ABO genotype alters the gut microbiota by regulating GalNAc levels in pigs.

The composition of the intestinal microbiome varies considerably between individuals and is correlated with health1. Understanding the extent to which, and how, host genetics contributes to this variation is essential yet has proved to be difficult, as few associations have been replicated, particularly in humans2. Here we study the effect of host genotype on the composition of the intestinal microbiota in a large mosaic pig population. We show that, under conditions of exacerbated genetic diversity and environmental uniformity, microbiota composition and the abundance of specific taxa are heritable. We map a quantitative trait locus affecting the abundance of Erysipelotrichaceae species and show that it is caused by a 2.3 kb deletion in the gene encoding N-acetyl-galactosaminyl-transferase that underpins the ABO blood group in humans. We show that this deletion is a ≥3.5-million-year-old trans-species polymorphism under balancing selection. We demonstrate that it decreases the concentrations of N-acetyl-galactosamine in the gut, and thereby reduces the abundance of Erysipelotrichaceae that can import and catabolize N-acetyl-galactosamine. Our results provide very strong evidence for an effect of the host genotype on the abundance of specific bacteria in the intestine combined with insights into the molecular mechanisms that underpin this association. Our data pave the way towards identifying the same effect in rural human populations.

The utilization of N-acetylgalactosamine and its effect on the metabolism of amino acids in Erysipelotrichaceae strain.

BACKGROUND: The metabolism of gut microbiota produces bioactive metabolites that modulate host physiology and promote self-growth. Erysipelotrichaceae is one of the most common anaerobic microorganism families in the gut, which has been discovered to play a vital role in host metabolic disorders and inflammatory diseases. Our previous study found that N-acetylgalactosamine (GalNAc) in caecal content of pigs significantly affected the abundance of Erysipelotrichaceae strains. However, it remains unknown how GalNAc feeding in vitro culture affects the expression levels of genes in the GalNAc metabolic pathway and the concentrations of intermediate metabolites in the Erysipelotrichaceae strain. Whether GalNAc feeding should influence the metabolism of other nutrients, such as amino acids, remains unrevealed. RESULTS: In this study, whole-genome sequence, transcriptome, and metabolome data were analyzed to assess the utilization of a Erysipelotrichaceae strain on GalNAc. The results showed the presence of a complete GalNAc catabolism pathway in the genome of this Erysipelotrichaceae strain. GalNAc feeding to this Erysipelotrichaceae strain significantly changed the expression levels of genes involved in glycolysis and tricarboxylic acid (TCA) cycle. Meanwhile, the concentrations of lactate, pyruvate, citrate, succinate and malate from the glycolysis and TCA cycle were significantly increased. In addition, transcriptome analysis indicated that the genes involved in the metabolism of amino acids were affected by GalNAc, including lysA (a gene involved in lysine biosynthesis) that was significantly down-regulated. The intracellular concentrations of 14 amino acids in the Erysipelotrichaceae strain were significantly increased after feeding GalNAc. CONCLUSIONS: Our findings comfirmed and extended our previous works that demonstrated the utilization of GalNAc by Erysipelotrichaceae strain, and explained the possible mechanism of GalNAc affecting the abundance of Erysipelotrichaceae strain in vitro.

Predictive value of serum retinol binding protein in severity and complications of acute pancreatitis: a retrospective cohort study.

OBJECTIVES: Retinol binding protein (RBP) is associated with an increased risk of insulin resistance, metabolic syndrome, atherosclerosis and hypertension. This study aimed to evaluate serum RBP levels in patients with acute pancreatitis (AP). METHODS: The study included 1,871 AP patients, including 1,411 with mild AP (MAP), 244 with moderately severe AP (MSAP), and 186 with severe AP (SAP). Retrospective analysis was conducted on RBP concentrations and other clinical data of AP patients. RESULTS: AP patients were subgrouped by RBP level into low RBP (LRBP), normal RBP (NRBP), and high RBP (HRBP) groups. The LRBP group showed a significantly higher proportion of SAP patients than NRBP and HRBP groups. Additionally, the LRBP group had the highest BISAP and CTSI scores among the three groups; WBC and CRP levels in the NRBP group were significantly lower than those in the LRBP and HRBP groups. RBP was better at predicting acute necrotic collection (ANC) than other local complications, with an area under the curve (AUC) of 0.821. RBP was also an independent risk factor for acute lung injury (ALI) and ANC in AP patients. The AUC of RBP for predicting ALI was 0.829, with 30.45 mg/L as the optimal cutoff value, and the sensitivity and specificity were 59.70% and 96.50%, respectively. The AUC of RBP for predicting ANC was 0.821, with 28.35 mg/L as the optimal cutoff value, and the sensitivity and specificity were 61.20% and 95.50%, respectively. CONCLUSIONS: Serum RBP had predictive value for AP severity, local and systemic complications.

