A radiomics model development via the associations with genomics features in predicting axillary lymph node metastasis of breast cancer: a study based on a public database and single-centre verification.

AIM: To evaluate the predictive performance of the radiomics model in predicting axillary lymph node (ALN) metastasis through the associations between radiomics features and genomic features in patients with breast cancer. MATERIALS AND METHODS: Patients with breast cancer were enrolled retrospectively from a public database (111 patients as training group) and one hospital (15 patients as external validation group). The genomics features from transcriptome data and radiomics features from dynamic contrast-enhanced magnetic resonance imaging (MRI) were collected. Firstly, overlapping genes were identified using the Kyoto Encyclopedia of Genes and Genomes and differentially expressed gene analysis, while radiomics features were reduced using a data-driven method. Then, the associations between overlapping genes and retained radiomics features were assessed to obtain key pairs of radiomics-genomics features. Furthermore, the least absolute shrinkage and selection operator (LASSO) algorithm was used to detect the key-pairs features. Finally, radiomics and genomics models were constructed to predict ALN metastasis. RESULTS: After using the hybrid data- and gene-driven selection method, key pairs of features were detected, which consisted of six radiomic features associated with four genomic features. The radiomics model exhibited comparable performance to the genomics model in predicting ALN metastasis (radiomic model: area under the curve [AUC] = 0.71, sensitivity = 77%, specificity = 56%; genomic model: AUC = 0.72, sensitivity = 85%, specificity = 74%). The four genomic features were enriched in six pathways and related to metabolism and human diseases. CONCLUSION: The radiomics model established using the gene-driven hybrid selection method could predict ALN metastasis in breast cancer, which showed comparable performance to the genomics model.

Assessing the construction of a Healthy City in China: a conceptual framework and evaluation index system.

OBJECTIVES: COVID-19 has brought challenges to the health of all mankind. It is particularly important to promote the construction of a 'Healthy China' and build a 'healthy community'. The aims of this study were to construct a reasonable conceptual framework for the Healthy City concept and to assess Healthy City construction in China. STUDY DESIGN: This study combined qualitative and quantitative research. METHODS: This study proposes the concept model of 'nature-human body-Healthy City' and accordingly constructs an evaluation index system for the construction of a Healthy City that integrates five dimensions, namely, the medical level, economic basis, cultural development, social services, and ecological environment to explore the spatial and temporal heterogeneity of Healthy City construction in China. Finally, the influencing factors of Healthy City construction patterns are explored using GeoDetector. RESULTS: (1) The pace of Healthy City construction is generally on the rise; (2) the construction of Healthy Cities exhibits significant global spatial autocorrelation and gradually increasing agglomeration. The spatial distribution of cold hotspot areas was relatively stable; (3) medical and health progress is an important factor; the level of economic development is the leading support; the endowment of resources and environment is the basic condition; public service support provides important support; and scientific and technological innovation capabilities provide technical support for the construction of a Healthy City. CONCLUSIONS: The spatial heterogeneity of Healthy City construction in China is evident, and the state of spatial distribution is relatively stable. The spatial pattern of Healthy City construction is shaped by a combination of factors. Our research will provide a scientific basis for promoting the construction of Healthy Cities and helping to implement the Health China Strategy.

TFP5, a Peptide Derived from Cdk5 Activator p35, Protects Pancreatic ß Cells from Glucose Toxicity.

We studied the effect of TFP5 on MIN6 cells (cultured mouse islet ß cells) treated with different concentrations of glucose (5 or 25 mM). The results were verified in C57BL/6J mice (control; n=12) and db/db mice with type 2 diabetes mellitus (n=12). To synthesize TFP5, peptide p5 (a derivative of p35 protein, activator of cyclin-dependent kinase 5, Cdk5) was conjugated with a FITC tag at the N-terminus and an 11-amino acid TAT protein transduction domain at the C-terminus. TFP5 was employed to inhibit Cdk5 activity and then to evaluate its efficiency in treating experimental type 2 diabetes mellitus. TFP5 effectively inhibited the pathological hyperactivity of Cdk5, enhanced insulin secretion, and protected pancreatic ß cells from apoptosis in vitro and in vivo. In addition, TFP5 inhibited inflammation in pancreatic islets by reducing the expression of inflammatory cytokines TGF-ß1, TNFα, and IL-1ß. These novel data indicates that TFP5 is a promising candidate for treatment of type 2 diabetes mellitus.

