Genome wide detection of CNV and their association with body size in Danzhou chickens.

Copy number variation (CNV) is a crucial component of genetic diversity in the genome, serving as the foundation for the genetic architecture and phenotypic variability of complex traits. In this study, we examined CNVs in the Danzhou (DZ) chicken, an indigenous breed exclusive to Hainan Province, China. By employing whole-genome resequencing data from 200 DZ chickens, we conducted a comprehensive genome-wide analysis of CNVs using CNVpytor and performed CNV-based genome-wide association studies (GWAS) on 6 body size traits, including body slope length (BSL), keel length (KeL), tibial length (TiL), tibial circumference (TiC), chest width (ChW), and chest depth (ChD) utilizing linear mixed model methods considering a genomic relationship matrix. We identified a total of 144,265 autosomal CNVs among the 200 individuals, comprising 67,818 deletions and 76,447 duplications. After merging these variants together, we obtained 4,824 distinct copy number variant regions, which accounted for approximately 20% of the chicken autosomal genome. Furthermore, we discovered several significantly associated CNV segments with body size traits located proximal to genes such as IHH, WNT6, WNT10A, LPR4, FZD2, WNT7B, and GNAS that have been extensively implicated in skeletal development and growth processes. These findings enhance our understanding of CNVs in chickens and their potential impact on body size traits by revealing candidate genes involved in the regulation of these traits. This establishes a solid framework for future studies and may prove particularly beneficial for exploring genetic structural variation in chickens.

Effect of Sex on Intestinal Microbial Metabolites of Hainan Special Wild Boars.

The intestinal microbiota and its metabolites are essential for the health and growth development of animals. Current research indicates that sex has a certain impact on the structure and function of the intestinal microbiota, but there are few reports on sex differences in intestinal microbiota metabolites, including those of castrated male animals. This study aimed to explore the impact of sex on the intestinal microbial metabolites of Hainan special wild boars (10 entire male pigs, 10 female pigs, and 10 castrated male pigs, denoted EM, FE, and CM, respectively) by employing non-targeted metabolomics and gas chromatography. A total of 1086 metabolites were detected, with the greatest number of differential metabolites observed between EM and FE (54 differential metabolites, including 18 upregulated and 36 downregulated metabolites), the fewest between CM and FE (7 differential metabolites, including 1 upregulated and 6 downregulated metabolites), and an intermediate number between CM and EM (47 differential metabolites, including 35 upregulated and 12 downregulated metabolites). Differential metabolites were involved in more pathways between EM and FE and between CM and EM, including amino acid metabolism and digestive system pathways, whereas differential metabolites were involved in the fewest pathways between CM and FE. Correlation analysis showed Ruminococcaceae UCG-009, uncultured_bacterium_o_SAR324_cladeMarine_group_B, and Candidatus Saccharimonas contributed to the production of metabolites such as trehalose, docosatrienoic acid, D(-)-beta-hydroxy butyric acid, and acetyl-DL-leucine. The levels of acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, and isovaleric acid were significantly higher in EM than in FE, with CM falling between the two. Streptococcus, Lachnospiraceae_NK4A136_group and Rikenellaceae_RC9_gut_group showed a significant positive correlation with the production of short-chain fatty acids (SCFAs), while [Eubacterium]_coprostanoligenes_group, uncultured_bacterium_f_p-251-o5 and Ruminococcaceae_UCG-005 showed a significant negative correlation with the generation of SCFAs. This study provides foundational data and significant insights into precision feeding strategies for Hainan special wild boars of different sexes, as well as the study of sex differences in intestinal microbial metabolites in animals.

Selection Signal Analysis Reveals Hainan Yellow Cattle Are Being Selectively Bred for Heat Tolerance.