Deficiency of ribosomal proteins reshapes the transcriptional and translational landscape in human cells.

Human ribosomes have long been thought to be uniform factories with little regulatory function. Accumulating evidence emphasizes the heterogeneity of ribosomal protein (RP) expression in specific cellular functions and development. However, a systematic understanding of functional relevance of RPs is lacking. Here, we surveyed translational and transcriptional changes after individual knockdown of 75 RPs, 44 from the large subunit (60S) and 31 from the small subunit (40S), by Ribo-seq and RNA-seq analyses. Deficiency of individual RPs altered specific subsets of genes transcriptionally and translationally. RP genes were under cotranslational regulation upon ribosomal stress, and deficiency of the 60S RPs and the 40S RPs had opposite effects. RP deficiency altered the expression of genes related to eight major functional classes, including the cell cycle, cellular metabolism, signal transduction and development. 60S RP deficiency led to greater inhibitory effects on cell growth than did 40S RP deficiency, through P53 signaling. Particularly, we showed that eS8/RPS8 deficiency stimulated apoptosis while eL13/RPL13 or eL18/RPL18 deficiency promoted senescence. We also validated the phenotypic impacts of uL5/RPL11 and eL15/RPL15 deficiency on retina development and angiogenesis, respectively. Overall, our study provides a valuable resource for and novel insights into ribosome regulation in cellular activities, development and diseases.

Ribosomes are the main effector of the translational machinery to synthesize proteins. In this study, the authors characterized genome-wide transcriptional and translational changes after knocking-down 75 individual human ribosomal proteins (RPs). They revealed that deficiency of individual RPs perturbed expression of specific subsets of genes, enriched in eight major functional classes, such as cell cycle and development. RPs were subjected to co-translational regulation under ribosomal stress where deficiency of the 60S RPs and the 40S RPs had opposite effects on the two subunits. They also showed that RPS8 deficiency stimulated cellular apoptosis while RPL13 and RPL18 deficiency promoted cellular senescence. They further showed functional and regulatory roles of RPL11 and RPL15 in retina development and angiogenesis, respectively.

Effectiveness of Roy Adaptation Model-Based Cognitive Stimulation Therapy in Elderly Patients with Non-Small Cell Lung Cancer Undergoing Curative Resection.

This study aimed to investigate the effects of a Roy adaptation model (RAM)-based cognitive stimulation therapy (CST) intervention on elderly patients diagnosed with primary non-small cell lung cancer (NSCLC) undergoing curative resection. A total of 280 patients diagnosed with primary NSCLC were randomized into RAM-based CST group and control group. Outcomes were assessed at three intervals: pre-surgery, discharge, and one-month post-discharge. Cognitive function was evaluated using Mini-Cognitive test. Postoperative delirium prevalence was determined within 48 hours post-surgery using Nursing Delirium Screening Scale. The Hospital Anxiety and Depression Scale evaluated anxiety and depression symptoms, while Quality of Life (QoL) was assessed via Short Form-36 (SF36) Health Survey. The RAM-based CST group demonstrated significantly higher Mini-Cog test scores than the control group upon discharge and post-intervention. Patients with RAM-based CST exhibited a decrease in postoperative delirium compared to the control group. The RAM-based CST intervention yielded an improvement in anxiety and depression at discharge and 1-month post-discharge compared to preoperative levels. Additionally, the RAM-based CST group exhibited substantial enhancements in SF36 subcategory scores at 1-month post-discharge compared to pre-surgery. At post-intervention, the RAM-based CST group demonstrated significantly higher scores than the control group across various health-related domains, including role limitations due to emotional problems, mental health, general health perception, bodily pain, and role limitations due to physical problems. The RAM-based CST intervention in elderly NSCLC patients undergoing curative resection yielded significant enhancements in cognitive function, reduced delirium incidence, improved emotional well-being, and better QoL postoperatively.

