Lipid Identification of Biomarkers in Esophageal Squamous Cell Carcinoma by Lipidomic Analysis.

Lipids participate in many important biological functions through energy storage, membrane structure stabilization, signal transduction, and molecular recognition. Previous studies have shown that patients with esophageal squamous cell carcinoma (ESCC) have abnormal lipid metabolism. However, studies characterizing lipid metabolism in ESCC patients through lipidomics are limited. Plasma lipid profiles of 65 ESCC patients and 42 healthy controls (HC) were characterized by lipidomics-based ultraperformance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Single-factor and multi-factor statistical analysis were used to screen the differences in blood lipids between groups, and combined with component ratio analysis and receiver operating characteristic (ROC) curve diagnostic efficiency assessment, to reveal the potential mechanisms and biomarkers of ESCC. There were significant differences in lipid profiles between the ESCC and HC groups. Thirty-six differential lipids (11 up-regulated and 25 down-regulated) were selected based on the criteria of p < .05 and fold change > 1.3 or < 0.77. Glycerophospholipids were the major differential lipids, suggesting that these lipid metabolic pathways exhibit a significant imbalance that may contribute to the development of esophageal squamous cell carcinoma. Among them, the seven candidate biomarkers for esophageal squamous cell carcinoma with the highest diagnostic value are three phosphatidylserine (PS), three fatty acids (FA) and one phosphatidylcholine (PC).

Non-linear associations of atherogenic index of plasma with prediabetes and type 2 diabetes mellitus among Chinese adults aged 45 years and above: a cross-sectional study from CHARLS.

Background: Dyslipidemia is strongly associated with the development of prediabetes and type 2 diabetes mellitus (T2DM). The atherogenic index of plasma (AIP), as a comprehensive index for assessing lipid metabolism, has received extensive attention from researchers in recent years. However, there are relatively few studies exploring the relationships between AIP and the risk of prediabetes and T2DM in the Chinese population. This study focuses on exploring the relationships of AIP with the risk of prediabetes and T2DM in the Chinese population. Methods: We conducted an analysis of the public data from the China Health and Retirement Longitudinal Study (CHARLS), involving a total of 12,060 participants aged 45 years and above in China. The study explored the relationships of AIP with prediabetes and T2DM risk through multivariate logistic regression, subgroup analysis, smooth curve fitting, and threshold effect analysis. Results: After adjusting for potential confounding factors, we observed positive associations between AIP and the risk of prediabetes [odds ratio (OR) = 1.75, 95% confidence interval (CI): 1.49-2.06] and T2DM (OR = 2.91, 95% CI: 2.38-3.57). Participants with higher AIP levels demonstrated a significantly elevated risk of prediabetes (OR = 1.52, 95% CI: 1.33-1.74) and T2DM (OR = 2.28, 95% CI: 1.92-2.71) compared to those with lower AIP levels. AIP showed consistent correlations with prediabetes and T2DM risk in different subgroups. The results showed the non-linear relationships between AIP and risk of prediabetes and T2DM, with inflection points at 0.29 and -0.04, respectively. When AIP > 0.29, there was a positive association between AIP and the risk of prediabetes (OR = 2.24, 95% CI: 1.67-3.00, p < 0.0001). Similarly, when AIP > -0.04, AIP was positively associated with the risk of T2DM (OR = 3.33, 95% CI: 2.67-4.16, p < 0.0001). Conclusions: This study demonstrated non-linear positive associations of AIP with the risk of prediabetes and T2DM among participants ≥ 45 years of age in China.

Association of Dietary Inflammatory Index with CKD progression and estimated glomerular filtration rate in the American CKD population: A cross-sectional study.

