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Abstract Lactobacillus species have excellent abilities to reduce intestinal inflammation and enhance gut barrier function. This study elucidated the potential mechanisms through which Lactobacillus mitigates lipopolysaccharide (LPS)-induced intestinal injury from the perspective of macrophage–intestinal epithelial cell interactions. Lactobacillus intervention improved the histopathological score; elevated ZO-1 and Occludin protein production; reduced CD16+ cell numbers; diminished IL-1β, IL-6, and TNF-α levels; decreased inducible nitric oxide synthase (iNOS) expression; increased CD163+ cell numbers; elevated IL-10 concentration; and increased arginase-1 (Arg1) expression in LPS-challenged piglets. Lactobacillus pretreatment also altered the colonic microbiota, thereby increasing the butyric acid concentration and GPR43 expression in the LPS-challenged piglets. Compared with those in the LPS group, sodium butyrate (SB) pretreatment decreased IL-1β, IL-6 and TNF-α secretion and iNOS expression but increased IL-10 secretion and Arg1 expression in macrophages. The SB-pretreated macrophages reduced the protein expression of TLR4, MyD88, and phosphorylated NF-κB p65 but increased the protein expression of ZO-1 and Occludin in intestinal epithelial cells. Moreover, GLPG0974 blocked the beneficial effects of SB on macrophages and intestinal epithelial cells. This study demonstrated that Lactobacillus improves intestinal barrier function by regulating the macrophage phenotype through the control of butyric acid and GPR43 levels to further control inflammation.

Background: Diabetic retinopathy (DR), one of the most common microvascular complications of diabetes mellitus (DM), is a major contributor of vision impairment and blindness worldwide. Studies have shown that air pollution exposure is adversely associated with DM. However, evidence is scarce regarding how air pollution exposure affects DR. This study aimed to investigate the association between ambient air pollution exposure and DR risk. Methods: The study population was based on the Fujian Eye Study (FJES), an ophthalmologic, epidemiologic survey investigating the eye health condition of residents in Fujian Province from 2018 to 2019. Daily average concentrations of ambient air pollutants (PM2.5, PM10, SO2, NO2, and O3) were acquired from a high-resolution air quality dataset in China from 2013 to 2018. We used a logistic regression model to examine the associations between DR risk and long-term air pollution at various exposure windows. Results: A total of 2405 out of the 8211 participants were diagnosed with diabetes, among whom 183 had DR. Ambient air pollution, especially particulate matter (i.e., PM2.5 and PM10) and NO2 were positively associated with DR prevalence among all the study subjects. Ambient SO2 and O3 concentrations were not associated with DR prevalence. PM2.5 and NO2 seemed to be borderline significantly associated with increased prevalence of DR in subjects with DM, especially under the model adjusted for sex, age, BMI, SBP, and DBP. Conclusions: These findings showed that long-term exposure to ambient particulate matter and NO2 was associated with a high DR risk in Fujian province, where ambient air pollution is relatively low.

The Jiangshan black pig is an indigenous pig breed in China, renowned for its superior meat quality and adaptability to roughage. However, the population of Jiangshan black pigs has dwindled due to the introduction of cosmopolitan pig breeds and the outbreak of African swine fever, putting them at risk of extinction. To offer insights into the conservation and breeding of Jiangshan black pigs, this study involved 118 Jiangshan black pigs as the research subjects and employed the Zhongxin-1 Porcine Breeding Array PLUS chip to detect whole-genome SNPs. Additionally, various software tools were utilized to accurately analyze the genetic diversity, phylogenetic relationship, inbreeding coefficient, and pedigree structure of the Jiangshan black pig conservation population. The findings indicated that the effective population size (Ne) of the Jiangshan black pig was 4.9, with an average inbreeding coefficient of 0.253 within the population. A genetic relationship analysis identified that the 16 male pigs were clustered into four families, and the 100 female pigs were also assigned to these familial groups. Furthermore, two female pigs were classified as “other” due to their distant genetic relatedness to all the males. These results contribute to a better understanding of the current status of the conservation of the Jiangshan black pig population and offer a theoretical foundation for the development of conservation strategies.

Objective This study was performed to investigate the dynamics of intracranial pressure (ICP) alterations and bilateral transverse–sigmoid sinus morphologies in patients with venous pulsatile tinnitus (PT). Methods This retrospective study involved 27 patients with venous PT associated with sigmoid sinus wall anomalies. ICP and ICP metrics were measured by cerebrospinal fluid manometry and internal jugular vein compression tests. Correlation analysis was performed to determine the statistical correlation between ICP and the morphological metrics. Results The mean ICP was 212.5 ± 47.3 mmH 2 O. The median Δ ICP total was 130 (range, 55–150) mmH 2 O. The Δ ICP total was linearly correlated with the open lumbar pressure, and a significant difference was found between patients with normal and elevated cerebrospinal fluid pressure. The Δ ICP difference was linearly correlated with the Len difference and Vol difference . Δ ICP was linearly correlated with Len difference . Conclusions Complete obstruction of flow patency should be avoided in patients with low ICP and large volumetric/patency differences in the bilateral transverse–sigmoid sinus systems.

