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Characteristics of genetic basis copy number variation in production and adaptation traits of Chinese indigenous sheep

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Journal of Genetics and Genomics 2024年第5期51卷 566-569页

作者： Meilin Jin Gang Liu Jian Lu Zhiqiang Chen Huihua Wang Taotao Li Caihong Wei State Key Laboratory of Animal biotech Breeding Institute of Animal SciencesChinese Academy of Agricultural Sciences(CAAS)Beijing 100193China College of Animal Science and Technology China Agricultural UniversityBeijing100193China National Animal Husbandry Service National Center of Preservation&Utilization of Animal Genetic ResourcesBeijing 100125China Glbizzia Biosciences Beijing 102629China

Copy number variations(CNVs)range in size from 50 base pairs(bp)to several megabases(Mb)and encompass various types of structural variations,such as insertions,deletions,duplications,and complex multiallelic events(MacDonald et al.,2014).These genomic alterations modulate phenotype by altering gene dosage and transcriptional regulation,and are key drivers of biological evolution and determinants of genetic diversity and phenotypic *** recent years,CNVs have been detected in the genomes of various livestock species(Yuan et al.,2021;Chen et al.,2022).Upadhyay et al.(2017)conducted a comprehensive analysis of CNV distribution in the European cattle genome and determined that the Kit gene is associated with color-sidedness in English longhorn *** study presented extensive genome-wide information on CNVs in wild,commercial,and local chicken breeds to gain an integrated understanding of the domestication process and exclusively identified the genes involved(Chen et al.,2022).

关键词： sided number dosage

Dual-objective two-photon microscope for volumetric imaging of dense scattering biological samples by bidirectional excitation and collection

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Photonics Research 2024年第6期12卷 1351-1361页

作者： MUYUE ZHAI JING YU YANHUI HU HANG YU BEICHEN XIE YI YU DAWEI LI AIMIN WANG HEPING CHENG National Biomedical Imaging center College of Future TechnologyPeking UniversityBeijing 100871China Research Unit of Mitochondria in Brain Diseases Chinese Academy of Medical SciencesPKU-Nanjing Institute of Translational MedicineNanjing 211500China Beijing Transcend Vivoscope biotech Beijing 100085China College of Engineering Peking UniversityBeijing 100871China Academy for Advanced Interdisciplinary Studies Peking UniversityBeijing 100871China center for Quantitative Biology Peking UniversityBeijing 100871China School of Electronics Peking UniversityBeijing 100871China State Key Laboratory of Advanced Optical Communication System and Networks Peking UniversityBeijing 100871China

Full view observation throughout entire specimens over a prolonged period is crucial when exploring the physiological functions and system-level ***-photon microscopy(MPM)has been widely employed for such purposes owing to its deep penetration ***,the current MPM struggles with balancing the imaging depth and quality while avoiding photodamage for the exponential increasement of excitation power with the imaging ***,we present a dual-objective two-photon microscope(Duo-2P),characterized by bidirectional two-photon excitation and fluorescence collection,for long-duration volumetric imaging of dense scattering ***-2P effectively doubles the imaging depth,reduces the total excitation energy by an order of magnitude for samples with a thickness five times the scattering length,and enhances the signal-to-noise ratio up to 1.4 *** these advantages,we acquired volumetric images of a 380-μm suprachiasmatic nucleus slice for continuous 4-h recording at a rate of 1.67 s/volume,visualized the calcium activities over 4000 neurons,and uncovered their state-switching *** conclude that Duo-2P provides an elegant and powerful means to overcome the fundamental depth limit while mitigating photodamages for deep tissue volumetric imaging.

关键词： excitation overcome exponential

Transcriptomic and epigenomic landscapes of muscle growth during the postnatal period of broilers

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Journal of Animal Science and biotechnology 2024年第5期15卷 1851-1865页

作者： Shuang Gu Qiang Huang Yuchen Jie Congjiao Sun Chaoliang Wen Ning Yang State Key Laboratory of Animal biotech Breeding and Frontier Science center for Molecular Design Breeding China Agricultural UniversityBeijing 100193China National Engineering Laboratory for Animal Breeding and Key Laboratory of Animal Genetics Breeding and ReproductionMinistry of Agriculture and Rural AffairsDepartment of Animal Genetics and BreedingCollege of Animal Science and Technology China Agricultural UniversityBeijing 100193China. Sanya Institute of China Agricultural University Hainan 572025China