PURPOSE: The number of CKD patients is on the rise worldwide, and diet has become an essential aspect influencing the treatment and prognosis of CKD. However, limited research has explored the association of the Dietary Inflammatory Index (DII) with CKD progression and the essential kidney function indicator, eGFR, in CKD patients. This study aimed to analyze the association between DII and CKD progression and eGFR in the US CKD population using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: This study utilized data obtained from the National Health and Nutrition Examination Survey (NHANES) spanning from 2007 to 2018, with a total sample size of 2,488 individuals. Study used multiple imputation, based on 5 replications and a chained equation approach method in the R MI procedure, to account for missing data. Weighted multiple logistic regression was used to analyze the relationship between DII and the risk of higher CKD stage and a weighted multiple regression analysis was used to assess the relationship between DII and eGFR. Weighted Generalized Additive Models and smoothed curve fitting were applied to detect potential non-linear relationships in this association. RESULTS: In all three models, it was found that DII was positively associated with the risk of higher CKD stage (P < 0.0001), and an increase in DII was associated with a decrease in eGFR (P < 0.0001). The trend across quartiles of DII remained statistically significant, revealing a gradual elevation in higher CKD stage risk and reduction in eGFR levels for the second, third, and fourth quartiles compared to the lowest quartile (P for trend < 0.0001). Upon adjusting for age, gender, race, education level, poverty income ratio (PIR), marital status, body mass index (BMI), metabolic equivalent (MET) score, drinking, smoking, history of hypertension, history of diabetes, cotinine, systolic blood pressure, diastolic blood pressure, total triglycerides, and total cholesterol, we found a positive correlation between DII and the risk of higher CKD stage (OR = 1.26, 95% CI: 1.14-1.40). Further investigation revealed that an increase in DII was associated with a decrease in eGFR (ß = -1.29, 95% CI: -1.75, -0.83). Smooth curves illustrated a non-linear positive correlation between DII and CKD risk, while a non-linear negative correlation was observed between DII and eGFR. CONCLUSIONS: Our study results indicate that an increase in DII is associated with an increased risk of higher CKD stage and a decrease in eGFR in all three models. In the fully adjusted model, the risk of higher CKD stage increased by 26% and the eGFR decreased by 1.29 ml/min/1.73 m2 for each unit increase in DII. This finding suggests that in patients with CKD in the US, improved diet and lower DII values may help slow the decline in eGFR and delay the progression of CKD.

[Decreased DNase1L3 secretion and associated antibodies induce impaired degradation of NETs in patients with sporadic SLE].

Objective To evaluate the correlation between alterations in DNase1 and DNase1L3 enzyme activities and impairment of NET degradation in patients with sporadic SLE, and to investigate the underlying mechanism. Methods 46 sporadic SLE patients and 30 age- and sex-matched healthy individuals were recruited. Serum levels of DNase1, DNase1L3 and corresponding autoantibodies were detected by ELISA. DNase1 and DNase1L3 were isolated by immunoprecipitation; NETs and enzyme degradation activities were detected using a modified immunofluorescence. DNase1L3 secretion by PBMCs was analyzed by ELISPOT, Western blotting and reverse transcription PCR. Results Levels of H3-dsDNA and Ela-dsDNA complexes were significantly elevated in SLE patients. LDGs in SLE population was significantly higher than in the control group, and LDGs was positively correlated with H3-dsDNA and Ela-dsDNA NETs complexes. The ability of SLE patients to degrade NET in vitro was significantly lower than that of the control group. Degradation experiments of DNase1 and DNase1L3 in different proportions showed that the decrease in DNase1L3 activity was the primary contributor to the elevated NET residue level. The concentration of DNase1L3 autoantibodies in SLE patients was significantly elevated compared to the control group. In addition, the capacity of PBMCs to secrete DNase1L3 was significantly lower in the SLE patients compared to the control group. Conclusion Decreased secretion of DNase1L3 and the presence of relevant autoantibodies notably impede NET degradation in patients with SLE, offering new directions for the monitoring and treatment of SLE patients.

Triglyceride-Glucose Index and Its Correlates: Associations with Serum Creatinine and Estimated Glomerular Filtration Rate in a Cross-Sectional Study from CHARLS 2011-2015.

Background: Chronic kidney disease (CKD) has emerged as a significant global public health challenge, and the estimated glomerular filtration rate (eGFR) is widely used due to its convenience, low cost, and broad clinical applicability. Concurrently, insulin resistance (IR) serves as a crucial marker of metabolic disturbance, and alternative indicators have garnered increasing attention in CKD research in recent years. Objective: This study aims to investigate the relationship between IR-related indices (TyG index, TyG-BMI index, and TyG-WC index) and serum creatinine levels, as well as the eGFR, with the intention of uncovering their potential roles in the assessment of renal function. Methods: We analyzed nationally representative cross-sectional data from a cohort of individuals aged 45 and above in China, comprising 11,608 participants. Participants were categorized into different groups based on quartiles of the TyG index, and multiple factors, including gender, age, lifestyle, and co-morbidities, were adjusted for using linear regression models. Results: By linear regression, TyG, TyG-BMI, and TyG-WC indices were significantly positively correlated with serum creatinine and significantly negatively correlated with eGFR. Results showed similar trends when TyG, TyG-BMI, and TyG-WC indices were used as categorical variables. In the fully adjusted model, the highest quartile of serum creatinine was higher than the first quartile for TyG, TyG-BMI, and TyG-WC indices, with ß values of 2.673, 3.67, and 1.937 mg/dL, respectively; the highest quartile of eGFR was lower than the first quartile, with ß values of -2.4, -2.955, and -1.823 mL/min/1.73 m2. P values were statistically significant. Conclusions: This study indicates a consistent correlation between the TyG index and its related indices with serum creatinine levels and eGFR among the middle aged and elderly population in China. These findings suggest the potential utility of these indices in early screening and management of the risk of chronic kidney disease.