PBAT-modified starch blended film extract induces in vitro toxicity in L-02 cells: induction of oxidative stress, inflammation, and modulation of AMPK pathway.

PBAT-modified starch blended film are thermoplastic biodegradable materials with good properties and a wide range of applications. In this study, L-02 cells were used as an in vitro toxicity evaluation system for risk assessment of PBAT-modified starch films with migration studies obtained in different food simulants. Determination of total migration and organic matter revealed that the results were in accordance with the standard except for the total organic matter under 95% (v/v) ethanol food simulant which exceeded the standard. The CCK-8 assay showed that these compounds affect the cell viability of L-02 cells. It was observed that the compounds made the cells express increased AST, ALT, TNF-α, IL-6, IL-1ß, and ROS, and decreased SOD, GSH, and ATP. In addition, we explored the effect of migration in PBAT-modified starch composites on protein and gene expression levels in L-02 cells using a transcriptomic approach and found that the AMPK signaling pathway was affected. The expression of AMPK signaling pathway-related proteins was detected by Western Blot, and the expression levels of p-AMPK/AMPK were found to be upregulated, and those of p-mTOR/mTOR, SIRT1, PGC-1α, NRF1 and TFAM were downregulated. The above data suggest that the compounds migrating into the PBAT-modified starch film when exposed to food may induce oxidative stress and inflammation in hepatocytes, and may cause damage to hepatocytes through the AMPK pathway.

Widespread translational control regulates retinal development in mouse.

Retinal development is tightly regulated to ensure the generation of appropriate cell types and the assembly of functional neuronal circuitry. Despite remarkable advances have been made in understanding regulation of gene expression during retinal development, how translational regulation guides retinogenesis is less understood. Here, we conduct a comprehensive translatome and transcriptome survey to the mouse retinogenesis from the embryonic to the adult stages. We discover thousands of genes that have dynamic changes at the translational level and pervasive translational regulation in a developmental stage-specific manner with specific biological functions. We further identify genes whose translational efficiencies are frequently controlled by changing usage in upstream open reading frame during retinal development. These genes are enriched for biological functions highly important to neurons, such as neuron projection organization and microtubule-based protein transport. Surprisingly, we discover hundreds of previously uncharacterized micropeptides, translated from putative long non-coding RNAs and circular RNAs. We validate their protein products in vitro and in vivo and demonstrate their potentials in regulating retinal development. Together, our study presents a rich and complex landscape of translational regulation and provides novel insights into their roles during retinogenesis.

Tissue- and stage-specific landscape of the mouse translatome.

The current understanding of how overall principles of translational control govern the embryo-to-adult transition in mammals is still far from comprehensive. Herein we profiled the translatomes and transcriptomes of six tissues from the mice at embryonic and adult stages and presented the first report of tissue- and stage-specific translational landscape in mice. We quantified the extent of gene expression divergence among different expression layers, tissues and stages, detected significant changes in gene composition and function underlying these divergences and revealed the changing architecture of translational regulation. We further showed that dynamic translational regulation can be largely achieved via modulation of translational efficiency. Translational efficiency could be altered by alternative splicing (AS), upstream and downstream open reading frames (uORFs and dORFs). We revealed AS-mediated translational repression that was exerted in an event type-dependent manner. uORFs and dORFs exhibited mutually exclusive usage and the opposing effects of translational regulation. Furthermore, we discovered many novel microproteins encoded by long noncoding RNAs and demonstrated their regulatory potential and functional relevance. Our data and analyses will facilitate a better understanding of the complexity of translation and translational regulation across tissue and stage spectra and provide an important resource to the translatome research community.

The gender-based facing bias in 3-D biological motion perception.

In biological motion perception, movements of several point lights can evoke a vivid impression of living animals, including humans. Recent studies have reported that male point-light walkers tend to be perceived as facing toward the viewer more than female walkers, and have hypothesized that the gender-based facing bias arises from motion signals. The purpose of this study was to test this hypothesis under experimental conditions where binocular disparity was added to biological motion stimuli. In the two experiments reported here, participants were presented with disparity-defined female and male point-light figures facing toward or away from the viewer. In Experiment 1, we measured "facing-the-viewer" responses in upright and inverted walker configurations. It was found that the facing bias was greater for the male walker than for the female walker in most disparity magnitudes, regardless of walker inversion. In Experiment 2, the walker stimuli were replaced by static snapshots of the walkers. The results showed that the facing bias did not differ between the female and male static figures. These results suggest that motion signals play an important role in producing the gender-based facing bias, even when binocular disparity is added to biological motion stimuli.

