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The objective of this experiment was to investigate the potential benefits of active dry yeast (ADY) on the growth performance, rumen fermentation, nutrient digestibility, and serum parameters of weaned beef calves. Thirty Simmental crossbred male calves (body weight = 86.47 ± 4.41 kg and 70 ± 4 d of age) were randomly divided into 2 groups: control (CON) (fed basal ration) and ADY (fed basal ration and 5 g/d ADY per calf). The dietary concentrate-to-roughage ratio was 35:65. All the calves were regularly provided rations 3 times a day at 07:00, 13:00, and 19:00 and had free access to water. The experiment lasted for 60 d. The average daily gain of ADY group was higher (P = 0.007) than that of the CON group, and the ratio of feed intake to average daily gain in the ADY group was reduced (P = 0.022) as compared to the CON group. The concentration of ruminal ammonia-N was higher (P = 0.023) in the CON group than that in the ADY group, but an opposite trend of microbial protein was found between the 2 groups. Also, the ruminal concentrations of propionate and butyrate were higher (P

Background Ovarian cancer (OC) is a gynecological malignancy with the highest mortality rate. Cisplatin (DDP) based chemotherapy is a standard strategy for ovarian cancer. Despite good response rates for initial chemotherapy, almost 80% of the patients treated with DDP based chemotherapy will experience recurrence due to drug-resistant, which will ultimately result in fatality. The aim of the present study was to examine the pathogenesis and potential molecular markers of cisplatin-resistant OC by studying the differential expression of mRNAs and miRNAs between cisplatin resistant OC cell lines and normal cell lines. Methods Two mRNA datasets (GSE58470 and GSE45553) and two miRNA sequence datasets (GSE58469 and GSE148251) were downloaded from the Gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were screened by the NetworkAnalyst. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to analyze the biological functions of DEGs. The protein-protein interaction network was constructed using STRING and Cytoscape software to identify the molecular mechanisms of key signaling pathways and cellular activities. FunRich and MiRNATip databases were used to identify the target genes of the DEMs. Results A total of 380 DEGs, and 5 DEMs were identified. Protein–protein interaction (PPI) network of DEGs containing 379 nodes and 1049 edges was constructed, and 4 key modules and 24 hub genes related to cisplatin-resistant OC were screened. Two hundred ninety-nine target genes of the 5 DEMs were found out. Subsequently, one of these 299 target genes (UBB) belonging to the hub genes of GSE58470 and GSE45553 was identified by MCODE and CytoHubba,which was regulated by one miRNA (mir-454). Conclusions One miRNA–mRNA regulatory pairs (mir-454-UBB) was established. Taken together, our study provided evidence concerning the alteration genes involved in cisplatin-resistant OC, which will help to unravel the mechanisms underlying drug resistant.

Vogt-Koyanagi-Harada disease (VKH) is a rare multisystemic inflammatory autoimmune disorder. Glaucoma secondary to VKH frequently occurs during the recurrent phase of anterior uveitis; however, acute angle-closure glaucoma (ACG) secondary to both VKH and human immunodeficiency virus (HIV) infection has rarely been reported. We describe a case of secondary acute ACG involving VKH, characterized by sudden vision loss, moderately elevated intraocular pressure (IOP), shallow anterior chamber, and fully or partially closed angle, in an HIV-infected patient. Both VKH and HIV infection contributed to the occurrence of ACG due to the leakage and forward rotation of the ciliary body, as well as choroidal effusion. The deterioration of IOP and serous macular detachment were observed after initial corticosteroid therapy. Visual acuity and IOP were improved with subretinal fluid absorption after continued corticosteroid therapy. Understanding the response of IOP and serous macular detachment after corticosteroid therapy is important for clinical practice.

