Knockdown of growth differentiation factor-15 restrains prostate cancer through regulating MAPK/ERK signaling pathway.

Prostate cancer, prevalent among males, is influenced by various molecular factors, including Growth Differentiation Factor 15 (GDF15). Despite its recognized role in multiple tumor types, GDF15's specific involvement in prostate cancer remains insufficiently explored. This study investigates the regulatory function of GDF15 in prostate cancer. To explore GDF15's impact, we established GDF15 knockdown and overexpression models in prostate cancer cells. We quantified mRNA and protein levels using RT-PCR and Western blotting. Functional assays, including CCK8, Transwell, wound healing, and flow cytometry, were employed to evaluate cell proliferation, invasion, migration, and apoptosis. Additionally, the effect of GDF15 on tumor growth was assessed using a metastatic tumor model in nude mice. Elevated GDF15 expression was identified in prostate cancer tissues and cells. The knockdown of GDF15 led to the activation of the MAPK/ERK signaling pathway. C16PAF was found to counteract the inhibitory effects of sh-GDF15 on cell proliferation, invasion, migration, and apoptosis in LNCaP cells. It also reversed the sh-GDF15-induced alterations in the epithelial-mesenchymal transition (EMT) process. In vivo, C16PAF notably mitigated the sh-GDF15-induced suppression of tumor growth. The study demonstrated that sh-GDF15 inhibits cell proliferation, invasion, migration, EMT process, and tumor growth, while it promotes apoptosis. However, these effects were significantly reversed by C16PAF. The study underscores the potential of GDF15 as a target for novel therapeutic interventions in prostate cancer treatment and prevention. These findings illuminate GDF15's multifaceted role in prostate cancer pathogenesis and suggest its viability as a therapeutic target.

Numerical Simulation on Erosion and Stress on a Small-Diameter Hydrajet Fracturing Tool.

Conventional hydrajet fracturing techniques are often frustrated when they are applied to some specific well types, such as casing-damaged and small-diameter wells. It is of great significance to investigate the erosion and stress on a small-diameter hydrajet fracturing tool during its service and clarify the relevant influencing factors. Based on the solid-liquid two-phase flow theory and erosion model, a numerical simulation was conducted on the erosion and stress on a small-diameter hydrajet fracturing tool by using the computational fluid dynamics approach in order to understand how the inlet flow rate, particle size, and particle mass concentration affect the erosion and stress on the tool. The results show that the erosion on the small-diameter hydrajet fracturing tool is generally a cutting erosion of proppant particles on the tool body. Such erosion occurs on the lower wall of the nozzle, and the erosion at the upper-0° nozzle is higher in rate and smaller in area than that at the lower-180° nozzle. The maximum stress of the small-diameter hydrajet fracturing tool is concentrated on the upper and lower walls of the upper and lower nozzles, especially the lower part inside the upper nozzle. The maximum erosion rate, average erosion rate, and maximum stress on the wall near the nozzle during fracturing increase as the inlet flow rate and particle mass concentration increase and decrease as the proppant particle size increases.

Weighted single-step GWAS identified candidate genes associated with carcass traits in a Chinese yellow-feathered chicken population.

