GenomicsPub Date : 2026-07-01Epub Date: 2026-06-13DOI: 10.1016/j.ygeno.2026.111277
Yuhan Gan, Jiawei Zhou, Bendong Li, Daqian Huang, Yuejun Ma, Lu Pei, Kaiwen Sheng, Liao Zhang, Ying Cheng, Jicong Du, Shengyun Cai, Cong Liu
{"title":"Evolocumab protects mice from radiation-induced damage by affecting hematopoietic cell lineage","authors":"Yuhan Gan, Jiawei Zhou, Bendong Li, Daqian Huang, Yuejun Ma, Lu Pei, Kaiwen Sheng, Liao Zhang, Ying Cheng, Jicong Du, Shengyun Cai, Cong Liu","doi":"10.1016/j.ygeno.2026.111277","DOIUrl":"10.1016/j.ygeno.2026.111277","url":null,"abstract":"<div><h3>Background</h3><div>The hematopoietic system is extremely sensitive to ionizing radiation(IR) and is easily damaged after exposure. Recent studies [1, 2] have shown that hematopoietic lineage differentiation may play a key role in Ionizing radiation -induced acute injury.</div></div><div><h3>Methods</h3><div>C57BL/6 mice matched for age, sex and weight were randomly grouped and intraperitoneal injected with PBS, Evolocumab (80.0 mg/kg) or MMP9-IN (20.0 mg/kg). Survival time, body weight, pathology, hematopoietic cell differentiation changes and organoids of the mice after IR (10.0 Gy) were compared, and the mechanism of action in tissues was verified by transcriptome sequencing.</div></div><div><h3>Results</h3><div>Ionizing radiation can inhibit hematopoietic cell lineage differentiation and affect cholesterol metabolism. The expression of the <em>Pcsk9</em> gene was significantly upregulated after IR. Treatment with a <em>Pcsk9</em> monoclonal antibody (Evolocumab) exerted significant radioprotective effects, including improving the survival rate of irradiated mice, reducing body weight loss, preserving the integrity of the bone marrow cavity, and promoting cellular proliferation. Flow cytometric analysis showed that Evolocumab significantly increased hematopoietic precursor cells and hematopoietic stem cells and promoted their differentiation into ST-LSKs and MPPs. In addition, the proportions of CMPs and GMPs were increased, whereas the proportion of MEPs was decreased. RNA sequencing results suggested that the IR-induced downregulation of <em>Cd3e</em> within the hematopoietic cell lineage pathway could be rescued by Evolocumab, which was further validated at the cellular level. CD3e is a T-cell-associated marker, and Evolocumab treatment was associated with an increased proportion of CD3e<sup>+</sup> T cells. Analysis of previously reported hematopoiesis-related factors [3–5] indicated that Evolocumab markedly upregulated <em>Mmp9</em> expression. Correlation analysis revealed that <em>Pcsk9</em> was negatively correlated with <em>Cd3e</em>, whereas <em>Cd3e</em> was positively correlated with <em>Mmp9</em>. Following ionizing radiation, <em>Mmp9</em> knockout (<em>Mmp9</em> KO) mice exhibited reduced survival compared with wild-type mice. Moreover, in wild-type mice, administration of an MMP9 inhibitor (MMP9-IN) attenuated the radioprotective effects of Evolocumab, indicating that <em>Mmp9</em> contributes to Evolocumab-mediated radioprotection.</div></div><div><h3>Conclusion</h3><div>Evolocumab exerts a positive effect on promoting the proliferation and differentiation of hematopoietic stem cells against IR-induced hematopoietic system injury, with its protective mechanism likely involving the activation of hematopoietic cell lineages to upregulate CD3e<sup>+</sup> T cells and Mmp9 expression.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 4","pages":"Article 111277"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148239100","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2026-07-01Epub Date: 2026-06-19DOI: 10.1016/j.ygeno.2026.111280
Hao Zhong, Zulaikha Mat Deris, Panpan Wang, Panpan Niu, Yu Wang, Shanshan Jiang, Jing Xu, Jie Kong, Sheng Luan, Yik Sung Yeong, Li Lian Wong, Huan Gao
