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High expression of SULF1 is associated with adverse prognosis in breast cancer brain metastasis

animal Models and Experimental Medicine 2025年第1期8卷 162-170页

作者： Yitong Li Tingting Feng Qinghong Wang Yue Wu Jue Wang Wenlong Zhang Qi Kong NHC Key Laboratory of Human Disease Comparative Medicine Beijing Engineering Research Center for Experimental Animal Models of Human Critical DiseasesInstitute of Laboratory Animal SciencesChinese Academy of Medical Sciences(CAMS)and Comparative Medicine CenterPeking Union Medical College(PUMC)BeijingChina

Background:Breast cancer is the most common cancer in women,and in advanced stages,it often metastasizes to the ***,research on the biological mechanisms of breast cancer brain metastasis and potential therapeutic targets are ***:Differential gene expression analysis(DEGs)for the datasets GSE43837 and GSE125989 from the GEO database was performed using online analysis tools such as GEO2R and *** investigation related to SULF1 was conducted using online databases such as Kaplan-Meier Plotter and ***,expression levels,variations,associations with HER2,biological processes,and pathways involv-ing SULF1 could be analyzed using UALCAN,cBioPortal,GEPIA2,and LinkedOmics ***,the sensitivity of SULF1 to existing drugs was explored using drug databases such as RNAactDrug and ***:High expression of SULF1 was associated with poor prognosis in advanced breast cancer brain metastasis and was positively correlated with the expression of *** the metastatic breast cancer population,SULF1 ranked top among the 16 DEGs with the highest mutation rate,reaching 11%,primarily due to *** and GSEA analyses revealed that the genes co-expressed with SULF1 were positively enriched in the‘ECM-receptor interaction’gene set and negatively enriched in the‘Ribosome’gene ***,docetaxel and vinorelbine can act as treatment options if the expression of SULF1 is ***:This study,through bioinformatics analysis,unveiled SULF1 as a poten-tial target for treating breast cancer brain metastasis(BM).

关键词： brain metastasis breast cancer potential therapeutic target SULF1

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The transcriptome of MHV-infected RAW264.7 cells offers an alternative model for macrophage innate immunity research

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animal Models and Experimental Medicine 2025年第1期8卷 57-66页

作者： Yun Liu Ting-Ting Feng Wei Tong Zhi Guo Xia Li Qi Kong Zhi-Guang Xiang Institute of Laboratory animal Sciences Chinese Academy of Medical Sciences(CAMS)and Comparative Medicine CenterPeking Union Medical College(PUMC)BeijingP.R.China

Background:Macrophages are the primary innate immune cells encountered by the invading coronaviruses,and their abilities to initiate inflammatory reactions,to main-tain the immunity homeostasis by differential polarization,to train the innate immune system by epigenic modification have been reported in laboratory animal ***:In the current in vitro research,murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus,a coronavirus existed in *** 3-,6-,12-,24-,and 48-h post infection(hpi.),the attached cells were washed with PBS and harvested in Trizol *** The harvest is subjected to transcriptome ***:The transcriptome analysis showed the immediate(3 hpi.)up regulation of DEGs related to inflammation,like Il1b and *** related to M2 differential po-larization,like Irf4 showed up regulation at 24 hpi.,the late term after viral *** addition,DEGs related to metabolism and histone modification,like Ezh2 were de-tected,which might correlate with the trained immunity of ***:The current in vitro viral infection study showed the key innated im-munity character of macrophages,which suggested the replacement value of viral infection cells model,to reduce the animal usage in preclinical research.

关键词： coronavirus innate immunity macrophage transcriptome

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The goat pan‑genome reveals patterns of gene loss during domestication

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Journal of animal Science and Biotechnology 2025年第1期16卷 49-58页

作者： Jiaxin Liu Yilong Shi Dongxin Mo Lingyun Luo Songsong Xu Fenghua Lv Frontiers Science center for Molecular Design Breeding(MOE) State Key Laboratory of Animal Biotech BreedingCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China