Carcass traits in broiler chickens are complex traits that are influenced by multiple genes. To gain deeper insights into the genetic mechanisms underlying carcass traits, here we conducted a weighted single-step genome-wide association study (wssGWAS) in a population of Chinese yellow-feathered chicken. The objective was to identify genomic regions and candidate genes associated with carcass weight (CW), eviscerated weight with giblets (EWG), eviscerated weight (EW), breast muscle weight (BMW), drumstick weight (DW), abdominal fat weight (AFW), abdominal fat percentage (AFP), gizzard weight (GW), and intestine length (IL). A total of 1,338 broiler chickens with phenotypic and pedigree information were included in this study. Of these, 435 chickens were genotyped using a 600K single nucleotide polymorphism chip for association analysis. The results indicate that the most significant regions for 9 traits explained 2.38% to 5.09% of the phenotypic variation, from which the region of 194.53 to 194.63Mb on chromosome 1 with the gene RELT and FAM168A identified on it was significantly associated with CW, EWG, EW, BMW, and DW. Meanwhile, the 5 traits have a strong genetic correlation, indicating that the region and the genes can be used for further research. In addition, some candidate genes associated with skeletal muscle development, fat deposition regulation, intestinal repair, and protection were identified. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that the genes are involved in processes such as vascular development (CD34, FGF7, FGFR3, ITGB1BP1, SEMA5A, LOXL2), bone formation (FGFR3, MATN1, MEF2D, DHRS3, SKI, STC1, HOXB1, HOXB3, TIPARP), and anatomical size regulation (ADD2, AKT1, CFTR, EDN3, FLII, HCLS1, ITGB1BP1, SEMA5A, SHC1, ULK1, DSTN, GSK3B, BORCS8, GRIP2). In conclusion, the integration of phenotype, genotype, and pedigree information without creating pseudo-phenotype will facilitate the genetic improvement of carcass traits in chickens, providing valuable insights into the genetic architecture and potential candidate genes underlying carcass traits, enriching our understanding and contributing to the breeding of high-quality broiler chickens.

Evaluation of the selection of key individuals for genotype imputation in Chinese yellow-feathered chicken.

Genotype imputation is a powerful technique employed by next-generation sequencing (NGS) and genotyping arrays, which can significantly enhance the cost-effectiveness and efficiency of genomic selection. The accuracy of imputation is largely determined by the choice of reference panel, with previous studies generally demonstrating that a closely related population as a reference panel leads to greater accuracy than a more distantly related population. Various strategies have been proposed for selecting desirable individuals via targeted resequencing, but their efficiencies need further improvement. In this study, we present a practical broiler selection methodology for a local Chinese chicken line that integrates established methods based on pedigree, genomics, and random sampling, and leverages genotype and pedigree information from the yellow-plumage dwarf chicken line. The efficacy of these selection strategies was assessed by evaluating their ability to accurately impute masked genotypes from data obtained using a 600K chip. Our findings reveal that the pedigree-based method yields superior accuracy in genotype imputation, whereas the haplotype-based method exhibits greater stability. Nonetheless, the impact of these targeted methods for selecting key individuals is slightly different when initiating a new sequencing project in a production context. Overall, this study highlights the advantages of using the pedigree-based approach as the preferred method for optimizing genotype imputation in broiler chickens.

Haplotype analysis of genomic prediction by incorporating genomic pathway information based on high-density SNP marker in Chinese yellow-feathered chicken.

Genomic selection using single nucleotide polymorphism (SNP) markers is now intensively investigated in breeding and has been widely utilized for genetic improvement. Currently, several studies have used haplotype (consisting of multiallelic SNPs) for genomic prediction and revealed its performance advantage. In this study, we comprehensively evaluated the performance of haplotype models for genomic prediction in 15 traits, including 6 growth, 5 carcass, and 4 feeding traits in a Chinese yellow-feathered chicken population. We adopted 3 methods to define haplotypes from high-density SNP panels, and our strategy included combining Kyoto Encyclopedia of Genes and Genomes pathway information and considering linkage disequilibrium (LD) information. Our results showed an increase in prediction accuracy due to haplotypes ranging from -0.04∼27.16% in all traits, where the significant improvements were found in 12 traits. The estimates of haplotype epistasis heritability were strongly correlated with the accuracy increase by haplotype models. In addition, incorporating genomic annotation information could further increase the accuracy of the haplotype model, where the further increase in accuracy is significantly relative to the increase of relative haplotype epistasis heritability. The genomic prediction using LD information for constructing haplotypes has the best prediction performance among the 4 traits. These results uncovered that haplotype methods were beneficial for genomic prediction, and the accuracy could be further increased by incorporating genomic annotation information. Moreover, using LD information would potentially improve the performance of genomic prediction.

Association of serum anion gap and risk of long-term mortality in patients following coronary artery bypass grafting: A propensity score matching study.

