multiple federated datasets - FedSAE improves testing accuracy by 22.19% and reduces stragglers by 90.69% on average. Moreover, holding the same accuracy as FedSAE, q-FedSAE allows for more robust convergence and fairer model performance than q-FedAvg, FedSAE.

Effects of Galactomannan Oligosaccharides on Growth Performance, Mycotoxin Detoxification, Serum Biochemistry, and Hematology of Goats Fed Mycotoxins-Contaminated Diets.

This study was conducted to investigate the protective effects of mycotoxin adsorbent galactomannan oligosaccharides (GMOS) on growth performance, fermentation parameters, mycotoxins residues, serum biochemistry and oxidative stress parameters of the goats. The in vitro test indicated that 0.05% GMOS outperformed yeast cell wall (YCW) and montmorillonite (MMT) in aflatoxins absorption. Then 20 3-month-old Xiangdong black goats (15.0 ± 1.9 kg) were randomly divided into two dietary treatments for the animal test. The control group (CON group) was fed a multi-mycotoxins contaminated diet, whereas the experimental group (GMOS group) received multi-mycotoxins contaminated diet plus 0.05% GMOS. The trail lasted for 60 days, with 12 days of adaptation period and 48 days of formal experiment period. There were no treatment effects (P > 0.10) on growth performance, serum antioxidant capacity and activities of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The concentrations of zearalenone in the rumen were lower (P < 0.05) in the GMOS group. GMOS significantly reduced (P < 0.05) propionate concentration in the cecum, resulting in a rise (P < 0.01) in acetate/propionate ratio in GMOS as compared to CON. Goats of GMOS exhibited considerably greater (P < 0.05) levels of creatine kinase but lower (P = 0.02) levels of creatinine than CON. Compared with CON, GMOS supplementation significantly increased (P < 0.05) platelet count (PLT), platelet volume distribution width (PDW), and platelet hematocrit (PCT), while decreased (P < 0.05) albumin content (ALB). The 0.05% GMOS protected goats in ruminal fermentation parameters, mycotoxins residues and serum biochemistry. Moreover, GMOS had no adverse effect on goat health. To our knowledge, this is the first report of GMOS in small ruminants. These findings suggested the feasibility of dietary GMOS as a health-maintaining addictive in goat diets.

Effects of different protein sources on nutrient disappearance, rumen fermentation parameters and microbiota in dual-flow continuous culture system.

Scarce high-quality protein feed resources has limited the development of animal husbandry. In this study, we used a dual-flow continuous culture system to evaluate effects of difference dietary protein sources including soybean meal (SBM), cottonseed meal (CSM), and rapeseed meal (RSM), on nutrient disappearance, rumen fermentation, and microbiota of XiongDong black goats. Dietary proteins of either CSM, RSM or SBM had no effect on nutrient disappearance (P > 0.05). CSM or RSM significantly reduced (P < 0.01) the pH and enhanced (P < 0.01) the ammonia nitrogen (NH3-N) concentration in fermentation liquid compared to SBM. The short-chain fatty acids (SCFAs) contents were greater (P = 0.05) and acetate was lower (P < 0.01) in SBM than those in RSM and CSM, whereas propionate was greater (P < 0.01) in RSM than that in SBM, consequently reducing the acetate to propionate ratio (A/P) in RSM. Bacteroidetes, Firmicutes, and Proteobacteria were detected as the dominant phyla, and the relative abundances of Spirochaetae (P < 0.01) and Chlorobi (P < 0.05) declined in the CSM and RSM groups as compared to those in the SBM group. At the genus level, Prevotella_1 was the dominant genus; as compared to SBM, its relative abundance was greater (P < 0.01) in CSM and RSM. The abundances of Prevotellaceae_Ga6A1 and Christensenellaceae_R7 were lower (P < 0.05) in CSM, whereas Eubacterium_oxidoreducens_group, and Treponema_2 were lower (P < 0.01) in both CSM and RSM, and other genera were not different (P > 0.10). Although the bacterial community changed with different dietary protein sources, the disappearances of nutrients were not affected, suggesting that CSM and RSM could be used by rumen bacteria, as in case with SBM, and are suitable protein sources for ruminant diets.

Role of Endoplasmic Reticulum Stress in Nano-Selenium Alleviating Prehierarchical Follicular Atresia Induced by Mercury in Laying Hens.