The molecular epidemiology and biological characteristics of Escherichia coli associated with hemorrhagic pneumonia (HP) mink from five Chinese Provinces were determined. From 2017 to 2019, 85 E. coli strains were identified from 115 lung samples of mink suffering from HP. These samples were subjected to serotyping, antimicrobial susceptibility, detection of virulence genes, phylogenetic grouping, whole-genome sequencing, drug resistant gene, multilocus sequence typing (MLST) and biofilm-forming assays. E. coli strains were divided into 18 serotypes. Thirty-nine E. coli strains belonged to the O11 serotype. Eighty-five E. coli strains were classified into seven phylogenetic groups: E (45.9%, 39/85), A (27.1%, 23/85), B1 (14.1%, 12/85), B2 (3.7%, 3/85), D (3.7%, 3/85), F (2.4%, 2/85) and clade I (1.2%, 1/85). MLST showed that the main sequence types (STs) were ST457 (27/66), All E. coli strains had ≥4 virulence genes. The prevalence of virulence was 98.8% for yijp and fimC, 96.5% for iucD, 95.3% for ompA, 91.8% for cnf-Ⅰ, 89.4% for mat, 82.3% for hlyF, and 81.2% for ibeB. The prevalence of virulence genes iss, cva/cvi, aatA, ibeA, vat, hlyF, and STa was 3.5–57.6%. All E. coli strains were sensitive to sulfamethoxazole, but high resistance was shown to tetracycline (76.5%), chloramphenicol (71.8%), ciprofloxacin (63.5%) and florfenicol (52.9%), resistance to other antibiotics was 35.3–16.5%. The types and ratios of drug-resistance genes were tet(A), strA, strB, sul2, oqxA, blaTEM-1B, floR, and catA1 had the highest frequency from 34%-65%, which were consistent with our drug resistance phenotype tetracycline, florfenicol, quinolones, chloramphenicol, the bla-NDM-I and mcr-I were presented in ST457 strains. Out of 85 E. coli strains, six (7.1%) possessed a strong ability, 12 (14.1%) possessed a moderate ability, and 64 (75.3%) showed a weak ability to form biofilm. Our data will aid understanding of the epidemiological background and provide a clinical basis for HP treatment in mink caused by E. coli.

PurposeThe prognostic value of caveolin-1 in prostate cancer remains uncertain. Hence, this meta-analysis was performed to evaluate the prognostic value of caveolin-1 in prostate cancer, as well as ascertain the relationship between caveolin-1 expression and clinicopathological characteristics of prostate cancer patients.MethodsThe PubMed, Embase, Chinese National Knowledge Infrastructure and Chinese Biology Medicine databases were electronically searched to retrieve published studies on caveolin-1 expression in prostate cancer. After study selection and data extraction, the meta-analysis was conducted using Review manager 5.3 software. Odds ratio (OR) with 95% confidence interval (CI) was used to estimate the pooled effect. Funnel plot was used to assess publication bias.ResultsA total of ten studies were enrolled, which included 3976 cases of prostate cancer, 72 cases of high-grade intraepithelial neoplasia (HGPIN), and 157 normal controls. Results of the meta-analysis showed that the positive rate of caveolin-1 expression in prostate cancer was 18.28 times higher than that in normal control (OR= 18.28, 95% CI: 9.02–37.04, p10 vs. ≤ 10 (OR=2.09, 95% CI: 1.35–3.22, pConclusionCaveolin-1 is overexpressed in prostate cancer, which can serve as a risk factor and adverse clinicopathological feature of prostate cancer. Caveolin-1 can also predict poor survival in prostate cancer patients after radical prostatectomy.