BACKGROUND: The present study aimed to explore the relationship between serum anion gap (AG) and long-term mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS: Clinical variables were extracted among patients undergoing CABG from Medical Information Mart for Intensive Care III (MIMIC III) database. The primary outcome was 4-year mortality following CABG. An optimal cut-off value of AG was determined by the receiver operating characteristic (ROC) curve. The Kaplan-Meier (K-M) analysis and multivariate Cox hazard analysis were performed to investigate the prognostic value of AG in long-term mortality after CABG. To eliminate the bias between different groups, propensity score matching (PSM) was conducted to validate the findings. RESULTS: The optimal cut-off value of AG was 17.00 mmol/L. Then a total of 3162 eligible patients enrolled in this study were divided into a high AG group (≥17.00, n = 1022) and a low AG group (<17.00, n = 2,140). A lower survival rate was identified in the high AG group based on the K-M curve (p < .001). Compared with patients in the low AG group, patients in the high AG group had an increased risk of long-term mortality [1-year mortality: hazard ratio, HR: 2.309, 95% CI (1.672-3.187), p < .001; 2-year mortality: HR: 1.813, 95% CI (1.401-2.346), p < .001; 3- year mortality: HR: 1.667, 95% CI (1.341-2.097), p < .001; 4-year mortality: HR: 1.710, 95% CI (1.401-2.087), p < .001] according to multivariate Cox hazard analysis. And further validation of above results was consistent in the matched cohort after PSM. CONCLUSIONS: The AG is an independent predictive factor for long-term all-cause mortality in patients following CABG, where a high AG value is associated with an increased mortality.

Cardiac venous malformation concurrent with multiple hepatic venous malformations: A case report.

A 50-year-old woman who had previously undergone right radical mastectomy presented with chest tightness and shortness of breath after physical activities. A cardiac mass and multiple hepatic lesions were successively detected. We first performed hepatic puncture biopsy. Histopathologic examination confirmed that the multiple hepatic lesions were venous malformations. Based on the imaging findings and previous reports in the literature, we boldly speculated that the cardiac mass was also a venous malformation. The cardiac venous malformation was successfully resected, and the postoperative pathology confirmed our suspicion.

MicroRNA-4735-3p Facilitates Ferroptosis in Clear Cell Renal Cell Carcinoma by Targeting SLC40A1.

Objective: Clear cell renal cell carcinoma (ccRCC) is the major histopathological subtype of renal cancer, and ferroptosis is implicated in the pathogenesis of ccRCC. The present study was aimed at investigating the role and underlying mechanisms of microRNA-4735-3p (miR-4735-3p) in ccRCC. Methods: Human ccRCC cell lines were transfected with the miR-4735-3p mimic or inhibitor to manipulate the expression of miR-4735-3p. Cell proliferation, colony formation, cell migration, cell invasion, cell death, oxidative stress, lipid peroxidation, and iron metabolism were determined. To validate the necessity of solute carrier family 40 member 1 (SLC40A1), human ccRCC cell lines were overexpressed with SLC40A1 using adenoviral vectors. Results: miR-4735-3p expression was reduced in human ccRCC tissues and cell lines but elevated upon ferroptotic stimulation. The miR-4735-3p mimic increased, while the miR-4735-3p inhibitor decreased oxidative stress, lipid peroxidation, iron overload, and ferroptosis of human ccRCC cell lines. Mechanistic studies identified SLC40A1 as a direct target of miR-4735-3p, and SLC40A1 overexpression significantly attenuated iron overload and ferroptosis in the miR-4735-3p mimic-treated human ccRCC cell lines. Conclusion: miR-4735-3p facilitates ferroptosis and tumor suppression in ccRCC by targeting SLC40A1.

Predictive Value of Blood Urea Nitrogen to Albumin Ratio in Long-Term Mortality in Intensive Care Unit Patients with Acute Myocardial Infarction: A Propensity Score Matching Analysis.

