Genome-wide detections for runs of homozygosity and selective signatures reveal novel candidate genes under domestication in chickens.

BACKGROUND: Indigenous chickens were developed through a combination of natural and artificial selection; essentially, changes in genomes led to the formation of these modern breeds via admixture events. However, their confusing genetic backgrounds include a genomic footprint regulating complex traits, which is not conducive to modern animal breeding. RESULTS: To better evaluate the candidate regions under domestication in indigenous chickens, we considered both runs of homozygosity (ROHs) and selective signatures in 13 indigenous chickens. The genomes of Silkie feather chickens presented the highest heterozygosity, whereas the highest inbreeding status and ROH number were found in Luhua chickens. Short ROH (< 1 Mb), were the principal type in all chickens. A total of 291 ROH islands were detected, and QTLdb mapping results indicated that body weight and carcass traits were the most important traits. An ROH on chromosome 2 covering VSTM2A gene was detected in 12 populations. Combined analysis with the Tajima's D index revealed that 18 genes (e.g., VSTM2A, BBOX1, and RYR2) were under selection and covered by ROH islands. Transcriptional analysis results showed that RYR2 and BBOX1 were specifically expressed in the heart and muscle tissue, respectively. CONCLUSION: Based on genome-wide scanning for ROH and selective signatures, we evaluated the genomic characteristics and detected significant candidate genes covered by ROH islands and selective signatures. The findings in this study facilitated the understanding of genetic diversity and provided valuable insights for chicken breeding and conservation strategies.

Verification of Outer Hair Cell Motor Protein, Prestin, as a Serological Biomarker for Mouse Cochlear Damage.

The motor protein prestin, found in the inner ear's outer hair cells (OHCs), is responsible for high sensitivity and sharp frequency selectivity in mammalian hearing. Some studies have suggested that prestin could be a serological biomarker for cochlear damage, as OHCs are highly vulnerable to damage from various sources. However, the reported data are inconsistent and lack appropriate negative controls. To investigate whether prestin can be used as a serological biomarker for cochlear damage or stress, we measured prestin quantities in the bloodstreams of mice using ELISA kits from different companies. Wildtype (WT) mice were exposed to different ototoxic treatments, including noise exposure and ototoxic reagents that rapidly kill OHCs. Prestin-knockout (KO) mice were used as a negative control. Our data show that some ELISA kits were not able to detect prestin specifically. The ELISA kit that could detect the prestin protein from cochlear homogenates failed to detect prestin in the bloodstream, despite there being significant damage to OHCs in the cochleae. Furthermore, the optical densities of the serum samples, which correlate to prestin quantities, were significantly influenced by hemolysis in the samples. In conclusion, Prestin from OHCs is not a sensitive and reliable serological biomarker for detecting cochlear damage in mice using ELISA.

Novel Insights into the Circadian Rhythms Based on Long Noncoding and Circular RNA Profiling.

Circadian rhythm disorders pose major risks to human health and animal production activity, and the hypothalamus is the center of circadian rhythm regulation. However, the epigenetic regulation of circadian rhythm based on farm animal models has been poorly investigated. We collected chicken hypothalamus samples at seven time points in one light/dark cycle and performed long noncoding RNA (lncRNA), circular RNA (circRNA), and mRNA sequencing to detect biomarkers associated with circadian rhythm. We enhanced the comprehensive expression profiling of ncRNAs and mRNAs in the hypothalamus and found two gene sets (circadian rhythm and retinal metabolism) associated with the light/dark cycle. Noncoding RNA networks with circadian expression patterns were identified by differential expression and circadian analysis was provided that included 38 lncRNAs, 15 circRNAs, and 200 candidate genes. Three lncRNAs (ENSGALT00000098661, ENSGALT00000100816, and MSTRG.16980.1) and one circRNA (novel_circ_010168) in the ncRNA-mRNA regulatory network were identified as key molecules influencing circadian rhythm by regulating AOX1 in retinal metabolism. These ncRNAs were predicted to be related to pernicious anemia, gonadal, eye disease and other disorders in humans. Together, the findings of this study provide insights into the epigenetic mechanisms of circadian rhythm and reveal AOX1 as a promising target of circadian rhythm regulation.

Association of Helicobacter pylori CagA seropositivity with gastric precancerous lesions: a systematic review and meta-analysis.