Hainan yellow cattle are indigenous Zebu cattle from southern China known for their tolerance of heat and strong resistance to disease. Generations of adaptation to the tropical environment of southern China and decades of artificial breeding have left identifiable selection signals in their genomic makeup. However, information on the selection signatures of Hainan yellow cattle is scarce. Herein, we compared the genomes of Hainan yellow cattle with those of Zebu, Qinchuan, Nanyang, and Yanbian cattle breeds by the composite likelihood ratio method (CLR), Tajima's D method, and identifying runs of homozygosity (ROHs), each of which may provide evidence of the genes responsible for heat tolerance in Hainan yellow cattle. The results showed that 5210, 1972, and 1290 single nucleotide polymorphisms (SNPs) were screened by the CLR method, Tajima's D method, and ROH method, respectively. A total of 453, 450, and 325 genes, respectively, were identified near these SNPs. These genes were significantly enriched in 65 Gene Ontology (GO) functional terms and 11 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways (corrected p < 0.05). Five genes-Adenosylhomocysteinase-like 2, DnaJ heat shock protein family (Hsp40) member C3, heat shock protein family A (Hsp70) member 1A, CD53 molecule, and zinc finger and BTB domain containing 12-were recognized as candidate genes associated with heat tolerance. After further functional verification of these genes, the research results may benefit the understanding of the genetic mechanism of the heat tolerance in Hainan yellow cattle, which lay the foundation for subsequent studies on heat stress in this breed.

Knowledge, attitudes and practices towards advance directives among clinical nurses: Multicenter cross-sectional survey.

AIMS AND OBJECTIVES: This study aimed to describe the knowledge, attitudes and practices (KAP) of nurses in implementing advance directives (ADs) for older patients and analyze the influencing factors before the establishment of the first advance directives act in China. DESIGN: Multicenter cross-sectional survey. The standards for reporting the STROBE checklist are used. METHODS: This cross-sectional study developed a self-designed structured questionnaire to assess nurses' knowledge, attitudes and practices about ADs. Nurses were recruited by stratified random sampling through the Nursing Departments of 12 hospitals in southwest China and were asked to fill out the questionnaire face to face about knowledge, attitudes and practices. Data were analyzed following descriptive statistics, rank-sum test and multiple linear regression. RESULTS: This study included 950 nurses. The study found that nurses were extremely supportive of ADs. Unmarried nurses had better knowledge of ADs than married ones. Nevertheless, there was a discrepancy between the participants' knowledge, attitude and practice. The participants' practice was lower (4.3%) compared with their attitude (81.9%) and knowledge (42.2%). Knowledge on, attitudes towards and standardized procedures for ADs in the workplace affected nursing practice. CONCLUSIONS: The study recommends that courses on ADs and appropriate support from medical institutions should be provided to nurses to increase their knowledge and confidence in implementing ADs. Healthcare professionals should be sufficiently equipped to implement ADs and handle their execution appropriately to provide adequate end-of-life care corresponding to patients' wishes. RELEVANCE TO CLINICAL PRACTICE: The study results inform rich insights as it discusses the numerous interrelating factors influencing these three fundamental aspects that affect the success of any AD policy by surveying the knowledge, attitudes and practices of clinical nurses. Furthermore, our results hint at distinct areas of improvement in the nursing practice to facilitate the wider implementation and acceptance of ADs in China. PATIENT OR PUBLIC CONTRIBUTION: This study involved no patient.

Association of nitric oxide synthase gene polymorphism with asthma: A systematic review and meta-analysis.

INTRODUCTION: This study examines the associations between asthma and nitric oxide (NO) synthase (NOS) gene polymorphisms. METHODS: After a systematic literature search in electronic databases, studies were selected based on eligibility criteria. Data were extracted from research articles and were synthesized and tabulated. Where a particular polymorphism data were reported by multiple studies, meta-analyses of odds ratios were performed, or odds ratios reported by individual studies were pooled. RESULTS: Twenty studies (4450 asthma patients and 5306 non-asthmatic individuals) were identified. Many studies did not find any association between CCTTT repeat polymorphism in NOS2 gene and asthma. However, a study reported that pretreatment mean exhaled NO levels in asthmatics were found to be significantly higher in genotypes with higher number of CCTTT repeats. Also, alleles with <11 CCTTT repeats were associated with poor asthma treatment outcomes. A single nucleotide polymorphism, G894T, in NOS3 gene was not found to be significantly associated with asthma by at least four studies. However, a T allele at this locus was associated with lower NO levels. Also, G894T frequency was significantly higher in asthmatic children who responded to inhaled corticosteroids along with long-lasting beta2-agonists. A T allele of NOS3 786C/T polymorphism increased the probability of bronchial asthma with comorbid essential hypertension in asthma patients. Asthma severity also differed for different Ser608Leu exon 16 variants of NOS2 gene. CONCLUSIONS: Several polymorph NOS gene variants are identified, some of which appear to have influence on asthma prevalence or outcomes. However, data are varying depending on the nature of variant, ethnicity, study design, and disease parameters.