Background: Blood urea nitrogen to albumin ratio (BAR) has been implicated in predicting outcomes of various inflammatory-related diseases. However, the predictive value of BAR in long-term mortality in patients with acute myocardial infarction (AMI) has not yet been evaluated. Methods: In this retrospective cohort study, the patients were recruited from the Medical Information Mart for Intensive Care III (MIMIC III) database and categorized into two groups by a cutoff value of BAR. Kaplan-Meier (K-M) analysis and Cox proportional hazard model were performed to determine the predictive value of BAR in long-term mortality following AMI. In order to adjust the baseline differences, a 1:1 propensity score matching (PSM) was carried out and the results were further validated. Results: A total of 1827 eligible patients were enrolled. The optimal cutoff value of BAR for four-year mortality was 7.83 mg/g. Patients in the high BAR group tended to have a longer intensive care unit (ICU) stay and a higher rate of one-, two-, three- and four-year mortality (all p<0.001) compared with those in the low BAR group. K-M curves indicated a significant difference in four-year survival (p<0.001) between low and high BAR groups. The Cox proportional hazards model showed that higher BAR (>7.83) was independently associated with increased four-year mortality in the entire cohort, with a hazard ratio (HR) of 1.478 [95% CI (1.254-1.740), p<0.001]. After PSM, the baseline characteristics of 312 pairs of patients in the high and low BAR groups were well balanced, and similar results were observed in K-M curve (p=0.003). Conclusion: A higher BAR (>7.83) was associated with four-year mortality in patients with AMI. As an easily available biomarker, BAR can predict the long-term mortality in AMI patients independently.

Blood Urea Nitrogen-to-Albumin Ratio in Predicting Long-Term Mortality in Patients Following Coronary Artery Bypass Grafting: An Analysis of the MIMIC-III Database.

BACKGROUND: This study examined the role of blood urea nitrogen-to-albumin ratio (BAR) in predicting long-term mortality in patients undergoing coronary artery bypass grafting (CABG). METHODS: In this retrospective cohort study, patients undergoing CABG were enrolled from the Medical Information Mart for Intensive Care III (MIMIC III) database. Patients were divided into the three groups according to the optimal cutoff values of BAR determined by X-tile software. The survival curve was constructed by the Kaplan-Meier method and multivariate Cox regression analysis was performed to explore the independent prognostic factors of 1- and 4-year mortality after CABG. The receiver operating characteristic (ROC) curves and the areas under the ROC curves (AUCs) were calculated to estimate the accuracy of BAR in predicting the outcomes. Subgroup analyses were also carried out. RESULTS: A total of 1,462 patients at 4-year follow-up were included, of which 933, 293, and 236 patients were categorized into the group 1 (≤ 6.45 mg/g), group 2 (>6.45 and ≤ 10.23 mg/g), and group 3 (>10.23 mg/g), respectively. Non-survivors showed an increased level of BAR at both 1- (p < 0.001) and 4-year (p < 0.001) follow-up compared with the survivors. The patients with a higher BAR had a higher risk of 1- and 4-year mortality following CABG (33.05 vs. 14.33 vs. 5.14%, p < 0.001 and 52.97 vs. 30.72 vs. 13.08%, p < 0.001, respectively). Cox proportional hazards regression model suggested a higher BAR as an independent risk factor of 1-year mortality (HR 3.904; 95% CI 2.559-5.956; P < 0.001) and 4-year mortality (HR 2.895; 95% CI 2.138-3.921; P < 0.001) after adjusting for confounders. Besides, the receiver operating characteristic (ROC) curves showed the better predictive ability of BAR compared to other grading scores at both 1- (0.7383, 95% CI: 0.6966-0.7800) and 4-year mortality (0.7189, 95% CI: 0.6872-0.7506). Subgroup analysis demonstrated no heterogeneous results of BAR in 4-year mortality in particular groups of patient. CONCLUSION: This report provided evidence of an independent association between 1- and 4-year mortality after CABG and BAR. A higher BAR was associated with a higher risk of long-term mortality and could serve as a prognostic predictor in patients following CABG.