Background Broilers stand out as one of the fastest-growing livestock globally,making a substantial contribution to animal meat ***,the molecular and epigenetic mechanisms underlying the rapid growth and development of broiler chickens are still *** study aims to explore muscle development patterns and regulatory networks during the postnatal rapid growth phase of fast-growing *** measured the growth performance of Cornish(CC)and White Plymouth Rock(RR)over a 42-d *** muscle samples from both CC and RR were randomly collected at day 21 after hatching(D21)and D42 for RNA-seq and ATAC-seq library *** The consistent increase in body weight and pectoral muscle weight across both breeds was observed as they matured,with CC outpacing RR in terms of weight at each stage of *** expression analysis identified 398 and 1,129 genes in the two dimensions of breeds and ages,respectively.A total of 75,149 ATAC-seq peaks were annotated in promoter,exon,intron and intergenic regions,with a higher number of peaks in the promoter and intronic *** age-biased genes and breed-biased genes of RNA-seq were combined with the ATAC-seq data for subsequent *** results spotlighted the upregulation of ACTC1 and FDPS at D21,which were primarily associated with muscle structure development by gene cluster ***,a noteworthy upregulation of MUSTN1,FOS and TGFB3 was spotted in broiler chickens at D42,which were involved in cell differentiation and muscle regeneration after injury,suggesting a regulatory role of muscle growth and *** This work provided a regulatory network of postnatal broiler chickens and revealed ACTC1 and MUSTN1 as the key responsible for muscle development and *** findings highlight that rapid growth in broiler chickens triggers ongoing muscle damage and subsequent *** findings provide a foundation for future research to i

关键词： ATAC-seq Broiler Pectoral muscle development Rapid growth RNA-seq

Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4

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Genes & Diseases 2024年第4期11卷 411-425页

作者： Mengmeng Guo Pan Hu Jiayi Xie Kefu Tang Shixiu Hu Jialiang Sun Yundong He Jing Li Weiqiang Lu Huirong Liu Mingyao Liu Zhengfang Yi Shihong Peng Shanghai Key Laboratory of Regulatory Biology School of Life SciencesEast China Normal UniversityShanghai 200241China Prenatal Diagnosis center Department of Clinical LaboratoryChangning Maternity and Infant Health HospitalEast China Normal UniversityShanghai 200051China Key Laboratory of Acupuncture and Immunological Effects Shanghai University of Traditional Chinese MedicineShanghai 201203China Fengxian Hospital Affiliated to Southern Medical University Shanghai 201400China Shanghai Yuyao biotech Co. Ltd.Shanghai 200241China

Gastric cancer is highly prevalent among digestive tract *** to the intri-cate nature of the gastric cancer immune microenvironment,there is currently no effective treatment available for advanced gastric ***,there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4(EP4)in gastric *** our previous study,we identified a novel small molecule EP4 receptor antagonist called *** with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse ***,adminis-tration of YYo01 stimulated a robust immune response within the tumor microenvironment,characterized by increased infiltration of antigen-presenting cells,T cells,and M1 ***,our research revealed that YYo01 exhibited remarkable synergistic ef-fects when combined with the PD-1 antibody and the clinically targeted drug apatinib,rather than *** findings suggest that YYo01 holds great promise as a potential therapeutic strategy for gastric cancer,whether used as a standalone treatment or in combination with other drugs.

关键词： EP4 Immunomodulation Synergy Tumor microenvironment YY001

Protective role of fruits of Rosa odorata var. gigantea against WIRSinduced gastric mucosal injury in rats by modulating pathway related to inflammation, oxidative stress and apoptosis

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Chinese Herbal Medicines 2024年第2期16卷 263-273页

作者： Xinnan Liu Zhen Yuan Lifei Luo Teng Wang Feng Zhao Jingze Zhang Dailin Liu National Key Laboratory of Chinese Medicine Modernization Tianjin University of Traditional Chinese MedicineTianjin 301617China Tianjin Modern Innovation Chinese Medicine Technology Co. Ltd.Tianjin 300380China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China

Objective: Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea(FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress(WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms ***: A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin(H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western ***: Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase(GSH-PX), superoxide dismutase(SOD) and catalase(CAT) contents;anti-inflammatory cytokines interleukin-10(IL-10) and prostaglandin E2(PGE2) levels as well as regulatory factors tumor necrosis factor-a(TGF-a) and somatostatin(SS) contents, while decreasing malondialdehyde(MDA), nitric oxide synthase(i NOS), tumor necrosis factor(TNF-a), interleukin-1β(IL-1β), interleukin-6(IL-6), gastrin(GAS)and endothelin(ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen(PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-ΚB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell ***: The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mecha