Dynamic Changes in the Gut Microbiota and Metabolites during the Growth of Hainan Wenchang Chickens.

Gut microbiota and their metabolites play important roles in animal growth by influencing the host's intake, storage, absorption, and utilization of nutrients. In addition to environmental factors, mainly diet, chicken breed and growth stage also affect changes in the gut microbiota. However, little research has been conducted on the development of gut microbiota and its metabolites in local chickens. In this study, the cecal microbiota and metabolites in different developmental stages of Hainan Wenchang chickens (a native breed of Bantam) were investigated using 16S rRNA sequencing and untargeted metabolomics. With aging, the structure of gut microbiota tended to be more stable. The relative proportions of dominant bacteria phyla Firmicutes, Bacteroidetes, and Proteobacteria showed stage changes with the development. With aging, gut microbiota and their metabolites may have structural and functional changes in response to nutrient metabolism and immune requirements in different physiological states. Several microbial and metabolic biomarkers with statistical differences were detected in different development stages. The bacteria that form networks with their significant related metabolites were different in various growth stages, including uncultured_bacterium_f_Ruminococcaceae, Ruminococcaceae_UCG-014, Faecalibacterium, uncultured_bacterium_o_Bacteroidales, and uncultured_bacterium_f_Lachnospiraceae. Partially differential bacteria were significantly correlated with short-chain fatty acids such as butyric acid. These findings may provide new insights into the physiological and molecular mechanisms of developmental changes of local chicken breeds, as well as resources for microbial and metabolic biomarker identification to improve growth efficiency.

Characterization of a novel recombinant halophilic ß-glucosidase of Trichoderma harzianum derived from Hainan mangrove.

BACKGROUND: ß-glucosidase is an important biomass-degrading enzyme and plays a vital role in generating renewable biofuels through enzymatic saccharification. In this study, we analyzed the transcriptome of Trichoderma harzianum HTASA derived from Hainan mangrove and identified a new gene encoding ß-glucosidase Bgl3HB. And the biochemically characterization of ß-glucosidase activity was performed. RESULTS: Bgl3HB showed substantial catalytic activity in the pH range of 3.0-5.0 and at temperatures of 40 ℃-60 ℃. The enzyme was found quite stable at 50 ℃ with a loss of only 33.4% relative activity after 240 min of heat exposure. In addition, all tested metal ions were found to promote the enzyme activity. The ß-glucosidase activity of Bgl3HB was enhanced by 2.12-fold of its original activity in the presence of 5 M NaCl. Surprisingly, Bgl3HB also showed a remarkable ability to hydrolyze laminarin compared to other measured substrates. Enzyme efficiency was examined in the sugarcane bagasse saccharification processes, in which Bgl3HB with 5 M NaCl worked better supplementing Celluclast 1.5L than the commercial Novozyme 188 ascertained it as an admirably suited biocatalyst for the utilization of agricultural waste. In this work, this is the first report of a halophilic ß-glucosidase from Trichoderma harzianum, and represents the ß-glucosidase with the highest known NaCl activation concentration. And adding 5 M NaCl could enhance saccharification performance even better than commercial cellulase. CONCLUSIONS: These results show that Bgl3HB has great promise as a highly stable and highly efficient cellulase with important future applications in the industrial production of biofuels.