Abstract Background Dissection of the regulatory pathways that control skeletal muscle development and atrophy is important for the treatment of muscle wasting. Long noncoding RNA (lncRNA) play important roles in various stages of muscle development. We previously reported that Synaptopodin‐2 (SYNPO2) intron sense‐overlapping lncRNA (SYISL) regulates myogenesis through an interaction with enhancer of zeste homologue 2 (EZH2). However, it remains unclear whether SYISL homologues exist in humans and pigs, and whether the functions and mechanisms of these homologues are conserved among species. Methods Bioinformatics, cell fractionation, and quantitative real‐time polymerase chain reaction (qRT‐PCR) analyses were used for the identification and molecular characterization of SYISL homologues in humans and pigs. Effects on myogenesis and muscle atrophy were determined via loss‐of‐function or gain‐of‐function experiments using C2C12 myoblasts, myogenic progenitor cells, dexamethasone (DEX), and aging‐induced muscle atrophy models. RNA pulldown, RNA immunoprecipitation, dual luciferase reporting, and co‐transfection experiments were used to explore the mechanisms of SYISL interactions with proteins and miRNAs. Results We identified SYISL homologues in humans (designated hSYISL) and pigs (designated pSYISL). Functional experiments demonstrated that hSYISL and pSYISL regulate myogenesis through interactions with EZH2. Interestingly, we showed that SYISL functions to regulate muscle atrophy and sarcopenia through comparative analysis. SYISL is significantly up‐regulated after muscle atrophy (P

BackgroundRemote ischemic postconditioning (RIPostC) induced by brief episodes of the limb ischemia is a potential therapeutic strategy for myocardial ischemia/reperfusion injury, achieved by reducing cardiomyocyte death, inflammation and so on. The actual mechanisms underlying cardioprotection conferred by RIPostC remain unclear. Exploring gene expression profiles in myocardium at transcriptional level is helpful to deepen the understanding on the cardioprotective mechanisms of RIPostC. This study aims to investigate the effect of RIPostC on gene expressions in rat myocardium using transcriptome sequencing.MethodsRat myocardium samples from the RIPostC group, the control group (myocardial ischemia/reperfusion group) and the sham group were performed transcriptome analysis using RNA sequencing. The levels of cardiac IL-1β, IL-6, IL-10 and TNFα were analyzed by Elisa. The expression levels of candidate genes were verified by qRT-PCR technique. Infarct size was measured by Evans blue and TTC staining. Apoptosis was assessed by TUNEL assays and caspase-3 levels were detected using western blotting.ResultsRIPostC can markedly decrease infarct size and reduce the levels of cardiac IL-1β, IL-6 and increase the level of cardiac IL-10. This transcriptome analysis showed that 2 genes were up-regulated (Prodh1 and ADAMTS15) and 5 genes (Caspase-6, Claudin-5, Sccpdh, Robo4 and AABR07011951.1) were down-regulated in the RIPostC group. Go annotation analysis showed that Go terms mainly included cellular process, metabolic process, cell part, organelle, catalytic activity and binding. The KEGG annotation analysis of DEGs found only one pathway, amino acid metabolism, was up-regulated. The relative mRNA expression levels of ADAMTS15, Caspase-6, Claudin-5 and Prodh1 were verified by qRT-PCR, which were consistent with the RNA-seq results. In addition, the relative expression of ADAMTS15 was negatively correlated with the level of cardiac IL-1β (r = −0.748, P = 0.005) and positively correlated with the level of cardiac IL-10 (r = 0.698, P = 0.012). A negative correlation statistical trend was found between the relative expression of ADAMTS15 and the level of cardiac IL-6 (r = −0.545, P = 0.067).ConclusionsADAMTS15 may be a potential inflammation-related gene in regulation of cardioprotection conferred by remote ischemic postconditioning and a possible therapeutic target for myocardial ischemia reperfusion injury in the future.

BackgroundWhite cord syndrome is an uncommon complication characterized by delayed neurologic deterioration with no other identified cause after spinal decompression surgery. Its etiology is attributed to spinal cord reperfusion injury. Here, we present the first case of an extended version of white cord syndrome, with concomitant involvement of the medulla oblongata and cervical cord reperfusion injury after intracranial vertebral artery angioplasty and stenting.Case presentationA 56-year-old male suffered an ischemic stroke in the right anteromedial medulla oblongata. Angiography revealed bilateral vertebral artery stenosis in the intracranial segment. We performed elective left vertebral artery angioplasty and stenting. An intraoperative flow arrest in the left VA occurred and was stopped after the withdrawal of the catheter. Several hours after the operation, the patient developed occipital headache, back neck pain, dysarthria, and worsening left-sided hemiplegia. Magnetic resonance imaging revealed hyperintensity and swelling in the medulla oblongata and cervical cord, in addition to small medullary infarction. A digital subtraction angiography revealed intact vertebrobasilar arteries and patency of the left vertebral artery, left posterior inferior cerebellar artery, and implanted stent. We considered that the reperfusion injury had caused the complication. After treatment, the patient’s symptoms and neurologic deficits greatly improved. He achieved a favorable outcome at the 1-year follow-up, with normal intensity restored in the medulla oblongata and cervical cord on magnetic resonance imaging.ConclusionConcomitant reperfusion injury in the medulla oblongata and cervical cord secondary to vertebral artery angioplasty and stenting is extremely rare. However, this potentially devastating complication requires early recognition and prompt treatment. Maintaining the antegrade flow during vertebral artery endovascular treatment is a precaution against reperfusion injury.

Shape morphing materials are usually difficult to operate in a continuous fashion. Nie et al. fabricate stripes with liquid crystalline elastomers that can be given a Möbius-like morphology with seamless material composition, and perpetually driven under photothermally induced actuation.

KPNA7 is an essential nuclear protein for early embryogenesis and normal fertility. The aim of our study was to determine the associations between single nucleotide polymorphisms (SNPs) in the KPNA7 gene and the reproductive traits in France Large White pigs. Six new SNPs were identified by sequencing. Sows with CT genotype of rs81308652 had a significantly higher total number born than sows with CC and TT genotype in first parity. Litters from sows with TT genotype of rs81308652 had a significantly lower number of weak births than litters from sows with CC and CT genotype in multi parity. Individuals with GG genotype of rs327848277 showed higher litter weight at birth (LWB) and number of healthy births than individuals with genotype GT and TT in first parity, and individuals with genotype GG had lower LWB compared to other genotypes in multi parity. However, we obtained no statistically significant results for association between the SNPs in other four loci and reproductive traits in both primiparous and multiparous pigs. In conclusion, our results show that there are significant association of identified SNPs located in KPNA7 gene with pig reproductive traits, and provided a theoretical basis for genetic improvement of pig reproductive traits.