Leukocyte immunoglobulin-like receptor A3 is increased in IBD patients and functions as an anti-inflammatory modulator.

Growing evidence shows that a homozygous 6·7-kb deletion of the novel anti-inflammatory molecule leukocyte immunoglobulin-like receptor A3 (LILRA3) is associated with many autoimmune disorders. However, its effects on pathogenesis of inflammatory bowel disease (IBD) have yet not been clarified. LILRA3 is mainly expressed in monocytes, whereas its effects on biological behaviors of monocytes have not been systematically reported. In our study, to investigate the association between LILRA3 polymorphism and IBD susceptibility, LILRA3 polymorphism was assessed in 378 IBD patients and 509 healthy controls. Quantitative real time PCR (qRT-PCR), Western blot and immunohistochemistry (IHC) were employed to detect the LILRA3 expression in IBD patient blood and intestinal samples. The human U937 monocyte cell line was employed to establish LILRA3 over-expressing cells and the effects of LILRA3 on the biological behaviors of U937 cells were systematically explored. Although no association of the polymorphism with IBD development was found, LILRA3 expression was markedly increased in IBD patients compared with healthy controls. Over-expression of LILRA3 in monocytes led to significant decreases in secretion of interferon (IFN)-γ, tumor necrosis factor (TNF)-α and interleukin (IL)-6. Additionally, LILRA3 abated monocyte migration by reducing the expression of several chemokines and enhanced monocyte phagocytosis by increasing CD36 expression. Furthermore, LILRA3 promoted monocyte proliferation through a combination of Akt and extracellular receptor kinase/mitogen-activated protein kinase (Erk/MEK) signaling pathways. We report for the first time, to our knowledge, that LILRA3 is related to IBD and functions as an anti-inflammatory modulator in U937 cells.

Improved Constraints on Global Methane Emissions and Sinks Using δ 13C-CH4.

We study the drivers behind the global atmospheric methane (CH4) increase observed after 2006. Candidate emission and sink scenarios are constructed based on proposed hypotheses in the literature. These scenarios are simulated in the TM5 tracer transport model for 1984-2016 to produce three-dimensional fields of CH4 and δ 13C-CH4, which are compared with observations to test the competing hypotheses in the literature in one common model framework. We find that the fossil fuel (FF) CH4 emission trend from the Emissions Database for Global Atmospheric Research 4.3.2 inventory does not agree with observed δ 13C-CH4. Increased FF CH4 emissions are unlikely to be the dominant driver for the post-2006 global CH4 increase despite the possibility for a small FF emission increase. We also find that a significant decrease in the abundance of hydroxyl radicals (OH) cannot explain the post-2006 global CH4 increase since it does not track the observed decrease in global mean δ 13C-CH4. Different CH4 sinks have different fractionation factors for δ 13C-CH4, thus we can investigate the uncertainty introduced by the reaction of CH4 with tropospheric chlorine (Cl), a CH4 sink whose abundance, spatial distribution, and temporal changes remain uncertain. Our results show that including or excluding tropospheric Cl as a 13 Tg/year CH4 sink in our model changes the magnitude of estimated fossil emissions by ∼20%. We also found that by using different wetland emissions based on a static versus a dynamic wetland area map, the partitioning between FF and microbial sources differs by 20 Tg/year, ∼12% of estimated fossil emissions.

Effects of oral sialic acid on gut development, liver function and gut microbiota in mice.

