Ochratoxin A (OTA) causes intestinal aging damage through the NLRP3 signaling pathway mediated by calcium overload and oxidative stress.

Ochratoxin A (OTA) is a widespread environmental toxin that poses a serious threat to human and animal health. OTA has been shown to cause cellular and tissue damage and is a global public health problem. However, the effects of OTA on gastrointestinal aging have not been reported. The aim of this study was to investigate the effects of OTA on intestinal aging in vitro and in vivo. In vitro experiments showed that OTA induced cellular inflammation through calcium overload and oxidative stress, significantly up-regulated the expression of P16, P21, and P53 proteins, markedly increased senescence-associated ß-galactosidase activity (SA-ß-gal) positive cells, and obviously decreased the expression of proliferating cell nuclear antigen (PCNA) proteins, which led to intestinal cell senescence. Meanwhile, we found that treatment with ß-carotene ameliorated OTA-induced intestinal cell senescence. Consistent with the results of the in vitro experiments, in vivo studies showed that the intestinal aging of mice fed OTA was significantly higher than that of the control group. In conclusion, OTA may induce intestinal aging through calcium overload, oxidative stress and inflammation. This study lays a foundation for further research on the toxicological effects of OTA.

Causality orientations and spontaneous mental contrasting.

Mental contrasting is a motivational behavior change strategy necessary for strong goal commitment. Meanwhile, general causality orientations are motivational patterns that represent individuals' motivation for behavior change and the reason for their goal commitment. The current study explored whether causality orientations predict spontaneous mental contrasting in Chinese university students. Study 1 investigated whether academic autonomy, control, and amotivated orientations correlate with spontaneous mental contrasting about an important academic goal. The findings of Study 1 reveal that autonomy orientation did not correlate with mental contrasting, whereas control and amotivated orientations were negatively correlated with mental contrasting. Study 2 investigated whether priming autonomy and control orientations, in addition to the neutral condition, would induce spontaneous mental contrasting about an academic goal related to the students' research topic. The results of Study 2 revealed that the autonomy condition orientation did not differ significantly from the controlled orientation condition. However, when compared to the neutral condition, the autonomy condition significantly predicted mental contrasting, whereas the controlled orientation condition did not show any significant difference. In Study 2, the autonomy-oriented participants generated more spontaneous mental contrast than the control orientation and neutral conditions. The findings show that controlled and amotivated orientations predicted negative mental contrasting. As a result, controlled and amotivated students must learn how to use mental contrasting to achieve high levels of goal commitment and achievement. Lastly, the study discussed its implications, limitations, and suggestions for future research.

A Novel Homozygous Deletion Including Exon 1 of FA2H Gene Causes Spastic Paraplegia-35: Genetic and Lipidomics Analysis of the Patients.

BACKGROUND: Fatty acid 2-hydroxylase (FA2H) is encoded by the FA2H gene, with mutations therein leading to the neurodegenerative condition, spastic paraplegia-35 (SPG35). We aim to elucidate the genetic underpinnings of a nonconsanguineous Chinese family diagnosed with SPG35 by examining the clinical manifestations, scrutinizing genetic variants, and establishing the role of FA2H mutation in lipid metabolism. METHODS: Using next-generation sequencing analysis to identify the pathogenic gene in this pedigree and family cosegregation verification. The use of lipidomics of patient pedigree peripheral blood mononuclear cells further substantiated alterations in lipid metabolism attributable to the FA2H exon 1 deletion. RESULTS: The proband exhibited gait disturbance from age 5 years; he developed further clinical manifestations such as scissor gait and dystonia. His younger sister also presented with a spastic gait from the same age. We identified a homozygous deletion in the region of FA2H exon 1, spanning from chr16:74807867 to chr16: 74810391 in the patients. Lipidomic analysis revealed significant differences in 102 metabolites compared with healthy controls, with 62 metabolites increased and 40 metabolites decreased. We specifically zeroed in on 19 different sphingolipid metabolites, which comprised ceramides, ganglioside, etc., with only three of these sphingolipids previously reported. CONCLUSIONS: This is the first study of lipid metabolism in the blood of patients with SPG35. The results broaden our understanding of the SPG35 gene spectrum, offering insights for future molecular mechanism research and laying groundwork for determining metabolic markers.