Background Yak (Bos grunniens) is an ancient bovine species on the Qinghai-Tibetan Plateau. Due to extremely harsh condition in the plateau, the growth retardation of yaks commonly exist, which can reduce the incomes of herdsman. The gastrointestinal barrier function plays a vital role in the absorption of nutrients and healthy growth. Functional deficiencies of the gastrointestinal barrier may be one of the contributors for yaks with growth retardation. Methods To this end, we compared the growth performance and gastrointestinal barrier function of growth-retarded (GRY) and normal yaks (GNY) based on average daily gain (ADG), serum parameters, tissue slice, real-time PCR, and western blotting, with eight yaks in each group. Results GRY exhibited lower (P P P = 0.004). In jejunum, with the exception of higher villus height, width, and surface area in GNY, numerical difference (P = 0.61) was detected between two groups for crypt depth. Both in rumen and jejunum, the mRNA expression of interleukin-1beta in GRY was markedly higher (P P P Conclusion The results indicated that the ruminal and jejunal barrier functions of GRY are disrupted as compared to GNY. In addition, our study provides a potential solution for promoting the growth of GRY by enhancing the gastrointestinal barrier function.

The ocean harbors a variety of bacteria that contain huge protease resources and offer a great potential for industrial and biotechnological applications. Here, we isolated a protease-secreting bacterium Vibrio pomeroyi strain 12613 from Atlantic seawater and purified a protease VP9 from strain 12613. VP9 was identified as a metalloprotease of the M4 family. VP9 could hydrolyze casein and gelatin but not elastin and collagen. With gelatin as the substrate, VP9 showed the highest activity at 40°C and pH 6.0–8.0. It was stable at temperatures of 50°C and less and in the range of pH 5.0–11.0. VP9 also had good tolerance to NaCl, non-ionic detergents, and organic solvent methanol. Unlike other M4 metalloproteases, VP9 has distinct collagen-swelling ability, and its collagen-swelling effect was concentration dependent. The relative expansion volume of collagen increased by approximately eightfold after treatment with 10 μM VP9 at 37°C for 12 h. The collagen-swelling mechanism of VP9 on bovine-insoluble type I collagen was further studied. Atomic force microscopy observation and biochemical analyses showed that VP9 can degrade proteoglycans in collagen fibers, resulting in the release of collagen fibrils from collagen fibers and the swelling of the latter. In addition, VP9 can degrade glycoproteins, a non-collagenous constituent interacting with collagen in the skin. The characteristics of VP9, such as sufficient specificity toward proteoglycans and glycoproteins but no activity toward collagen, suggest its promising potential in the unhairing and fiber-opening processing in leather industry.

Simple Summary The specific enzymes secreted by microorganisms in the gastrointestinal tract (GIT) of ruminants, such as phytase, can catalyze the decomposition of calcium compounds (e.g., phytic acid) and release bound calcium for the absorption of animals. Therefore, we speculate that gastrointestinal microbes could be a factor affecting digestion and absorption of dietary calcium. However, little related research has been reported. In the present study, we found that the true digestibility of calcium (TDC) in goats is related to gastrointestinal bacteria. Some gastro-intestinal bacteria, such as ruminal Prevotella, were beneficial for true host digestibility of dietary calcium. Abstract The current study was performed to examine the relationship between the true digestibility of calcium (TDC) in the diet and bacterial community structure in the gastrointestinal tract (GIT) of goats. Twenty-six Nubian healthy female goats were selected as experimental animals, and their TDC was determined using metabolic experiments. Eight goats were grouped into the high digestibility of Calcium (HC) phenotype, and another eight were grouped into the low digestibility of Calcium (LC) phenotype. Their bacterial 16S rRNA gene amplicons from the rumen, abomasum, jejunum, cecum, and colon contents were sequenced using next-generation high-throughput sequencing technology. In the rumen, 239 genera belonging to 23 phyla, 319 genera belonging to 30 phyla in the abomasum, 248 genera belonging to 36 phyla in the jejunum, 248 genera belonging to 25 phyla in the colon and 246 genera belonging to 23 phyla in the cecum were detected. In addition, there was a significant correlation between the TDC and the relative abundance of Candidatus_Saccharimonas, Christensenellaceae_R-7_group, Mogibacterium, Prevotella_1, Prevotella_UCG_004, Ruminococcus_2, Saccharibacteria in the rumen, Eubacterium_coprostanoligens_group, Lachnospiraceae_ND3007_group, Lachnospiraceae_NK3A20_group, p-1088-a5_gut_group, and Planctomycetes in the abomasum, Butyrivibrio in the cecum, and Fibrobacter in the cecum were observed. This study suggests an association of GIT microbial communities as a factor influencing TDC in goats.