Sialic acid (N-acetylneuraminic acid), a 9-carbon monosaccharide, has been widely studied in immunology, oncology and neurology. However, the effects of sialic acid on organ and intestinal development, liver function and gut microbiota were rarely studied. In this study, we found that oral sialic acid tended to increase the relative weight of liver and decreased the serum aspartate aminotransferase (GPT) activity. In addition, sialic acid treatment markedly reduced gut villus length, depth, the ratio of villus length/depth (L/D), areas, width and the number of goblet cells. Furthermore, gut microbes were changed in response to oral sialic acid, such as Staphylococcus lentus, Corynebacterium stationis, Corynebacterium urealyticum, Jeotgalibaca sp_PTS2502, Ignatzschineria indica, Sporosarcina pasteurii, Sporosarcina sp_HW10C2, Facklamia tabacinasalis, Oblitimonas alkaliphila, Erysipelatoclostridium ramosum, Blautia sp_YL58, Bacteroids thetaiotaomicron, Morganella morganii, Clostridioides difficile, Helicobacter tryphlonius, Clostridium sp_Clone47, Alistipes finegoldii, [pseudomonas]_geniculata and Pseudomonas parafulva at the species level. In conclusion, oral sialic acid altered the intestinal pathological state and microbial compositions, and the effect of sialic acid on host health should be further studied.

MiR-503 Contributes to Glucocorticoid Sensitivity in Acute Lymphoblastic Leukaemia via Targeting WNT3A.

Abnormal accumulation of lymphoblasts in the blood and bone marrow is the main characteristic of acute lymphoblastic leukaemia (ALL). Glucocorticoids are effective drugs for ALL, while glucocorticoid resistance is an obstacle to ALL therapy. MicroRNAs (miRNAs) are implicated in the drug resistance and modulate the response of ALL to glucocorticoids. The role of miR-503 in glucocorticoid sensitivity of ALL was investigated in this study. Firstly, T-leukaemic cells were isolated from patients with ALL. The human ALL cell line (CCRF/CEM) was incubated with dexamethasone to establish a glucocorticoid- resistant ALL cell line (CCRF/CEM-R). Data from MTT showed that IC50 (50% inhibitory concentration) of dexamethasone in T-leukaemic cells isolated from glucocorticoid-resistant ALL patients or CCRF/CEM-R was increased compared with IC50 in T-leukaemic cells isolated from glucocorticoid- sensitive ALL patients or CCRF/CEM. MiR- 503 was down-regulated in glucocorticoid-resistant leukaemic cells and CCRF/CEM-R. Secondly, overexpression of miR-503 sensitized CCRF/CEM-R to dexamethasone. Moreover, over-expression of miR- 503 also promoted the sensitivity of ALL cells to dexamethasone. Thirdly, miR-503 bound to WNT3A mRNA and negatively regulated the expression of WNT3A. Over-expression of miR-503 reduced protein expression of nuclear ß-catenin, and over-expression of WNT3A attenuated the miR-503 overexpression- induced decrease in nuclear ß-catenin. Lastly, the over-expression of miR-503-induced increased sensitivity of ALL-resistant cells and CCRF/ CEM-R to dexamethasone was attenuated by overexpression of WNT3A. In conclusion, miR-503 targeted WNT3A mRNA to sensitize ALL cells to glucocorticoids through inactivation of the Wnt/ß-catenin pathway.

[Value of PET/MRI in the diagnosis of malignant pleural effusion in comparison with PET/CT].