CD155 and its receptors in cancer immune escape and immunotherapy.

In recent years, there have been multiple breakthroughs in cancer immunotherapy, with immune checkpoint inhibitors becoming the most promising treatment strategy. However, available drugs are not always effective. As an emerging immune checkpoint molecule, CD155 has become an important target for immunotherapy. This review describes the structure and function of CD155, its receptors TIGIT, CD96, and CD226, and summarizes that CD155 expressed by tumor cells can upregulate its expression through the DNA damage response pathway and Ras-Raf-MEK-ERK signaling pathway. This review also elaborates the mechanism of immune escape after binding CD155 to its receptors TIGIT, CD96, and CD226, and summarizes the current progress of immunotherapy research regarding CD155 and its receptors. Besides, it also discusses the future direction of checkpoint immunotherapy.

Dietary replacement of inorganic trace minerals with lower levels of organic trace minerals leads to enhanced antioxidant capacity, nutrient digestibility, and reduced fecal mineral excretion in growing-finishing pigs.

Introduction: More effective and environment-friendly organic trace minerals have great potential to replace the inorganic elements in the diets of livestock. This study aimed to investigate the effects of dietary replacement of 100% inorganic trace minerals (ITMs) with 30-60% organic trace minerals (OTMs) on the performance, meat quality, antioxidant capacity, nutrient digestibility, and fecal mineral excretion and to assess whether low-dose OTMs could replace whole ITMs in growing-finishing pigs' diets. Methods: A total of 72 growing-finishing pigs (Duroc × Landrace × Yorkshire) with an initial average body weight of 74.25 ± 0.41 kg were selected and divided into four groups with six replicates per group and three pigs per replicate. The pigs were fed either a corn-soybean meal basal diet containing commercial levels of 100% ITMs or a basal diet with 30, 45, or 60% amino acid-chelated trace minerals instead of 100% ITMs, respectively. The trial ended when the pigs' weight reached ~110 kg. Results: The results showed that replacing 100% ITMs with 30-60% OTMs had no adverse effect on average daily gain, average daily feed intake, feed/gain, carcass traits, or meat quality (P > 0.05) but significantly increased serum transferrin and calcium contents (P < 0.05). Meanwhile, replacing 100% ITMs with OTMs tended to increase serum T-SOD activity (0.05 ≤ P < 0.1), and 30% OTMs significantly increased muscle Mn-SOD activity (P < 0.05). Moreover, replacing 100% ITMs with OTMs tended to increase the apparent digestibility of energy, dry matter, and crude protein (0.05 ≤ P < 0.1) while significantly reducing the contents of copper, zinc, and manganese in feces (P < 0.05). Discussion: In conclusion, dietary supplementation with 30-60% OTMs has the potential to replace 100% ITMs for improving antioxidant capacity and nutrient digestibility and for reducing fecal mineral excretion without compromising the performance of growing-finishing pigs.

Effects of zinc oxide and condensed tannins on the growth performance and intestinal health of weaned piglets in ETEC-challenged environment.