The objective of this meta-analysis is to delineate the association between H. pylori CagA serological status and the prevalence of gastric precancerous lesions (GPL). We searched peer-reviewed articles up to October 2023. The extraction of data from the included studies was carried out as well as the quality assessment. Pooled effect sizes were calculated using a random effect model. Thirteen studies met the inclusion criteria, comprising 2728 patients with GPL and 17 612 controls. The aggregate odds ratio (OR) for the association between serum CagA and GPL was 2.74 (95% CI = 2.25-3.32; P  = 0.00; I 2  = 60.4%), irrespective of H. pylori infection status. Within the H. pylori -infected cohort, the OR was 2.25 (95% CI = 1.99-2.56; P  = 0.00; I 2  = 0.0%). Conversely, among the non-infected individuals, the OR was 1.63 (95% CI = 1.04-2.54; P  = 0.038; I 2  = 0.0%). Heterogeneity was explored using subgroup and meta-regression analyses, indicating that the variability between studies likely stemmed from differences in disease classification. Our results demonstrated robustness and negligible publication bias. The meta-analysis underscores a more pronounced association between H. pylori CagA seropositivity and the risk of developing GPL than between seronegativity and the same risk, irrespective of H. pylori infection status at the time. Additionally, the strength of the association was heightened in the presence of an active H. pylori infection. The implications of these findings advocate for the utility of CagA serostatus as a potential biomarker for screening GPL.

Diagnostic and prognostic value of circulating exosomal glypican-1 in pancreatic cancer: a meta-analysis.

BACKGROUND: Pancreatic cancer (PC) is usually detected in the advanced stages. Liquid biopsy has become a revolutionary strategy for cancer diagnosis and prognosis prediction. This study aims to investigate the diagnostic and prognostic value of circulating exosomal glypican-1 (GPC-1) in PC. METHODS: We systematically searched relevant studies. For diagnostic accuracy, pooled sensitivity and specificity and the area under the summary receiver operating characteristic curve (AUC) were calculated. Regarding prognostic value, hazard ratios (HRs) and 95% CIs for overall survival (OS) were summarized by using a random-effects model. RESULTS: We found 8 studies that examined the diagnostic value of circulating exosomal GPC-1 in PC, and 3 studies that investigated its prognostic value. Pooled sensitivity and specificity were 0.88 (95% CI, 0.65-0.97) and 0.86 (95% CI, 0.72-0.94). The AUC was 0.93 (95% CI, 0.90-0.95). Prognostic analysis showed that higher levels of circulating exosomal GPC-1 were associated with poorer OS in PC patients, and the combined HR for OS was 4.59 (random-effects model, 95% CI = 1.17-18.03, P = .022). The results of both studies were robust and neither had publication bias. CONCLUSION: Circulating exosomal GPC-1 may be used as a diagnostic and prognostic biomarker for PC. However, this result needs to be validated by further research using a larger sample size.

Whole-genome variants dataset of 209 local chickens from China.

Compared to commercial chickens, local breeds exhibit better in meat quality and flavour, but the productivity (e.g., growth rate, body weight) of local chicken breeds is rather low. Genetic analysis based on whole-genome sequencing contributes to elucidating the genetic markers or putative candidate genes related to some economic traits, facilitating the improvement of production performance, the acceleration of breeding progress, and the conservation of genetic resources. Here, a total of 209 local chickens from 13 breeds were investigated, and the observation of approximately 91.4% high-quality sequences (Q30 > 90%) and a mapping rate over 99% for each individual indicated good results of this study, as confirmed by a genome coverage of 97.6%. Over 19 million single nucleotide polymorphisms (SNPs) and 1.98 million insertion-deletions (InDels) were identified using the reference genome (GRCg7b), further contributing to the public database. This dataset provides valuable resources for studying genetic diversity and adaptation and for the cultivation of new chicken breeds/lines.

Large-scale transcriptomic and genomic analyses reveal a novel functional gene SERPINB6 for chicken carcass traits.

BACKGROUND: Carcass traits are crucial indicators of meat production efficiency. However, the molecular regulatory mechanisms associated with these traits remain unclear. RESULTS: In this study, we conducted comprehensive transcriptomic and genomic analyses on 399 Tiannong partridge chickens to identify key genes and variants associated with carcass traits and to elucidate the underlying regulatory mechanisms. Based on association analyses with the elastic net (EN) model, we identified 12 candidate genes (AMY1A, AP3B2, CEBPG, EEF2, EIF4EBP1, FGFR1, FOXD3, GOLM1, LOC107052698, PABPC1, SERPINB6 and TBC1D16) for 4 carcass-related traits, namely live weight, dressed weight, eviscerated weight, and breast muscle weight. SERPINB6 was identified as the only overlapping gene by 3 analyses, EN model analysis, weighted gene co-expression network analysis and differential expression analysis. Cell-level experiments confirmed that SERPINB6 promotes the proliferation of chicken DF1 cells and primary myoblasts. Further expression genome-wide association study and association analysis indicated that rs317934171 is the critical site that enhances SERPINB6 expression. Furthermore, a dual-luciferase reporter assay proved that gga-miR-1615 targets the 3'UTR of SERPINB6. CONCLUSIONS: Collectively, our findings reveal that SERPINB6 serves as a novel gene for chicken carcass traits by promoting fibroblast and myoblast proliferation. Additionally, the downstream variant rs317934171 regulates SERPINB6 expression. These results identify a new target gene and molecular marker for the molecular mechanisms of chicken carcass traits.