Relationship between quality of professional capacity building for kindergarten teachers and children's language development: the mediating role of kindergarten language education activities quality.

Strengthening the professional capacity building for kindergarten teachers is crucial for improving the quality of kindergarten education and promoting children's development. In order to explore the impact of the quality of professional capacity building for kindergarten teachers and kindergarten language education activities quality on children's language development, a study was conducted. A total of 1,584 children from 90 kindergartens in 5 provinces in China were randomly selected as research participants. Utilizing an independent sample t-test and correlation analysis (with SPSS 26.0 as the tool), the study analyzed the disparities in the professional capacity building for kindergarten teachers of different types, kindergarten language education activities quality, and the children's language developmental levels, as well as the interrelationships among these factors. A multilevel structural equation model (using MPLUS 8.3 as the tool) was employed to analyze the mediating role that the kindergarten language education activities quality plays between the quality of professional capacity building for kindergarten teachers and children's language development levels. The results indicate that children in public kindergartens demonstrate significantly higher language development levels than those in private kindergartens. A positive correlation exists between the quality of professional capacity building for kindergarten teachers, kindergarten language education activities quality and children's language development levels. Furthermore, kindergarten language education activities quality shows partial mediating effects on the relationship between them. These findings highlight the need to enhance the quality of education in private kindergartens, reduce the disparities in language development levels between private and public kindergartens, and reinforce the quality of professional capacity building for kindergarten teachers to provide effective support for children's language development. Ultimately, the study suggests concentrating on the organization and implementation of kindergarten language education activities as a means of evaluating the quality of professional capacity building for kindergarten teachers.

IP3R1 regulates calcium balance in porcine oocyte maturation and early embryonic development.

The dynamic balance of Ca2+ in oocytes promotes the recovery of the meiotic arrest phase, consequently promoting oocyte maturation. Hence, the analysis of the maintenance and role of calcium homeostasis in oocytes has important guiding significance for obtaining high-quality eggs and maintaining the development of preimplantation embryos. Inositol 1,4,5-trisphosphate receptors (IP3Rs) are calcium channel proteins that regulate the dynamic balance between the endoplasmic reticulum (ER) and mitochondrial Ca2+. Nevertheless, the expression and role of IP3R in normal pig oocytes have not been reported, and other studies have focused on the role of IP3R in damaged cells. The purpose of this study was to investigate the potential role of IP3R in regulating calcium homeostasis in oocyte maturation and early embryonic development. Our results showed that IP3R1 is stably expressed at different stages of porcine oocyte meiosis, IP3R1 gradually converges to the cortex, and cortical clusters are formed in MII stages. The loss of IP3R1 activity contributeds to the failure of porcine oocyte maturation and cumulus cell expansion, as well as the obstruction of polar body excretion. Further analysis showed that IP3R1 plays an important role in affecting calcium balance by regulating the IP3R1-GRP75-VDAC1 channel between mitochondria and the endoplasmic reticulum (ER) during porcine oocyte maturation. Inhibiting IP3R1 expression-induced ER dysfunction, contributeding to ER calcium concentration ([Ca2+]ER) release outwards into mitochondria and causing mitochondrial free calcium concentration ([Ca2+]m) overload and mitochondrial oxidative stress, which was confirmed by the increase in the level of reactive oxygen species (ROS) and apoptosis. Thereby, IP3R1 plays an important role in affecting calcium balance by regulating the IP3R1-GRP75 -VDAC1 channel between mitochondria and the ER during porcine oocyte maturation, inhibiting IP3R1 expression-induced calcium overload and mitochondrial oxidative stress, and increasing ROS levels and apoptosis.