This experiment was conducted to evaluate effects of zine oxide (ZnO) and condensed tannins (CT), independently or in combination, on the growth performance and intestinal health of weaned piglets in enterotoxigenic Escherichia coli (ETEC-K88)-challenged environment. Randomly divided 72 weaned piglets into 4 groups. Dietary treatments included the following: basic diet group (CON), 1,500 mg/kg zinc oxide group (ZnO), 1,000 mg/kg condensed tannins group (CT), and 1,500 mg/kg zinc oxide +1,000 mg/kg condensed tannins group (ZnO + CT). Dietary ZnO supplementation decreased diarrhea rate from 0 to 14 days, 15 to 28 days, and 0 to 28 days (p < 0.05) and no significant on growth performance. The effect of CT on reducing diarrhea rate and diarrhea index was similar to the results of ZnO. Compared with the CON group, ZnO increased the ileum villus height and improved intestinal barrier function by increasing the content of mucin 2 (MUC-2) in jejunum and ileum mucosa and the mRNA expression of zonula occludens-1 (ZO-1) in jejunum (p < 0.05) and the expression of Occludin in duodenum and ileum (p < 0.05). The effects of CT on intestinal barrier function genes were similar to that of ZnO. Moreover, the mRNA expression of cystic fibrosis transmembrane conductance regulator (CFTR) in jejunum and ileum was reduced in ZnO group (p < 0.05). And CT was also capable of alleviating diarrhea by decreasing CFTR expression and promote water reabsorption by increasing AQP3 expression (p < 0.05). In addition, pigs receiving ZnO diet had higher abundance of phylum Bacteroidetes, and genera Prevotella, and lower phylum Firmicutes and genera Lactobacillus in colonic contents. These results indicated that ZnO and CT can alleviate diarrhea and improve intestinal barrier function of weaned pigs in ETEC-challenged environment. In addition, the application of ZnO combined with CT did not show synergistic effects on piglet intestinal health and overall performance. This study provides a theoretical basis for the application of ZnO in weaning piglet production practices, we also explored effects of CT on the growth performance and intestinal health of weaned piglets in ETEC-challenged environment.

Single-neuron analysis of dendrites and axons reveals the network organization in mouse prefrontal cortex.

The structures of dendrites and axons form the basis for the connectivity of neural network, but their precise relationship at single-neuron level remains unclear. Here we report the complete dendrite and axon morphology of nearly 2,000 neurons in mouse prefrontal cortex (PFC). We identified morphological variations of somata, dendrites and axons across laminar layers and PFC subregions and the general rules of somatodendritic scaling with cytoarchitecture. We uncovered 24 morphologically distinguishable dendrite subtypes in 1,515 pyramidal projection neurons and 405 atypical pyramidal projection neurons and spiny stellate neurons with unique axon projection patterns. Furthermore, correspondence analysis among dendrites, local axons and long-range axons revealed coherent morphological changes associated with electrophysiological phenotypes. Finally, integrative dendrite-axon analysis uncovered the organization of potential intra-column, inter-hemispheric and inter-column connectivity among projection neuron types in PFC. Together, our study provides a comprehensive structural repertoire for the reconstruction and analysis of PFC neural network.

Alpha-Melanocyte-Stimulating Hormone-Mediated Appetite Regulation in the Central Nervous System.

Understanding the complex action mechanism of appetite regulation peptides can significantly impact therapeutic options in the treatment of obesity and other metabolic diseases. Hypothalamic alpha-melanocyte-stimulating hormone (α-MSH) is an anorexigenic peptide, closely related to the occurrence of obesity, playing a central role in food intake and energy expenditure. In the central nervous system, α-MSH is cleaved from proopiomelanocortin and then released into different hypothalamic regions to act on melanocortin 3/4 receptor-expressing neurons, lowering food intake, and raising energy expenditure via appetite suppression and sympathetic nervous system. Furthermore, it can increase the transmission of some anorexigenic hormones (e.g., dopamine) and interact with other orexigenic factors (e.g., agouti-related protein, neuropeptide Y) to influence food reward rather than merely feeding behavior. Therefore, α-MSH is a critical node of the hypothalamus in transmitting appetite suppression signals and is a key component of the central appetite-regulating circuits. Herein, we describe the role of α-MSH in appetite suppression in terms of specific receptors, effector neurons, sites of action, and the interaction with other appetite-relative peptides, respectively. We focus on the role of α-MSH in obesity. The status of research on α-MSH-related drugs is also discussed. With the intention of illuminating a new approach for targeting α-MSH in the hypothalamus as a strategy to manage obesity, we hope to further understand the direct or indirect mechanisms by which α-MSH exerts its appetite-regulating effects.

Hypothalamic Supramammillary Nucleus Selectively Excites Hippocampal CA3 Interneurons to Suppress CA3 Pyramidal Neuron Activity.