Learning and memory impairment induced by 1,4-butanediol is regulated by ERK1/2-CREB-BDNF signaling pathways in PC12 cells.

1,4-butanediol (1,4-BD) is a known γ-hydroxybutyric acid (GHB) precursor which affects the nervous system after ingestion, leading to uncontrolled behavioral consequences. In the present study, we investigated whether 1,4-BD induces oxidative stress and inflammation in PC12 cells and evaluated the toxic effects of 1,4-BD associates with learning and memory. CCK-8 results revealed a dose-effect relationship between the cell viability of PC12 cells and 1,4-BD when the duration of action was 2 h or 4 h. Assay kits results showed that 1,4-BD decreased the levels of Glutathione (GSH), Glutathione peroxidase (GSH-px), Superoxide dismutase (SOD), Acetylcholine (Ach) and increased the levels of Malondialdehyde (MDA), Nitric oxide (NO) and Acetylcholinesterase (AchE). Elisa kits results indicated that 1,4-BD decreased the levels of synaptophysin I (SYN-1), Postsynaptic density protein-95 (PSD-95), Growth associated protein-43 (GAP-43) and increased the levels of Tumor necrosis factor alpha (TNF-α) and Interleukin- 6 (IL-6). RT-PCR results showed that the mRNA levels of PSD-95, SYN-1 and GAP-43 were significantly decreased. The expression of phosphorylation extracellular signal-regulated protein kinase 1/2 (p-ERK1/2), phosphorylation cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) proteins were significantly decreased in PC12 cells by protein blotting. Overall, these results suggest that 1,4-BD may affect synaptic plasticity via the ERK1/2-CREB-BDNF pathway, leading to Ach release reduction and ultimately to learning and memory impairment. Furthermore, oxidative stress and inflammation induced by 1,4-BD may also result in learning and memory deficits. These findings will enrich the toxicity data of 1.4-BD associated with learning and memory impairment.

A pedagogical study on promoting students' deep learning through design-based learning.

This paper illustrates the design-based learning (DBL) approach to promoting the deep learning of students and improving the quality of teaching in engineering design education. We performed three aspects of research with students in a typical educational activity. The first study investigated students' deep learning before and after the DBL approach, both in terms of deep learning status and deep learning ability. The second study examined the effectiveness of the DBL approach by comparative research of a control class (traditional teaching method) and an experimental class (DBL method). The third study examined students' evaluations of the DBL approach. It is approved that the DBL approach has distinctively stimulated the students' motivation to learn, making them more actively engaged in study. The students' higher-order thinking and higher-order capabilities are enhanced, such as critical thinking ability and problem-solving ability. At the same time, they are satisfied with the DBL approach. These findings suggest that the DBL approach is effective in promoting students' deep learning and improving the quality of teaching and learning.

Isolation and genomic characterization of five novel strains of Erysipelotrichaceae from commercial pigs.

BACKGROUND: Members of the Erysipelotrichaceae family have a high abundance in the intestinal tract of mammals, and have been reported to be associated with host metabolic disorders and inflammatory diseases. In our previous study, we found that the abundance of Erysipelotrichaceae strains in the cecum was associated with the concentration of N-acetylgalactosamine (GalNAc). However, only a few members of Erysipelotrichaceae have been isolated and cultured, and their main characteristics, genomic information and the functional capacity of carbohydrate metabolism remain unknown. RESULTS: In this study, we tested 10 different kinds of commercially available media and successfully isolated five Erysipelotrichaceae strains from healthy porcine feces. The five isolates were Gram-positive, and their colonies on Gifu anaerobic medium (GAM) or modified GAM were approximately 0.25-1.0 mm in diameter, and they were circular, white, convex, moist, translucent, and contained colony margins. These isolates were subjected to Oxford Nanopore and Illumina whole-genome sequencing, genome assembly, and annotation. Based on whole-genome sequences, the five strains belong to Erysipelotrichaceae bacterium OH741_COT-311, Eubacterium sp. AM28-29, and Faecalitalea cylindroides. The GC content of the five strains ranged from 34.1 to 37.37%. Functional annotation based on the Kyoto encyclopedia of genes and genomes pathways revealed tens to hundreds of strain-specific proteins among different strains, and even between the strains showing high 16S rRNA gene sequence identity. Prediction analysis of carbohydrate metabolism revealed different capacities for metabolizing carbohydrate substrates among Erysipelotrichaceae strains. We identified that genes related to the GalNAc metabolism pathway were enriched in the genomes of all five isolates and 16 Erysipelotrichaceae strains downloaded from GenBank, suggesting the importance of GalNAc metabolism in Erysipelotrichaceae strains. Polysaccharide utilization loci (PUL) analysis revealed that the strains of Erysipelotrichaceae may have the ability to utilize plant polysaccharides. CONCLUSIONS: The present study not only reports the successful isolation of novel Erysipelotrichaceae strains that enrich the cultured strains of Erysipelotrichaceae, but also provided the genome information of Erysipelotrichaceae strains for further studying the function roles of Erysipelotrichaceae in host phenotypes.