{"title":"A single-nucleus transcriptomic atlas of early marine shrimp embryogenesis reveals cell-type specification and eye pigment transport mechanisms","authors":"Hao Zhong, Zulaikha Mat Deris, Panpan Wang, Panpan Niu, Yu Wang, Shanshan Jiang, Jing Xu, Jie Kong, Sheng Luan, Yik Sung Yeong, Li Lian Wong, Huan Gao","doi":"10.1016/j.ygeno.2026.111280","DOIUrl":"10.1016/j.ygeno.2026.111280","url":null,"abstract":"<div><div>Early embryogenesis and their underlying regulatory mechanisms in crustaceans remains unclear at the cellular level. Here, we mapped the early developmental stages of marine shrimp <em>Palaemon carinicauda</em> using single nucleus RNA sequencing (snRNA-seq), spanning the transitional stages of blastula to protozoea. Profiling over 60,000 nuclei, we identify six distinct embryonic cell types, including the multiple neuronal subtypes, extracellular matrix- producing cells, cuticle-forming cells, and an eye-related cells that emerged during protozoea development. Cell-type identities were validated using selected marker genes expression and spatial expression patterns via fluorescent in situ hybridization (FISH). <em>PcWhite</em> and <em>PcScarlet</em> contain a highly conserved nucleotide-binding domain (NBD) motif, including Walker A, ABC signature sequence and Walker B domain and a conserved six transmembrane domain (TMD). RNA interference (RNAi) analysis targeting the ABC transporter genes White (W) and Scarlet (St) demonstrated that these genes are essential for eye pigment precursor transport, morphogenesis, and embryonic viability. Collectively, this integrative approach demonstrates the robustness of snRNA-seq for dissecting early embryogenesis in non-model species, linking cell-type-specific gene expression to key developmental processes that enables comparative evolutionary genomics across crustaceans.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 4","pages":"Article 111280"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148283426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Shifting genomes, rising threats: Adaptive evolution and antimicrobial resistance of E. coli ST10 across African ecologies","authors":"Refiloe Malesa, Rian Pierneef, Kudakwashe Magwedere, Thendo Mafuna, Itumeleng Matle","doi":"10.1016/j.ygeno.2026.111278","DOIUrl":"10.1016/j.ygeno.2026.111278","url":null,"abstract":"<div><div><em>Escherichia coli</em> sequence type 10 (ST10) is an emerging zoonotic lineage with global distribution and a high antimicrobial resistance (AMR) burden, yet its population dynamics across Africa remain poorly understood. Here, we analysed 159 <em>E. coli</em> ST10 genomes including four newly sequenced isolates and 155 publicly available genomes from 19 African countries spanning human, animal, food, and environmental sources. Whole genome sequencing revealed high species-level similarity (mean average nucleotide identity: 99.44%), but single nucleotide polymorphism (SNP)-based phylogenetics delineated 122 distinct clusters, indicating substantial intra-lineage diversity. Over 71% of isolates were multidrug-resistant, with 29% carrying the extended-spectrum β-lactamase gene <em>bla_CTX-M-15</em>. Plasmid replicon analysis highlighted the widespread presence of IncFIB and ColRNAI plasmids, strongly linked to AMR gene carriage. Human-derived isolates predominated both phylogenetic clusters and resistance profiles. SNP-based comparisons revealed evidence of both localized evolution and long-distance dissemination across countries. These interconnected pathways underscore the bacterium's ecological ubiquity and the limitations of siloed surveillance strategies. The predominance of human-derived isolates and evidence of both local and cross-border transmission highlight humans as key reservoirs and underscore the need for coordinated surveillance. These findings underscore the urgent need for integrated continent-wide One Health approach strategies to monitor and combat antimicrobial resistance, economic impact on trade restrictions and health security threats.