A key mode of neuronal communication between distant brain regions is through excitatory synaptic transmission mediated by long-range glutamatergic projections emitted from principal neurons. The long-range glutamatergic projection normally forms numerous en passant excitatory synapses onto both principal neurons and interneurons along its path. Under physiological conditions, the monosynaptic excitatory drive onto postsynaptic principal neurons outweighs disynaptic feedforward inhibition, with the net effect of depolarizing principal neurons. In contrast with this conventional doctrine, here we report that a glutamatergic projection from the hypothalamic supramammillary nucleus (SuM) largely evades postsynaptic pyramidal neurons (PNs), but preferentially target interneurons in the hippocampal CA3 region to predominantly provide feedforward inhibition. Using viral-based retrograde and anterograde tracing and ChannelRhodopsin2 (ChR2)-assisted patch-clamp recording in mice of either sex, we show that SuM projects sparsely to CA3 and provides minimal excitation onto CA3 PNs. Surprisingly, despite its sparse innervation, the SuM input inhibits all CA3 PNs along the transverse axis. Further, we find that SuM provides strong monosynaptic excitation onto CA3 parvalbumin-expressing interneurons evenly along the transverse axis, which likely mediates the SuM-driven feedforward inhibition. Together, our results demonstrate that a novel long-range glutamatergic pathway largely evades principal neurons, but rather preferentially innervates interneurons in a distant brain region to suppress principal neuron activity. Moreover, our findings reveal a new means by which SuM regulates hippocampal activity through SuM-to-CA3 circuit, independent of the previously focused projections from SuM to CA2 or dentate gyrus.SIGNIFICANCE STATEMENT The dominant mode of neuronal communication between brain regions is the excitatory synaptic transmission mediated by long-range glutamatergic projections, which form en passant excitatory synapses onto both pyramidal neurons and interneurons along its path. Under normal conditions, the excitation onto postsynaptic neurons outweighs feedforward inhibition, with the net effect of depolarization. In contrast with this conventional doctrine, here we report that a glutamatergic input from hypothalamic supramammillary nucleus (SuM) largely evades PNs but selectively targets interneurons to almost exclusively provide disynaptic feedforward inhibition onto hippocampal CA3 PNs. Thus, our findings reveal a novel subcortical-hippocampal circuit that enables SuM to regulate hippocampal activity via SuM-CA3 circuit, independent of its projections to CA2 or dentate gyrus.

Neural Circuit Mechanisms Involved in Animals' Detection of and Response to Visual Threats.

Evading or escaping from predators is one of the most crucial issues for survival across the animal kingdom. The timely detection of predators and the initiation of appropriate fight-or-flight responses are innate capabilities of the nervous system. Here we review recent progress in our understanding of innate visually-triggered defensive behaviors and the underlying neural circuit mechanisms, and a comparison among vinegar flies, zebrafish, and mice is included. This overview covers the anatomical and functional aspects of the neural circuits involved in this process, including visual threat processing and identification, the selection of appropriate behavioral responses, and the initiation of these innate defensive behaviors. The emphasis of this review is on the early stages of this pathway, namely, threat identification from complex visual inputs and how behavioral choices are influenced by differences in visual threats. We also briefly cover how the innate defensive response is processed centrally. Based on these summaries, we discuss coding strategies for visual threats and propose a common prototypical pathway for rapid innate defensive responses.

A synaptic filtering mechanism in visual threat identification in mouse.

Predator detection is key to animal's survival. Superior colliculus (SC) orchestrates the animal's innate defensive responses to visually detected threats, but how threat information is transmitted from the retina to SC is unknown. We discovered that narrow-field neurons in SC were key in this pathway. Using in vivo calcium imaging and optogenetics-assisted interrogation of circuit and synaptic connections, we found that the visual responses of narrow-field neurons were correlated with the animal's defensive behaviors toward visual stimuli. Activation of these neurons triggered defensive behaviors, and ablation of them impaired the animals' defensive responses to looming stimuli. They receive monosynaptic inputs from looming-sensitive OFF-transient alpha retinal ganglion cells, and the synaptic transmission has a unique band-pass feature that helps to shape their stimulus selectivity. Our results describe a cell-type specific retinotectal connection for visual threat detection, and a coding mechanism based on synaptic filtering.

Dietary supplementation with potassium-magnesium sulfate modulates the antioxidant capacity, immunity, and gut microbiota in weaned piglets.