Inhibition of nicotinamide phosphoribosyltransferase protects against acute pancreatitis via modulating macrophage polarization and its related metabolites.

BACKGROUND & OBJECTIVES: Acute pancreatitis is a common inflammatory disorder of the exocrine pancreas with no specific therapy. Intracellular nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in nicotinamide adenine dinucleotide (NAD) salvage pathway, is involved in many inflammatory disorders. In this study, we investigated the role of NAMPT in experimental acute pancreatitis. METHODS: Acute pancreatitis was induced in mice using three disparate models: (1) caerulein hyperstimulation, (2) ethanol plus palmitoleic acid, and (3) retrograde biliopancreatic ductal infusion of sodium taurocholate. The NAMPT inhibitor FK866 and NAMPT downstream product nicotinamide mononucleotide (NMN) was administered. Serum and pancreas were collected and analyzed biochemically and histologically. Bone marrow derived macrophages were isolated, cultured with cytokines or pancreatic acini, then analyzed by quantitative PCR and non-targeted metabolomics. RESULTS: The levels of pancreatic NAMPT and NAD were down-regulated upon acute pancreatitis. NAMPT inhibitor FK866 suppressed M1 macrophage polarization while NMN boosted it. In co-culture of macrophages with acinar cells, inhibition of NAMPT prevented M1-like macrophage differentiation induced by injured pancreatic acini. The injured pancreatic acinar milieu induced a unique metabolic signature linked to macrophage polarization, and inhibition of NAMPT reversed these metabolites changes. Furthermore, NMN supplementation aggravated caerulein hyperstimulation pancreatitis and alcoholic pancreatitis, and inhibition of NAMPT protected against caerulein hyperstimulation, alcoholic and biliary acute pancreatitis and reducing pancreatic macrophage infiltration in vivo. CONCLUSIONS: NAMPT inhibition protects against acute pancreatitis via preventing M1 macrophage polarization and restoring the metabolites related to macrophage polarization and that NAMPT could be a promising therapeutic target for acute pancreatitis.

Live Combined B. subtilis and E. faecium Alleviate Liver Inflammation, Improve Intestinal Barrier Function, and Modulate Gut Microbiota in Mice with Non-Alcoholic Fatty Liver Disease.

BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a chronic, progressive liver disease with an increasing incidence rate. This study investigated the protective effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on NAFLD, and its possible mechanisms. MATERIAL AND METHODS Five-week-old C57BL/6 mice were randomly divided into 3 groups: chow, HFD, and HFD+LCBE groups. The levels of serum biochemical markers, glucose tolerance, insulin, the inflammatory cytokines IL-1ß, IL-6, and TNF-alpha, LPS, and histological staining were measured using commercial kits. qPCR was used to examine the mRNA expression levels of inflammatory cytokines in the liver. Western blotting was used to determine the protein levels of TLR4, NF-kappaB p65, PPAR-alpha, and CPT-1 in the liver, and occludin and Claudin1 in the intestine. The intestinal flora of the mice was analyzed by high-throughput sequencing of the V3-V4 region of 16S rDNA. RESULTS LCBE significantly lowered the body weight, liver/body weight ratio, and serum glucose level, and increased the serum insulin level in NAFLD mice. In addition, LCBE treatment improved the liver function and lipid profile, decreased the levels of LPS and inflammatory cytokines, and downregulated the expression of TLR4 and NF-kappaB p65. Moreover, LCBE enhanced the intestinal barrier function by increasing the expression of occludin and Claudin1. Furthermore, LCBE modulated the composition of the gut microbiota by reducing the Firmicutes to Bacteroidetes ratio, and the proportion of inflammation-related and LPS-producing bacteria, thus re-arranging the structure of the gut microbiota. CONCLUSIONS LCBE protects against NAFLD by alleviating inflammation, restoring the intestinal barrier, and modulating gut microbiota composition.