Lipid is the chief energy source for starved animals. &beta, hydroxybutyrate (BHBA) is the main ketone body produced by lipid decomposition. In Chinese hamster ovary (CHO) cell experiment, it was found that BHBA could be used not only as an energy substance, but also as a ligand of GPR109A for regulating lipid metabolism. However, whether BHBA can regulate lipid metabolism of yaks, and its effective concentration and signal pathway are not clear. This study investigated the effects and mechanism of starvation and BHBA on the lipid metabolism of yak. Eighteen male Jiulong yaks were selected and then randomly divided into three groups: normal feeding group (NG), starvation group (SG), and starvation with BHBA infusion group (SBG). The yaks in the NG group were freely fed during the trial, while the yaks in the SG and SBG groups fasted, from 7th to 9th days of the experiment, the NG and SG were infused continuous with 0.9% normal saline and SBG was infused 1.7 mmol/L BHBA solution respectively. The blood samples were collected on the 0th, 1st, 3rd, 5th, 7th, and 9th day of experiment. The subcutaneous adipose tissue of all the yaks in this study were taken from live bodies after infusion. Serum glucose, lipid metabolites, hormone concentrations, and mRNA and protein expressions of key factors of lipid metabolism and signaling pathway in subcutaneous adipose tissue were measured. The results showed that, as compared with NG, starvation significantly reduced the body weight of yak in SG, and significantly increased the concentration of BHBA in serum and the mRNA expression of PKA and CREB1 in subcutaneous adipose tissue, while the mRNA expression of MEK, PKC, ERK1/2, the area of adipocytes, and the proportion of saturated fatty acid were decreased. Whereas, further increase of BHBA concentration through infusion promoted the mRNA expression of GPR109A receptor in the subcutaneous adipose tissue of SBG, inhibited the mRNA expression of AC and PKA, and decreased the phosphorylation protein abundance of CREB1, and significantly increased the diameter and area of adipocytes. These findings suggest that starvation led to enhanced lipid catabolism in yaks. An increasing BHBA concentration could increase the mRNA expression of GPR109A receptor in subcutaneous adipose tissue and inhibit the cAMP/PKA/CREB signaling pathway and lipid decomposition.

Yak suffers severe starvation and body weight reduction in the cold season and recovers relatively rapid growth in the warm season every year. Herein, we investigated the effects of starvation and refeeding on the growth, feed efficiency, blood biochemistry and rumen microbial community as well as functions of yaks. The results showed that starvation significantly reduced the body weight of yaks. Serum glucose and triglyceride concentrations significantly decreased, and &beta, hydroxybutyric acid and non-esterified fatty acid levels were significantly increased during the starvation period. Starvation also dramatically inhibited rumen microbial fermentations. Whereas, refeeding with the same diet significantly increased the feed efficiency, nutrient digestibility together with rumen acetate, propionate and microbial protein productions compared with those before starvation. The 16S rDNA sequencing results showed that starvation mainly decreased the ruminal protein-degrading bacteria Prevotella and propionate-producing bacteria Succiniclasticum populations and dramatically increased the denitrifying bacteria Thauera populations. Refeeding reduced the Euryarchaeota population and increased propionate-producing bacteria Succinivibrionaceae UCG-002 and starch-degrading bacteria Ruminobacter populations when compared with those before starvation. The predicted microbial metabolic pathways, related to amino acid and starch metabolisms, were also significantly altered during the starvation and refeeding. The results indicated that the rumen microorganisms and their metabolism pathways changed with feed supply, and these alterations in part contributed to yak adaption to starvation and re-alimentation. This study is helpful for enhancing the understanding and utilization of this natural character of yaks to explore and improve their growth potential.