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 4","pages":"Article 111278"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148264080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DeepGEP: Deep learning for gene expression prediction from multi-omics in mammals","authors":"Jiali Cai, Ruiqi Wang, Yipeng Li, Wentao Gong, Xiangchun Pan, Bin Ma, Penghao Wang, Xiaolong Yuan","doi":"10.1016/j.ygeno.2026.111285","DOIUrl":"10.1016/j.ygeno.2026.111285","url":null,"abstract":"<div><div>Deep neural networks offer great potential for integrating multi-omics data to predict gene expression and uncover regulatory mechanisms. Here, we developed DeepGEP, an attention-based Long Short-Term Memory model trained on 228 datasets, including RNA-seq, ATAC-seq, and ChIP-seq of four histone modifications (H3K4me3, H3K4me1, H3K27ac, H3K27me3) from humans, pigs, and cattle. DeepGEP outperformed several other machine learning methods, achieving Pearson correlation coefficients (PCCs) of 0.70–0.82, with accuracy improving up to 0.93 after K-means clustering. Attention weight analysis highlighted regulatory regions within ±1000 bp of transcription start sites and revealed that H3K4me3 and chromatin accessibility contributed most strongly to gene expression prediction, while H3K4me1, H3K27ac, and H3K27me3 played less prominent roles. Our study demonstrates the value of integrating chromatin accessibility and histone modifications for accurate cross-species gene expression prediction, providing a versatile framework for multi-omics modeling and advancing understanding of mammalian gene regulation.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 4","pages":"Article 111285"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2026-07-01Epub Date: 2026-05-10DOI: 10.1016/j.ygeno.2026.111254
Keqiang Wang, Xiaorui Yang, Chuntao Feng, Zengyuan Zhao, Yishu Li, Hongyu Liu, Jing Guo, Yang Lyu, He Ding, Yang Zhou, Yi Fang, Wenfa Lyu
{"title":"Development and validation of an integrated single-tube whole-genome amplification and library construction system for genomic selection in bovine preimplantation embryos","authors":"Keqiang Wang, Xiaorui Yang, Chuntao Feng, Zengyuan Zhao, Yishu Li, Hongyu Liu, Jing Guo, Yang Lyu, He Ding, Yang Zhou, Yi Fang, Wenfa Lyu","doi":"10.1016/j.ygeno.2026.111254","DOIUrl":"10.1016/j.ygeno.2026.111254","url":null,"abstract":"<div><div>Genomic selection technology has significantly shortened the generation interval of large single-offspring animals and accelerated genetic improvement, but its application at the early embryonic stage still faces the high risk of embryonic micromanipulation damage, the high cost of whole genome amplification, and the complex and time-consuming workflow. To address these limitations, this study established an integrated whole genome amplification system (named iSALC). The system combines universal primers with specific adapter sequences, allowing the primers to bind to the complementary regions of the adapters, thereby enabling simultaneous amplification and library construction in a single PCR reaction. In terms of sample handling, the system uses phosphate-buffered saline to preserve bovine blastocyst trophoblast cells, with a minimum starting quantity as low as 5 cells. It is recommended to maintain at least 3× sequencing depth to achieve stable coverage uniformity. Whether it is fresh embryo transfer or frozen embryo transfer, pregnancy rates show that embryo micromanipulation not only does not reduce the embryo's implantation ability, but can actually increase the pregnancy rate after embryo transfer. Compared with traditional kits, this system optimized the workflow, eliminated the separate library preparation step, and offered high-throughput compatibility and cost-effectiveness. Overall, this study successfully overcame the dual limitations of early embryo whole genome amplification in terms of cost and operational complexity.