Objective: To investigate the diagnostic value of PET/MRI for malignant pleural effusion (MPE), and compare its diagnostic difference with PET/CT. Methods: The data of 57 patients with suspected MPE admitted into Union Hospital of Tongji Medical College of Huazhong University of Science and Technology from October 2017 to January 2020 was analyzed. A total of 53 patients were included in the prospective study, and the whole body PET/CT and thoracic PET/MRI were performed on them respectively. Two physicians used a blind method to evaluate the morphological features of PET/CT and PET/MRI images, delineate the region of interest (ROI), obtain the maximum standard uptake value (SUVmax) of the ROI in the PET/CT and PET/MRI images. The target-to-background ratio (TBR) of the lesion was calculated. The diffusion-weighted imaging (DWI) characteristics of the pleura in PET/MRI images were analyzed. Taking pathological diagnosis as the gold standard, the diagnostic effect of PET/CT and PET/MRI on MPE were evaluated. Results: The 53 patients who were finally included were (62.8±1.7) years old, consisting of 31 males. Pathological results showed that 41 cases were MPE and 12 cases were benign pleural effusion (BPE). There were no statistical differences in age, gender and smoking history between the two groups (P>0.05). Bland-Altman analysis showed that the SUVmax of pleural lesions by PET/MRI was higher than that by PET/CT (6.4±0.6 vs 5.3±0.5, P<0.001). The TBR of PET/MRI was higher than that of PET/CT (2.2±0.2 vs 1.8±0.2, P<0.001). The sensitivity, specificity, and accuracy of PET/MRI in the diagnosis of MPE by combining imaging features such as SUVmax and DWI of pleural lesions were 75.6%, 100%, and 81.1%, respectively. The sensitivity, specificity, and accuracy of PET/CT combined with SUVmax and imaging features of pleural lesions in the diagnosis of MPE were 85.4%, 83.3%, and 77.4%, respectively. There was no statistically significant difference between PET/MRI and PET/CT in the area under the curve (AUC) for diagnosing MPE (0.934 vs 0.873, P>0.05). Conclusions: PET/MRI and PET/CT have the equivalent diagnostic efficiency for MPE. However, PET/MRI shows higher SUVmax and TBR for pleural lesions, and has specific pleural DWI imaging characteristics, which is worthy of further clinical research.

[Association between dietary vitamin A intake and gestational diabetes mellitus in the first trimester].

Objective: To investigate the relationship between dietary vitamin A intake and its sources in the first trimester and gestational diabetes mellitus (GDM). Methods: A prospective study was conducted to select women at 6-14 weeks of gestation in an obstetric clinic of a maternal and child health care medical institution in Chengdu in 2017. The types and quantities of food during the first trimester were collected by 3-day 24-hour dietary recalls. Dietary vitamin A intake was calculated based on the Chinese Food Composition Table (2018), and it was divided into animal and plant vitamin A intakes according to its food sources. An oral glucose tolerance test was performed at 24-28 weeks of gestation to diagnose GDM according to the Chinese guidelines for diagnosis and treatment of gestational diabetes mellitus (2014). According to the estimated average requirement (EAR) and recommended nutrient intake (RNI), dietary vitamin A intake was divided into low-level group (RNI). Animal and plant vitamin A intakes were divided into four groups (Q1-Q4) according to the quartile method, respectively. The association between dietary vitamin A intake, its different sources of vitamin A intake and GDM in the first trimester was analyzed by log-binomial regression models. Results: A total of 1 298 valid samples were finally included. The average dietary vitamin A intake, animal and plant vitamin A intakes in the first trimester were 341.1 (227.8-501.0) µgRAE/d, 139.3 (69.6-195.3) µgRAE/d and 184.2 (99.4-301.1) µgRAE/d, respectively. After adjusting for confounding factors, log-binomial regression analysis showed that the risk of GDM in high-level group of dietary vitamin A intake was lower than that in low-level group [RR (95%CI):0.53 (0.36-0.80)]. Pregnant women in the highest quartile of animal vitamin A intake had a lower risk of GDM than those in the lowest quartile [RR (95%CI):0.66 (0.47-0.95)]. No relationship between plant vitamin A intake and GDM was found. Conclusion: Dietary vitamin A intake in the first trimester is associated with the occurrence of GDM, and higher intake than RNI may reduce the risk of GDM. Higher vitamin A intake from animal-derived food is associated with decreased risk of GDM.

Correction to: Nuclear medicine services after COVID-19: gearing up back to normality.

The authors P. Orellana and N. El-Haj were inadvertently deleted in the original paper.

InDels within caprine IGF2BP1 intron 2 and the 3'-untranslated regions are associated with goat growth traits.

Insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1) is involved in the Hedgehog pathway and has been shown to regulate the RNA stability of several growth-related target genes. It is located in a quantitative trait locus showing a strong association with traits related to body size in ducks. Fibroblast growth factor receptor 1 (FGFR1) also participates in Hedgehog signaling pathways and has been reported to be associated with organic growth and development. FGFR1-knockout mice have been shown to have severe postnatal growth defects, including an approximately 50% reduction in body weight and bone mass. Meanwhile, nonsense-mediated mRNA decay factor (SMG6) can maintain genomic stability, which is associated with organic growth and development. Therefore, we hypothesized that IGF2BP1, FGFR1 and SMG6 genes may play important roles in the growth traits of goats. In this study, the existence of two insertion/deletion (InDel) variants within IGF2BP1, one InDel within FGFR1 and two InDels within SMG6 was verified and their correlation with growth traits was analyzed in 2429 female Shaanbei white cashmere goats. Results showed both the 15 bp InDel in intron 2 and the 5 bp InDel in the 3' regulatory region within IGF2BP1 were significantly associated with growth traits (P < 0.05) and goats with the combinatorial homozygous insertion genotypes of these two loci had the highest body weight (P = 0.046). The other InDels within FGFR1 and SMG6 were not obviously associated with growth traits (P > 0.05). Therefore, the two InDels in IGF2BP1 were vital mutations affecting goat growth traits.

CAFs secreted exosomes promote metastasis and chemotherapy resistance by enhancing cell stemness and epithelial-mesenchymal transition in colorectal cancer.

BACKGROUND: Cancer associated fibroblasts (CAFs) are key stroma cells that play dominant roles in tumor progression. However, the CAFs-derived molecular determinants that regulate colorectal cancer (CRC) metastasis and chemoresistance have not been fully characterized. METHODS: CAFs and NFs were obtained from fresh CRC and adjacent normal tissues. Exosomes were isolated from conditioned medium and serum of CRC patients using ultracentrifugation method and ExoQuick Exosome Precipitation Solution kit, and characterized by transmission electronic microscopy, nanosight and western blot. MicroRNA microarray was employed to identify differentially expressed miRNAs in exosomes secreted by CAFs or NFs. The internalization of exosomes, transfer of miR-92a-3p was observed by immunofluorescence. Boyden chamber migration and invasion, cell counting kit-8, flow cytometry, plate colony formation, sphere formation assays, tail vein injection and primary colon cancer liver metastasis assays were employed to explore the effect of NFs, CAFs and exosomes secreted by them on epithelial-mesenchymal transition, stemness, metastasis and chemotherapy resistance of CRC. Luciferase report assay, real-time qPCR, western blot, immunofluorescence, and immunohistochemistry staining were employed to explore the regulation of CRC metastasis and chemotherapy resistance by miR-92a-3p, FBXW7 and MOAP1. RESULTS: CAFs promote the stemness, epithelial-mesenchymal transition (EMT), metastasis and chemotherapy resistance of CRC cells. Importantly, CAFs exert their roles by directly transferring exosomes to CRC cells, leading to a significant increase of miR-92a-3p level in CRC cells. Mechanically, increased expression of miR-92a-3p activates Wnt/ß-catenin pathway and inhibits mitochondrial apoptosis by directly inhibiting FBXW7 and MOAP1, contributing to cell stemness, EMT, metastasis and 5-FU/L-OHP resistance in CRC. Clinically, miR-92a-3p expression is significantly increased in CRC tissues and negatively correlated with the levels of FBXW7 and MOAP1 in CRC specimens, and high expression of exosomal miR-92a-3p in serum was highly linked with metastasis and chemotherapy resistance in CRC patients. CONCLUSIONS: CAFs secreted exosomes promote metastasis and chemotherapy resistance of CRC. Inhibiting exosomal miR-92a-3p provides an alternative modality for the prediction and treatment of metastasis and chemotherapy resistance in CRC.

Maintenance of SOX9 stability and ECM homeostasis by selenium-sensitive PRMT5 in cartilage.