The purpose of this study was to evaluate the effects of different levels of potassium magnesium sulfateon (PMS) on growth performance, diarrhea rate, intestinal morphology, antioxidant capacity, intestinal immunity, and gut microbiota in weaned piglets. A total of 216 weaned piglets were randomly divided into six dietary groups: the basal diet with 0% (CON), 0.15, 0.3, 0.45, 0.6, and 0.75% PMS. The results showed that the ADFI of 29-42 days and 1-42 days was linearly and quadratically increased by the PMS supplementation (P < 0.05), and significantly reduced the diarrhea rate in weaned piglets (P < 0.05). Moreover, dietary supplementation with PMS significantly reduced the serum adrenaline and noradrenaline levels in weaned piglets (P < 0.05). Furthermore, 0.3% PMS significantly increased the activity of glutathione peroxidase (GSH-Px) in the jejunum (P < 0.05) and tended to increase the activity of superoxide dismutase (SOD) in the jejunal mucosa of piglets (P < 0.1). Additionally, dietary supplementation with PMS significantly reduced the interleukin-1ß (IL-1ß) level in the jejunal mucosa (P < 0.05), and 0.3% PMS increased the serum IgM content in piglets (P < 0.05). Furthermore, the analysis of colonic microbiota by 16S RNA sequencing showed that the addition of PMS increased the Shannon index (P < 0.05) and Observed Species index (P < 0.05). Based on linear discriminant analysis effect size (LEfSe) and T-test analysis, the addition of PMS increased the relative abundance of Ruminococcaceae and Peptostreptococcaceae in the colonic digesta (P < 0.05). Spearman analysis showed that there was a positive correlation between intestinal GSH-Px activity and the relative abundance of Peptostreptococcaceae. These results showed that dietary supplementation with PMS could improve growth performance, alleviate diarrhea incidence, and modulate the antioxidant capacity and intestinal immunity in weaned piglets, which was partially related to the significant changes in colonic microbiota composition.

Influences of Dietary Vitamin E, Selenium-Enriched Yeast, and Soy Isoflavone Supplementation on Growth Performance, Antioxidant Capacity, Carcass Traits, Meat Quality and Gut Microbiota in Finishing Pigs.

This study investigated the effects of dietary compound antioxidants on growth performance, antioxidant capacity, carcass traits, meat quality, and gut microbiota in finishing pigs. A total of 36 barrows were randomly assigned to 2 treatments with 6 replicates. The pigs were fed with a basal diet (control) or the basal diet supplemented with 200 mg/kg vitamin E, 0.3 mg/kg selenium-enriched yeast, and 20 mg/kg soy isoflavone. Dietary compound antioxidants decreased the average daily feed intake (ADFI) and feed to gain ratio (F/G) at d 14−28 in finishing pigs (p < 0.05). The plasma total protein, urea nitrogen, triglyceride, and malondialdehyde (MDA) concentrations were decreased while the plasma glutathione (GSH) to glutathione oxidized (GSSG) ratio (GSH/GSSG) was increased by compound antioxidants (p < 0.05). Dietary compound antioxidants increased loin area and b* value at 45 min, decreased backfat thickness at last rib, and drip loss at 48 h (p < 0.05). The relative abundance of colonic Peptococcus at the genus level was increased and ileal Turicibacter_sp_H121 abundance at the species level was decreased by dietary compound antioxidants. Spearman analysis showed a significant negative correlation between the relative abundance of colonic Peptococcus and plasma MDA concentration and meat drip loss at 48 h. Collectively, dietary supplementation with compound antioxidants of vitamin E, selenium-enrich yeast, and soy isoflavone could improve feed efficiency and antioxidant capacity, and modify the backfat thickness and meat quality through modulation of the gut microbiota community.

Effects of niacin on intestinal epithelial Barrier, intestinal Immunity, and microbial community in weaned piglets challenged by PDCoV.

