Zhixiang Xu

Huazhong Agricultural University

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Jiyue Zheng

Shanghai Jiao Tong University

Xiaohu Zhang

University of Chinese Academy of Sciences

Hao Peng

San Joaquin Valley Agricultural Sciences Center

Renzhuo Kuang

Huazhong Agricultural University

Lusong Luo

BeiGene (China)

Ying Li

Tongji University

Jiajun Li

Baoding People's Hospital

Zhilin Hu

Sichuan Agricultural University

Yunxia Zhao

Qingdao University

Xueguang Zhang

Soochow University

Cooperative Institutions

Huazhong Agricultural University

Ministry of Agriculture and Rural Affairs

Soochow University

Chinese Academy of Sciences

Sichuan University

Lanzhou University

Shanghai Jiao Tong University

Chinese Academy of Medical Sciences & Peking Union Medical College

Nanjing Medical University

University of Chinese Academy of Sciences

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H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig

Animal Genetics (2024)

Renzhuo Kuang Zhixiang Xu Honghong Zhou Zhao Zhang Hao Peng

Abstract The establishment of high‐quality pork breeds for improving meat quality in the pig industry is needed. The Chuxiang Black (CX) pig is a new breed developed from Chinese local pigs and Western lean pigs that has a high proportion of lean meat and excellent meat quality. However, the characteristics of cis‐regulatory elements in CX pigs are still unknown. In this study, cis‐regulatory elements of muscle and adipose tissues in CX pigs were investigated using ChIP‐seq and RNA sequencing. Compared with the reported cis‐regulatory elements of muscle and adipose tissues, 1768 and 1012 highly activated enhancers and 433 and 275 highly activated promoters in CX muscle and adipose tissues were identified, respectively. Motif analysis showed that transcription factors, such as MEF2A and MEF2C , were core regulators of highly activated enhancers and promoters in muscle. Similarly, the transcription factors JUNB and CUX1 were identified as essential for highly activated enhancers and promoters in CX adipose tissue. These results enrich the resources for the analysis of cis‐regulatory elements in the pig genome and provide new basic data for further meat quality improvement through breeding in pigs.

MEF2C

10.1111/age.13400

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Positive Selection on Rare Variants Underlying the Cold Adaptation of Wild Boar

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Jianhai Chen Ivan Jakovlić Mikhail Sablin Shengqian Xia Zhixiang Xu

Abstract The wide geographical distribution of Eurasian wild boar ( Sus scrofa ) offers a natural experiment to study the thermoregulation. Here, we conducted whole-genome resequencing and chromatin profiling experiments on the local populations from cold regions (northern and northeastern Asia) and warm regions (southeastern Asia and southern China). Using genome-wide scans of four methods, we detected candidate genes underlying cold-adaptation with significant enrichment of pathways related to thermogenesis, fat cell development, and adipose tissue regulation. We also found two enhancer variants under positive selection, an intronic variant of IGF1R (rs341219502) and an exonic variant of BRD4 (rs327139795), which showed the highest differentiation between cold and warm region populations of wild boar and domestic pigs. Moreover, these rare variants were absent in outgroup species and warm-region wild boar but nearly fixed in cold-region populations, suggesting their de novo origins in cold-region populations. The experiments of CUT&Tag chromatin profiling showed that rs341219502 of IGF1R is associated with the gain of three novel transcription factors involving regulatory changes in enhancer function, while rs327139795 of BRD4 could result in the loss of a phosphorylation site due to amino acid alteration. We also found three genes ( SLCO1C1, PDE3A , and TTC28 ) with selection signals in both wild boar and native human populations from Siberia, which suggests convergent molecular adaptation in mammals. Our study shows the adaptive evolution of genomic molecules underlying the remarkable environmental flexibility of wild boar.

Wild boar

BOAR

10.1101/2024.04.07.588424

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Epigenomic features associated with body temperature stabilize tissues during cold exposure in cold-resistant pigs

Journal of genetics and genomics/Journal of Genetics and Genomics (2024)

Yaping Guo Mingyang Hu Hao Peng Yan Zhang Renzhuo Kuang

Cold stress in low-temperature environments can trigger changes in gene expression, but epigenomics regulation of temperature stability in vital tissues, including the fat and diencephalon, is still unclear. Here, we explore the cold-induced changes in epigenomic features in the diencephalon and fat tissues of two cold-resistant Chinese pig breeds, Min and Enshi black (ES) pigs, utilizing H3K27ac CUT&Tag, RNA-seq, and selective signature analysis. Our results show significant alterations in H3K27ac modifications in the diencephalon of Min pigs and the fat of ES pigs after cold exposure. Dramatic changes in H3K27ac modifications in the diencephalon of Min pig are primarily associated with genes involved in energy metabolism and hormone regulation, whereas those in the fat of ES pig are primarily associated with immunity-related genes. Moreover, transcription factors PRDM1 and HSF1, which show evidence of selection, are enriched in genomic regions presenting cold-responsive alterations in H3K27ac modification in the Min pig diencephalon and ES pig fat, respectively. Our results indicate the diversity of epigenomic response mechanisms to cold exposure between Min and ES pigs, providing unique epigenetic resources for studies of low-temperature adaptation in large mammals.