Establishment of a novel human induced pluripotent stem cell line (SIPDi001-A) with compound heterozygous mutations in the UBR7 gene from a Li-Campeau syndrome patient.

Li-Campeau syndrome (LICAS) is a syndromic neurodevelopmental disorder characterized by autosomal recessive inheritance and global developmental delay. In this study, we reported the generation of a novel induced pluripotent stem cell (iPSC) line derived from peripheral blood mononuclear cells (PBMCs) obtained from a 7-year-old male patient with Li-Campeau syndrome. The patient carries compound heterozygous variants in the UBR7 gene (c.35_54dup, p.S19Rfs*42; c.863 T > C, p.L288P). The iPSC line showed typical cell morphology, robust expression of pluripotent and self-renewal markers, normal karyotype, and trilineage differentiation potential. This iPSC cell line could be valuable for investigating the underlying pathological mechanisms of neurodevelopmental disorders caused by UBR7 mutations.

Effects of ß-carotene supplementation in the diet of laying breeder hens on the growth performance and liver development of offspring chicks.

This experiment was conducted to evaluate the growth performance, growth regulating factors, and liver morphology of chicks hatched from egg-laying breeding hens dietary supplemented with additives (ß-carotene). Hy-line breeding hens were allocated into three groups with three replicates/group. The dietary treatments were as follows: basal diet as a control (Con), basal diet supplemented with 120 (ßc-L) or 240 (ßc-H) mg/kg of ß-carotene diet. After 6 weeks, the eggs were collected and incubated. The hatched chicks were fed the same diet. The results showed that chicks in the ßc-L group increased in body weight at 21 days (p < 0.01). At 42 days, chicks in the ßc-H group showed a significant increase in tibia length (p < 0.05). The liver index increased in the ßc-L and ßc-H groups at 7 days (p < 0.05). Serum HGF (7, 14, 21, and 42 days) and leptin (14 days) were significantly increased in the group supplemented with ßc. Hepatic GHR (14 days), IGF-1R (14 days), and LEPR (21 days) mRNA expression were significantly increased. In addition, there was an increase in PCNA-positive cells in the liver of chicks in the ßc group. In conclusion, the addition of ß-carotene to the diet of laying breeder hens was more advantageous in terms of growth performance and liver development of the offspring.

Novel maternal duplication of 6p22.3-p25.3 with subtelomeric 6p25.3 deletion: new clinical findings and genotype-phenotype correlations.

BACKGROUND: Copy-number variants (CNVs) drive many neurodevelopmental-related disorders. Although many neurodevelopmental-related CNVs can give rise to widespread phenotypes, it is necessary to identify the major genes contributing to phenotypic presentation. Copy-number variations in chromosome 6, such as independent 6p deletion and 6p duplication, have been reported in several live-born infants and present widespread abnormalities such as intellectual disability, growth deficiency, developmental delay, and multiple dysmorphic facial features. However, a contiguous deletion and duplication in chromosome 6p regions have been reported in only a few cases. CASE PRESENTATION: In this study, we reported the first duplication of chromosome band 6p25.3-p22.3 with deletion of 6p25.3 in a pedigree. This is the first case reported involving CNVs in these chromosomal regions. In this pedigree, we reported a 1-year-old boy with maternal 6p25-pter duplication characterized by chromosome karyotype. Further analysis using CNV-seq revealed a 20.88-Mb duplication at 6p25.3-p22.3 associated with a contiguous 0.66-Mb 6p25.3 deletion. Whole exome sequencing confirmed the deletion/duplication and identified no pathogenic or likely pathogenic variants related with the patient´s phenotype. The proband presented abnormal growth, developmental delay, skeletal dysplasia, hearing loss, and dysmorphic facial features. Additionally, he presented recurrent infection after birth. CNV-seq using the proband´s parental samples showed that the deletion/duplication was inherited from the proband´s mother, who exhibited a similar phenotype to the proband. When compared with other cases, this proband and his mother presented a new clinical finding: forearm bone dysplasia. The major candidate genes contributing to recurrent infection, eye development, hearing loss features, neurodevelopmental development, and congenital bone dysplasia were further discussed. CONCLUSIONS: Our results showed a new clinical finding of a contiguous deletion and duplication in chromosome 6p regions and suggested candidate genes associated with phenotypic features, such as FOXC1, SERPINB6, NRN1, TUBB2A, IRF4, and RIPK1.