BackgroundThe life cycle of Taenia solium is characterized by different stages of development, requiring various kinds of hosts that can appropriately harbor the eggs (proglottids), the oncospheres, the larvae and the adults. Similar to other metazoan pathogens, T. solium undergoes transcriptional and developmental regulation via epigenetics during its complex lifecycle and host interactions.ResultIn the present study, we integrated whole-genome bisulfite sequencing and RNA-seq technologies to characterize the genome-wide DNA methylation and its effect on transcription of Cysticercus cellulosae of T. solium. We confirm that the T. solium genome in the cysticercus stage is epigenetically modified by DNA methylation in a pattern similar to that of other invertebrate genomes, i.e., sparsely or moderately methylated. We also observed an enrichment of non-CpG methylation in defined genetic elements of the T. solium genome. Furthermore, an integrative analysis of both the transcriptome and the DNA methylome indicated a strong correlation between these two datasets, suggesting that gene expression might be tightly regulated by DNA methylation. Importantly, our data suggested that DNA methylation might play an important role in repressing key parasitism-related genes, including genes encoding excretion-secretion proteins, thereby raising the possibility of targeting DNA methylation processes as a useful strategy in therapeutics of cysticercosis.ConclusionOur study will provide a foundation for future studies to explore this key epigenetic modification in development of Cysticercus cellulosae and in human cysticercus disease.

In the present report, we examined the responses of diabetic Goto-Kakizaki (GK) rats and control Wistar-Kyoto (WKY) rats fed either a standard chow or high-fat diet (HFD) from weaning to 20 weeks of age. This comparison included gene expression profiling of skeletal muscle using Affymetrix gene array chips. The expression profiling is interpreted within the context of a wide array of physiological measurements. Genes whose expressions are different between the 2 strains regardless of diet, as well as genes that differ between strains only with HFD, were identified. In addition, genes that were regulated by diet in 1 or both strains were identified. The results suggest that both strains respond to HFD by an increased capacity to oxidize lipid fuels in the musculature but that this adaptation occurs more rapidly in WKY rats. The results also demonstrated an impaired cytokine signalling and heightened inflammatory status in the GK rats.

Background and aims: We aimed to evaluate the association between famine exposure during early life and obesity and obesity(max) (obese at the highest weight) in adulthood. Methods and results: Data were from two population-based cross-sectional surveys conducted in 2006 and 2009 in Qingdao, China. A total of 8185 subjects born between 1/1/1941 and 12/31/1971 were categorized into unexposed (born between 01/01/1962 and 12/31/1971), fetal/ infant exposed (born between 01/01/1959 and 12/31/1961), childhood exposed (born between 01/01/1949 and 12/31/1958) and adolescence exposed (born between 01/01/1941 and 12/31/1948) according to their age when exposed to the Chinese famine from 1959 to 1961. Obesity was defined as BMI (body mass index) >= 28.0 and obesitymax was defined as BMImax (BMI at the highest weight) >= 28.0. We compared fetal/ infant exposed, childhood exposed and adolescence exposed to the unexposed using logistic regression models to assess the effect of famine exposure on later obesity and obesitymax. Fetal/infant exposed (OR = 1.59, P

Bacterial extracellular proteases are important for bacterial nutrition and marine sedimentary organic nitrogen degradation. However, only a few proteases from marine sedimentary bacteria have been characterized. Some subtilases have a protease-associated (PA) domain inserted in the catalytic domain. Although structural analysis and deletion mutation suggests that the PA domain in subtilases is involved in substrate binding, direct evidence to support this function is still absent. Here, a protease, P57, secreted by Photobacterium sp. A5-7 isolated from marine sediment was characterized. P57 could hydrolyze casein, gelatin and collagen. It showed the highest activity at 40°C and pH 8.0. P57 is a new subtilase, with 63% sequence identity to the closest characterized protease. Mature P57 contains a catalytic domain and an inserted PA domain. The recombinant PA domain from P57 was shown to have collagen-binding ability, and Phe349 and Tyr432 were revealed to be key residues for collagen binding in the PA domain. This study first shows direct evidence that the PA domain of a subtilase can bind substrate, which provides a better understanding of the function of the PA domain of subtilases and bacterial extracellular proteases from marine sediment.