Here the authors report the construction of a genome-scale porcine CRISPR/Cas9 library, called PigGeCKO, for screening and analyses of host resistance genes and factors associated with Japanese encephalitis virus replication.

lncMGPF is a novel positive regulator of myogenic differentiation, muscle growth and regeneration in mouse, pig, and human. But whether natural mutations within lncMGPF gene regulate animal meat production traits is unclear. In this study, ten single nucleotide polymorphisms (SNPs) of pig lncMGPF (plncMGPF) gene were identified among commercial pig breeds and Chinese local pig breeds. These SNPs are highly linked and constructed into multiple haplotypes, and haplotype ATTCATGTTC (H1) mainly exists in commercial pig breeds while haplotype GCCTGCACCT (H3) is more frequent in Chinese local pig breeds. Association analysis indicated that all SNPs are significantly associated with the backfat thickness and loin muscle area (P < 0.05), respectively, and homologous H1 individuals have higher loin muscle area and lower backfat thickness than H3 pigs. Bioinformatics and functional analysis showed that haplotype H1 has a longer half-life and more stable RNA secondary structure than haplotype H3. plncMGPF haplotype H1 has stronger effects on pig primary myogenic progenitor cells differentiation and muscle growth than haplotype H3. Further experiments showed that two SNPs (rs81403974 and rs325492834) function together to confer plncMGPF stability and function. Our observation suggested that the SNPs in lncMGPF can change the RNA stabilities and lncMGPF function, thereby affecting the porcine meat production traits.

Light-guided robotic soft actuators have attracted intense scientific attention but it remains challenging to modulate the moving directions and shape morphing modes. Here the authors report a stimuli-responsive soft actuator system which is capable of performing multi-directional movement as well as different shape morphing modes.

Genetically modified pigs have shown considerable application potential in the fields of life science research and livestock breeding. Nevertheless, a barrier impedes the production of genetically modified pigs. There are too few safe harbor loci for the insertion of foreign genes into the pig genome. Only a few loci (pRosa26, pH11 and Pifs501) have been successfully identified to achieve the ectopic expression of foreign genes and produce gene-edited pigs. Here, we use CRISPR/Cas9-mediated homologous directed repair (HDR) to accurately knock the exogenous gene-of-interest fragments into an endogenous CKM gene in the porcine satellite cells. After porcine satellite cells are induced to differentiate, the CKM gene promoter simultaneously initiates the expression of the CKM gene and the exogenous gene. We infer preliminarily that the CKM gene can be identified as a potential muscle-specific safe harbor locus in pigs for the integration of exogenous gene-of-interest fragments.

Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 and contains a SET domain that catalyzes histone H3 trimethylation on lysine 27 (H3K27me3) to generate an epigenetic silencing mark. EZH2 interacts with transcription factors or RNA transcripts to perform its function. In this study, we applied RNA immunoprecipitation sequencing and long intergenic non-coding RNA (lincRNA) sequencing methods to identify EZH2-binding lincRNAs. A total of 356 novel EZH2-binding lincRNAs were identified by bioinformatics analysis and an EZH2-binding lincRNA TCONS-00036665 was characterized. TCONS-00036665 promoted pig skeletal satellite cell proliferation but inhibited cell differentiation, and this function was conserved between pigs and mice. Further mechanistic studies indicated that TCONS-00036665 can bind to EZH2 and recruits EZH2 to the promoters of the target genes p21, MyoG, and Myh4, which leads to the enrichment of H3K27me3 and the repression of target gene expression and pig myogenesis. In conclusion, the lincRNA TCONS-00036665 regulates pig myogenesis through its interaction with EZH2.

Skeletal muscle is a highly heterogeneous tissue that plays a crucial role in mammalian metabolism and motion maintenance. Myogenesis is a complex biological process that includes embryonic and postnatal development, which is regulated by specific signaling pathways and transcription factors. Various non-coding RNAs (ncRNAs) account for the majority of total RNA in cells and have an important regulatory role in myogenesis. In this review, we introduced the research progress in miRNAs, circRNAs, and lncRNAs related to embryonic and postnatal muscle development. We mainly focused on ncRNAs that regulate myoblast proliferation, differentiation, and postnatal muscle development through multiple mechanisms. Finally, challenges and future perspectives related to the identification and verification of functional ncRNAs are discussed. The identification and elucidation of ncRNAs related to myogenesis will enrich the myogenic regulatory network, and the effective application of ncRNAs will enhance the function of skeletal muscle.