Age-based dynamic changes of phylogenetic composition and interaction networks of health pig gut microbiome feeding in a uniformed condition.

BACKGROUND: The gut microbiota impacts on a range of host biological processes, and the imbalances in its composition are associated with pathology. Though the understanding of contribution of the many factors, e.g. gender, diet and age, in the development of gut microbiota has been well established, the dynamic changes of the phylogenetic composition and the interaction networks along with the age remain unclear in pigs. RESULTS: Here we applied 16S ribosomal RNA gene sequencing, enterotype-like clustering (Classification of the gut microbiome into distinct types) and phylogenetic co-occurrence network to explore the dynamic changes of pig gut microbiome following the ages with a successive investigation at four ages in a cohort of 953 pigs. We found that Firmicutes and Bacteroidetes are two predominant phyla throughout the experimental period. The richness of gut microbiota was significantly increased from 25 to 240 days of age. Principal coordinates analysis showed a clear difference in the gut microbial community compositions between pre-weaning piglets and the pigs at the other three age groups. The gut microbiota of pre-weaning piglets was clearly classified into two enterotypes, which were dominated by Fusobacterium and p-75-a5, respectively. However, Prevotella and Treponema were the main drivers of the enterotypes for pigs at the age of 80, 120 and 240 days. Besides the piglets, even some adult pigs switched putative enterotypes between ages. We confirmed that the topological features of phylogenetic co-occurrence networks, including scale, stability and complexity were increased along with the age. The biological significance for modules in the network of piglets were mainly associated with the utilization of simple carbohydrate and lactose, whereas the sub-networks identified at the ages of 80, 120 and 240 days may be involved in the digestion of complex dietary polysaccharide. The modules related to the metabolism of protein and amino acids could be identified in the networks at 120 and 240 days. This dynamic change of the functional capacities of gut microbiome was further supported by functional prediction analysis. CONCLUSIONS: The present study provided meaningful biological insights into the age-based dynamic shifts of ecological community of porcine gut microbiota.

Neutrophil-to-lymphocyte ratio can specifically predict the severity of hypertriglyceridemia-induced acute pancreatitis compared with white blood cell.

OBJECTIVES: We aimed to evaluate the values of neutrophil-to-lymphocyte ratio (NLR) and white blood cell (WBC) in predicting severity of acute pancreatitis (AP) with different etiologies. METHODS: We compared NLR and WBC levels in patients with different etiologies and AP severity. The optimal cutoff value for them to predict severe acute pancreatitis (SAP) was determined by receiver operating characteristic (ROC) curve analysis. RESULTS: Both NLR and WBC were elevated in patients with SAP. After subgrouping AP by etiology, NLR was predictive of SAP only in hypertriglyceridemia-induced AP (HTG-AP), while WBC could effectively predict severity in both gallstone and HTG-AP. The best cutoff value of WBC for predicting SAP in gallstone AP patients was 12.81 × 109 /L, with sensitivity and specificity of 78.9% and 70.2%. The best cutoff value for NLR and WBC to differentiate HTG-SAP was more than 5.88 and 15.89 × 109 /L, respectively, with sensitivity and specificity of 87% and 50% for NLR and 56.5% and 75.76% for WBC. CONCLUSIONS: Our study firstly demonstrated that NLR selectively played a role in HTG-AP, while WBC could predict the severity of both gallstone and HTG-AP. Furthermore, we firstly elucidated that NLR was more sensitive and accurate in judging the severity of HTG-AP compared with WBC.

Identification of Sox6 as a regulator of pancreatic cancer development.