Protective effect of orange essential oil on the formation of non-alcoholic fatty liver disease caused by high-fat diet.

The purpose of this study was to investigate the protective effect of sniffing orange essential oil (OEO) on the formation of non-alcoholic fatty liver disease (NAFLD) caused by a high-fat diet. The results confirmed that sniffing OEO could reduce obesity caused by a high-fat diet (HFD) by reducing the levels of triglycerides (TGs), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). In addition, the observation of liver tissue sections showed that sniffing OEO could reduce lipid accumulation in liver cells. Further analysis by western blot analysis showed that OEO treatment made the expression levels of acetyl-CoA carboxylase (ACC) and Cytochrome P450 2E1 (CYP2E1) down-regulated and the expression levels of peroxisome proliferator-activated receptor-α (PPAR-α) and carnitine palmitoyltransferase-1 (CPT-1) up-regulated. These results indicate that the treatment of sniffing OEO could enhance the antioxidant capacity of mice and reduce liver damage caused by a high-fat diet. Furthermore, sniffing OEO could inhibit lipid synthesis and oxidative stress stimulated by a high-fat diet. Overall, OEO treatment had a certain protective effect on NAFLD-related diseases caused by a high-fat diet. Therefore, aromatherapy may be introduced as a treatment of long-term chronic diseases.

Screening of Reference Genes for RT-qPCR in Chicken Adipose Tissue and Adipocytes.

Reverse transcription quantitative real-time PCR is the most commonly used method to detect gene expression levels. In experiments, it is often necessary to correct and standardize the expression level of target genes with reference genes. Therefore, it is very important to select stable reference genes to obtain accurate quantitative results. Although application examples of reference genes in mammals have been reported, no studies have investigated the use of reference genes in studying the growth and development of adipose tissue and the proliferation and differentiation of preadipocytes in chickens. In this study, GeNorm, a reference gene stability statistical algorithm, was used to analyze the expression stability of 14 candidate reference genes in the abdominal adipose tissue of broilers at 1, 4, and 7 weeks of age, the proliferation and differentiation of primary preadipocytes, as well as directly isolated preadipocytes and mature adipocytes. The results showed that the expression of the TATA box binding protein (TBP) and hydroxymethylbilane synthase (HMBS) genes was most stable during the growth and development of abdominal adipose tissue of broilers, the expression of the peptidylprolyl isomerase A (PPIA) and HMBS genes was most stable during the proliferation of primary preadipocytes, the expression of the TBP and RPL13 genes was most stable during the differentiation of primary preadipocytes, and the expression of the TBP and HMBS genes was most stable in directly isolated preadipocytes and mature adipocytes. These results provide reference bases for accurately detecting the mRNA expression of functional genes in adipose tissue and adipocytes of chickens.

Multi-Omics Association Reveals the Effects of Intestinal Microbiome-Host Interactions on Fat Deposition in Broilers.

Growing evidence indicates that gut microbiota factors cannot be viewed as independent in the occurrence of obesity. Because the gut microbiome is highly dimensional and complex, studies on interactions between gut microbiome and host in obesity are still rare. To explore the relationship of gut microbiome-host interactions with obesity, we performed multi-omics associations of gut metagenome, intestinal transcriptome, and host obesity phenotypes in divergently selected obese-lean broiler lines. Metagenomic shotgun sequencing generated a total of 450 gigabases of clean data from 80 intestinal segment contents of 20 broilers (10 of each line). The microbiome comparison showed that microbial diversity and composition in the duodenum, jejunum, ileum, and ceca were altered variously between the lean- and fat-line broilers. We identified two jejunal microbes (Escherichia coli and Candidatus Acetothermia bacterium) and four cecal microbes (Alistipes sp. CHKCI003, Ruminococcaceae bacterium CPB6, Clostridiales bacterium, and Anaeromassilibacillus sp. An200), which were significantly different between the two lines (FDR < 0.05). When comparing functional metagenome, the fat-line broilers had an intensive microbial metabolism in the duodenum and jejunum but degenerative microbial activities in the ileum and ceca. mRNA-sequencing identified a total of 1,667 differentially expressed genes (DEG) in the four intestinal compartments between the two lines (| log2FC| > 1.5 and FDR < 0.05). Multi-omics associations showed that the 14 microbial species with abundances that were significantly related with abdominal fat relevant traits (AFRT) also have significant correlations with 155 AFRT-correlated DEG (p < 0.05). These DEG were mainly involved in lipid metabolism, immune system, transport and catabolism, and cell growth-related pathways. The present study constructed a gut microbial gene catalog of the obese-lean broiler lines. Intestinal transcriptome and metagenome comparison between the two lines identified candidate DEG and differential microbes for obesity, respectively. Multi-omics associations suggest that abdominal fat deposition may be influenced by the interactions of specific gut microbiota abundance and the expression of host genes in the intestinal compartments in which the microbes reside. Our study explored the interactions between gut microbiome and host intestinal gene expression in lean and obese broilers, which may expand knowledge on the relationships between obesity and gut microbiome.