Effects of high fat diet (HFD) on obesity and, subsequently, on diabetes are highly variable and modulated by genetics in both humans and rodents. In this report, we characterized the response of Goto-Kakizaki (GK) rats, a spontaneous polygenic model for lean diabetes and healthy Wistar-Kyoto (WKY) controls, to high fat feeding from weaning to 20 weeks of age. Animals fed either normal diet or HFD were sacrificed at 4, 8, 12, 16 and 20 weeks of age and a wide array of physiological measurements were made along with gene expression profiling using Affymetrix gene array chips. Mining of the microarray data identified differentially regulated genes (involved in inflammation, metabolism, transcription regulation, and signaling) in diabetic animals, as well as the response of both strains to HFD. Functional annotation suggested that HFD increased inflammatory differences between the two strains. Chronic inflammation driven by heightened innate immune response was identified to be present in GK animals regardless of diet. In addition, compensatory mechanisms by which WKY animals on HFD resisted the development of diabetes were identified, thus illustrating the complexity of diabetes disease progression.

As surgical skills develop in spinal field, transpedicular screw fixation of the lower thoracic, thoracolumbar, and lumbar spines have already been performed successfully, even using freehand technique by trained surgeons. The benefits of transpedicular screw fixation are widely accepted in the thoracolumbar spinal region for very stable fixation effect. Abumi et al first introduced transpedicular screw fixation in the subaxial cervical spinal region in 1991 and reported their initial clinical results in 1994 [1]. Since then, some other spinal surgeons began to accept transpedicular screw fixation in the subaxial cervical region as one choice [5]. But whether this fixation method can be accepted widely as a routine choice has been disputed till now. The main concern comes from the potential violation of the pedicle cortices and following damages to adjacent neurovascular structures [6][12]. To diminish subaxial cervical pedicle (SCP) screw malposition ratio as low as possible and to ensure successful clinical results, the complex morphologic features and projections of subaxial cervical pedicles should be clearly understood. That is, the exact diameter, inclinations at transverse and sagittal plane, cortical thicknesses at different orientations, and cortical thicknesses adjacent to pedicle entrance should be determined before any transpedicular screw fixation was performed, even by experienced surgeons using meticulous surgical techniques[Fig.1]. Although morphologic studies of the cervical spine have been reported as a way to evaluate the feasibility and safety of the technique, many have focused on transverse diameter of the pedicles, which is far from enough [3].Thorough understanding of the subaxial cervical spinal pedicle anatomy is mandatory to avoid injury to the vertebral artery, spinal cord or a nerve root [8][11][14]. Because of their inherent ability to render bony anatomy in three dimensions, CT scans can provide the best osseous detail of subaxial cervical pedicles. Volumetric CT could reconstruct multiplanar CT images based on raw sequential transaxial CT images [7]. Multiple planar reconstruction (MPR) CT images could provide vivid anatomic data of subaxial cervical pedicles at different planes and different orientations for further detailed study. MPR CT images can be reconstructed using the CT-machine attached Advantage Workstation. If time permitted, quantitative measurement of MPR CT images can be fulfilled using the measurement tools of the CT machine-attached Advantage Workstation. But in clinical practice, large clinical CT scanning tasks are under schedule,the Advantage