[Influence of different treatments of unilateral testicular torsion on the long-term fertility of the patient].

OBJECTIVE: To evaluate the effects of different treatments of unilateral testicular torsion on the long-term fertility of the patient. METHODS: We reviewed the clinical and fertility-related follow-up data on 92 cases of unilateral testicular torsion treated by orchiectomy (the OE group, n = 49) or orchiopexy (the OP group, n = 43) between January 2000 and December 2014. We compared the testis volume, semen parameters, reproductive hormone indexes, natural pregnancy rate (NPR) and time to pregnancy (TTP) between the two groups, and analyzed the influence of orchiectomy and orchiopexy on the fertility of the patients. RESULTS: Totally, 77 of the men met the inclusion criteria and included in this study, 40 in the OE and 37 in the OP group. Follow-up data exhibited no statistically significant difference between the two groups of patients in the age of marriage, mean frequency of intercourse or sexual function. The men in the OE group, compared with those in the OP group, showed a larger volume of the opposite testis (ï¼»17.62 ± 2.15ï¼½ vs ï¼»16.86 ± 2.05ï¼½ ml, P > 0.05), but lower semen volume (ï¼»4.09 ± 0.89ï¼½ vs ï¼»4.11 ± 0.76ï¼½ ml, P > 0.05), sperm concentration (ï¼»27.60 ± 7.58ï¼½ vs ï¼»27.74 ± 6.80ï¼½ ×106/ml, P > 0.05), sperm motility (ï¼»60.14 ± 14.50ï¼½% vs ï¼»60.29 ± 16.36ï¼½%, P > 0.05), and percentages of progressively motile sperm (PMS) (ï¼»38.37 ± 10.88ï¼½% vs ï¼»38.82 ± 9.73ï¼½%, P > 0.05) and morphologically abnormal sperm (MAS) (ï¼»29.80 ± 7.29ï¼½% vs ï¼»29.55 ± 7.03ï¼½%, P > 0.05), lower levels of FSH (ï¼»8.01 ± 2.31ï¼½ vs ï¼»8.12 ± 2.63ï¼½ IU/L, P > 0.05), LH (ï¼»15.05 ± 4.20ï¼½ vs ï¼»15.46 ± 4.76ï¼½ IU/L,P > 0.05) and T (ï¼»19.06 ± 3.60ï¼½ vs ï¼»19.46 ± 4.02ï¼½ nmol/L, P > 0.05), lower NPR (75.0% ï¼»30/40ï¼½ vs 83.8% ï¼»31/37ï¼½, P > 0.05) and longer TTP (ï¼»18.0 ± 5.7ï¼½ vs ï¼»14.6 ± 3.8ï¼½ mo, P > 0.05). CONCLUSIONS: For patients with unilateral testicular torsion, orchiectomy achieved a lower semen quality and NPR and a longer TTP than orchiopexy, but induced no significant fertility decrease. Detorsion of the torsioned testis little affects the fertility of the patient.

[Significance of atypical small acinar proliferation and high-grade prostatic intraepithelial neoplasia in prostate biopsy in China].

OBJECTIVE: To assess the rates of atypical small acinar proliferation (ASAP) and high-grade prostatic intraepithelial neoplasia (HGPIN) detected in prostate biopsy in China and the risk of PCa found in subsequent repeat biopsy. METHODS: A total of 2,456 patients underwent TRUS-guided prostate biopsy with the samples of ASAP and/or HGPIN tissues in our hospital at least twice between July 2014 and June 2019. We analyzed the findings of digital rectal examination, prostate volumes, PSA levels, and the results of prostate biopsies. RESULTS: Initial prostate biopsies revealed 737 cases of PCa (30.0%), 215 cases of ASAP (8.8%), 98 cases of HGPIN (4.0%), and 18 cases of ASAP+HGPIN (0.7%). Totally, 313 of the patients met the inclusion criteria and included in this study. Of the 215 cases of ASAP confirmed in the first biopsy, 72 and 25 were diagnosed with PCa in the second and third biopsies, respectively, 83 with Gleason score (GS) 6, 14 with GS7, 57 with T1c and 40 with T2a tumors. Of the 98 cases of HGPIN confirmed in the first biopsy, 1 was diagnosed with PCa in the second and another 1 in the third biopsy, both with GS6 and T1c tumors. Of the 18 cases of ASAP+HGPIN confirmed in the first biopsy, 7 and 3 were diagnosed with PCa in the second and third biopsies, respectively, 7 with GS6, 3 with GS7, 6 with T1c and 4 with T2a tumors. CONCLUSIONS: ASAP is a significant risk factor for PCa and repeat prostate biopsy should be performed for patients diagnosed with ASAP in the first biopsy. Whether repeat biopsy is necessary for those diagnosed with HGPIN depends on other related clinical parameters./.