Regulation of Hippo/YAP axis in colon cancer progression by the deubiquitinase JOSD1.

Colon cancer is a prevalent malignancy, while recent studies revealed the dys-regulation of Hippo signaling as the important driver for colon cancer progression. Several studies have indicated that post-translational modifications on YAP play crucial roles in both Hippo signaling activity and cancer progression. This raises a puzzling question about why YAP/TAZ, an auto-inhibitory pathway, is frequently over-activated in colon cancer, despite the suppressive cascade of Hippo signaling remaining operational. The protein stability of YAP is subject to a tiny balance between ubiquitination and deubiquitination processes. Through correlation analysis of DUBs (deubiquitinases) expression and Hippo target gene signature in colon cancer samples, we found JOSD1 as a critical deubiquitinase for Hippo signaling and colon cancer progression. JOSD1 could facilitate colon cancer progression and in colon cancer, inhibition of JOSD1 via shRNA has been demonstrated to impede tumorigenesis. Furthermore, molecular mechanism studies have elucidated that JOSD1 enhances the formation of the Hippo/YAP transcriptome by impeding K48-linked polyubiquitination on YAP. ChIP assays have shown that YAP binds to JOSD1's promoter region, promoting its gene transcription. These results suggest that JOSD1 is involved in both activating and being targeted by the Hippo signaling pathway in colon cancer. Consequently, a positive regulatory loop between JOSD1 and Hippo signaling has been identified, underscoring their interdependence during colon cancer progression. Thus, targeting JOSD1 may represent a promising therapeutic approach for managing colon cancer.

Mechanism of Zhishi Xiebai Guizhi decoction to treat atherosclerosis: Insights into experiments, network pharmacology and molecular docking.

ETHNOPHARMACOLOGICAL RELEVANCE: Zhishi Xiebai Guizhi Decoction (ZSXBGZD) is a traditional herbal manuscript used to treat cardiovascular disease, including atherosclerosis and coronary heart disease. The decoction has demonstrated its capability to protect arteries and resist atherosclerosis. Its mechanisms for anti-atherosclerosis effect, nevertheless, remain unknown. AIMS OF THE STUDY: The goal of the present study is to explore the effectiveness of ZSXBGZD acting on atherosclerosis and its key components based on experimental verification and network pharmacology analysis. MATERIALS AND METHODS: The ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) and databases were used to identify chemical components in ZSXBGZD. Network pharmacological analysis and molecular docking were implemented in order to reveal the possible therapeutic targets of ZSXBGZD. To form the model of atherosclerosis, we gave Apolipoprotein E knocked out mice a high-fat diet. H&E staining was performed to observe the effects of ZSXBGZD on atherosclerosis. Immunofluorescence and Western blot were used to investigate whether ZSXBGZD could affect autophagy, apoptosis, AGE-RAGE signaling pathway and other related mechanisms. RESULTS: In total, 30 core compounds were screened through intersecting UPLC-Q-TOF-MS and the databases. The anti-atherosclerotic effect of ZSXBGZD might relate to the AGE-RAGE signaling pathway via network pharmacology analysis. ZSXBGZD could inhibit apoptosis, activate autophagy and ease inflammation by modifying AGE-RAGE signaling pathway to reduce the area of atherosclerotic plaque. CONCLUSION: ZSXBGZD could treat atherosclerosis by regulating autophagy and apoptosis via adjusting the AGE-RAGE signaling pathway.

Artificial intelligence to predict T4 stage of pancreatic ductal adenocarcinoma using CT imaging.

BACKGROUND: The accurate assessment of T4 stage of pancreatic ductal adenocarcinoma (PDAC) has consistently presented a considerable difficulty for radiologists. This study aimed to develop and validate an automated artificial intelligence (AI) pipeline for the prediction of T4 stage of PDAC using contrast-enhanced CT imaging. METHODS: The data were obtained retrospectively from consecutive patients with surgically resected and pathologically proved PDAC at two institutions between July 2017 and June 2022. Initially, a deep learning (DL) model was developed to segment PDAC. Subsequently, radiomics features were extracted from the automatically segmented region of interest (ROI), which encompassed both the tumor region and a 3 mm surrounding area, to construct a predictive model for determining T4 stage of PDAC. The assessment of the models' performance involved the calculation of the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: The study encompassed a cohort of 509 PDAC patients, with a median age of 62 years (interquartile range: 55-67). The proportion of patients in T4 stage within the model was 16.9%. The model achieved an AUC of 0.849 (95% CI: 0.753-0.940), a sensitivity of 0.875, and a specificity of 0.728 in predicting T4 stage of PDAC. The performance of the model was determined to be comparable to that of two experienced abdominal radiologists (AUCs: 0.849 vs. 0.834 and 0.857). CONCLUSION: The automated AI pipeline utilizing tumor and peritumor-related radiomics features demonstrated comparable performance to that of senior abdominal radiologists in predicting T4 stage of PDAC.