[Over-expression of circNR4A1/Hsa-circ-0026352 inhibits proliferation and induces apoptosis in MCF-7 cells].

Objective To investigate the expression of circNR4A1/Hsa-circ-0026352 in breast tumor tissue, peripheral blood, cell lines and its effect on the proliferation and apoptosis of MCF-7 breast cancer cells. Methods Using circRNA microarray, different expression of human circRNAs was found out between the breast cancer tissues and adjacent normal tissues. The expression of circNR4A1 in breast cancer tissues, peripheral blood and breast cancer cell lines including MCF-7, HCC-1937, MDA-MB-231, T-47D and MCF-10A were detected by quantitative real-time PCR (qRT-PCR). Circular RNA interactome software and KEGG software were used to predict its target miRNA and bio-function. The circNR4A1 over-expression vector was constructed and transfected into MCF-7 cells. The effect of circNR4A1 on the proliferation of MCF-7 cells was detected by CCK-8 assay and clone formation assay. The cell apoptosis and cell cycle distribution were analyzed by flow cytometry and Hoechst 33258 stainning. The qRT-PCR was performed to detect the mRNA expression levels of MEK/ERK signal pathway genes (K-RAS, MEK, ERK) and apoptosis-related genes (Bcl2, BAX, BAD, caspase-3). Western blotting was used to detect the expression of MEK, ERK, Bcl2, BAD and caspase-3 proteins. Results The expression of circNR4A1(Hsa-circ-0026352) was lower in breast cancer tissues, peripheral blood and breast cancer cell lines than in adjacent normal tissues, healthy individuals' peripheral blood and human breast epithelial cells. Over-expression of circNR4A1 in MCF-7 cells inhibited the cell proliferation, promoted cell apoptosis and blocked the cell cycle in G1/S phase. The mRNA and protein expression of MEK, ERK, Bcl2 were significantly depressed, while the expression of BAD, caspase-3 were enhanced in the MCF-7 cells over-expressing circNR4A1. Conclusion The expression of circNR4A1/Hsa-circ-0026352 is lower in breast cancer tissues, peripheral blood and breast cancer cells. Over-expression of circNR4A1 can inhibit cell proliferation and induce cell apoptosis in MCF-7 cells.

Haplotype-based genome-wide association studies for carcass and growth traits in chicken.