OBJECTIVES: Selenium (Se) plays pivotal roles in maintaining optimal health. Nevertheless, how Se influences the metabolism of extracellular matrix (ECM) in cartilage remains unclear. The aim of the present study was to observe protein dimethylation by certain Se-sensitive PRMT and to elucidate its effects on the key transcriptional factor in cartilage. METHODS: We observed the expression of selenoproteins and markers of ECM metabolism in chondrocytes and articular cartilage of the rats under Se-deficiency by RT-qPCR, immunoblotting and immunohistochemistry. Then, we analyzed the expression of total dimethylated protein by using specific antibody under different Se statuses. After Se sensitive PRMT was identified, we used siRNA or PRMT inhibitor or stably overexpressing vector to intervene in the PRMT expression and identified the key transcriptional factor. Co-immunoprecipitation was applied to verify the interaction between PRMT and the key transcriptional factor. Finally, we measured the half-life time of the key transcriptional factor by immunoblotting after cycloheximide treatment. RESULTS: In chondrocytes and cartilage of the rats with Se deficiency, we found an aberrant metabolism manifesting decreased expression of Col2a1 and increased expression of Mmp-3. Then, we identified that PRMT5 was the unique type II PRMT, sensitive to Se status. PRMT5 upregulation led to the increased COL2A1 expression but decreased MMP-3 expression in chondrocytes. Furthermore, we revealed that PRMT5 improved SOX9 stability by dimethylating the protein, which contributed to maintain the matrix metabolic homeostasis of the chondrocytes. CONCLUSIONS: Se-sensitive PRMT5 increases the half-life of SOX9 protein via PTM and helps to maintain ECM homeostasis of the articular cartilage.

[Relationship between morphological characteristics and prognosis of non-nasopharyneal EBV-associated carcinoma].

Objective: To analyze the pathological features and their influence on the clinical outcome of non-nasopharyngeal EBV-associated carcinomas. Methods: One hundred and twenty cases of non-nasopharyngeal EBV-associated carcinoma confirmed by in situ hybridization were identified at Zhejiang Cancer Hospital from January 1, 2006 to May 1, 2018, and the clinicopathological data were collected and analyzed using Kaplan-Meier survival analysis, Cox univariate and multivariate analysis. Results: One hundred and twenty cases were involved in the study; the male to female ratio was 1∶1; patients' age range was 24 to 89 years (median 50 years). The primary sites were large parotid glands (62 cases), lung(26 cases), stomach(15 cases), and others (oral, oropharynx, larynx, cervix, liver; totally 17cases). Non-nasopharyngeal EBV-associated cancer could be divided into two histological types according to the amount of interstitial lymphocytes: type Ⅰ was "lymphoepithelial-like carcinoma" and rich in stromal lymphocytes; type Ⅱ lacked lymphocytic infiltration. Ninety-eight primary tumor samples could be classified morphologically: 43 cases were as type Ⅰ and 55 cases as typeⅡ; the distribution of type Ⅰ was 57.4% (27/47) in large parotid glands, 20.8% (5/24) in lung, 4/13 in stomach, and 7/14 in other sites. Complete treatment and survival data were obtained for 114 patients. According to the TNM staging criteria of WHO, 52 patients were at early stages (Ⅰ-Ⅱ) and 62 were at advanced stages (Ⅲ-Ⅳ); 102 patients underwent surgery. Seventy-four patients received adjuvant chemotherapy before or after surgery, and 52 patients received local radiotherapy. Kaplan-Meier survival analysis showed that patients with type Ⅱ EBV-associated carcinoma had a worse prognosis than patients with type Ⅰtumors (P=0.010 2). In addition, vascular invasion(P=0.021 8),neural recidivism(P=0.000 1),advanced stage(P=0.017 1),lymph node metastasis (P=0.005 0) and chemotherapy (P=0.013 2) were poor prognostic factors; female patients had better survival than male (P=0.028 4). Cox multivariate regression analysis found that lymph node metastasis (95%CI: 1.489-13.830, P=0.007 6) and neural recidivism (95%CI: 1.228-6.544, P=0.014 7) were independent adverse prognostic factors. Cox multivariate regression analysis after stratification by site revealed that radiotherapy was a preferable prognostic factor for EBV-associated carcinoma of the large salivary glands (95%CI: 0.003-0.569, P=0.016 8). Conclusion: EBV associated carcinoma can be divided into two types, for which type Ⅰ was with abundant interstitial lymphocytes and type Ⅱ was lack of interstitial lymphocytes. TypeⅡ EBV-associated carcinoma has a worse prognosis than type Ⅰ. Radiation therapy can prolong the survival time of patients with primary EBV-associated carcinoma of large salivary glands.