Pancreatic cancer (PC) is an aggressive malignancy associated with a poor prognosis and low responsiveness to chemotherapy and radiotherapy. Most patients with PC have metastatic disease at diagnosis, which partly accounts for the high mortality from this disease. Here, we explored the role of the transcription factor sex-determining region Y-box (Sox) 6 in the invasiveness of PC cells. We showed that Sox6 is down-regulated in patients with PC in association with metastatic disease. Sox6 overexpression suppressed PC cell proliferation and migration in vitro and tumour growth and liver metastasis in vivo. Sox6 inhibited epithelial-mesenchymal transition (EMT), and Akt signalling. Sox6 was shown to interact with the promoter of Twist1, a helix-loop-helix transcription factor involved in the induction of EMT, and to modulate the expression of Twist1 by recruiting histone deacetylase 1 to the promoter of the Twist1 gene. Twist1 overexpression reversed the effect of Sox6 on inhibiting EMT, confirming that the effect of Sox6 on suppressing tumour invasiveness is mediated by the modulation of Twist1 expression. These results suggest a novel mechanism underlying the aggressive behaviour of PC cells and identify potential therapeutic targets for the treatment of PC.

Evaluating the profound effect of gut microbiome on host appetite in pigs.

BACKGROUND: There are growing evidences showing that gut microbiota should play an important role in host appetite and feeding behavior. However, what kind of microbe(s) and how they affect porcine appetite remain unknown. RESULTS: In this study, 280 commercial Duroc pigs were raised in a testing station with the circadian feeding behavior records for a continuous period of 30-100 kg. We first analyzed the influences of host gender and genetics in porcine average daily feed intake (ADFI), but no significant effect was observed. We found that the Prevotella-predominant enterotype had a higher ADFI than the Treponema enterotype-like group. Furthermore, 12 out of the 18 OTUs positively associated with the ADFI were annotated to Prevotella, and Prevotella was the hub bacteria in the co-abundance network. These results suggested that Prevotella might be a keystone bacterial taxon for increasing host feed intake. However, some bacteria producing short-chain fatty acids (SCFAs) and lactic acid (e.g. Ruminococcaceae and Lactobacillus) showed negative associations with the ADFI. Predicted function capacity analysis showed that the genes for amino acid biosynthesis had significantly different enrichment between pigs with high and low ADFI. CONCLUSIONS: The present study provided important information on the profound effect of gut microbiota on porcine appetite and feeding behavior. This will profit us to regulate porcine appetite through modulating the gut microbiome in the pig industry.

Copy number variation in the MSRB3 gene enlarges porcine ear size through a mechanism involving miR-584-5p.

BACKGROUND: The size and type of ears are important conformation characteristics that distinguish pig breeds. A significant quantitative trait locus (QTL) for ear size has been identified on SSC5 (SSC for Sus scrofa chromosome) but the underlying causative gene and mutation remain unknown. Thus, our aim was to identify the gene responsible for enlarged ears in pig. RESULTS: First, we narrowed down the QTL region on SSC5 to a 137.85-kb interval that harbors only the methionine sulfoxide reductase B3 (MSRB3) gene. Then, we identified a 38.7-kb copy number variation (CNV) that affects the last two exons of MSRB3 and could be the candidate causative mutation for this QTL. This CNV showed complete concordance with genotype at the QTL of the founder animals in a white Duroc × Erhualian F2 intercross and was found only in pigs from six Chinese indigenous breeds with large ears and from the Landrace breed with half-floppy ears. Moreover, it accounted for the significant association with ear size on SSC5 across the five pig populations tested. eQTL mapping revealed that this CNV was significantly associated with the expression of the microRNA (miRNA) miR-584-5p, which interacts with MSRB3, one of its target genes. In vivo and in vitro experiments confirmed that miR-584-5p inhibits the translation of MSRB3 mRNA. Taken together, these results led us to conclude that presence of the 38.7-kb CNV in the genome of some pig breeds affects ear size by altering the expression of miR-584-5p, which consequently hinders the expression of one of its target genes (e.g. MSRB3). CONCLUSIONS: Our findings shed insight into the underlying mechanism of development of external ears in mammals and contribute to a better understanding of how the presence of CNV can regulate gene expression.

[Screening of nucleic acid aptamer of lung cancer cells based on cell exponential enrichment ligand system evolution and its application in tumor diagnosis and treatment].

Nucleic acid aptamer is an oligonucleotide sequence screened by the exponential enrichment ligand system evolution technology (SELEX). Previous studies have shown that nucleic acid aptamer has a good application prospect in tumor diagnosis and treatment. Therefore, we reviewed the selection and identification of nucleic acid aptamer of lung cancer cells in recent years, and discussed the effect of aptamer as targeting drugs and targeting vectors on the diagnosis of tumors, which provide a new idea for early diagnosis and treatment of tumor.