There have been several genome-wide association study (GWAS) reported for carcass, growth, and meat traits in chickens. Most of these studies have been based on single SNPs GWAS. In contrast, haplotype-based GWAS reports have been limited. In the present study, 2 Northeast Agricultural University broiler lines divergently selected for abdominal fat content (NEAUHLF) and genotyped with the chicken 60K SNP chip were used to perform a haplotype-based GWAS. The lean and fat chicken lines were selected for abdominal fat content for 11 yr. Abdominal fat weight was significantly different between the 2 lines; however, there was no difference for body weight between the lean and fat lines. A total of 132 haplotype windows were significantly associated with abdominal fat weight. These significantly associated haplotype windows were primarily located on chromosomes 2, 4, 8, 10, and 26. Seven candidate genes, including SHH, LMBR1, FGF7, IL16, PLIN1, IGF1R, and SLC16A1, were located within these associated regions. These genes may play important roles in the control of abdominal fat content. Two regions on chromosomes 3 and 10 were significantly associated with testis weight. These 2 regions were previously detected by the single SNP GWAS using this same resource population. TCF21 on chromosome 3 was identified as a potentially important candidate gene for testis growth and development based on gene expression analysis and the reported function of this gene. TCF12, which was previously detected in our SNP by SNP interaction analysis, was located in a region on chromosome 10 that was significantly associated with testis weight. Six candidate genes, including TNFRSF1B, PLOD1, NPPC, MTHFR, EPHB2, and SLC35A3, on chromosome 21 may play important roles in bone development based on the known function of these genes. In addition, several regions were significantly associated with other carcass and growth traits, but no candidate genes were identified. The results of the present study may be helpful in understanding the genetic mechanisms of carcass and growth traits in chickens.

Study on the performance of NiO/Zn x Zr1-x catalysts for CO2 hydrogenation.

The NiO/Zn x Zr1-x (x represents the molar mass of Zn) catalyst was prepared by the impregnation method and tested in CO2 methanation. The activity results show that NiO/Zn0.3Zr0.7 has a higher CO2 conversion rate and methane selectivity than NiO/ZnO and NiO/ZnO-ZrO2. Combined with N2 adsorption-desorption, H2-TPR, CO2-TPD, H2-TPD, XRD, TEM, XPS and FTIR and other characterization methods, the physical and chemical properties of NiO/ZnO-ZrO2 were studied. The incorporation of ZnO into NiO/ZrO2 forms a ZnO-ZrO2 solid solution, and the combination of the solid solution weakens the interaction between NiO and the oxide support, thereby promoting the reduction and dispersion of NiO. The H2-TPR experiment results show that, because ZnO-ZrO2 forms a solid solution, NiO is better dispersed on the surface, resulting in a significant reduction in the reduction temperature of NiO. Using FTIR to conduct CO2 adsorption and methanation experiments on NiO/Zn x Zr1-x to determine the adsorbed species and intermediates, the results show that CO2 methanation follows the formate pathway.

Past, Present, and Future of Groundwater Remediation Research: A Scientometric Analysis.

In this study, we characterize the body of knowledge of groundwater remediation from 1950 to 2018 by employing scientometric techniques and CiteSpace software, based on the Science Citation Index Expanded (SCI-E) databases. The results indicate that the United States and China contributed 56.4% of the total publications and were the major powers in groundwater remediation research. In addition, the United States, Canada, and China have considerable capabilities and expertise in groundwater remediation research. Groundwater remediation research is a multidisciplinary field, covering water resources, environmental sciences and ecology, environmental sciences, and engineering, among other fields. Journals such as Environmental Science and Technology, Journal of Contaminant Hydrology, and Water Research were the major sources of cited works. The research fronts of groundwater remediation were transitioning from the pump-and-treat method to permeable reactive barriers and nanoscale zero­valent iron particles. The combination of new persulfate ion­activation technology and nanotechnology is receiving much attention. Based on the visualized networks, the intelligence base was verified using a variety of metrics. Through landscape portrayal and developmental trajectory identification of groundwater remediation research, this study provides insight into the characteristics of, and global trends in, groundwater remediation, which will facilitate the identification of future research directions.

EXT1, Regulated by MiR-665, Promotes Cell Apoptosis via ERK1/2 Signaling Pathway in Acute Lymphoblastic Leukemia.