Abstract Background The protective effect of Neuregulin-1 (NRG-1) on heart failure is well established. In this study, we assessed whether NRG-1 could protect the heart by mimicking the cardioprotective effects of ischaemic postconditioning (IP). Methods We used a myocardial reperfusion injury rat model in vivo to compare the cardioprotective effects of NRG-1(3 μg/kg, iv. at the onset of reperfusion) and IP. In Langendorff isolated heart perfusion experiments, we used the erythroblastic leukaemia viral oncogene homolog 4 (ErbB4) inhibitor AG1478, a phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and a mitogen-activated protein/extracellular signal regulated kinase (MEK) inhibitor PD98059 to clarify whether the protective effects of NRG-1and IP depend on the NRG-1/ErbB4 signals and the reperfusion injury salvage kinase (RISK) pathway. Infarct size was detected by Evans blue and TTC. Apoptosis was detected by TUNEL assays. The expression of NRG-1/ErbB4 and downstream ERK1/2, AKT, AMPK and p70s6K were detected by western blotting. Hematoxylin/eosin (H&E) staining was used for histological analysis. Results We found that NRG-1 and IP had similar effects on reducing myocardial infarct size and apoptosis in vivo. NRG-1 heart protein levels were upregulated in the IP group. Phosphorylation of AKT, ERK1/2 and ErbB4 were also increased in both the IP and NRG-1 groups. Furthermore, in Langendorff analyses, the ErbB4 inhibitor AG1478 suppressed the phosphorylation of ErbB4 and the RISK pathway and aggravated myocardial edema and fiber fracture, thereby inhibited the cardioprotective effects in both the IP and NRG-1 groups. For assessment of downstream signals, the PI3K inhibitor LY294002 and the MEK inhibitor PD98059 suppressed the phosphorylation of AKT and ERK1/2 respectively and abolished the cardioprotective effects induced by IP and NRG-1. Conclusion In conclusion, both IP and NRG-1 could reduce infarct size and apoptosis through ErbB4-dependent activation of the RISK pathway in the same model; these results indicated the therapeutic potential of NRG-1 as a pharmacological postconditioning agent against myocardial reperfusion injury.

Abstract Myogenic differentiation factor (MyoD) is a master transcription factor in muscle development and differentiation. Although several long non-coding RNAs (lncRNAs) linked to MyoD have been found to influence muscle development, the functions of many lncRNAs have not been explored. Here we utilized lncRNA and mRNA microarray analysis to identify potential lncRNAs regulated by MyoD in muscle cells. A total of 997 differentially expressed lncRNAs (335 up-regulated and 662 down-regulated) and 1,817 differentially expressed mRNAs (148 up-regulated and 1,669 down-regulated) were identified after MyoD knockdown in C2C12 cells. Functional predictions suggested that most lncRNAs are involved in the biological pathways related to muscle differentiation and cell cycle with co-expressed genes. To gain further insight into the MyoD-mediated lncRNA expression in muscle differentiation, tissue expression profiles and MyoD overexpression were performed, and we found one of the candidate lncRNAs-AK143003 was significantly regulated by MyoD. Further analyses showed its noncoding ability and cytoplasmic localisation. Silencing of AK143003 stimulated the accumulation of myogenic marker genes, whereas AK143003 overexpression led to their decreased synthesis. This study identified a multitude of MyoD-mediated lncRNAs for further investigation and identified a novel lncRNA, lnc-AK143003, which plays a role in controlling muscle differentiation.

Abstract Background We aimed to explore whether monocyte to lymphocyte ratio (MLR) provides predictive value of the lesion severity in patients with coronary artery disease (CAD). Methods Five hundred forty-three patients undergoing coronary angiography were analyzed in this retrospective study. Patients with coronary stenosis were divided into three groups on the basis of Syntax score. The control group consisted of patients with normal coronary arteries. MLR was calculated by dividing monocytes count by lymphocytes count obtained from routine blood examination. Multivariate logistic analysis was used to assess risk factors of CAD. Ordinal logistic regression analysis was used to assess the relationship between MLR and the lesion severity of coronary arteries. Results MLR was found to be an independent risk factor of the presence of CAD (OR: 3.94, 95% CI: 1.20–12.95) and a predictor of the lesion severity (OR: 2.05, 95% CI: 1.15–3.66). Besides, MLR was positively correlated with Syntax score(r = 0.437, p

Abstract Background Carotid artery stenosis, mainly caused by carotid atherosclerosis, is related to ischemic stroke. This study was to investigate whether monocyte/lymphocyte ratio (MLR) was associated with increased severity of carotid stenosis in patients with ischemic stroke. Methods A total of 395 participants with ischemic stroke were retrospectively analyzed. The severity of carotid stenosis was evaluated by ultrasound examination. Patients were divided into two groups: nonsevere stenosis group and severe stenosis group. Multivariate logistic analysis was used to evaluate risk factors. Results A significant correlation was found between MLR and the severity of carotid stenosis in patients with ischemic stroke. MLR was the independent risk factor of carotid stenosis (OR: 9.74, 95% CI: 1.16–81.54). In the ROC curves analysis, a cutoff value of 0.20 for MLR predicted the severity of carotid stenosis with a sensitivity of 80.40% and specificity of 26.40% (ROC area under the curve: 0.598, 95% CI: 0.53–0.67, p = .004). Conclusion Monocyte/lymphocyte ratio plays important roles in carotid stenosis in patients with ischemic stroke and is an independent risk factor of the severity of carotid stenosis. Therefore, MLR might be considered a potential index in the diagnosis of carotid stenosis in patients with ischemic stroke.

Fat-induced transcript 1 (FIT1/FITM1) gene is a member of the conserved gene family important for triglyceride-rich lipid droplet accumulation. FIT1 gene displays a similar muscle-specific expression across pigs, mice, and humans. Thus pigs can act as a useful model of many human diseases resulting from misexpression of FIT1 gene. Triglyceride content in skeletal muscle plays a key role in pork meat quality and flavors. An insertion/deletion mutation in porcine FIT1 coding region shows a high correlation with a series of fat traits. To gain better knowledge of the potential role of FIT1 gene in human diseases and the correlations with pork meat quality, our attention is given to the region upstream of the porcine FIT1 coding sequence. We cloned ~1 kb of the 5′-flanking region of porcine FIT1 gene to define the role of this sequence in modulating the myogenic expression. A canonical E-box element that activated porcine FIT1 promoter activity during myogenesis was identified. Further analysis demonstrated that promoter activity was induced by overexpression of MyoD1, which bound to this canonical E-box during C2C12 differentiation. This is the first evidence that FIT1 as the direct novel target of MyoD is involved in muscle development.