[Impact of immune inflammation on the proliferation and apoptosis of benign prostatic hyperplasia cells].

Objective: To investigate the impact of macrophage-induced immune inflammation on the proliferation and apoptosis of BPH cells and its possible mechanism. METHODS: Macrophages were stimulated with phorbol myristate acetate, co-cultured with BPH-1 cells, and then treated with the androgen receptor (AR) inhibitor or anti-CD40L antibody. The immunohistochemical biomarkers of the T lymphocytes (CD4 and CD8), B lymphocyte (CD20) and macrophages (CD68), AR, CD40/CD40L, and inflammatory factors IL-1, IL-6 and TNF-α were measured before and after treatment. The proliferation and apoptosis of the cells were observed by MTT assay, colony-forming assay and flow cytometry, and the expressions of cell apoptosis- and MAPK signaling pathway-related proteins were determined by qRT-PCR and Western blot. RESULTS: Significantly increased proliferation and decreased apoptosis of the cells, up-regulated expressions of Bcl-2, IL-1, IL-6, TNF-α, AR, CD40 and CD40L, and down-regulated expression of Bax were observed in the BPH-1 cells co-cultured with macrophages (the M-BPH-1 group) compared with those in the blank control (B-BPH-1) group (P < 0.01). In comparison with the BPH-1 cells treated with normal saline, those treated with either low-dose CD40L (L-CD40L) or high-dose CD40L (H-CD40L) showed markedly inhibited proliferation, increased apoptosis, up-regulated expression of Bax, and down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α (P < 0.01), and those in the low- and high-dose AR (L-AR and H-AR) inhibitor groups exhibited remarkably reduced proliferation, increased apoptosis, down-regulated expressions of Bcl-2, IL-1, IL-6 and TNF-α, and up-regulated expression of Bax (P < 0.01). The phosphorylation levels of JNK, ERK and P38 were significantly elevated in the M-BPH-1 group, but declined in the H-CD40L and the H-AR inhibitor groups compared with those in the B-BPH-1 group, all in a concentration-dependent manner (P < 0.01). CONCLUSIONS: Macrophage-induced immune inflammation regulates AR and CD40/CD40L expressions and promotes the proliferation and inhibits the apoptosis of BPH-1 cells by activating the MAPK signaling pathway. /.

Integrative Bioinformatics Analysis Revealed Mitochondrial Defects Underlying Hypoplastic Left Heart Syndrome.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is one of the most complex congenital cardiac malformations, and the molecular mechanism of heart failure (HF) in HLHS is still elusive. METHODS: Integrative bioinformatics analysis was performed to unravel the underlying genes and mechanisms involved in HF in HLHS. Microarray dataset GSE23959 was screened out for the differentially expressed genes (DEGs), after which the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analyses were carried out using the Metascape. The protein-protein interaction (PPI) network was generated, and the modules and hub genes were identified with the Cytoscape-plugin. And the integrated network of transcription factor (TF)-DEGs and miRNA-DEGs was constructed, respectively. RESULTS: A total of 210 DEGs were identified, including 135 up-regulated and 75 down-regulated genes. The functional enrichment analysis of DEGs pointed towards the mitochondrial-related biological processes, cellular components, molecular functions and signaling pathways. A PPI network was constructed including 155 nodes as well as 363 edges. And 15 hub genes, such as NDUFB6, UQCRQ, SDHD, ATP5H, were identified based on three topological analysis methods and mitochondrial components and functions were the most relevant. Furthermore, by integrating network interaction construction, 23 TFs (NFKB1, RELA, HIF1A, VHL, GATA1, PPAR-γ, etc.) as well as several miRNAs (hsa-miR-155-5p, hsa-miR-191-5p, hsa-mir-124-3p, hsa-miR-1-3p, etc.) were detected and indicated the possible involvement of NF-κB signaling pathways in mitochondrial dysfunction in HLHS. CONCLUSION: The present study applied the integrative bioinformatics analysis and revealed the mitochondrial-related key genes, regulatory pathways, TFs and miRNAs underlying the HF in HLHS, which improved the understanding of disease mechanisms and the development of novel therapeutic targets.