[Cloning and expression analysis of U6 promoters in Panax quinquefolius].

The U6 promoter is an important element driving sgRNA transcription in the CRISPR/Cas9 system. Seven PqU6 promo-ter sequences were cloned from the gDNA of Panax quinquefolium, and the transcriptional activation ability of the seven promoters was studied. In this study, seven PqU6 promoter sequences with a length of about 1 300 bp were cloned from the adventitious roots of P. quinquefolium cultivated for 5 weeks. Bioinformatics tools were used to analyze the sequence characteristics of PqU6 promoters, and the fusion expression vectors of GUS gene driven by PqU6-P were constructed. Tobacco leaves were transformed by Agrobacterium tumefaciens-mediated method for activity detection. The seven PqU6 promoters were truncated from the 5'-end to reach 283, 287, 279, 289, 295, 289, and 283 bp, respectively. The vectors for detection of promoter activity were constructed with GUS as a reported gene and used to transform P. quinquefolium callus and tobacco leaves. The results showed that seven PqU6 promoter sequences(PqU6-1P to PqU6-7P) were cloned from the gDNA of P. quinquefolium, with the length ranged from 1 246 bp to 1 308 bp. Sequence comparison results showed that the seven PqU6 promoter sequences and the AtU6-P promoter all had USE and TATA boxes, which are essential elements affecting the transcriptional activity of the U6 promoter. The results of GUS staining and enzyme activity test showed that all the seven PqU6 promoters had transcriptional activity. The PqU6-7P with a length of 1 269 bp had the highest transcriptional activity, 1.31 times that of the positive control P-35S. When the seven PqU6 promoters were truncated from the 5'-end(PqU6-1PA to PqU6-7PA), their transcriptional activities were different in tobacco leaves and P. quinquefolium callus. The transcriptional activity of PqU6-7PA promoter(283 bp) was 1.59 times that of AtU6-P promoter(292 bp) when the recipient material was P. quinquefolium callus. The findings provide more ideal endogenous U6 promoters for CRISPR/Cas9 technology in ginseng and other medicinal plants.

Gonadal Transcriptome Analysis and Sequence Characterization of Sex-Related Genes in Cranoglanis bouderius.

In China, the Cranoglanis bouderius is classified as a national class II-protected animal. The development of C. bouderius populations has been affected by a variety of factors over the past few decades, with severe declines occurring. Considering the likelihood of continued population declines of the C. bouderius in the future, it is critical to investigate the currently unknown characteristics of gonadal differentiation and sex-related genes for C. bouderius conservation. In this study, the Illumina sequencing platform was used to sequence the gonadal transcriptome of the C. bouderius to identify the pathways and genes related to gonadal development and analyze the expression differences in the gonads. A total of 12,002 DEGs were identified, with 7220 being significantly expressed in the ovary and 4782 being significantly expressed in the testis. According to the functional enrichment results, the cell cycle, RNA transport, apoptosis, Wnt signaling pathway, p53 signaling pathway, and prolactin signaling pathway play important roles in sex development in the C. bouderius. Furthermore, the sequence characterization and evolutionary analysis revealed that AMH, DAX1, NANOS1, and AR of the C. bouderius are highly conserved. Specifically, the qRT-PCR results from various tissues showed significant differences in AMH, DAX1, NANOS1, and AR expression levels in the gonads of both sexes of C. bouderius. These analyses indicated that AMH, DAX1, NANOS1, and AR may play important roles in the differentiation and development of C. bouderius gonads. To our best knowledge, this study is the first to analyze the C. bouderius gonadal transcriptome and identify the structures of sex-related genes, laying the foundation for future research.