Myogenesis is a complex biological process, and understanding the regulatory network of skeletal myogenesis will contribute to the treatment of human muscle related diseases and improvement of agricultural animal meat production. Long noncoding RNAs (lncRNAs) serve as regulators in gene expression networks, and participate in various biological processes. Recent studies have identified functional lncRNAs involved in skeletal muscle development and disease. These lncRNAs regulate the proliferation, differentiation, and fusion of myoblasts through multiple mechanisms, such as chromatin modification, transcription regulation, and microRNA sponge activity. In this review, we presented the latest advances regarding the functions and regulatory activities of lncRNAs involved in muscle development, muscle disease, and meat production. Moreover, challenges and future perspectives related to the identification of functional lncRNAs were also discussed.

The MYF5 gene is first inducibly expressed in muscle cell during embryonic muscle development and plays an important role in regulating the differentiation of skeletal muscle precursors. In this study we used PCR-RFLP to investigate two pig (Sus scrofa) populations (n = 302) for two MYF5 gene polymorphisms, a previously unreported novel Met-Leu shift single nucleotide polymorphism (SNP) MYF5/Hsp92II located on exon 1 and the previously identified intron 1 MYF5/HinfI SNP. Haplotype and association analysis showed that haplotypes of the two SNPs were significantly associated with drip loss rate (DLR, p < 0.05), water holding capacity (WHC, p < 0.05), biceps femoris meat color value (MCV2, p < 0.05), biceps femoris marbling score (MM2, p < 0.01), longissimus dorsi intramuscular fat percentage (IMF, p < 0.01) and longissimus dorsi Water moisture content (WM, p < 0.01) in the population 2. However, further studies are needed to confirm these preliminary results.

Peroxisome proliferator-activated receptor delta (PPARD) is a key regulator of lipid metabolism, insulin sensitivity, cell proliferation and differentiation. In this study, we identified two Single Nucleotide Polymorphisms (SNPs, g.1015 A>G and g.1018 T>C) constituting four haplotypes (GT, GC, AC and AT) in the 5' regulatory region of porcine PPARD gene. Functional analysis of the four haplotypes showed that the transcriptional activity of the PPARD promoter fragment carrying haplotype AC was significantly lower than that of the other haplotypes in 3T3-L1, C2C12 and PK-15 cells, and haplotype AC had the lowest binding capacities to the nuclear extracts. Transcription factor 7-like 2 (TCF7L2) enhanced the transcription activities of promoter fragments of PPARD gene carrying haplotypes GT, GC and AT in C2C12 and 3T3-L1 cells, and increased the protein expression of PPARD gene in C2C12 myoblasts. TCF7L2 differentially bound to the four haplotypes, and the binding capacity of TCF7L2 to haplotype AC was the lowest. There were significant associations between -655A/G and fat deposition traits in three pig populations including the Large White × Meishan F2 pigs, France and American Large White pigs. Pigs with genotype GG had significantly higher expression of PPARD at both mRNA and protein level than those with genotype AG. These results strongly suggested that the SNPs in 5' regulatory region of PPARD genes had significant impact on pig fat deposition traits.

Peroxiredoxin6 (Prdx6) is one of the peroxiredoxin (Prdxs) family members that play an important role in maintaining cell homeostasis. Our previous studies demonstrated that Prdx6 was significantly associated with pig meat quality, especially meat tenderness. However, the transcriptional regulation of porcine Prdx6 remains unclear. In this study, we determined the transcription start site (TSS) of porcine Prdx6 gene by 5' rapid-amplification of cDNA ends (5' RACE). Several regulatory elements including CCAAT/enhancer-binding proteinβ (C/EBPβ), Myogenic Differentiation (MyoD), cAMP response element binding protein (CREB), stimulating protein1 (Sp1) and heat shock factor (HSF) binding sites were found by computational analyses together with luciferase reporter system. Overexpression and RNA interference experiments showed that C/EBPβ or CREB could up-regulate the expression of porcine Prdx6 gene at both mRNA and protein level. Electrophoretic mobility shift assays (EMSA) and chromatin immunoprecipitation assays (ChIP) confirmed that C/EBPβ and CREB could interact with Prdx6 promoter. Immuoprecipitation results also showed that C/EBPβ could interact with Prdx6 in vivo. Taken together, our findings identified C/EBPβ and CREB as the important regulators of porcine Prdx6 gene expression, and offered clues for further investigation of Prdx6 gene function.

Glycogen synthase kinase 3 (GSK3α and GSK3β) are serine/threonine kinases involved in numerous cellular processes and diverse diseases including mood disorders, Alzheimer's disease, diabetes, and cancer. However, in pigs, the information on GSK3 is very limited. Identification and characterization of pig GSK3 are not only important for pig genetic improvement, but also contribute to the understanding and development of porcine models for human disease prevention and treatment.Five different isoforms of GSK3β were identified in porcine different tissues, in which three isoforms are novel. These isoforms had differential expression patterns in the fetal and adult of the porcine different tissues. The mRNA expression level of GSK3β isoforms was differentially regulated during the course of the insulin treatment, suggesting that different GSK3β isoforms may have different roles in insulin signaling pathway. Moreover, GSK3β5 had a different role on regulating the glycogen synthase activity, phosphorylation and the expression of porcine GYS1 and GYS2 gene compared to other GSK3β isoforms.We are the first to report five different isoforms of GSK3β identified from the porcine different tissues. Splice variants of GSK3β exhibit differential activity towards glycogen synthase. These results provide new insight into roles of the GSK3β on regulating glycogen metabolism.