This study investigated that the effect of nano-selenium (nano-Se) addition preventing prehierarchical follicular atresia induced by mercury (Hg) exposure in laying hens. Furthermore, endoplasmic reticulum (ER) stress pathway was explored to reveal the protective mechanism of nano-Se in vitro. The results revealed that Hg could significantly reduce laying performance (P < 0.05) and egg quality (P < 0.05), whereas nano-Se addition partially reversed the reductions. Besides, Hg significantly induced the deposition of Hg in prehierarchical follicles (P < 0.05) and prehierarchical follicular atresia (P < 0.05), whereas nano-Se addition could alleviate these toxicities in vitro. In addition, Hg exposure could significantly reduce cell viability (P < 0.05) and induce pyknotic nucleus in prehierarchical granulosa cells, while nano-Se addition reversed these effects. The levels of follicle-stimulating hormone (P < 0.05), luteinizing hormone (P < 0.05), progesterone (P < 0.05), and estradiol (P < 0.05) were significantly decreased after Hg exposure in vitro. However, nano-Se addition reversed the decreases of sex hormone levels. Furthermore, Hg exposure significantly increased the gene expressions of CHOP (P < 0.05), PERK (P < 0.05), ATF4 (P < 0.05), ATF6 (P < 0.05), ASK1 (P < 0.05), IRE1α (P < 0.05), TRAF2 (P < 0.05), caspase-9 (P < 0.05), caspase-3 (P < 0.05), and Bax/Bcl-2 (P < 0.05), whereas nano-Se addition reversed these increases of gene expressions in vitro. In summary, this study provides that Hg can induce prehierarchical follicular atresia, whereas nano-Se addition can ameliorate it, and elucidates an important role of ER stress in nano-Se alleviating prehierarchical follicular atresia induced by Hg in laying hens.

Protective Effect of Nanoselenium on Renal Oxidative Damage Induced by Mercury in Laying Hens.

This study investigated the effects of dietary nanoselenium (nano-Se) supplementation protecting from renal oxidative damages induced by mercury (Hg) exposure in laying hens. Furthermore, endoplasmic reticulum (ER) stress pathway was explored to reveal the protective mechanism of nano-Se. A total of 576 40-week-old Hyline-White laying hens were randomly allocated to 4 groups with 6 pens per group and 24 hens per pen. The experimental groups were as follows: control (basal diet), control + 27.0 mg/kg Hg, control + 5.0 mg/kg nano-Se, and Hg27.0 + 5.0 mg/kg nano-Se. The results revealed that dietary Hg exposure significantly reduced laying performance (P < 0.05) and egg quality (P < 0.05), whereas nano-Se supplementation partially reversed the reductions. Besides, dietary Hg exposure could induce histopathology damages and apoptosis in kidney, whereas nano-Se addition could alleviate these toxicities effectively. After Hg exposure, the activities and gene expressions of superoxidative dismutase (SOD) (P < 0.05), catalase (CAT) (P < 0.01), glutathione reductase (GR) (P < 0.05) and glutathione peroxidase (GSH-Px) (P < 0.05), and glutathione (GSH) content (P < 0.05) were significantly decreased, while the malondialdehyde (MDA) level was significantly increased (P < 0.05) in kidney. However, nano-Se supplementation partially reversed the levels and gene expressions of these antioxidant biomarkers in kidney. Furthermore, dietary Hg exposure significantly increased the gene expressions of PERK (P < 0.05), ATF4 (P < 0.05), CHOP (P < 0.05), IRE1α (P < 0.05), TRAF2 (P < 0.05), ASK1 (P < 0.05), Caspase-9 (P < 0.05), Caspase-8 (P < 0.05), Caspase-3 (P < 0.05), and Bax/Bcl-2 (P < 0.05), whereas nano-Se supplementation partially reversed these increases of gene expressions. In summary, this study provides evidence that dietary Hg exposure can induce renal oxidative damages, and elucidates an important role of ER stress pathway in nano-Se alleviating renal apoptosis in laying hens.

Dietary amylose:amylopectin ratio influences the expression of amino acid transporters and enzyme activities for amino acid metabolism in the gastrointestinal tract of goats.