Energy consumption and intestinal microbiome disorders of yellow catfish (Pelteobagrus fulvidraco) under cold stress.

The yellow catfish (P. fulvidraco), as one of the economically-relevant freshwater fish found in China, cannot tolerate cold stress. Understanding the physiological and biochemical mechanisms under cold stress may provide insights for improving yellow catfish management in the cold. Therefore, we investigated the metabolic and intestinal microbiota changes in cold stress in response to induced cold stress. We found that cold stress in yellow catfish lead to a significant increase in the consumption of glucose and triglycerides, as well as increased use of cholesterol as an alternate energy source. Moreover, cold stress also activated several significant biological processes in the fish such as thermogenesis, oxidative phosphorylation, the spliceosome machinery, RNA transport, protein processing that occurs in the ER, and purine and pyrimidine metabolism pathways involved in energy production. On the other hand, many other mechanisms like insulin resistance, starch and sucrose metabolism, and the glyoxylate and dicarboxylate metabolic pathways that also served as energy production pathways were weakened. Furthermore, organic acids and their derivatives as well as the lipids and lipid-like molecules were mainly altered in cold stress; prenol lipids, steroids, and their derivatives were significantly upregulated, while fatty acyls and glycerophospholipids were significantly downregulated. Transcriptomic and metabolomic integrated analysis data revealed that carbohydrate metabolism, lipid metabolism, amino acid metabolism, and nucleotide metabolism were involved in cold stress resistance. In addition, the intestinal microbiota abundance was also reduce and the pathogenic bacteria of plesiomonas was rapidly appreciation, which suggesting that cold stress also impaired intestinal health. This research study could offer insights into winter management or the development of feed to promote cold resistance in yellow catfish.

Glycine ameliorates MBP-induced meiotic abnormalities and apoptosis by regulating mitochondrial-endoplasmic reticulum interactions in porcine oocytes.

Monobutyl phthalate (MBP) is the main metabolite of dibutyl phthalate (DBP) in vivo. MBP has a stable structure, can continuously accumulate in living organisms, and has the potentially to harm animal and human reproductive function. In the ovarian follicle microenvironment, MBP may lead to defects in follicular development and steroid production, abnormal meiotic maturation, impaired ovarian function and other reproductive deficits. In this study, SMART-seq was used to investigate the effects of MBP exposure on the in vitro maturation (IVM) and development of porcine oocytes. The results showed that differentially expressed genes after MBP exposure were enriched in the biological processes cytoskeleton, cell apoptosis, endoplasmic reticulum (ER) and mitochondria. Glycine (Gly) improved the developmental potential of porcine oocytes by regulating mitochondrial and ER function. The effect of Gly in protecting oocytes against MBP-induced damage was studied. The results showed that the addition of Gly significantly decreased the rate of MBP-induced spindle abnormalities, decreased the frequency of MBP-induced mitochondria-associated ER membrane (MAM) interactions, and downregulated the protein and gene expression of the linkage molecules Mitofusin 1 (MFN1) and Mitofusin 2 (MFN2) in the MAM. Additionally, treatment with Gly restored the distribution of the 1,4,5-triphosphate receptor 1 (IP3R1) and voltage-dependent anion channel 1 (VDAC1), further decreasing the intracellular free calcium concentration ([Ca2+]i) levels and mitochondrial Ca2+ ([Ca2+]m) , increasing the ER Ca2+ ([Ca2+]ER) levels, and thus significantly increasing the ER levels and mitochondrial membrane potential (ΔΨ m). Gly also decreased the levels of reactive oxygen species (ROS) and increased the levels of Glutathione (GSH), oocyte apoptosis-related indicators (Caspase-3 activity and Annexin V) and oocyte apoptosis-related genes (BAX, Caspase 3 and AIFM1). Our results suggest that Gly can ameliorate microtubule cytoskeleton abnormalities and improve oocyte maturation by reducing the defective mitochondrial-ER interactions caused by MBP exposure in vitro.