BACKGROUND EXT1 is an endoplasmic reticulum-resident glycosyl transferase whose intracellular expression alters the biosynthesis and distribution of heparan sulfate. EXT1 is regarded as a classic tumor suppressor. MiR-665 can act as either an oncogene or tumor-suppressing gene in different tumors. The aim of the current study was to determine the function and molecular mechanisms of EXT1 and miR-665 in acute lymphoblastic leukemia (ALL). MATERIAL AND METHODS EXT1 expression in ALL was evaluated by real-time polymerase chain reaction (RT-PCR) and western blotting. The effects of EXT1 in ALL were explored by Cell Counting Kit-8 (CCK-8)/EdU assays, western blotting, flow cytometry, and in vivo tumorigenesis assays. Label-free quantification was used to detect differentially expressed proteins in EXT1-overexpressing Reh cells. RESULTS EXT1 expression is downregulated in ALL and negatively correlated with miR-665 expression. Moreover, low EXT1 and high miR-665 expression levels in adult ALL bone marrow tissues are correlated with poor patient survival. Our study showed that EXT1 modulates the proliferation and apoptosis of ALL cells in vitro and in vivo and that miR-665 promotes cell growth and inhibits apoptosis by suppressing EXT1. EXT1 promotes cell apoptosis via deactivating the ERK1/2 pathway. CONCLUSIONS In conclusion, this study is the first to confirm the association between low EXT1 levels and several clinical features of ALL. Low bone marrow EXT1 levels independently predict poor prognoses in adult ALL patients. Thus, our study suggests that EXT1- or miR-665-targeted strategies can confer the therapeutic effect of promoting apoptosis by deactivating the ERK1/2 pathway.

NSE from diffuse large B-cell lymphoma cells regulates macrophage polarization.

Background/aims: Diffuse large B-cell lymphoma (DLBCL) is a highly common type of malignant and heterogeneous non-Hodgkin's lymphoma. Tumor-associated macrophages, specially the M2-type, promote tumor progression and drug resistance. The clinical outcome of patients with high neuron-specific enolase (NSE) expression is worse than that with low NSE expression. The tumor-promoting mechanism of NSE, however, remains unclear. This study explored the role of NSE in macrophage polarization associated with the immune microenvironment of DLBCL. Results: Our results showed that NSE protein expression was higher in lymphoma cell lines than in the B lymphocytes. Functional studies demonstrated that upregulation of NSE in lymphoma cells could promote M2 polarization and migration ability of macrophage, thereby consequently promoting the progression of lymphoma in vitro and in vivo. Further mechanism studies revealed that lymphoma-derived exosomes could mediate NSE into macrophages, NSE enhanced nuclear p50 translocation with subsequent defective classical nuclear factor-κB activity in macrophages. Conclusions: These results indicate that NSE may be a potential target for lymphoma therapy and a prognosis marker for lymphoma.

Elevated BNP caused by recombinant human interleukin-11 treatment in patients with chemotherapy-induced thrombocytopenia.

Thrombocytopenia is a condition characterized by abnormally low levels of thrombocytes and often induced by chemotherapy. Recombinant human interleukin-11 (rhIL-11) is a cytokine that can stimulate thrombopoiesis and is commonly used to treat thrombocytopenia. We observed the side effects of rhIL-11 in 24 leukemia patients with chemotherapy-induced thrombocytopenia. To determine the cardiovascular effects of rhIL-11, we detected changes in the patients' serum brain natriuretic peptide (BNP), blood pressure fluctuations, weight change, and whether edema or heart failure occurred in leukemia patients after chemotherapy. The results showed that BNP was significantly elevated after using rhIL-11 (P < 0. 05) but regressed after 2-4 days. Furthermore, nine patients had edema and experienced weight gain, and four experienced acute left heart failure. In addition, the average blood pressure was 119/75 mmHg (range 139/86 mmHg to 99/64 mmHg) before rhIL-11 administration and 127/79 mmHg (range 146/89 mmHg to 108/69 mmHg) after rhIL-11 use. In conclusion, although rhIL-11 is useful for treating chemotherapy-induced thrombocytopenia, it is important to monitor the patients' clinical status and re-examine BNP levels frequently during the use of rhIL-11. Furthermore, senile patients should be given special attention. However, the appropriate timing to begin and discontinue rhIL-11 treatment needs further investigation.