This study was designed to investigate the effects of dietary starch structure on muscle protein synthesis and gastrointestinal amino acid (AA) transport and metabolism of goats. Twenty-seven Xiangdong black female goats (average body weight = 9·00 ± 1·12 kg) were randomly assigned to three treatments, i.e., fed a T1 (normal maize 100 %, high amylose maize 0 %), T2 (normal maize 50 %, high amylose maize 50 %) and T3 (normal maize 0 %, high amylose maize 100 %) diet for 35 d. All AA in the ileal mucosa were decreased linearly as amylose:amylopectin increased in diets (P < 0·05). The plasma valine (linear, P = 0·03), leucine (linear, P = 0·04) and total AA content (linear, P = 0·03) increased linearly with the increase in the ratio of amylose in the diet. The relative mRNA levels of solute carrier family 38 member 1 (linear, P = 0·01), solute carrier family 3 member 2 (linear, P = 0·02) and solute carrier family 38 member 9 (linear, P = 0·02) in the ileum increased linearly with the increase in the ratio of amylose in the diet. With the increase in the ratio of amylose:amylopectin in the diet, the mRNA levels of acetyl-CoA dehydrogenase B (linear, P = 0·04), branched-chain amino acid transferase 1 (linear, P = 0·02) and branched-chain α-keto acid dehydrogenase complex B (linear, P = 0·01) in the ileum decreased linearly. Our results revealed that the protein abundances of phosphorylated mammalian target of rapamycin (p-mTOR) (P < 0·001), phosphorylated 4E-binding protein 1 (P < 0·001) and phosphorylated ribosomal protein S6 kinases 1 (P < 0·001) of T2 and T3 were significantly higher than that of T1. In general, a diet with a high amylose ratio could reduce the consumption of AA in the intestine, allowing more AA to enter the blood to maintain higher muscle protein synthesis through the mTOR pathway.

Offering soybean molasses adsorbed to agricultural by-products improved lactation performance through modulating plasma metabolic enzyme pool of lactating cows.

BACKGROUND: Agricultural by-products, such as corncob powder (CRP), wheat bran (WB), rice husk (RH), defatted bran (DB), and soybean hulls (SH), were widely used as ruminant feed. However, the combination effect of soybean molasses mixed with agricultural by-products on cow lactating performance remains poorly understood. METHODS: In vitro fermentation simulation technique was used to select the high ruminal fermentation performance of agricultural by-products mixed with soybean molasses. The selected mixtures were conducted to further explore the feeding effect on milk performance and blood metabolic enzyme on lactating dairy cows. RESULTS: In in vitro simulation, it was confirmed that SH-SM showed better fermentation performance (including higher maximum gas production, acetate, propionate, and total VFA, but less initial fractional rate of degradation) than other four molasses-adsorbents, while WB-SM had the greatest DM and NDF disappearance and NH3-N and butyrate concentrations among substrates. After the simulation selection, we performed the feed experiment with SH-SM and WB-SM compared to the control. For lactating performance, higher (p < .01) milk fat and total milk solid content were observed in WB-SM, and a tendency improvement of milk protein content (p < .01) was observed in both of the cows fed with WB-SM and SH-SM. Among lactating periods, the blood glutamic-pyruvic transaminase, α-amylase, and lactate dehydrogenase which associated with amino acid metabolism and carbohydrate metabolism were improved in lactating dairy cows fed with WB-SM and SH-SM. CONCLUSION: Dietary agricultural by-products (like wheat bran and soybean hulls) mixed with soybean molasses enhance the lactating performance of dairy cows by improving the host metabolism process of amino acids and carbohydrates. The mixed strategy for agricultural by-products shows another strong evidence for the resource reuse on dairy industry and reducing the by-product pollution.

Maternal intake restriction programs the energy metabolism, clock circadian regulator and mTOR signals in the skeletal muscles of goat offspring probably via the protein kinase A-cAMP-responsive element-binding proteins pathway.