Type 2 diabetes (T2DM) is a heterogeneous group of diseases that is progressive and involves multiple tissues. Goto-Kakizaki (GK) rats are a polygenic model with elevated blood glucose, peripheral insulin resistance, a non-obese phenotype, and exhibit many degenerative changes observed in human T2DM. As part of a systems analysis of disease progression in this animal model, this study characterized the contribution of adipose tissue to pathophysiology of the disease. We sacrificed subgroups of GK rats and appropriate controls at 4, 8, 12, 16 and 20 weeks of age and carried out a gene array analysis of white adipose tissue. We expanded our physiological analysis of the animals that accompanied our initial gene array study on the livers from these animals. The expanded analysis included adipose tissue weights, HbA1c, additional hormonal profiles, lipid profiles, differential blood cell counts, and food consumption. HbA1c progressively increased in the GK animals. Altered corticosterone, leptin, and adiponectin profiles were also documented in GK animals. Gene array analysis identified 412 genes that were differentially expressed in adipose tissue of GKs relative to controls. The GK animals exhibited an age-specific failure to accumulate body fat despite their relatively higher calorie consumption which was well supported by the altered expression of genes involved in adipogenesis and lipogenesis in the white adipose tissue of these animals, including Fasn, Acly, Kklf9, and Stat3. Systemic inflammation was reflected by chronically elevated white blood cell counts. Furthermore, chronic inflammation in adipose tissue was evident from the differential expression of genes involved in inflammatory responses and activation of natural immunity, including two interferon regulated genes, Ifit and Iipg, as well as MHC class II genes. This study demonstrates an age specific failure to accumulate adipose tissue in the GK rat and the presence of chronic inflammation in adipose tissue from these animals.

Background Epidermal growth factor (EGF) is an important growth factor in regulation of cell proliferation, differentiation, survival and apoptosis. Studies showed that food-grade Lactococcus lactis (L. lactis) and NICE expression system have superior performance in exogenous protein expression. This study aimed to construct and express porcine EGF (pEGF), and use L. lactis as vehicle for producing and delivering pEGF. Furthermore, investigating biological activity of pEGF and exploring applications feasibility of combination effects of L. lactis and pEGF on early weaned piglets’ production. Results A recombinant Lactococcus lactis which produced and secreted pEGF at 1000 ng/ml in culture supernatant was generated. Secreted pEGF was a fully biologically active protein, as demonstrated by its capacity to stimulate L929 mouse fibroblast cell line proliferation in vitro. For in vivo study, forty piglets were randomly allocated to control, antibiotic control, empty vector-expressing L. lactis (LL-EV) and pEGF-secreting L. lactis (LL-pEGF). After 14 d of rearing, final body weight and average daily gain in LL-pEGF were greater (P < 0.05, 8.95 vs. 8.37 kg, 206.1 vs. 157.7 g/day, respectively) than those in control, but no significant differences between LL-pEGF, LL-EV and antibiotic control. Overall period average daily feed intake was higher in LL-pEGF, LL-EV and antibiotic control than in control (P < 0.05, 252.9, 255.6, 250.0, 207.3 g/day, respectively). No significant difference was observed on ADFI/ADG. LL-pEGF increased villous height in the duodenum, jejunum and ileum than in control and LL-EV (P < 0.05). Sucrase in the 3 intestinal segments, aminopeptidase A in the duodenum and Jejunum, aminopeptidase N and dipeptidase IV in the duodenum in LL-pEGF were higher than those in control (P < 0.05). Furthermore, Escherichia coli and Enterococcus counts decreased in the ileum and Lactobacillus increased in the ileum and cecum digesta in LL-pEGF compare with the control (P < 0.05). Lactobacillus increased in the cecum in LL-EV compared with control and antibiotic control (P < 0.05). Conclusion We have generated a recombinant Lactococcus lactis which produced and secreted fully biologically active porcine EGF. Oral administration of pEGF-secreting L. lactis had beneficial effects on intestinal health and performance of early-weaned piglets.

