PO-011 Effect of Exercise on the Body Composition of Simple Obesity in China: A Meta-analysis

Objective To systematically review the effect of exercise on the body composition of simple obesity in China. Methods We electronically searched databases including CNKI、VIP、WanFang Data、PubMed、Medline、Web of Science databases to collect the studies on exercise therapy for simple obesity from inception to June 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed by using RevMan 5.3 software. Results  A total of 17 papers involving 627 patients were included. The results of meta-analysis showed that:①Exercise significantly ameliorated BMI of obesity children(MD= -2.72，95%CI[-3.83，-1.61]，P<0.00001).②Exercise significantly ameliorated BMI (MD= -3.22，95%CI[-4.10，-2.34]，P<0.00001)、BF% (MD= -4.44，95%CI[-6.09，-2.79]，P<0.00001)、Body Weight(MD= -7.92，95%CI[-11.28，-4.56]，P<0.00001) and waist circumference (MD= -5.01，95%CI[-8.56，-1.46]，P=0.006) of obesity teenagers.③Exercise significantly ameliorated BMI BMI (MD= -3.18，95%CI[-3.64，-2.72]，P<0.00001)、BF% (MD= -0.80，95%CI[-1.53，-0.07]，P=0.03)、Body Weight (MD= -6.56，95%CI[-7.89，-5.23]，P<0.00001)、chest circumference (MD= -4.22，95%CI[-5.00，-3.45]，P<0.00001)、waist circumference (MD= -7.49，95%CI[-9.19，-5.78]，P<0.00001)and hip circumference (MD= -3.68，95%CI[-5.19，-2.17]，P<0.00001) of obesity adults. Conclusions  Exercise can significantly improve the body composition of simple obesity people in China. Due to the limited quantity and quality of included studies, more high quality studies are needed to verify the above conclusion

Understanding Large Language Model Based Fuzz Driver Generation

Fuzz drivers are a necessary component of API fuzzing. However, automatically generating correct and robust fuzz drivers is a difficult task. Compared to existing approaches, LLM-based (Large Language Model) generation is a promising direction due to its ability to operate with low requirements on consumer programs, leverage multiple dimensions of API usage information, and generate human-friendly output code. Nonetheless, the challenges and effectiveness of LLM-based fuzz driver generation remain unclear. To address this, we conducted a study on the effects, challenges, and techniques of LLM-based fuzz driver generation. Our study involved building a quiz with 86 fuzz driver generation questions from 30 popular C projects, constructing precise effectiveness validation criteria for each question, and developing a framework for semi-automated evaluation. We designed five query strategies, evaluated 36,506 generated fuzz drivers. Furthermore, the drivers were compared with manually written ones to obtain practical insights. Our evaluation revealed that: while the overall performance was promising (passing 91% of questions), there were still practical challenges in filtering out the ineffective fuzz drivers for large scale application; basic strategies achieved a decent correctness rate (53%), but struggled with complex API-specific usage questions. In such cases, example code snippets and iterative queries proved helpful; while LLM-generated drivers showed competent fuzzing outcomes compared to manually written ones, there was still significant room for improvement, such as incorporating semantic oracles for logical bugs detection.Comment: 17 pages, 14 figure

The single-cell landscape of cystic echinococcosis in different stages provided insights into endothelial and immune cell heterogeneity

IntroductionHydatid cysts and angiogenesis are the key characteristics of cystic echinococcosis, with immune cells and endothelial cells mediating essential roles in disease progression. Recent single-cell analysis studies demonstrated immune cell infiltration after Echinococcus granulosus infection, highlighting the diagnostic and therapeutic potential of targeting certain cell types in the lesion microenvironment. However, more detailed immune mechanisms during different periods of E. granulosus infection were not elucidated.MethodsHerein, we characterized immune and endothelial cells from the liver samples of mice in different stages by single-cell RNA sequencing.ResultsWe profiled the transcriptomes of 45,199 cells from the liver samples of mice at 1, 3, and 6 months after infection (two replicates) and uninfected wild-type mice. The cells were categorized into 26 clusters with four distinct cell types: natural killer (NK)/T cells, B cells, myeloid cells, and endothelial cells. An SPP1+ macrophage subset with immunosuppressive and pro-angiogenic functions was identified in the late infection stage. Single-cell regulatory network inference and clustering (SCENIC) analysis suggested that Cebpe, Runx3, and Rora were the key regulators of the SPP1+ macrophages. Cell communication analysis revealed that the SPP1+ macrophages interacted with endothelial cells and had pro-angiogenic functions. There was an obvious communicative relationship between SPP1+ macrophages and endothelial cells via Vegfa–Vegfr1/Vegfr2, and SPP1+ macrophages interacted with other immune cells via specific ligand–receptor pairs, which might have contributed to their immunosuppressive function.DiscussionOur comprehensive exploration of the cystic echinococcosis ecosystem and the first discovery of SPP1+ macrophages with infection period specificity provide deeper insights into angiogenesis and the immune evasion mechanisms associated with later stages of infection

Whole-exome sequencing identifies genes associated with Tourette’s disorder in multiplex families