The biological activity and signaling profile of EGF/EGFR were affected under heat stress conditions in IEC6 cells.

Epidermal growth factor (EGF) is an effective cytoprotective peptide. It is the main nutritional factor involved in the development of the intestinal tract. It has many important biological effects on the intestinal mucosa. After binding to epidermal growth factor receptor (EGFR), it initiates a signal transduction cascade to jointly promote the migration, proliferation, and differentiation of various cell types. Heat stress severely affects the intestinal health of livestock and is becoming increasingly prevalent due to the yearly increase in ambient temperature and intestinal diseases. However, the effect of heat stress on the activity and signaling of EGF/EGFR in intestinal cells is still unclear. Therefore, rat intestinal crypt epithelial cell line (IEC6) was used as a model to explore this issue, and the results showed that EGF/EGFR is internalized into IEC6 cells in a time-dependent manner under physiological conditions. However, the activity of EGF/EGFR was altered under heat stress. Furthermore, we explored the effect of heat stress on EGF/EGFR-activated signaling transduction in IEC6 cells, and the results showed that levels of factors involved in EGFR-mediated intracellular signaling (such as EGFR, signal transducers and activators of transcription 3/protein kinase B, and extracellular regulatory kinase 1/2) were downregulated under heat stress. In summary, this study shows that heat stress could damage the biological activity and intracellular signaling of EGF/EGFR. These findings have scientific importance in the field of animal husbandry; and lay the foundation for the further study of the biological activities of EGF/EGFR in the intestine.

Extracellular Vesicle-Derived miR-105-5p Promotes Malignant Phenotypes of Esophageal Squamous Cell Carcinoma by Targeting SPARCL1 via FAK/AKT Signaling Pathway.

Objective: Esophageal squamous cell carcinoma (ESCC) presents high morbidity and mortality. It was demonstrated that blood-derived vesicles can facilitate ESCC development and transmit regulating signals. However, the molecular mechanism of vesicle miRNA secreted by tumor cells affecting ESCC progression has not been explored. Methods: The mRNA-related signaling pathways and differentially expressed genes were screened out in TCGA dataset. The levels of miRNA-105-5p and SPARCL1 were determined by qRT-PCR. Protein level determination was processed using Western blot. The interaction between the two genes was verified with the dual-luciferase method. A transmission electron microscope was utilized to further identify extracellular vesicles (EVs), and co-culture assay was performed to validate the intake of EVs. In vitro experiments were conducted to evaluate cell function changes in ESCC. A mice tumor formation experiment was carried out to observe tumor growth in vivo. Results: MiRNA-105-5p expression was increased in ESCC, while SPARCL1 was less expressed. MiRNA-105-5p facilitated cell behaviors in ESCC through targeting SPARCL1 and regulating the focal adhesion kinase (FAK)/Akt signaling pathway. Blood-derived external vesicles containing miRNA-105-5p and EVs could be internalized by ESCC cells. Then, miRNA-105-5p could be transferred to ESCC cells to foster tumorigenesis as well as cell behaviors. Conclusion: EV-carried miRNA-105-5p entered ESCC cells and promoted tumor-relevant functions by mediating SPARCL1 and the FAK/Akt signaling pathway, which indicated that the treatment of ESCC via serum EVs might be a novel therapy and that miRNA-105-5p can be a molecular target for ESCC therapy.

Selection and validation of reference genes for quantitative real-time PCR in Cymbidium sinense.

Selection of reference genes (RGs) is important for the accurate analysis of real-time quantitative PCR (RT-qPCR) results. This study screened RGs of Cymbidium sinense for more accurate quantification of target genes. The two most stable RGs for all tissues were ACT and EF1α, those for vegetative organs were UBQ3 and ACT, while those for reproductive organs as well as organs in the full flowering stage were EF1α and ACT. The AGAMOUS (CsAG1) expression level was verified using EF1α, ACT, GAPDH, UBQ2 and UBQ3 as RG. The expression profile of CsAG1 was consistent when normalized with EF1α, ACT and UBQ3. The results have practical value for the expression of key genes during the development of C. sinense.