Genetic variants in fat- and short-tailed sheep from high-throughput RNA-sequencing data.

The identification of genetic variations underlying desired phenotypes is one of the main challenges of current livestock genetic research. High-throughput transcriptome sequencing has been recognized as an efficient way to unravel the rich genetic variants across various species. The Lanzhou Fat-Tail sheep is an endangered sheep breed in China with a notable feature of an exaggerated fat tail that also independently occurs in other sheep breeds. However, the genetic mechanism underlying this particular trait has not been fully elucidated yet. In this study, we used RNA-seq on tissue samples (longissimus dorsi muscle, perinephric fat and tail fat) from three sheep breeds with either fat or thin tails and characterized the genetic variation in Lanzhou Fat-Tail sheep with the ultimate goal of identifying the causal genes and genetic networks responsible for the fat tail in this rare sheep breed. In total, 7 122 920 SNPs and 901 518 indels were detected in the nine individual sheep investigated, of which 606 952 SNPs (8.5%) and 77 633 indels (8.6%) overlapped with QTL associated with fat traits in sheep. Furthermore, we detected 26 613 specific SNPs in Lanzhou Fat-Tail sheep and 44 SNPs located in the same genomic position reported in another sheep breed with fat tails. Interestingly, 33 SNPs are selectively distributed on a chromosome 3 region (39.58-40.91 Mb) that was reported as a strong candidate genomic region for fat deposition in tails of sheep. Our research has also suggested that three genes (CREB1, WDR92 and ETAA1) may be associated with fat tail development. In summary, the resultant genetic variants data in this study provide a valuable resource for marker-assisted selection of the trait in Lanzhou Fat-Tail sheep populations.

Population structure and ancestry of Qinchuan cattle.

The aim of this study was to estimate population structure and ancestry of Qinchuan cattle by genotyping 27 individuals using the GeneSeek HD 77k BeadChip, and another 1355 cattle representing breeds distributed worldwide, which had been genotyped using the Illumina Bovine 50k BeadChip. Qinchuan cattle were characterized by a dominant Bos taurus ancestry, accompanied by a considerable proportion of Bos indicus ancestry based on principal components analysis and supervised admixture analysis. A small proportion of Bos javanicus ancestry was detected as well. A similar admixture pattern in both Qinchuan and Turkish cattle breeds reflects their similar degrees of zebu introgression. Our study presents a relatively clear view of the population structure and ancestry of Qinchuan cattle, serving to benefit our understanding of this breed and leading to better targeted conservation approaches moving forward.

Prevalence and genetic features of hepatitis E virus in swine, in Gansu, China.

The prevalence of hepatitis E virus (HEV) in domestic swine threats the public health, due to the risk of zoonotic transmission. In this study, we investigated the prevalence and genetic features of HEV in swine, in Gansu, which is geographically an important province in China. 377 fecal samples were collected from pig farms in Gansu province of China and tested for HEV RNA by RT-PCR. The prevalence rate is about 23% in pig farms of Gansu province. By RT-nPCR, 5' and 3' RACE methods, a whole genome with 7,284 nt in length, termed as swCH189, was obtained and investigated by nucleotide, codon and amino acid usage analyses. Phylogenetic tree analysis classified swCH189 strain into genotype 4e. Although this subtype has never been reported in the local population, genotype 4 is known as zoonotic and more pathogenic than other genotypes. According to the synonymous codon usage patterns of the three open reading frames (ORFs) of swCH189, compositional constraint mainly influences usage patterns of synonymous codons with A-end, while natural selections dominate in usage patterns of synonymous codons with G, C and U-ends. Genetic diversities of each ORFs, in respect to codon and amino acid usage patterns, are closely related to other members of genotype 4 in general, but with distinct features. Thus, the prevalence rate and the genetic features of HEV determined by this study are important for the prevention of zoonotic transmission of HEV from swine to human in this region as well as in China.