Tourette’s Disorder (TD) is a neurodevelopmental disorder (NDD) that affects about 0.7% of the population and is one of the most heritable NDDs. Nevertheless, because of its polygenic nature and genetic heterogeneity, the genetic etiology of TD is not well understood. In this study, we combined the segregation information in 13 TD multiplex families with high-throughput sequencing and genotyping to identify genes associated with TD. Using whole-exome sequencing and genotyping array data, we identified both small and large genetic variants within the individuals. We then combined multiple types of evidence to prioritize candidate genes for TD, including variant segregation pattern, variant function prediction, candidate gene expression, protein–protein interaction network, candidate genes from previous studies, etc. From the 13 families, 71 strong candidate genes were identified, including both known genes for NDDs and novel genes, such as HtrA Serine Peptidase 3 (HTRA3), Cadherin-Related Family Member 1 (CDHR1), and Zinc Finger DHHC-Type Palmitoyltransferase 17 (ZDHHC17). The candidate genes are enriched in several Gene Ontology categories, such as dynein complex and synaptic membrane. Candidate genes and pathways identified in this study provide biological insight into TD etiology and potential targets for future studies.This study was supported by a grant from the National Institute of Mental Health (R01MH092293 to GAH and JAT) and by a grant from the New Jersey Center for Tourette Syndrome (to GAH and JAT). This study was also supported by grants from the National Institute of Mental Health (K08MH099424 to TVF) and the National Institute for Environmental Health Science (R01 ES021462 for YSK and BLL). PM has received grants from the Instituto de Salud Carlos III (PI10/01674, PI13/01461), the Consejería de Economía, Innovación, Ciencia y Empresa de la Junta de Andalucía (CVI-02526, CTS-7685), the Consejería de Salud y Bienestar Social de la Junta de Andalucía (PI-0741/2010, PI-0437-2012, PI-0471-2013), the Sociedad Andaluza de Neurología, the Fundación Alicia Koplowitz, the Fundación Mutua Madrileña, and the Jaques and Gloria Gossweiler Foundation. AM has received grants from the Fundacion Alicia Koplowitz and belongs to the research group of the Comissionat per Universitats i Recerca del Departmanent d’Innovacio (DIUE) 2009SGR1119. AM has received grants from the Deutsche Forschungsgemeinschaft (DFG: MU 1692/3-1, MU 1692/4-1, and FOR 2698). AJW received a Young Investigator Award from Tourette Association of America. IH declares that all research at Great Ormond Street Hospital NHS Foundation Trust and UCL Great Ormond Street Institute of Child Health is made possible by the NIHR Great Ormond Street Hospital Biomedical Research Centre

Phylogenomic analysis of transcriptome data elucidates co-occurrence of a paleopolyploid event and the origin of bimodal karyotypes in Agavoideae (Asparagaceae)

Premise of the study: The stability of the bimodal karyotype found in Agave and closely related species has long interested botanists. The origin of the bimodal karyotype has been attributed to allopolyploidy, but this hypothesis has not been tested. Next-generation transcriptome sequence data were used to test whether a paleopolyploid event occurred on the same branch of the Agavoideae phylogenetic tree as the origin of the Yucca-Agave bimodal karyotype. Methods: Illumina RNA-seq data were generated for phylogenetically strategic species in Agavoideae. Paleopolyploidy was inferred in analyses of frequency plots for synonymous substitutions per synonymous site (K-s) between Hosta, Agave, and Chlorophytum paralogous and orthologous gene pairs. Phylogenies of gene families including paralogous genes for these species and outgroup species were estimated to place inferred paleopolyploid events on a species tree. Key results: K-s frequency plots suggested paleopolyploid events in the history of the genera Agave, Hosta, and Chlorophytum. Phylogenetic analyses of gene families estimated from transcriptome data revealed two polyploid events: one predating the last common ancestor of Agave and Hosta and one within the lineage leading to Chlorophytum. Conclusions: We found that polyploidy and the origin of the Yucca-Agave bimodal karyotype co-occur on the same lineage consistent with the hypothesis that the bimodal karyotype is a consequence of allopolyploidy. We discuss this and alternative mechanisms for the formation of the Yucca-Agave bimodal karyotype. More generally, we illustrate how the use of next-generation sequencing technology is a cost-efficient means for assessing genome evolution in nonmodel species

A genome triplication associated with early diversification of the core eudicots

Background: Although it is agreed that a major polyploidy event, gamma, occurred within the eudicots, the phylogenetic placement of the event remains unclear. Results: To determine when this polyploidization occurred relative to speciation events in angiosperm history, we employed a phylogenomic approach to investigate the timing of gene set duplications located on syntenic gamma blocks. We populated 769 putative gene families with large sets of homologs obtained from public transcriptomes of basal angiosperms, magnoliids, asterids, and more than 91.8 gigabases of new next-generation transcriptome sequences of non-grass monocots and basal eudicots. The overwhelming majority (95%) of well-resolved gamma duplications was placed before the separation of rosids and asterids and after the split of monocots and eudicots, providing strong evidence that the gamma polyploidy event occurred early in eudicot evolution. Further, the majority of gene duplications was placed after the divergence of the Ranunculales and core eudicots, indicating that the gamma appears to be restricted to core eudicots. Molecular dating estimates indicate that the duplication events were intensely concentrated around 117 million years ago. Conclusions: The rapid radiation of core eudicot lineages that gave rise to nearly 75% of angiosperm species appears to have occurred coincidentally or shortly following the gamma triplication event. Reconciliation of gene trees with a species phylogeny can elucidate the timing of major events in genome evolution, even when genome sequences are only available for a subset of species represented in the gene trees. Comprehensive transcriptome datasets are valuable complements to genome sequences for high-resolution phylogenomic analysis