Background As a key link between innate and adaptive immune responses, the interferon (IFN) system is the first line of defense against viral infection. IFN, and in particular, IFN-α, has been used clinically as an effective therapeutic agent for viral infections. However, different subtypes of IFN-α demonstrate distinct antiviral activity. Therefore, it is important to identify IFN-α subtypes with high antiviral activity for the development of genetically engineered antiviral drugs. Results In this study, we cloned the genes for 13 IFN-α subtypes from peripheral blood lymphocytes of the mink. The homologies of the 13 mink IFN-α genes were 93.6–99.3% and 88.8–98.4% at the nucleotide and amino acid sequence levels, respectively. In contrast to human and canine IFN-α subtypes, most mink IFN-α subtypes contained two N-glycosylation sites. We expressed and purified 13 mink IFN-α subtypes in Escherichia coli. The cytopathic effect inhibition assay showed that all the 13 recombinant mink IFN-α subtypes inhibited the propagation of vesicular stomatitis virus in WISH cells, with IFN-α2 and IFN-α12 demonstrating the highest activities. Furthermore, recombinant mink IFN-α2 and IFN-α12 significantly suppressed the propagation of canine distemper virus in Vero cells, with IFN-α2 demonstrating the highest activity. Conclusions We identified the mink IFN-α2 subtype as a promising candidate for the development of effective antiviral drugs.

Brain-derived neurotrophic factor (BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The mRNA expression levels of BDNF and its processing enzymes and receptors (Furin, matrix metallopeptidase 9, tissue-type plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury; however, the expression levels of these mRNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia (approval No. U12-18) on July 30, 2018 Refereed/Peer-reviewed

Spinal cord injury (SCI) is a fatal disease that can cause severe disability. Cortical reorganization subserved the recovery of spontaneous function after SCI, although the potential molecular mechanism in this remote control is largely unknown. Therefore, using proteomics analysis, RNA interference/overexpression, and CRISPR/Cas9 in vivo and in vitro, we analyzed how the molecular network functions in neurological improvement, especially in the recovery of motor function after spinal cord transection (SCT) via the remote regulation of cerebral cortex. We discovered that the overexpression of pyridoxal kinase (PDXK) in the motor cortex enhanced neuronal growth and survival and improved locomotor function in the hindlimb. In addition, PDXK was confirmed as a target of miR-339 but not miR-124. MiR-339 knockout (KO) significantly increased the neurite outgrowth and decreased cell apoptosis in cortical neurons. Moreover, miR-339 KO rats exhibited functional recovery indicated by improved Basso, Beattie, and Bresnehan (BBB) score. Furthermore, bioinformatics prediction showed that PDXK was associated with GAP43, a crucial molecule related to neurite growth and functional improvement. The current research therefore confirmed that miR-339 targeting PDXK facilitated neurological recovery in the motor cortex of SCT rats, and the underlying mechanism was associated with regulating GAP43 in the remote cortex of rats subjected to SCT. These findings may uncover a new understanding of remoting cortex control following SCI and provide a new therapeutic strategy for the recovery of SCI in future clinical trials.

International audience; Lysine acetylation is a dynamic and highly conserved post-translational modification that plays a critical role in regulating diverse cellular processes. Trichinella spiralis is a foodborne parasite with a considerable socio-economic impact. However, to date, little is known regarding the role of lysine acetylation in this parasitic nematode. In this study, we utilized a proteomic approach involving anti-acetyl lysine-based enrichment and highly sensitive mass spectrometry to identify the global acetylated proteome and investigate lysine acetylation in T. spiralis. In total, 3872 lysine modification sites were identified in 1592 proteins that are involved in a wide variety of biological processes. Consistent with the results of previous studies, a large number of the acetylated proteins appear to be involved in metabolic and biosynthetic processes. Interestingly, according to the functional enrichment analysis, 29 acetylated proteins were associated with phagocytosis, suggesting an important role of lysine acetylation in this process. Among the identified proteins, 15 putative acetylation motifs were detected. The presence of serine downstream of the lysine acetylation site was commonly observed in the regions surrounding the sites. Moreover, protein interaction network analysis revealed that various interactions are regulated by protein acetylation. These data represent the first report of the acetylome of T. spiralis and provide an important resource for further explorations of the role of lysine acetylation in this foodborne pathogen.