Effects of dietary sodium butyrate on growth, digestive enzymes, body composition and nutrient retention-related gene expression of juvenile yellow catfish (Pelteobagrus fulvidraco).

An 8-week feeding trial was conducted to evaluate the effects of sodium butyrate (SB) on growth, digestive enzymes, body composition and nutrient retention-related gene expression of juvenile yellow catfish (Pelteobagrus fulvidraco). Five isonitrogenous and isolipidic diets (420 g/kg protein and 90 g/kg lipid) were formulated to contain 0 (control), 250, 500, 1,000 or 2,000 mg/kg SB. Triplicate groups of 40 fish (BW = 1.26 ± 0.01 g) per tank (300-L cylindrical fiberglass tanks) for each diet were fed to apparent satiation twice daily. Stomach, hepatopancreas and intestine samples were obtained for digestive enzymes activities analyses. A real-time quantitative PCR analysis was performed to determine the relative expression of target of rapamycin (TOR) and lipoprotein lipase (LPL) in the hepatopancreas and intestine. Fish fed the diets supplemented with SB at 500 and 1,000 mg/kg showed significantly higher specific growth rate and significantly lower feed conversion ratio compared to the control (P < 0.05). Dietary SB inclusion did not alter activities of intestinal amylase, creatine kinase and sodium-potassium adenosine triphosphatase (Na+/K+-ATPase), but increased activities of hepatic trypsin, stomachic lipase, intestinal lipase, alkaline phosphatase and γ-glutamyl transpeptidase for fish fed 1,000 mg/kg SB compared to the control (P < 0.05). Intestine length index, intestine somatic index, fold height and muscular thickness of distal intestine were significantly higher in 1,000 mg/kg SB groups compared to the control (P < 0.05). Significantly higher levels of whole-body crude protein, ash, calcium, phosphorus, nutrition retention and relative mRNA of intestinal TOR were observed in 1,000 mg/kg SB group (P < 0.05). Whole-body lipid content and hepatopancreas LPL mRNA expression in 2,000 mg/kg SB group were significantly higher than the control (P < 0.05). Relative mRNA levels of intestinal LPL and hepatopancreas TOR were significantly higher in the 500 mg/kg SB group compared to those in other groups (P < 0.05). The increased growth performance, digestive enzymes and nutrient retention in fish fed the diets supplemented with SB at 500 and 1,000 mg/kg suggests that SB can be a desirable growth promoter as an antibiotic alternative in diets.

Establishment of iPSC line from a Chinese infant (XACHi012-A) with Jervell and Lange-Nielsen syndrome carrying combined KCNQ1 frameshift c.431delC(p.I145Sfs*92) and nonsense c.1175G > A (p.W392X) variants and two iPSC lines from the parents (XACHi013-A, XACHi014-A).

Induced pluripotent stem cell lines (iPSCs) were generated from peripheral blood mononuclear cells (PBMCs) isolated from the peripheral blood of a two month-old boy and the parents. Jervell and Lange-Nielsen syndrome (JLNS) was diagnosed in the boy carrying combined KCNQ1 frameshift c.431delC (p.I145Sfs*92) and nonsense c.1175G > A(p.W392X) variants inherited from his mother and father respectively. PBMCs were reprogrammed using non-integrative Sendai viral vectors containing reprogramming factors OCT4, SOX2, KLF4 and C-MYC. IPSCs were shown to express pluripotent markers, have trilineage differentiation potential, carrying identified KCNQ1 variants with corresponding PBMC, and have a normal karyotype. Thus we established three iPSC lines as useful tools for studying the pathophysiological mechanism of JLNS and drug testing.

A Meta-Analysis of the Effects of Mental Contrasting With Implementation Intentions on Goal Attainment.