Genome­wide association study and genomic prediction for growth traits in yellow-plumage chicken using genotyping-by-sequencing.

BACKGROUND: Growth traits are of great importance for poultry breeding and production and have been the topic of extensive investigation, with many quantitative trait loci (QTL) detected. However, due to their complex genetic background, few causative genes have been confirmed and the underlying molecular mechanisms remain unclear, thus limiting our understanding of QTL and their potential use for the genetic improvement of poultry. Therefore, deciphering the genetic architecture is a promising avenue for optimising genomic prediction strategies and exploiting genomic information for commercial breeding. The objectives of this study were to: (1) conduct a genome-wide association study to identify key genetic factors and explore the polygenicity of chicken growth traits; (2) investigate the efficiency of genomic prediction in broilers; and (3) evaluate genomic predictions that harness genomic features. RESULTS: We identified five significant QTL, including one on chromosome 4 with major effects and four on chromosomes 1, 2, 17, and 27 with minor effects, accounting for 14.5 to 34.1% and 0.2 to 2.6% of the genomic additive genetic variance, respectively, and 23.3 to 46.7% and 0.6 to 4.5% of the observed predictive accuracy of breeding values, respectively. Further analysis showed that the QTL with minor effects collectively had a considerable influence, reflecting the polygenicity of the genetic background. The accuracy of genomic best linear unbiased predictions (BLUP) was improved by 22.0 to 70.3% compared to that of the conventional pedigree-based BLUP model. The genomic feature BLUP model further improved the observed prediction accuracy by 13.8 to 15.2% compared to the genomic BLUP model. CONCLUSIONS: A major QTL and four minor QTL were identified for growth traits; the remaining variance was due to QTL effects that were too small to be detected. The genomic BLUP and genomic feature BLUP models yielded considerably higher prediction accuracy compared to the pedigree-based BLUP model. This study revealed the polygenicity of growth traits in yellow-plumage chickens and demonstrated that the predictive ability can be greatly improved by using genomic information and related features.

Influence of Androgen Receptor Antagonist MDV3100 Therapy on Rats With Benign Prostatic Hyperplasia.

PURPOSE: To probe the effect and mechanism of androgen receptor antagonist MDV3100 on benign prostatic hyperplasia (BPH) of rats. METHODS: BPH rat model was induced by testosterone propionate. Then antagomir-miR-21-3p or agomir-miR-21-3p was injected into rats before MDV3100 treatment. The prostate index was measured by weighing the wet weight of the rat prostate. The structural morphology of rat prostate was observed after hematoxylin & eosin staining. Immunohistochemistry was applied to evaluate the expression levels of Ki-6 and inflammatory cytokines (interleukin [IL]-6, IL-18, and tumor necrosis factor-α) in rat prostate tissues. Quantitative reverse transcription polymerase chain reaction was utilized for assessment of miR-21-3p expression, and Western blot for the performance of the phosphorylation levels of IKKα and p65. RESULTS: Injection of testosterone propionate caused increased prostate gland hyperplasia, heightened miR-21-3p level, and activated nuclear factor-kappa B (NF-κB) signaling pathway. Additionally, BPH was accompanied by inflammatory response, as evidenced by enhanced expressions of Ki-67 and inflammatory cytokines. MDV3100 exposure ameliorated BPH and suppressed miR-21-3p expression. Overexpression of miR-21-3p intensified BPH and inflammation level, while knockdown of miR-21-3p relieved BPH. The coeffect of miR-21-3p upregulation and MDV3100 subjection led to higher inflammatory response, elevated phosphorylation levels of IKKα and p65 than MDV3100 treatment alone. CONCLUSION: Androgen receptor antagonist MDV3100 alleviates BPH and inflammatory response through miR-21-3p downregulation and NF-κB signaling pathway blockade.