Down-regulation of DAB2IP promotes colorectal cancer invasion and metastasis by translocating hnRNPK into nucleus to enhance the transcription of MMP2.

DOC-2/DAB2 interacting protein (DAB2IP) is a RasGAP protein that shows a suppressive effect on cancer progression. Our previous study showed the involvement of transcription regulation of DAB2IP in metastasis of colorectal cancer (CRC). However, the molecular mechanisms of DAB2IP in regulating the progression of CRC need to be further explored. Here, we identified heterogeneous nuclear ribonucleoprotein K (hnRNPK) and matrix metalloproteinase 2 (MMP2) as vital downstream targets of DAB2IP in CRC cells by two-dimensional fluorescence difference gel electrophoresis and cDNA microassay, respectively. Mechanistically, down-regulation of DAB2IP increased the level of hnRNPK through MAPK/ERK signaling pathway. Subsequently, translocation of hnRNPK into nucleus enhanced the transcription activity of MMP2, and therefore promoted invasion and metastasis of CRC. Down-regulation of DAB2IP correlated negatively with hnRNPK and MMP2 expressions in CRC tissues. In conclusion, our study elucidates a novel mechanism of the DAB2IP/hnRNPK/MMP2 axis in the regulation of CRC invasion and metastasis, which may be a potential therapeutic target.

HSFY and ZNF280BY show copy number variations within 17 water buffalo populations.

Recent transcriptomic analysis of the bovine Y chromosome revealed abundant presence of multi-copy protein coding gene families on the male-specific region of the Y chromosome (MSY). Copy number variations (CNVs) of several MSY genes are closely related to semen quality and male reproduction in cattle. However, the CNVs of MSY genes in water buffalo are largely unknown. Therefore, this study aimed to investigate the CNVs of HSFY and ZNF280BY of 298 buffaloes from 17 populations distributed in China, Vietnam and Laos using quantitative PCR. Our results revealed that the median copy numbers of the HSFY and ZNF280BY genes were 47 (ranging from 20 to 145) and 269 (ranging from 73 to 974) respectively. In conclusion, this study indicated that HSFY and ZNF280BY showed abundant CNVs within swamp buffalo populations.

Short communication: Microbiological quality of raw cow milk and its association with herd management practices in Northern China.

Contamination of raw milk with bacterial pathogens is potentially hazardous to human health. The aim of this study was to evaluate the total bacteria count (TBC) and presence of pathogens in raw milk in Northern China along with the associated herd management practices. A total of 160 raw milk samples were collected from 80 dairy herds in Northern China. All raw milk samples were analyzed for TBC and pathogens by culturing. The results showed that the number of raw milk samples with TBC <2 × 106 cfu/mL and <1 × 105 cfu/mL was 146 (91.25%) and 70 (43.75%), respectively. A total of 84 (52.50%) raw milk samples were Staphylococcus aureus positive, 72 (45.00%) were Escherichia coli positive, 2 (1.25%) were Salmonella positive, 2 (1.25%) were Listeria monocytogenes positive, and 3 (1.88%) were Campylobacter positive. The prevalence of S. aureus was influenced by season, herd size, milking frequency, disinfection frequency, and use of a Dairy Herd Improvement program. The TBC was influenced by season and milk frequency. The correlation between TBC and prevalence of S. aureus or E. coli is significant. The effect size statistical analysis showed that season and herd (but not Dairy Herd Improvement, herd size, milking frequency, disinfection frequency, and area) were the most important factors affecting TBC in raw milk. In conclusion, the presence of bacteria in raw milk was associated with season and herd management practices, and further comprehensive study will be powerful for effectively characterizing various factors affecting milk microbial quality in bulk tanks in China.