Mental contrasting with implementation intentions (MCII) is a self-regulation strategy that enhances goal attainment. This meta-analysis evaluated the efficacy of MCII for goal attainment and explored potential moderators. A total of 21 empirical studies with 24 independent effect sizes (15,907 participants) were included in the analysis. Results showed that MCII to be effective for goal attainment with a small to medium effect size (g = 0.336). The effect was mainly moderated by intervention style. Specifically, studies with interventions based on interactions between participants and experimenters (g = 0.465) had stronger effects than studies with interventions based on interactions between participants and documents (g = 0.277). The results revealed that MCII is a brief and effective strategy for goal attainment with a small to moderate effect; however, because of some publication bias, the actual effect sizes may be smaller. Due to small number of studies in this meta-analysis, additional studies are needed to determine the role of moderator variables.

Comparative genome analysis of multidrug-resistant and susceptible Glaesserella parasuis strains isolated from diseased pigs in China.

Glaesserella parasuis (G. parasuis) is a respiratory pathogen of swine and the etiological agent of Glässer's disease. Although the emergence of multidrug-resistant (MDR) G. parasuis is a critical problem in the swine industry, there are few publications on the genetic basis of antimicrobial resistance of G. parasuis. In this study, comparative genome analyses were used to identify genomic differences between two phenotypically distinct isolates, an MDR isolate (HPS-1) and a susceptible isolate (HPS-2), from diseased swines in China. These isolates were both serovar 4, which is predominant in cases of Glässer's disease and is the most prevalent serovar in China. Based on clusters of orthologous group (COG) annotations, genes assigned to the extracellular structure category were only detected in HPS-1 and genes related to cell motility were more abundant in HPS-1 than in HPS-2. A comparative genomic analysis showed that these two isolates are closely related, although there was a large-scale genomic rearrangement. Eighteen percent of the genome consisted of strain-specific accessory genes of HPS-1. Notably, only the two genes aac(6')-Ie-aph(2'')-Ia and blaROB-1 on a plasmid were specific to HPS-1. We also detected 30,599 single nucleotide polymorphisms (SNPs), including nonsynonymous SNPs in the aminoglycoside resistance gene aph(3'')-Ib, the fusidic acid resistance gene fusA, and the two rifampicin resistance genes rpoC and rpoB in HPS-1. These findings improve our understanding of the differences between MDR and susceptible isolates and will aid the development of treatment strategies to decrease the prevalence and disease burden caused by G. parasuis.

[Isovaleric acidemia due to compound heterozygous variants of IVD gene in a case].

OBJECTIVE: To analyze the clinical features, biochemical characteristics and molecular pathogenesis of a girl with isovaleric acidemia. METHODS: Clinical features, blood spot amino acid profiles and urinary organic acid profiles of the patient were analyzed. Targeted capture, next generation sequencing and Sanger sequencing were carried out to detect potential variant of the IVD gene. RESULTS: The patient presented with poor weight gain, poor feeding, lethargy, and a "sweaty feet" odor 10 days after birth. Biochemical test suggested hyperammonemia. Blood spot amino acid profiles displayed a dramatic increase in isovalerylcarnitine (C5: 3. 044, reference range 0.04 - 0.4 µmol/L). Organic acid analysis of her urine sample revealed a high level of isovaleric glycine (669. 53, reference range 0 - 0.5). The child was ultimately diagnosed with isovaleric acidemia, and was found to harbor a paternally derived heterozygous variant c.149G>A (p.R50H) and a maternally derived heterozygous variant c.1123G>A (p.G375S) of the IVD gene. Her elder brother was a heterozygous carrier of c.1123G>A (p.G375S) variant. The c.149G>A (p.R50H) was a known pathogenic variant, while the c.1123G>A (p.G375S) variant was previously unreported. CONCLUSION: The pathogenesis of the patient was delineated from the perspective of genetics, which has provided a basis for clinical diagnosis, treatment as well as genetic counseling.