BackgroundMicroRNAs (miRNAs) are short non-coding RNA molecules which are proved to be involved in mammalian spermatogenesis. Their expression and function in the porcine germ cells are not fully understood.MethodologyWe employed a miRNA microarray containing 1260 unique miRNA probes to evaluate the miRNA expression patterns between sexually immature (60-day) and mature (180-day) pig testes. One hundred and twenty nine miRNAs representing 164 reporter miRNAs were expressed differently (pConclusionsOverall, the results of this study indicated specific miRNAs expression in porcine testes and suggested that miRNAs had a role in regulating spermatogenesis.

Casting speed, casting temperature and secondary cooling water flow rate are the main process parameters affecting the DC casting process. These parameters significantly influence the flow and temperature fields during casting, which are crucial for the quality of the ingot and can determine the success or failure of the casting operation. Numerical simulation, with the advantages of low cost, rapid execution, and visualized results, is an important method to study and optimize the DC casting process. In the present work, a simulation model of DC casting 2024 aluminum alloy was established, and the reliability of the model was verified. Then, the influence of casting parameters on flow field and temperature field was studied in detail by numerical simulation method. Results show that with the increase of casting speed, the melt flow becomes faster, the depths of slurry zone and mushy zone increase, and the variation of slurry zone depth is greater than that of mushy zone. With an increase in casting temperature, the melt flow rate increases, the depth of the slurry zone becomes shallower, and the depth of the mushy zone experiences only minor changes. The simulation results further indicate that the increase of the flow rate of the secondary cooling water slightly reduces the depths of both slurry and mushy zone. [ABSTRACT FROM AUTHOR]

Soil nitrogen forms are important for exotic plant invasions. However, little effort has been made to study the molecular mechanisms underlying the utilization of different N forms in co-occurring invasive and native plants. The invasive plant Xanthium strumarium prefers nitrate relative to ammonium, and mainly invades nitrate-dominated environments, while it co-occurring native congener X. sibiricum prefers ammonium. Here, we addressed the genetic bases for the interspecific difference in ammonium use and the effects of gibberellin (GA). Twenty-six transcripts related with GA biosynthesis and ammonium utilization were induced by ammonium in X. sibiricum, while only ten in X. strumarium and none for ammonium uptake. XsiAMT1.1a, XsiGLN1.1 and XsiGLT1b may be crucial for the strong ability to absorb and assimilate ammonium in X. sibiricum. All tested transcripts were significantly up-regulated by GA1 and GA4 in X. sibiricum. XsiGA3OX1a, which was also induced by ammonium, may be involved in this regulation. Consistently, glutamine synthetase activity increased significantly with increasing ammonium-N/nitrate-N ratio for X. sibiricum, while decreased for X. strumarium. Our study is the first to determine the molecular mechanisms with which invasive and native plants use ammonium differently, contributing to understanding the invasion mechanisms of X. strumarium and its invasion habitat selection. [ABSTRACT FROM AUTHOR]

10-Hydroxy-2-decenoic acid (10-HDA), also known as royal jelly acid, has a variety of physiological functions, and recent studies have shown that it also has anticancer effects. However, its anticancer mechanisms have not been clearly defined. In this study, we investigated the underlying mechanisms of 10-HDA in A549 human lung cancer cells. We used Cell Counting Kit-8 assay, scratch wound healing assay, flow cytometry, and western blot analysis to investigate its apoptotic effects and underlying mechanism. Our results showed that 10-HDA inhibited the proliferation of three types of human lung cancer cells and had no significant toxic effects on normal cells. Accompanying reactive oxygen species (ROS), 10-HDA induced A549 cell apoptosis by regulating mitochondrial-associated apoptosis, and caused cell cycle arrest at the G0/G1 phase in a time-dependent manner. Meanwhile, 10-HDA also regulated mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) signaling pathways by increasing the expression levels of phosphorylated c-Jun N-terminal kinase, p-p38, and I-κB, and additionally, by decreasing the expression levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, and NF-κB. These effects were blocked by MAPK inhibitors and N-acetyl-L-cysteine. Furthermore, 10-HDA inhibited cell migration by regulating transforming growth factor beta 1 (TGF-β1), SNAI1, GSK-3β, E-cadherin, N-cadherin, and vimentin. Taken together, the results of this study showed that 10-HDA induced cell cycle arrest and apoptosis in A549 human lung cancer cells through ROS-mediated MAPK, STAT3, NF-κB, and TGF-β1 signaling pathways. Therefore, 10-HDA may be a potential therapy for human lung cancer. [ABSTRACT FROM AUTHOR]

Effects of cooling rates on the morphology, sizes and species of primary vanadium-containing phases in Al-10V master alloys were investigated. The results show that the primary vanadium-containing phases with different morphologies and compositions present in Al-10V master alloys at different cooling rates with the pouring temperature of 1,170 °C. When the Al-10V master alloy is solidified in the refractory mold at a cooling rate of 2 °C·s-1, the vanadium-containing phases are mainly plate-like Al10V phases, with the average size of 100.0 µm in the center and 93.2 µm at the edge of the ingot. When the master alloy is solidified in the graphite mold at a cooling rate of 24.3 °C·s-1, the primary vanadium-containing phases are dendritic Al3V phases, with the average length of 297.0 µm for the first dendrite in the center and 275.0 µm at the edge of the ingot. The secondary dendrite arm spacing (SDAS) is 9.5 µm in the center and 9.3 µm at the edge of the ingot, respectively. When the solidification is carried out in the copper mould at a cooling rate of 45.7 °C·s-1, the primary vanadium-containing phases are also Al3V phases but with smaller size, compared with that prepared at the cooling rate of 24.3 °C·s-1. As a result, the average length is 190.0 µm for the first dendrite in the center and 150.0 µm at the edge of the ingot. The SDAS is 9.8 µm in the center and 4.4 µm at the edge of the ingot, respectively. [ABSTRACT FROM AUTHOR]

Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, SYISL promotes myoblast proliferation and fusion but inhibits myogenic differentiation. SYISL knockout in mice results in significantly increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and epigenetic silencing of target genes. Taken together, our results reveal that SYISL is a repressor of muscle development and plays a vital role in PRC2- mediated myogenesis. [ABSTRACT FROM AUTHOR]

The monotypic lichenised genus Anamylopsora (Baeomycetaceae, Baeomycetales), with its single species A. pulcherrima, is distributed in the arid areas of the Northern Hemisphere, including China. In this paper, we introduce another species new to science, Anamylopsora pruinosa. The new species is characterised by a densely pruinose upper surface, abundantly thick and strong rhizines and terricolous habitat. It is also strongly supported by the phylogenetic and species delimitation analyses based on nrDNA ITS sequences, in which A. pruinosa forms well-supported clade separated from A. pulcherrima. [ABSTRACT FROM AUTHOR]

Like many complex human diseases, esophageal squamous cell carcinoma (ESCC) is known to cluster in families. Familial ESCC cases often show early onset and worse prognosis than the sporadic cases. However, the molecular genetic basis underlying the development of familial ESCC is mostly unknown. We reported that SLC22A3 is significantly down-regulated in nontumor esophageal tissues from patients with familial ESCC compared with tissues from patients with sporadic ESCCs. A-to-I RNA editing of the SLC22A3 gene results in its reduced expression in the nontumor esophageal tissues of familial ESCCs and is significantly correlated with lymph node metastasis. The RNA-editing enzyme ADAR2, a familial ESCC susceptibility gene identified by our post hoc genome-wide association study, is positively correlated with the editing level of SLC22A3. Moreover, functional studies showed that SLC22A3 is a metastasis suppressor in ESCC, and deregulation of SLC22A3 facilitates cell invasion and filopodia formation by reducing its direct association with α-actinin-4 (ACTN4), leading to the increased actin-binding activity of ACTN4 in normal esophageal cells. Collectively, we now show that A-to-I RNA editing of SLC22A3 contributes to the early development and progression of familial esophageal cancer in high-risk individuals. [ABSTRACT FROM AUTHOR]

The combined electromagnetic fields were achieved by the application of an alternating magnetic field and a stationary magnetic field and were used during direct chill (DC) casting process to control the microstructure and macrosegregation of an Al-Zn-Mg-Cu alloy. Ingot microstructures were analyzed under an optical microscope (Leica DMR). The composition at different locations in the ingots was measured with inductively coupled plasma mass spectrometry (ICP) method. The results showed that the grain structure is transformed from dendrite to equiaxed structure and significantly refined with the application of combined electromagnetic fields. The uniformity of microstructure is also greatly improved. The combined electromagnetic fields show a significant effect on the distribution of elements. The negative macrosegregation in the centre area of the ingot is obviously reduced. [ABSTRACT FROM AUTHOR]

Degassing is very important for aluminum alloys especially for 7xxx series alloys. In the present study, a high shear technology was used to degas 7032 aluminum alloy in order to study its degassing efficiency. The experimental results showed that the high shear technology can significantly degas 7032 aluminum alloy. By applying intensive melt shearing and an Ar injection of 60 seconds, the density index, Di, was reduced from 13.25% to 0.28% and the hydrogen concentration was significantly reduced from 0.31 to 0.10 mL/100g Al. Compared with the conventional rotary degassing, high shear technology showed a much higher degassing efficiency, achieving a lower concentration of hydrogen in a shorter time. The water simulation experiment was used to study the mechanism of the high degassing efficiency. The small bubble size and the uniform distribution of Ar bubbles with the application of high shear technology are believed to be the main cause for the high degassing efficiency. [ABSTRACT FROM AUTHOR]

Angled-surface slot-compensated hydrostatic bearing (ASHB) is a novel type of hydrostatic bearing which is potentially applicable in rotary tables. However, it has not been sufficiently studied in available literature. In this paper the mathematic model for ASHB was built and solved by the finite element method (FEM). The influence ofsemicone angle on static and dynamic performance characteristics was theoretically investigated. The simulated results have been compared with that of the traditional fixed slot-compensated hydrostatic bearing (FSHB) on the same geometric and operating conditions. Results show that the performance of ASHB is better than that of FSHB; the studied bearing with a large semicone angle is superior in power consumption; the clearance width ratio of the restricting gap to the bearing gap has an obvious effect on bearing performance. [ABSTRACT FROM AUTHOR]

Background Marie Unna hereditary hypotrichosis (MUHH) is an autosomal dominant disorder characterised by coarse, wiry, twisted hair developed in early childhood and subsequent progressive hair loss. MUHH is a genetically heterogeneous disorder. No gene in 1p21.1-1q21.3 region responsible for MUHH has been identified. Methods Exome sequencing was performed on two affected subjects, who had normal vertex hair and modest alopecia, and one unaffected individual from a four-generation MUHH family of which our previous linkage study mapped the MUHH locus on chromosome 1p21.1-1q21.3. Results We identified a missense mutation in EPS8L3 (NM024526.3: exon2: c.22G->A:p.Ala8Thr) within 1p21.1-1q21.3. Sanger sequencing confirmed the cosegregation of this mutation with the disease phenotype in the family by demonstrating the presence of the heterozygous mutation in all the eight affected and absence in all the seven unaffected individuals. This mutation was found to be absent in 676 unrelated healthy controls and 781 patients of other disease from another unpublished project of our group. Conclusions Taken together, our results suggest that EPS8L3 is a causative gene for MUHH, which was helpful for advancing us on understanding of the pathogenesis of MUHH. Our study also has further demonstrated the effectiveness of combining exome sequencing with linkage information for identifying Mendelian disease genes [ABSTRACT FROM AUTHOR]