Background Unveiling genetic diversity features and understanding the genetic mechanisms of diverse goat pheno-types are pivotal in facilitating the preservation and utilization of these genetic ***,the total genetic diversity within a species can’t be captured by the reference genome of a single *** pan-genome is a col-lection of all the DNA sequences that occur in a species,and it is expected to capture the total genomic diversity of the specific *** We constructed a goat pan-genome using map-to-pan assemble based on 813 individuals,including 723 domestic goats and 90 samples from their wild relatives,which presented a broad regional and global *** total,146 Mb sequences and 974 genes were identified as absent from the reference genome(ARS1.2;GCF_001704415.2).We identified 3,190 novel single nucleotide polymorphisms(SNPs)using the pan-genome *** novel SNPs could properly reveal the population structure of domestic goats and their wild ***/absence variation(PAV)analysis revealed gene loss and intense negative selection during domestication and *** Our research highlights the importance of the goat pan-genome in capturing the missing genetic *** reveals the changes in genomic architecture during goat domestication and improvement,such as gene *** improves our understanding of the evolutionary and breeding history of goats.

关键词： Domestication Goat Improvement Pan-genome Presence/absence variation

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The gut microbial metabolite indole‑3‑aldehyde alleviates impaired intestinal development by promoting intestinal stem cell expansion in weaned piglets

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Journal of animal Science and Biotechnology 2025年第1期16卷 455-470页

作者： Jiaqi Zhang Yahui Chen Xin Guo Xuan Li Ruofan Zhang Mengting Wang Weiyun Zhu Kaifan Yu Laboratory of Gastrointestinal Microbiology Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal HealthCollege of Animal Science and TechnologyNanjing Agricultural UniversityNanjing 210095China National center for International Research on animal Gut Nutrition Nanjing Agricultural UniversityNanjing 210095China Wujiang animal Health Inspection Institute Suzhou 215200China

Background Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota ***,it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned *** In this study,we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score,and elevated levels of lipopolysaccharide(LPS)and D-lactate(D-LA)compared to healthy ***,we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned *** piglets demonstrated intestinal microbiota dysbiosis,characterized pri-marily by a higher Firmicutes to Bacteroidota ratio,a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri,and an increased abundance of Bacteroides ***-5287 and Bacteroides *** pro-filing of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes(KEGG)data was performed,and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with *** tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy ***,we explored the effects of dietary indole-3-aldehyde(IAld),a key tryptophan metabolite,on intestinal development and gut barrier function in weaned *** with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell(ISC)expansion in *** promotion of ISC expansion by IAld was also confirmed in porcine intestinal *** These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intesti-nal development by promoting ISC expansion in weaned piglets.

关键词： Indole-3-aldehyde Intestinal development Intestinal microbiota Intestinal stem cell Weaned piglets

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Dietary supplementation with N‑acetyl‑L‑cysteine ameliorates hyperactivated ERK signaling in the endometrium that is linked to poor pregnancy outcomes following ovarian stimulation in pigs

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Journal of animal Science and Biotechnology 2025年第1期16卷 167-181页

作者： Linghua Cheng Zhicheng Shi Yuan Yue Yue Wang Yusheng Qin Wei Zhao Yupei Hu Qin Li Min Guo Lei An Shumin Wang Jianhui Tian Frontiers Science center for Molecular Design Breeding(MOE) State Key Laboratory of Animal Biotech BreedingKey Laboratory of Animal GeneticsBreeding and Reproduction of the Ministry of Agriculture and Rural AffairsNational Engineering Laboratory for Animal BreedingCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193People’s Republic of China

Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management,such as pig,sheep,bovine and other *** helps synchronize ovulation or stimulate multiple ***,a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian *** study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue *** Compared with those in the control group,gilts that underwent ovarian stimulation showed a decrease in pregnancy rate,farrowing rate,and total number of piglets *** gilts also showed an increase in estra-diol(E_(2))*** supraphysiologicalE_(2) level was correlated with the decrease in the number of piglets ***,we found that high levels ofE_(2) impair uterine receptivity,as shown by the overproliferation of endo-metrial epithelial *** vitro mechanistic studies demonstrated that high levels ofE_(2) hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium,and in turn induces overproliferation of endometrial epithelial *** note,N-acetyl-L-cysteine(NAC)supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial ***,in vivo experiments indicated that dietary NAC supplementa-tion,compared with ovarian stimulation group,improves the uterine receptivity in gilts,and significantly increases the pregnancy rate and total number of piglets *** Ovarian stimulation-induced supraphysiological levels ofE_(2) impairs uterine receptivity by hyperactivat-ing FGF-FGFR-ERK signaling cascade,thereby reducing pregnancy rate and litter *** NAC to a con-ventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity,thus rescuing adverse pregnancy outcomes following ovarian stimulation.