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 4","pages":"Article 111254"},"PeriodicalIF":3.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147927602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LncRNAs modulate nitrogen metabolism gene expression in rice leaves under elevated CO₂ and/or Cd stress","authors":"Aihua Liu, Liyuan Fu, Caixia Wen, Wenyong Liu, Qi Ma, Xuemei Li, Lianju Ma, Yueying Li, Bin Yang, Wei Fu, Yu Zhou, Yonghui Zhao, Danni Wu, Lanlan Wang","doi":"10.1016/j.ygeno.2026.111255","DOIUrl":"10.1016/j.ygeno.2026.111255","url":null,"abstract":"<div><div>With rising atmospheric CO₂ and intensifying cadmium (Cd) pollution negatively affect rice growth and development. Rice seedlings “Liaoxing No. 1” (<em>Oryza sativa</em> L.) were treated under four treatments (AC: CO<sub>2</sub> 400 ± 20 μmol<strong>·</strong>mol<sup>−1</sup> and CdCl<sub>2</sub> 0 μmol<strong>·</strong>L<sup>−1</sup>; EC: CO<sub>2</sub> 800 ± 20 μmol<strong>·</strong>mol<sup>−1</sup> and CdCl<sub>2</sub> 0 μmol<strong>·</strong>L<sup>−1</sup>; Cd: CO<sub>2</sub> 400 ± 20 μmol<strong>·</strong>mol<sup>−1</sup> and CdCl<sub>2</sub>150 μmol<strong>·</strong>L<sup>−1</sup>; EC + Cd: CO<sub>2</sub> 800 ± 20 μmol<strong>·</strong>mol<sup>−1</sup>and CdCl<sub>2</sub> 150 μmol<strong>·</strong>L<sup>−1</sup>) for 7 days. Integrated transcriptome sequencing and quantitative real-time PCR (qPCR) were used to analyze the expression patterns and regulatory networks of long non-coding RNAs (lncRNAs) in rice leaves under elevated CO₂ and/or Cd stress. A total of 841 lncRNAs were identified, and KEGG enrichment analysis showed that differentially expressed lncRNAs (DE-lncRNAs) were primarily associated with nitrogen metabolism. Cd stress significantly inhibited nitrogen assimilation via a lncRNA-mediated network: MSTRG.25360.1 downregulated nitrate reductase (NR) genes, reducing NR activity; MSTRG.19531.1 positively regulated glutamate synthase (GOGAT) activity; and MSTRG.16002.2 was involved in inhibiting carbonic anhydrase (CA) activity. Elevated CO₂ (EC) also suppressed the activities of key enzymes, including NR, nitrite reductase (NIR), GOGAT, and CA, while shifting ammonia assimilation toward the glutamine synthetase (GS) pathway, a process involving MSTRG.1264.1. Under combined stress (EC + Cd), EC partially alleviated Cd toxicity by activating NIR and glutamate dehydrogenase (GDH), leading to a higher nitrogen metabolism efficiency than under Cd stress alone. However, the activities of NR and GOGAT failed to recover, and CA activity was further suppressed synergistically via MSTRG.25184.5. In conclusion, elevated CO₂ only partially mitigates Cd-induced inhibition of nitrogen assimilation in an enzyme-specific manner, which is mediated by distinct lncRNA regulatory networks targeting key nitrogen metabolism enzymes.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 3","pages":"Article 111255"},"PeriodicalIF":3.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147768289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2026-03-01Epub Date: 2026-01-11DOI: 10.1016/j.ygeno.2026.111203
Yu Zhou , Yuxi Tong , Yonggang Wang , Xiaoqin Fu , Chen Zhang , Genlou Sun , Qifei Wang , Sisi Huang , Xifeng Ren
{"title":"Dynamics of deleterious mutation and selection at seven nuclear genes during barley domestication and de-domestication","authors":"Yu Zhou , Yuxi Tong , Yonggang Wang , Xiaoqin Fu , Chen Zhang , Genlou Sun , Qifei Wang , Sisi Huang , Xifeng Ren","doi":"10.1016/j.ygeno.2026.111203","DOIUrl":"10.1016/j.ygeno.2026.111203","url":null,"abstract":"<div><div>Understanding how barley domestication affects deleterious mutations is crucial for breeding and germplasm conservation. This study analyzed seven single-copy nuclear genes (<em>Alcohol dehydrogenase 2</em> (<em>ADH2</em>), <em>Alcohol dehydrogenase 3</em> (<em>ADH3</em>), <em>Dehydrin9</em> (<em>DHN9</em>), <em>Glyceraldehyde-3-phosphate dehydrogenase</em> (<em>GAPDH</em>), <em>Phosphoenolpyruvate