The biological mechanism by which maternal undernutrition increases the metabolic disorder risk of skeletal muscles in offspring is not fully understood. We hypothesize that maternal intake restriction influences metabolic signals in the skeletal muscles of offspring via a glucagon-mediated pathway. Twenty-four pregnant goats were assigned to the control group (100% of the nutrients requirement, n = 12) and restricted group (60% of the control feed allowance from pregnant days 45 to 100, n = 12). Blood and L ongissimus thoracis muscle were sampled from dams (100 d of gestation), fetuses (100 d of gestation), and kids (90 d after birth) in each group. The data were analyzed using the linear MIXED model, with the multiple comparison method of SIDAK applied. Intake restriction reduced (P < 0.05) the total blood protein of dams and fetuses. Maternal restriction decreased (P < 0.05) the cAMP-responsive element-binding protein 1 (CREB1), CREB-binding protein (CREBBP), protein kinase A (PKA), aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1), protein kinase B (AKT1), mammalian target of rapamycin (mTOR), and regulatory-associated protein of mTOR (RPTOR) mRNA expression in the fetuses, and reduced (P < 0.05) the CREBBP, nuclear receptor subfamily 1 group H member 3 (NR1H3), D-box binding PAR bZIP transcription factor (DBP) and PKA mRNA levels in the kids, but increased (P < 0.05) the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1 A) and tuberous sclerosis 2 (TSC2) mRNA levels in the fetuses. The mRNA expression of clock circadian regulator (CLOCK) and TSC2 genes was increased (P < 0.05) in the restricted kids. The protein expression of total PKA and phosphorylated PKA in the restricted fetuses and kids were downregulated (P < 0.05), and the protein expression of total mTOR and phosphorylated mTOR were reduced (P < 0.05) in the restricted fetuses and kids. Maternal intake restriction regulated fat oxidation, protein synthesis, and circadian clock expression in the muscles of the offspring probably via the glucagon-mediated PKA-CREB pathway, which reveals a noteworthy molecular pathway that maternal undernutrition leads to metabolic adaptation of skeletal muscle in offspring.

Effects of dietary supplementation with glutamine on the lymphocyte proliferation and intestinal immune gene expression in broiler chickens infected with Salmonella Enteritidis.

An experiment was conducted to investigate the effects of glutamine (Gln) on the lymphocyte proliferation and intestinal immune relevant gene expression in broilers infected with Salmonella Enteritidis. 240 1-day-old broilers were divided randomly into four groups in a completely randomized design, each of which had 6 replicates. Birds were reared in battery cages for 21 days. The experimental groups were as follows: control group (unchallenged group, CON), basal diet; Salmonella Enteritidis challenged group (challenged with 2.0 × 104 CFU/mL of Salmonella Enteritidis, SCC), basal diet; Gln 1, basal diet plus Salmonella Enteritidis challenged plus Gln at 0.5% diet; Gln 2, basal diet plus Salmonella Enteritidis challenged plus Gln at 1.0% diet. The results showed that Salmonella Enteritidis infection led to some decrease in the relative weight of spleen and bursa (except at 21 d), lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and increased the heterophil percentage, H/L ratio, mRNA expression levels of TNF-α, NF-κB p65, IL-1ß, IL-6, and IL-8 in the jejunal and ileal mucosa compared with the measurements of these parameters in the CON group at d 4, 7, 14, and 21 (p < 0.05). On the other hand, chickens fed the Gln showed improved the relative weight of spleen and bursa, increased the lymphocyte percentage, number of proliferation peripheral blood T and B lymphocytes, and decreased the heterophil percentage, H/L ratio, and immune relevant gene expression in the jejunal and ileal mucosa compared with the measurements of these parameters in the SCC group (p < 0.05). These results suggest that Gln as a feed additive could be effective for reducing the detrimental effects of Salmonella Enteritidis infection, and increase the intestinal immune barrier function of broilers.

Inhibition of NLRC5 regulates cytokine expression in CD4+ T helper lymphocytes and prolongs murine islet and skin allograft survival.

The purpose of this study was to study the effect of inhibiting NLRC5 expression and function on CD4 + T cells, and islet and skin transplantation in mice. A murine skin graft model and islet cell transplantation model were established, and the expression of NLRC5 was compared in rejection and immune tolerance groups. Mice spleen-derived CD4 + T cells were cultured, purified, and enriched in vitro, and transfected with the shRNA lentiviral vector NLRC5-RNAi-GFP. Changes in cytokine secretion were detected to understand changes in immunological function. Murine islet and skin transplantation models were injected with CD4 + T cells transfected with the lentivirus, and the survival time of the grafts and the levels of IFN-γ and IL-10 were compared between groups. The expression of NLRC5 mRNA in islet and skin grafts was significantly increased. In vitro experiments showed that the expression of IL-4 and IL-10 was up-regulated in CD4 + T cells, and T cells differentiation turned to Th2 after inhibition of NLRC5. In vivo experiments showed that inhibition of NLRC5 prolonged islet and skin graft survival. Pathological examination showed that the rejection of transplanted skin and islets in the NLRC5-RNAi group was mild, and there was a correlation between high expression of NLRC5 and rejection of mouse islet and skin grafts. In summary, inhibition of NLRC5 can prolong islet and skin graft survival induce transplant immune tolerance through induction of the secretion of Th2 cytokines by CD4 + T cells.