关键词： Estradiol Gonadotropin Implantation N-acetyl-L-cysteine Ovarian stimulation Uterine receptivity

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Single-cell sequencing reveals the features of adaptive immune responses in the liver of a mouse model of dengue fever

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animal Models and Experimental Medicine 2025年第1期8卷 30-43页

作者： Yizhen Yuan Qian Chen Zhe Li Fangzhou Cai Dan Li Wei Wang National center of Technology Innovation for animal Model State Key Laboratory of Respiratory Health and MultimorbidityKey Laboratory of Pathogen Infection Prevention and Control(Peking Union Medical College)Ministry of EducationNHC Key Laboratory of Comparative MedicineInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences(CAMS)&Peking Union Medical College(PUMC)BeijingChina

Background:Dengue fever,an acute insect-borne infectious disease caused by the dengue virus(DENV),poses a great challenge to global public *** involve-ment is the most common complication of severe dengue and is closely related to the occurrence and development of ***,the features of adaptive immune responses associated with liver injury in severe dengue are not ***:We used single-cell sequencing to examine the liver tissues of mild or se-vere dengue mice model to analyze the changes in immune response of T cells in the liver after dengue virus infection,and the immune interaction between macrophages and T *** cytometry was used to detect T cells and macrophages in mouse liver and blood to verify the single-cell sequencing ***:Our result showed CTLs were significantly activated in the severe liver injury group but the immune function-related signal pathway was *** rea-son may be that the excessive immune response in the severe group at the late stage of DENV infection induces the polarization of macrophages into M2 type,and the macrophages then inhibit T cell immunity through the TGF-βsignaling *** ad-dition,the increased proportion of Treg cells suggested that Th17/Treg homeostasis was disrupted in the livers of severe liver injury ***:In this study,single-cell sequencing and flow cytometry revealed the characteristic changes of T cell immune response and the role of macrophages in the liver of severe dengue fever *** study provides a better understanding of the pathogenesis of liver injury in dengue fever patients.

关键词： adaptive immunity dengue fever model liver injury single-cell sequencing

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Targeting IGF1 to alleviate obesity through regulating energy expenditure and fat deposition

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Science China Life Sciences 2025年

作者： Ping Rong Yinqiu Mu Meiqin Wang Liang Chen Fangtong Liu Yuxin Jin Weikuan Feng Kun Zhou Hui Liang Hongyu Wang Shuai Chen State Key Laboratory of Pharmaceutical Biotechnology Department of Endocrinology Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School Model Animal Research Center Nanjing University MOE Key Laboratory of Model animal for Disease Study Model Animal Research Center School of Medicine Nanjing University College of Life Sciences Anhui Medical University Department of General Surgery First Affiliated Hospital Nanjing Medical University

Insulin-like growth factor 1 (IGF1) is a regulator of both cellular hypertrophy and lipogenesis,which are two key processes for pathogenesis of ***,the in vivo role of IGF1 in the development of obesity remains ***,we show that IGF1 expression is increased in adipose tissue in obese human patients and animal *** of IGF1 is associated with increased lipogenic gene expression and decreased energy *** down-regulation of IGF1 normalizes lipogenic gene expression,restores aberrant energy metabolism and alleviates obese phenotype of a genetic mouse model with ***,genetic down-regulation of IGF1 exerts similar effects on development of diet-induced ***,berberine that is an AMP-activated protein kinase (AMPK) activator in medicinal herbs inhibits IGF1 secretion,decreases lipogenic gene expression and alleviates diet-induced ***,our findings demonstrate that hypersecretion of IGF1 is a critical factor for the development of obesity and can be targeted using AMPK activators to alleviate obesity.