关键词： anti-apoptosis anti-inflammation anti-oxidation gastric mucosal injury Rosa odorata Sweet var.gigantea(Coll.et Hemsl.)Rehd.et Wils water immersion restrained stress

Antithetical impacts of deleterious LRP1B mutations in non-squamous and squamous NSCLCs on predicting benefits from immune checkpoint inhibitor alone or with chemotherapy over chemotherapy alone: retrospective analyses of the POPLAR/OAK and CHOICE-01 trial

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Science China Life Sciences 2024年

作者： Jinliang Wang Wenyong Zhou Yu Xu Jianchun Duan Qiaoxia Zhou Guoqiang Wang Leo Li Chunwei Xu Wenxian Wang Shangli Cai Zhijie Wang Jie Wang Department of Oncology The Fifth Medical Center of Chinese PLA General Hospital Department of Thoracic Surgery Shanghai Chest Hospital School of Medicine Shanghai Jiao Tong University Burning Rock biotech CAMS Key Laboratory of Translational Research on Lung Cancer State Key Laboratory of Molecular Oncology Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Basic Medicine and Cancer (IBMC) Chinese Academy of Sciences Department of Clinical Trial The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)

In non-small cell lung cancers, the non-squamous and squamous subtypes （nsqNSCLC and sqNSCLC） exhibit disparities in pathophysiology,tumor immunology, and potential genomic correlates affecting responses to immune checkpoint inhibitor （ICI）-based treatments. In our inhouse training cohort （n=85）, the presence of the LRP1B deleterious mutation （LRP1B-del） was associated with longer and shorter progression-free survival （PFS） on ICIs alone in nsqNSCLCs and sqNSCLCs, respectively (Pinteraction=0.008). These results were validated using a larger public ICI cohort (n=208, Pinteraction<0.001). Multiplex immunofluorescence staining revealed an association between LRP1B-del and increased and decreased numbers of tumor-infiltrating CD8+T cells in nsqNSCLCs （P=0.040） and sqNSCLCs （P=0.014）, respectively. In the POPLAR/OAK cohort, nsqNSCLCs with LRP1B-del demonstrated improved PFS benefits from atezolizumab over docetaxel (hazard ratio （HR）=0.70, P=0.046), whereas this benefit was negligible in those without LRP1B-del （HR=1.05, P=0.64）. Conversely, sqNSCLCs without LRP1Bdel benefited more from atezolizumab （HR=0.60, P=0.002） than those with LRP1B-del （HR=1.30, P=0.31）. Consistent results were observed in the in-house CHOICE-01 cohort, in which nsqNSCLCs with LRP1B-del and sqNSCLCs without LRP1B-del benefited more from toripalimab plus chemotherapy than from chemotherapy alone (Pinteraction=0.008). This multi-cohort study delineates the antithetical impacts of LRP1Bdel in nsqNSCLCs and sqNSCLCs on predicting the benefits from ICI alone or with chemotherapy over chemotherapy alone. Our findings highlight the distinct clinical utility of LRP1B-del in guiding treatment choices for nsqNSCLCs and sqNSCLCs, emphasizing the necessity for a detailed analysis based on pathological subtypes when investigating biomarkers for cancer therapeutics.

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A Meta-Analysis of the Prognostic and Clinicopathological Significance of circZFR in Human Gastrointestinal Cancers

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International Journal of Clinical Medicine 2024年第3期15卷 134-144页

作者： Christian Cedric Bongolo Erick Thokerunga Yu Zhang Jian-Cheng Tu Wuhan Life Origin biotech Joint Stock Co Ltd. Wuhan China College of Life Sciences and Technology Huazhong Agricultural University Wuhan China Department & Program of Clinical Laboratory Medicine and center for Gene Diagnosis Zhongnan Hospital of Wuhan University Wuhan China