Production of transgenic broilers by non-viral vectors via optimizing egg windowing and screening transgenic roosters.

The generation of transgenic chickens is of both biomedical and agricultural significance, and recently chicken transgenesis technology has been greatly advanced. However, major issues still exist in the efficient production of transgenic chickens. This study was designed to optimize the production of enhanced green fluorescence protein (EGFP)-transgenic broilers, including egg windowing at the blunt end (air cell) of egg, and the direct transfection of circulating primordial germ cells by microinjection of the Tol2 plasmid-liposome complex into the early embryonic dorsal aorta. For egg windowing, we discovered that proper manipulation of the inner shell membrane at the blunt end could improve the rate of producing G0 transgenic roosters. From 27 G0 roosters, we successfully collected semen with EGFP-positive sperms from 16 and 19 roosters after direct fluorescence observation and fluorescence-activated cell sorting analyses (13 detected by both methods), respectively. After artificial insemination using the G0 rooster with the highest number of EGFP fluorescent sperm, one G1 EGFP transgenic broiler (1/81, 1.23%) was generated. Our results indicate that appropriate egg windowing and screening of potentially transgene-positive roosters can improve the production of germline-transmitted transgenic birds.

Important candidate genes for abdominal fat content identified by linkage disequilibrium and fixation index information.

Selection for rapid growth in chickens has always been accompanied by increased fat deposition and excessive fat deposition, especially abdominal fat, cannot only decrease feed efficiency but also cause many diseases. Finding the candidate genes associated with abdominal fat deposition is essential for breeding. To identify these candidate genes, we applied linkage disequilibrium and selection signature analysis using chicken 60 k single nucleotide polymorphism (SNP) chips in two broiler lines divergently selected for abdominal fat content for 11 generations. After quality control, 46,033 SNPs were left for analysis. Using these SNPs, we found that r2 was 0.06 to 0.14 in the lean line and 0.07 to 0.13 in the fat line for all 28 chromosomes (except GGA16). Pairwise SNP distances <25 kb showed a mean r2 = 0.33 in the lean line and r2 = 0.32 in the fat line. The fixation index (FST) analysis was carried out and 46 SNPs with the top 0.1% of the FST value was detected as the loci with selection signatures. Besides FST, hapFLK was also used to detect selection signatures for abdominal fat content. A total of 11 genes, including transient receptor potential cation channel subfamily C member 4, estrogen related receptor gamma, fibroblast growth factor 13, G-protein-signaling modulator 2, RAR related orphan receptor A, phospholipase A2 group X, mitochondrial ribosomal protein L28, metadherin, calcitonin receptor like receptor, serine/threonine kinase 39, and nuclear factor I A, were detected as the important candidate genes for abdominal fat deposition based on their basic functions. The results of the present study may benefit the understanding of genetic mechanism of abdominal fat deposition in chicken.

Asparagine synthetase expression is associated with the sensitivity to asparaginase in extranodal natural killer/T-cell lymphoma in vivo and in vitro.

BACKGROUND: Although asparagine synthetase (AsnS) is associated with drug resistance in leukemia, its function in extranodal natural killer (NK)/T-cell lymphoma (ENKTL) remains unclear. METHODS: The present study investigated the relationship between baseline AsnS mRNA levels and response to asparaginase in ENKTL cell lines. It also determined whether upregulating or downregulating the AsnS mRNA level induces or reverses asparaginase-resistant phenotype. RESULTS: Interestingly, considerable differences were observed in the sensitivity to asparaginase of the five ENKTL cell lines. The AsnS expression levels were positively correlated with the IC50 values. In addition, the asparaginase resistance was induced or reversed by upregulating or downregulating the AsnS mRNA level in vivo and in vitro. Functional analyses indicated that AsnS did not affect the proliferation and apoptosis of ENKTL cells in the absence of asparaginase. CONCLUSION: Together, the data stress the importance of AsnS in the sensitivity to asparaginase in ENKTL and suggest a different therapeutic strategy for patients with a different level of AsnS expression.