The objective was to evaluate effects of niacin on the intestinal epithelial barrier, intestinal immunity, and microbial community in weaned piglets challenged by Porcine Deltacoronavirus (PDCoV). In this study, fifteen weaned piglets were randomly assigned to 1 of 3 groups, (1) control group, normal diet; (2) PDCoV group, infected with 1 × 107 TCID50 of the PDCoV CHN-HN-17 strain by oral administration; (3) NA + PDCoV group, infected with 1 × 107 TCID50 of the PDCoV CHN-HN-17 strain by oral administration following administration of 40 mg of niacin for three days. The results showed that PDCoV infection induced diarrhea and other clinical symptoms with intestinal villi shedding and atrophy in weaned piglets. Niacin alleviated the symptoms of diarrhea and intestinal damage of PDCoV-infected weaned piglets. Additionally, PDCoV increased (P < 0.05) the mRNA expression of tight junction proteins [zonula occludens-1 (ZO-1) and Claudin] and antimicrobial peptides [porcine ß defensin 1 (pBD1), pBD2, proline-arginine rich 39-amino acid peptide (PR39) and protegrin 1-5 (PG1-5) in the jejunum and ileum of weaned piglets, while niacin increased (P < 0.05) the expression of PG1-5 compared with PDCoV. PDCoV increased (P < 0.05) the contents of serum interleukin-1ß (IL-1ß), IL-8 and intestinal IL-8, and up-regulated the mRNA expression of tumor necrosis factor-α (TNF-α), IL-1ß, IL-6, IL-10, IL-12, and IL-18 in ileum of weaned piglets compared with control. However, niacin decreased (P < 0.05) the contents of serum IL-1ß, IL-6 and intestinal IL-10 and IL-8, and also reduced (P < 0.05) the mRNA expression of ileal TNF-α, IL-10 and IL-12 in the PDCoV-infected piglets. Compared with control, PDCoV up-regulated (P < 0.05) the mRNA expression of key genes related to innate immune and antiviral molecules [toll-like receptor 4 (TLR4), NOD1, NOD2, DDX58, CCL2, STAT2, Mx1, IFN-γ, and protein kinase R (PKR) in the ileum of weaned piglets. Niacin decreased (P < 0.05) the mRNA expression of NOD1, NOD2, STAT2, IFN-γ, and PKR in PDCoV-infected weaned piglets. Moreover, the mRNA expression of IL-6 decreased (P < 0.05) and 2'-5'-oligoadenylate synthetase (OAS), IFN-α, and PKR increased (P < 0.05) in PDCoV-infected IPEC-J2 cells treated with niacin in vitro. Furthermore, niacin decreased (P < 0.05) the elevation of protein expression including inducible NOS (iNOS), nuclear factor-κB (NF-κB p65), inhibitor kappa B (IKKß), histone deacetylase [Sirtuin 1 (SIRT1) and histone deacetylase 7 (HDAC7) and phosphorylation of histone H3 at serine s10 (pH3s10) in the ileum of PDCoV-infected piglets, and increased (P < 0.05) the expression of G protein-coupled receptor (GPR109A). PDCoV disrupted the composition and structure of microflora in the colon of weaned piglets, and reduced the relative abundance of the beneficial bacteria Spirobacterium, but niacin could improve the intestinal microbial flora of the PDCoV-infected piglets associated with increasing the relative abundance of Lactobacillus. Overall, niacin could alleviate diarrhea, intestinal barrier damages, intestinal immune response and colonic microflora disfunction in PDCoV-infected weaned piglets.

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

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

The Responses of Lactobacillus reuteri LR1 or Antibiotic on Intestinal Barrier Function and Microbiota in the Cecum of Pigs.

This study aimed to investigate responses of the Lactobacillus reuteri or an antibiotic on cecal microbiota and intestinal barrier function in different stages of pigs. A total of 144 weaned pigs (Duroc × Landrace × Yorkshire, 21 days of age) were randomly assigned to the control group (CON, fed with a basal diet), the antibiotic group (AO, fed with basal diet plus 100 mg/kg olaquindox and 75 mg/kg aureomycin), and the L. reuteri group (LR, fed with the basal diet + 5 × 1010 CFU/kg L. reuteri LR1) throughout the 164-d experiment. A total of 45 cecal content samples (5 samples per group) from different periods (14th, 42th, and 164th days) were collected for 16S rRNA gene amplification. The results revealed that although LR and AO did not change the diversity of cecal microbiota in pigs, the abundance of some bacteria at the genus level was changed with age. The proportion of Lactobacillus was increased by LR in early life, whereas it was decreased by AO compared with the control group. The relative abundance of Ruminococcaceae was increased along with age. In addition, the gas chromatography results showed that age, not AO or LR, has significant effects on the concentrations of SCFAs in the cecum of pigs (P < 0.05). However, the mRNA expression of tight junction proteins zonula occluden-1 (ZO-1) and occludin were increased by AO in the cecum of pigs on day 14, while LR increased the mRNA expression of intestinal barrier-related proteins ZO-1, occludin, mucin-1, mucin-2, PG1-5, and pBD2 in the cecum of pigs on days 14 and 164 (P < 0.05). In conclusion, LR and AO have different effects on the intestinal barrier function of the cecum, and neither LR nor AO damaged the intestinal barrier function of pig cecum. In addition, LR and AO have little effects on cecal microflora in different stages of the pigs. The microflora and their metabolite SCFAs were significantly changed along with age. These findings provide important information to understand the homeostasis of the cecum of pigs after antibiotic or probiotic treatment.