Background: Studies of gastrointestinal (GIT) cancers have shown that circZFR could be involved in the development and progression of various GIT cancers. However, small sample sizes limit the clinical significance of these studies. Here, a meta-analysis was conducted to ascertain the actual involvement of circZFR in the development and prognosis of GIT cancers. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched up to December 31, 2023. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were pooled to evaluate the association between circZFR expression and overall survival (OS). Publication bias was measured using the funnel plot and Egger’s test. Results: 10 studies having 659 participants were enrolled for meta-analysis. High circZFR expression was associated with poor OS (HR = 1.4, 95% CI: 1.20, 1.70). High circZFR expression also predicted larger tumor size (OR = 4.38, 95% CI 2.65, 7.25), advanced clinical stage (OR = 5.33, 95% CI 3.10, 9.16), and tendency for distant metastasis (OR = 2.89, 95% CI: 1.62, 5.11), but was not related to age, gender, and histological grade. Conclusions: In summary, high circZFR expression was associated with poor OS, larger tumor size, advanced stage cancer and tendency for distant metastasis. These findings suggested that circZFR could be a prognostic marker for GIT cancers.

关键词： CircZFR Gastrointestinal Prognostic Significance Meta-Analysis

Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1283-1301页

作者： Qian Zhao Jiale Dong Han Liu Hui Chen Huan Yu Shuyin Ye Shuangjin Yu Yu Li Longhui Qiu Nazi Song Hongjiao Xu Qi Liu Zhiteng Luo Yuyi Li Rui Wang Guodong Chen Xianxing Jiang School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of Chiral Molecule and Drug DiscoverySun Yat-sen UniversityGuangzhou 510006China Organ Transplant center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510006China Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510006China Shenzhen Turier biotech.Co. Ltd.Shenzhen 518118China School of Life Sciences Key Laboratory of Preclinical Study for New Drugs of Gansu ProvinceSchool of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China

The role of co-agonists of glucagon-like peptide-1 receptor(GLP-1R)and glucagon receptor(GCGR)in chronic kidney disease(CKD)remains *** we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease ***,GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction(UUO).Based on the importance of GLP-1R and GCGR in CKD,we reported a novel monomeric peptide,1907-B,with dual-agonism on both GLP-1R and *** data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys(~2-3 fold)and exhibited better therapeutic contribution to CKD than best-in-class monoagonists,semaglutide,or glucagon,in db/db mice and UUO *** lock-of-function models,including selective pharmacological activation and genetic knockdown,confirmed that 1907-B’s effects on ameliorating diabetic nephropathy in db/db mice,as well as inhibiting kidney fibrosis in UUO mice,were mediated through GLP-1 and glucagon *** findings highlight that 1907-B,a novel GLP-1R and GCGR co-agonist,exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.

关键词： GLP-1 receptor Glucagon receptor Chronic kidney disease Diabetic nephropathy Kidney fibrosis Dual-agonism

The role of melatonin receptor 1B gene(MTNR1B)in the susceptibility to depression and type 2 diabetes comorbidity

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Genes & Diseases 2024年第3期11卷 113-115页

作者： Mutaz Amin Benjamin Rafla Rongling Wu Teodor T.Postolache Cclaudia Gragnoli INSERM US14-OrphanetParis 75014France Department of Biochemistry and Molecular Biology Faculty of MedicineAl-Neelain UniversityKhartoum 11121Sudan Division of Endocrinology Department of MedicineCreighton University School of MedicineOmahaNE 68124USA Department of Public Health Sciences Penn State College of MedicineHersheyPA 17033USA Department of Statistics Penn State College of MedicineHersheyPA 17033USA Mood and Anxiety Program Department of PsychiatryUniversity of Maryland School of MedicineBaltimoreMD 21201USA Rocky Mountain Mental llness Research Education and Clinical center(MIRECC) Veterans Integrated Service Network(VISN)19Military and Veteran Microbiome:Consortium for Research and Education(MVM-CoRE)DenverCO 80246USA Mental Ilness Research Education and Clinical center(MIRECC) Veterans Integrated Service Network(VISN)5VA Capitol Health Care NetworkBaltimoreMD 21090USA Molecular Biology Laboratory Bios Biotech Multi-Diagnostic Health CenterRome00197Italy

Melatonin is an endogenous monoamine hormone secreted by the pineal *** signaling has been shown to play a role in circadian rhythm regulation,lipid and glucose metabolism,and obesity,and it has anti-inflammatory and antioxidant *** melatonin receptor 1B gene(MTNR1B)is expressed in,among other tissues,the brain and pancreatic beta cells,and risk variants for T2D have been reported as impairing early insulin secretion and increasing fasting glucose levels.^(1) Variants in the MTNR1B gene also have been reported in patients with depression(MDD).

关键词： MTNR1B metabolism properties.