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Copper homeostasis and neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3124-3143页

作者： Yuanyuan Wang Daidi Li Kaifei Xu Guoqing Wang Feng Zhang International Research Laboratory of Ethnomedicine of Ministry of Education Key Laboratory of Basic Pharmacology of Ministry of EducationLaboratory Animal Center and Key Laboratory of Basic Pharmacology of Guizhou ProvinceZunyi Medical UniversityZunyiGuizhou ProvinceChina

Copper,one of the most prolific transition metals in the body,is required for normal brain physiological activity and allows various functions to work normally through its range of *** homeostasis is meticulously maintained through a complex network of copper-dependent proteins,including copper transporters(CTR1 and CTR2),the two copper ion transporters the Cu-transporting ATPase 1(ATP7A)and Cu-transporting beta(ATP7B),and the three copper chaperones ATOX1,CCS,and *** in copper homeostasis can lead to either the deficiency or accumulation of copper in brain *** evidence suggests that abnormal copper metabolism or copper binding to various proteins,including ceruloplasmin and metallothionein,is involved in the pathogenesis of neurodegenerative ***,the exact mechanisms underlying these processes are not *** is a potent oxidant that increases reactive oxygen species production and promotes oxidative *** reactive oxygen species levels may further compromise mitochondrial integrity and cause mitochondrial *** oxygen species serve as key signaling molecules in copper-induced neuroinflammation,with elevated levels activating several critical inflammatory ***,copper can bind aberrantly to several neuronal proteins,including alphasynuclein,tau,superoxide dismutase 1,and huntingtin,thereby inducing neurotoxicity and ultimately cell *** study focuses on the latest literature evaluating the role of copper in neurodegenerative diseases,with a particular focus on copper-containing metalloenzymes and copper-binding proteins in the regulation of copper homeostasis and their involvement in neurodegenerative disease *** synthesizing the current findings on the functions of copper in oxidative stress,neuroinflammation,mitochondrial dysfunction,and protein misfolding,we aim to elucidate the mechanisms by which copper contributes to a wide range of heredit

关键词： Alzheimer's disease amyotrophic lateral sclerosis disease copper homeostasis copper toxicity Huntington's disease Menkes'disease multiple sclerosis neurodegenerative disease Parkinson's disease Wilson's disease

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NECAB family of neuronal calcium-binding proteins in health and disease

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Neural Regeneration Research 2025年第5期20卷 1236-1243页

作者： Diones Bueno Michael K.E.Schafer Sudena Wang Michael J.Schmeisser Axel Methner Institute for Molecular Medicine University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Department of Anesthesiology University Medical Center of the Johannes Gutenberg-UniversityMainzGermany Institute of Anatomy University Medical Center of the Johannes Gutenberg-UniversityMainzGermany

The N-terminal EF-hand calcium-binding proteins 1–3(NECAB1–3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-β A4 precursor protein-binding family A members 2 and 3, key regulators of amyloid-β production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not wellcharacterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein–protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interac

关键词： calcium EF hand mitochondria nervous system signal transduction

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Systematic analysis of innate immune-related genes in the silkworm:Application to antiviral research

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Insect Science 2025年第1期32卷 151-171页

作者： Junming Xia Ruoxuan Peng Shigang Fei Mian Muhammad Awais Wenxuan Lai Yigui Huang Hailin Wu Yue Yu Lingying Liang Luc Swevers Jingchen Sun Min Feng Guangdong Provincial Key Laboratory of Agro-animal Genomics and Molecular Breeding College of Animal ScienceSouth China Agricultural UniversityGuangzhouChina Insect Molecular Genetics and Biotechnology National Center for Scientific Research DemokritosInstitute of Biosciences and ApplicationsAthensGreece

The silkworm,a crucial model organism of the Lepidoptera,offers an excellent platform for investigating the molecular mechanisms underlying the innate immune response of insects toward *** the years,researchers worldwide have identified numerous immune-related genes in ***,these identified silkworm immune genes are not well classified and not well known to the scientific *** the availability of the latest genome data of silkworms and the extensive research on silkworm immunity,it has become imperative to systematically categorize the immune genes of silkworms with different database *** this study,we present a meticulous organization of prevalent immune-related genes in the domestic silkworm,using the SilkDB 3.0 database as a reliable source for updated gene ***,utilizing the available data,we classify the collected immune genes into distinct categories:pattern recognition receptors,classical immune pathways,effector genes and ***-depth data analysis has enabled us to predict some potential antiviral ***,we performed antiviral experiments on selected genes,exploring their impact on Bombyx mori nucleopolyhedrovirus *** outcomes of this research furnish novel insights into the immune genes of the silkworm,consequently fostering advancements in the field of silkworm immunity research by establishing a comprehensive classification and functional understanding of immune-related genes in the *** study contributes to the broader understanding of insect immune responses and opens up new avenues for future investigations in the domain of host–pathogen interactions.

关键词： antiviral defense BmNPV Bombyx mori innate immunity SilkDB 3.0

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