Low Protein Diet Improves Meat Quality and Modulates the Composition of Gut Microbiota in Finishing Pigs.

This study investigated the effect of a low protein (LP) diet on growth performance, nitrogen emission, carcass traits, meat quality, and gut microbiota in finishing pigs. Fifty-four barrows (Duroc × Landrace × Yorkshire) were randomly assigned to three treatments with six replicates (pens) of three pigs each. The pigs were fed with either high protein (HP, 16% CP), medium protein (MP, 12% CP), and LP diets (10% CP), respectively. The LP diets did not influence the growth performance, but significantly decreased the plasma urea nitrogen contents and fecal nitrogen emission (P < 0.05). The LP diet significantly decreased the plasma contents of malondialdehyde (MDA) and increased the plasma glutathione (GSH) contents (P < 0.05). The LP diets significantly increased the backfat thickness at the first and last ribs, L* (lightness) value of meat color, and muscle fiber density in the longissimus dorsi (P < 0.05). The messenger RNA (mRNA) expression of fatty acid synthetase (FAS), peroxisome proliferator-activated receptor-gamma (PPARγ), leptin, and acetyl-CoA carboxylase (ACC) was significantly downregulated, while that of carnitine palmitoyltransferase 1 (CPT1) and myosin heavy chain (MYHC) IIx in the longissimus Dorsi muscle was significantly upregulated by LP diets (P < 0.05). The 16S sequencing analysis showed that the abundance of unidentified Bacteria at the phylum level, and Halanaerobium and Butyricicoccusat at the genus level in the colonic digesta were significantly decreased by LP diet (P < 0.05). The LP diet significantly decreased the observed species of α-diversity in both ileal and colonic microbiota (P < 0.05). Spearman correlation analysis identified a significant positive correlation between the abundance of the ileal genera Streptococcus and L* value at 24 and 48 h, and a significant negative correlation between unidentified_Ruminococcasceae in both ileum and colon with L* value at 24 h (P < 0.05). Collectively, the LP diet supplemented with lysine, methionine, threonine, and tryptophan could reduce the fecal nitrogen emission without affecting growth performance and improve meat quality by regulating the antioxidant capacity and gene expression involved in fat metabolism as well as modulating the gut microbiota composition in finishing pigs.

Effects of Fermented Feed on the Growth Performance, Intestinal Function, and Microbiota of Piglets Weaned at Different Age.

The beneficial function of fermented feed in livestock industry has been widely investigated. However, little is known about the effects of fermented feed on different weaned-day piglets. This study aimed to investigate the effects of fermented diet on the growth performance, intestinal function, and microbiota of piglets weaned at the age of 21 and 28 days. The results found that weaning on day 21 significantly increased (p < 0.05) average daily gain (ADG), and average daily feed intake (ADFI) (calculated based on wet weight and dry matter), while reduced (p < 0.05) feed to gain ratio (F:G), the activities of trypsin and lipase of jejunum and the villus height of ileum, compared with 28-days weaning. The protein levels of Occludin, Claudin-1, and ZO-1 of ileum in the groups weaning on day 21 were less (p < 0.05) than the groups weaning on day 28. Moreover, dietary supplementation with fermented diet upregulated (p < 0.05) the Occludin, Claudin-1, and ZO-1 proteins of ileum, compared with the groups treated with control diet both weaning on day 21 and 28. In addition, dietary supplementation with fermented diet decreased (p < 0.05) the relative abundance of Clostridia (class) and increased (p < 0.05) the Bacteroidia (class) level of cecal microbiota, compared with the groups treated with control diet both weaning on day 21 and 28. However, supplementation with fermented diet did not affect the concentrations of short-chain fatty acids in the cecum (p > 0.05). Therefore, our data suggest that the feed digestibility is improved in piglets weaned at 21 days, but intestinal barrier function is weaker than in piglets weaned at 28 days. However, compared with feeding control diet, supplementation with fermented diet both improved the feed conversion and intestinal barrier function of weaned piglets by modulating intestinal microbiota.