Atopic diseases, such as atopic dermatitis (AD) and asthma, are closely related to clinical phenotypes with hypersensitivity, and often share some similar genetic and pathogenic bases. Our recent GWAS identified three susceptibility gene/loci FLG (rs11204971 and rs3126085), 5q22.1 (rs10067777, rs7701890, rs13360927 and rs13361382) and 20q13.33 (rs6010620) to AD. The effect of these AD associated polymorphisms in asthma is so far unknown. To investigate whether AD relevant genetic variants is identical to asthma and reveal the differences in genetic factors between AD and asthma in Chinese Han population, seven AD associated single nucleotide polymorphisms (SNPs) as well as 3 other SNPs (rs7936562 and rs7124842 at 11q13.5 and rs4982958 at 14q11.2) from our previous AD GWAS were genotyped in 463 asthma patients and 985 controls using Sequenom MassArray system. We found rs4982958 at 14q11.2 was significantly associated with asthma (P = 3.04×10-4, OR = 0.73). We also detected one significant risk haplotype GGGA from the 4 SNPs (rs10067777, rs7701890, rs13360927 and rs13361382) at 5q22.1 in AD cases (Pcorrection = 3.60×10-10, OR = 1.26), and the haplotype was suggestive of risk in asthma cases in this study (P = 0.014, Pcorrection = 0.084, OR = 1.38). These SNPs (rs11204971, rs3126085, rs7936562, rs712484 and rs6010620) at AD susceptibility genes/loci FLG, 11q13.5 and 20q13.33 were not associated with asthma in this study. Our results further comfirmed that 14q11.2 was an important candidate locus for asthma and demonstrated that 5q22.1 might be shared by AD and asthma in Chinese Han population. [ABSTRACT FROM AUTHOR]

Psoriasis is a common inflammatory skin disease with genetic components of both immune system and the epidermis. PSOR1 locus (6q21) has been strongly associated with psoriasis; however, it is difficult to identify additional independent association due to strong linkage disequilibrium in the MHC region. We performed stepwise regression analyses of more than 3,000 SNPs in the MHC region genotyped using Human 610-Quad (Illumina) in 1,139 cases with psoriasis and 1,132 controls of Han Chinese population to search for additional independent association. With four regression models obtained, two SNPs rs9468925 in HLA-C/HLA-B and rs2858881 in HLA-DQA2 were repeatedly selected in all models, suggesting that multiple loci outside PSOR1 locus were associated with psoriasis. More importantly we find that rs9468925 in HLA-C/HLA-B is associated with both psoriasis and vitiligo, providing first important evidence that two major skin diseases share a common genetic locus in the MHC, and a basis for elucidating the molecular mechanism of skin disorders. [ABSTRACT FROM AUTHOR]

Atopic dermatitis is a chronic, relapsing form of inflammatory skin disorder that is affected by genetic and environmental factors. We performed a genome-wide association study of atopic dermatitis in a Chinese Han population using 1,012 affected individuals (cases) and 1,362 controls followed by a replication study in an additional 3,624 cases and 12,197 controls of Chinese Han ethnicity, as well as 1,806 cases and 3,256 controls from Germany. We identified previously undescribed susceptibility loci at 5q22.1 (TMEM232 and SLC25A46, rs7701890, Pcombined = 3.15 × 10?9, odds ratio (OR) = 1.24) and 20q13.33 (TNFRSF6B and ZGPAT, rs6010620, Pcombined = 3.0 × 10?8, OR = 1.17) and replicated another previously reported locus at 1q21.3 (FLG, rs3126085, Pcombined = 5.90 × 10?12, OR = 0.82) in the Chinese sample. The 20q13.33 locus also showed evidence for association in the German sample (rs6010620, P = 2.87 × 10?5, OR = 1.25). Our study identifies new genetic susceptibility factors and suggests previously unidentified biological pathways in atopic dermatitis. [ABSTRACT FROM AUTHOR]

SRPK3 is a protein kinase belonging to serine/arginine protein kinases (SRPK) family, which phosphorylates serine/arginine repeat-containing proteins, and is controlled by a muscle-specific enhancer directly regulated by MEF2. In this study, a full-length cDNA of the porcine SRPK3 gene encoding a 566 amino acid protein was isolated. It contains 14 exons over approximately 4.3 kb. The deduced amino acid sequence of porcine SRPK3 contains a bipartite kinase domain, and shows high similarities to their corresponding human and cattle homologues. Tissue distribution analysis indicated that porcine SRPK3 mRNAs are highly expressed in heart and skeletal muscle especially in uterus and parorchis, but at low level in brain, stomach, small intestine, and ovary. Expression pattern of SRPK3 was similar in Large White and Chinese Meishan breeds. Both the two breeds had the highest expression levels at fetal 65 days ( P < 0.01), and decreased while the age increased until 60 days old, then increased at 120 days ( P < 0.01) and decreased at 180 days ( P < 0.05). However, at fetal 65 days, the mRNA abundance of SRPK3 in Large White was 12.5-fold higher than in Meishan pigs ( P < 0.01), whereas at 180 days, the abundance in Meishan was 3.4-fold higher than in Large White pigs ( P < 0.01). These results suggest that the SRPK3 gene might be an important gene of skeletal muscle development and also provides basic molecular information useful for further studies on its roles in porcine skeletal muscle. [ABSTRACT FROM AUTHOR]