carboxylase</em> (<em>PEPC</em>), <em>Photoperiod response gene</em> (<em>PPD-H1</em>), and <em>Granule-bound starch synthase</em> (<em>WAXY</em>)) in 179 wild, 185 domesticated, and 21 de-domesticated barley accessions. Results showed that wild barley has the highest genetic diversity and the most private haplotypes. Deleterious SNPs were identified, with fewer in domesticated and de-domesticated groups compared to wild. Deleterious mutation load decreased from wild to domesticated barley as nucleotide diversity decreased (<em>R</em> = 0.78; <em>p</em> < 0.05), suggesting that domestication bottlenecks may purge these mutations. In wild barley, Nonsynonymous-to-synonymous substitution rate (dN/dS) ratios were ∼ 1 or > 1, indicating neutral or weak positive selection. These findings highlight how domestication shapes deleterious mutation patterns and provide insights for breeding and germplasm management.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111203"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145965882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
GenomicsPub Date : 2026-03-01Epub Date: 2026-01-08DOI: 10.1016/j.ygeno.2026.111198
Jinxing Su , Shangquan Jiang , Min Chu , Xiang Dong , Caiyun Zhang , Xiaoxing Li , Kan He
{"title":"Time-course with multi-omics reveals hyperlipidemia dysregulates diurnal rhythms in gut-liver axis","authors":"Jinxing Su , Shangquan Jiang , Min Chu , Xiang Dong , Caiyun Zhang , Xiaoxing Li , Kan He","doi":"10.1016/j.ygeno.2026.111198","DOIUrl":"10.1016/j.ygeno.2026.111198","url":null,"abstract":"<div><h3>Background</h3><div>Chronic overconsumption of high-fat diets contributes to obesity, with hyperlipidemia being a common comorbidity. The cardiovascular system is strongly influenced by diurnal rhythms, which regulate key functions such as endothelial activity, thrombosis, and blood pressure. Diurnal rhythms are central regulators of metabolic and physiological processes, and dietary pattern shifts can disrupt the synchronization of the internal clock within metabolic systems.</div></div><div><h3>Results</h3><div>Using a hyperlipidemic mouse model, we investigated diurnal rhythm-related effects on the liver and intestine through transcriptomic, metagenomic, and metabolomic profiling. We identified several key genes—including CD36, Hmgcs1, Ehhadh, Cyp4a12b, Ifi27l2b, Ugt2b1, Ces2a, Cyp3a11, Selenbp2, and Gal3st1—that are regulated by the hepatic circadian clock and modulate metabolites via the gut–liver axis. The gut microbiota exhibited diurnal rhythmicity that coordinates intestinal digestion and metabolism, forming a synergistic circadian metabolic network. Hyperlipidemia disrupted normal circadian regulation in the liver and intestine, affecting lipid synthesis, transport, accumulation, and catabolism.</div></div><div><h3>Discussion</h3><div>Our hepatic transcriptomic analysis revealed that a high-fat diet induces aberrant expression of lipid metabolism genes during the night. This diet also perturbs the diurnal rhythm of the gut microbiota, leading to intestinal metabolic dysregulation. Metabolites entering the portal circulation act as signaling molecules that bind to hepatic receptors and directly regulate the transcription of lipid metabolism genes. The loss of rhythmic metabolite secretion consequently disrupts circadian gene expression, contributing to hepatic lipid dysregulation via the gut–liver axis—a key mechanism in hyperlipidemia pathogenesis.</div></div><div><h3>Conclusions</h3><div>This study identifies critical temporal windows and core microbial taxa involved in microbiota–metabolite–gene crosstalk via the gut–liver axis, offering a theoretical foundation for diurnal rhythm-targeted interventions in metabolic diseases.</div></div>","PeriodicalId":12521,"journal":{"name":"Genomics","volume":"118 2","pages":"Article 111198"},"PeriodicalIF":3.0,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}