Diencephalon

Epigenomics

10.1016/j.jgg.2024.06.017

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Design, synthesis, and evaluation of novel porcupine inhibitors featuring a fused 3-ring system based on the ‘reversed’ amide scaffold

Bioorganic & Medicinal Chemistry (2016)

Zhixiang Xu Xiangxiang Xu Ruadhan O’Laoi Haikuo Ma Jiyue Zheng

WNT3A

10.1016/j.bmc.2016.09.041

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Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase

Bioorganic & Medicinal Chemistry (2014)

Zhixiang Xu Yin Wei Leonardo Martinelli Joanna C. Evans Jinglei Chen

Coenzyme A

Metabolic intermediate

10.1016/j.bmc.2014.01.017

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Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system

European Journal of Medicinal Chemistry (2015)

Zhixiang Xu Jiajun Li Yiyuan Wu Zhijian Sun Lusong Luo

Palmitoylation

10.1016/j.ejmech.2015.11.026

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Hepatoprotective effects of Radix Bupleuri extract on aflatoxin B1-induced liver injury in ducks

Ecotoxicology and Environmental Safety (2024)

Tianyi Feng Siyu Li Pengpeng Wang Di Zhu Zhixiang Xu

Aflatoxin B1 (AFB1) is recognized as the most toxic mycotoxin, widely present in nature and known to specifically target the liver, leading to severe consequences to animal and human health. The mechanisms underlying AFB1-induced hepatotoxicity involve oxidative stress and apoptosis. Radix Bupleuri (RB) and its extracts (RBE), traditional Chinese herbs with a rich history spanning over 2000 years, have been reported to possess hepatoprotective properties. Nevertheless, the impact of RBE on AFB1-induced liver injury remains to be fully elucidated. The current study utilized Pekin ducks as experimental models to explore the effects of RBE on AFB1-induced liver injury both in vitro and in vivo. In vitro findings indicated that RBE mitigated AFB1-induced cytotoxicity, improved primary duck hepatocytes (PDHs) morphology, and reduced intracellular reactive oxygen species (ROS) levels. In vivo experiments demonstrated that: I) RBE alleviated the growth inhibitory caused by AFB1, as evidenced by improved final body weight and weight gain. II) AFB1 led to significant alterations in serum biochemical parameters (AST, ALT, TP, and ALB) and liver lesions attenuated by RBE supplementation at 2.5 g/kg. III) RBE significantly mitigated oxidative stress induced by AFB1. IV) AFB1-induced changes in mRNA and protein levels associated with oxidative stress and apoptosis were counteracted by RBE. In conclusion, our results suggest that RBE offers protection against AFB1-induced liver injury in ducks, primarily through its antioxidative and anti-apoptotic properties. These findings indicate the potential of RBE in preventing and treating AFB1 poisoning.

10.1016/j.ecoenv.2024.116781

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Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors

International Immunopharmacology (2015)

Zhixiang Xu Jing Wu Jiyue Zheng Haikuo Ma Hongjian Zhang

Neurotoxicity

10.1016/j.intimp.2015.02.033

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F1t3 receptor expression on the surface of malignant hematopoietic cells and responses to F1t3 ligand stimulation

Chinese Journal of Cancer Research (2000)

Zhixiang Xu Ying Xu Jian-kun Zhu Caixia Li Ying Li

Objective: To investigate the F1t3 receptor expression on the surface of malignant hematopoietic cells, the effect of TNFα and dexamethasone (DXM) on its expression and the responses of those cells to recombinant human F1t3 ligand (rhFL). Methods: Eighteen malignant hematopoietic cell lines were determined for the F1t3 receptor expression by flow cytometric analysis. The effect of rhFL on the proliferation of malignant hematopoietic cellsin vitro was measured using MTT assay. Results: The expressions of F1t3 receptor on the surface of Raji, Daudi, HL-60, 8266 and XG-6 cells were detected by flow cytometric analysis. Following incubation with 20 ng/ml TNFα for 24h, the number of F1t3 receptor positive cells decreased in Raji and 8266, increased in HL-60 and XG-6, and no difference in Daudi cells. After incubation with 10−6 mol/L DXM for 24h, the number of F1t3 receptor positive cells decreased in all the 5 F1t3 receptor positive cell lines. rhFL stimulated the proliferation of HL-60 and Raji cells. Conclusion: For most of the malignant hematopoietic cells, there was neither the expression of F1t3 receptor nor the response to rhFL. DXM may be useful to reduce the effect of FL on the proliferation of some F1t3 receptor positive malignant hematopoietic cells in vitro andin vivo.

Raji cell

Receptor expression

Cell surface receptor

10.1007/bf02983502

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Recombinant human FLT 3 ligand exerts both direct and indirect effects on hematopoiesis

Indian Journal of Pharmacology (2000)

Zhixiang Xu Zhu Jiankun Zhihong Zhang Ying Xu Qin Shi

Objective: To investigate the direct and the indirect effects of flt3 ligand (FL) on hematopoiesis. Methods: Mononuclear cells from human cord blood were plated in methylcellulose medium containing different cytokines for inducing hematopoietic colony formation. Dendritic cells were induced from the mononuclear cells with a cytokine cocktail with or without recombinant human soluble FL (rhFL; 100ng/ ml). The flt3 receptors on the surface of a human microvascular endothelial cell line (ECV) were analyzed by flow cytometry. The proliferation of ECV stimulated by FL was measured with the microculture tetrazolium assay. We also measured the level of FL in the supernatant of ECV cultures. Results: RhFL stimulates colony formation from cord blood when used as sole stimulant. FL in combination with other cytokines increased colony formation significantly. The number of DC was approximately 2.5 times higher when rhFL was used. RhFL stimulates the proliferation of ECV on which flt3 receptors is expressed. Furthermore, ECV secretes FL and this effect is augmented by tumor necrosis factor-?(?(TNF( ) and reduced by glucocorticoid. Conclusions: FL enhances hematopoietic colony formation and DC proliferation from human cord blood cells. FL not only stimulates the proliferation of ECV, but it is also secreted by ECV. It appears that FL may act as an autocrine growth cytokine of endothelial cells.

Cord blood

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