Polymorphisms of AMY1A gene and their association with growth, carcass traits and feed intake efficiency in chickens.

Investigations on the association between chicken traits and genetic variations can provide basic information to improve production performance in chickens. In our previous work, we genotyped 450 male chickens with a 600 K SNP array [1] and found that several SNPs in the genomic regions of the amylase alpha 1A (AMY1A) gene were significantly associated with feed intake efficiency and carcass traits. Given the lower accuracy of the SNP array, we performed direct sequencing with male and female chickens to further test chicken AMY1A polymorphisms and investigate their association with 17 traits in chickens. The results showed that 7 SNPs in the 5' flanking region, exon, intron and 3' UTR (3' untranslated region) of AMY1A, were significantly associated with daily gain (DG), average daily feed intake (ADFI), leg muscle weight (LMW) and abdominal fat (AF) (p < 0.05). Additionally, the haplotypes based on three SNPs, rs15910189, rs314354067 and rs316026696, showed significant associations with DG (p < 0.01), ADFI and AF (p < 0.05). To better understand the transcriptional regulation of AMY1A, we cloned its 5' flanking region and found that the SNPs rs316436216 and rs314213090 which might change the transcriptional regulator binding sites, were in the suppressor and enhancer regions, respectively. In addition, luciferase assays revealed that the SNP rs314613110 in the 3' UTR influenced the binding of the miRNA gga-miR-1764-3p. To validate whether there is any copy number variation in AMY1A in our population, we performed a genome-wide assessment of CNVs through whole-genome resequencing data. However, no CNV was found in AMY1A in our population, which is different from the increased copy number of AMY1A found in humans who consume a high-starch diet. Therefore, the present study provides substantial evidence for the association of AMY1A polymorphisms with growth traits and feed intake efficiency, which might contribute to chicken breeding programs.

HnRNPA2B1 promotes the proliferation of breast cancer MCF-7 cells via the STAT3 pathway.

HnRNPA2/B1 is highly expressed in many tumors. However, the role of hnRNPA2/B1 in breast cancer is not clear. In this study, we found the proliferation rate was decreased after knockout of hnRNPA2/B1 by CRISPR-CAS9 in MCF-7 cells, as demonstrated by the reduced expression of CDK4 and p-AKT, and the increased expression of P27. Besides this, the western blot results showed that knockout of hnRNPA2/B1 increased the rate of apoptosis and declined autophagy. By in vivo assay, we found that knockout of hnRNPA2/B1 suppressed tumor growth in a xenograft mouse model. Immunohistochemical staining results confirmed knockout of hnRNPA2/B1 impaired tumor angiogenesis, as illustrated by downregulated expression of VEGF-A. Besides this, interacting proteins with hnRNPA2/B1 were identified by mass spectrometry and the PPI network was constructed. GO analysis suggests that the Interacting proteins are mainly enriched in the Wnt signaling pathway, tumor necrosis factor-mediated signaling pathway, translation, and so on. We then identified hnRNPA2/B1 interacted with signal transducer and activator of transcription 3 (STAT3), as supported by the colocalization of hnRNPA2/B1 and STAT3. Meanwhile, knockout of hnRNPA2/B1 inhibited the phosphorylation of STAT3. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth in vitro and in vivo by activating the STAT3 pathway, regulating apoptosis and autophagy.