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Activation ofγ-globin expression by a common variant disrupting IKAROS-binding motif inβ-thalassemia

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Journal of genetics and Genomics 2025年第2期52卷 157-167页

作者： Hualei Luo Jueheng Wang Lang Qin Xinhua Zhang Hailiang Liu Chao Niu Mengyang Song Congwen Shao Peng Xu Miao Yu Haokun Zhang Yuhua Ye Xiangmin Xu Innovation Center for Diagnostics and Treatment of Thalassemia Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Department of Medical genetics School of Basic Medical SciencesSouthern Medical UniversityGuangzhouGuangdong 510515China State Key Laboratory of genetic Engineering School of Life SciencesFudan UniversityShanghai 201114China Department of Pediatrics 923rd Hospital of the People's Liberation ArmyNanningGuangxi 530021China Cyrus Tang Medical institute National Clinical Research Centre for Hematologic DiseasesCollaborative Innovation Centre of HematologyState Key Laboratory of Radiation Medicine and ProtectionSoochow University SuzhouSuzhouJiangsu 215031China State Key Laboratory of genetic Engineering MOE Engineering Research Center of Gene TechnologySchool of Life SciencesFudan UniversityShanghai 200438China

Programmed silencing ofγ-globin genes in adult erythropoiesis is mediated by several chromatin remodeling complexes,which determine the stage-specific genome architecture in this *** of cis-or trans-acting mutations contributing to the diverse extent of fetal hemoglobin(Hb F)might illustrate the underlying mechanism ofγ-β-globin ***,we recruit a cohort of 1142β-thalassemia patients and dissect the natural variants in the wholeβ-globin gene cluster through a targeted next-generation sequencing panel.A previously unreported SNP rs7948668,predicted to disrupt the binding motif of IKAROS as a key component of chromatin remodeling complexes,is identified to be significantly associated with higher levels of Hb F and age at ***-editing on this SNP leads to the elevation of Hb F in both HUDEP-2 and primary CD34+cells while the extent of elevation is amplified in the context ofβ-thalassemia mutations,indicating epistasis effects of the SNP in the regulation of Hb ***,we perform ChIP-qPCR and 4C assays to prove that this variant disrupts the binding motif of IKAROS,leading to enhanced competitiveness of HBG promoters to locus control *** study highlights the significance of common regulatory SNPs and provides potential targets for treatingβ-hemoglobinopathy.

关键词： β-thalassemia Fetal hemoglobin Single nucleotidepolymorphism IKAROS Locus control region

An enhancer–promoter-transcription factor module orchestrates plant immune homeostasis by constraining camalexin biosynthesis

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Molecular Plant 2025年第1期18卷 95-113页

作者： Ying Zhang Meng Tang Yi Zhang Qinglin Cheng Lijiang Liu Wei Chen Jiatao Xie Jiasen Cheng Yanping Fu Bo Li Daohong Jiang Xiao Yu National Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhanHubei 430070China The Provincial Key Lab of Plant Pathology of Hubei Province College of Plant Science and TechnologyHuazhong Agricultural UniversityWuhanHubei 430070China Hubei Hongshan Laboratory WuhanHubei 430070China National Key Laboratory of Crop genetic Improvement and National Center of Plant Gene Research(Wuhan) Huazhong Agricultural UniversityWuhan 430070China Oil Crops Research institute of the Chinese Academy of Agricultural Sciences Key Laboratory of Biology and Genetic Improvement of Oil Crops of the Ministry of AgricultureWuhan 430062China

Effective plant defense against pathogens relies on highly coordinated regulation of immune gene ***,as cis-regulatory elements,are indispensable determinants of dynamic gene regulation,but the molecular functions in plant immunity are not well *** this study,we identified a novel enhancer,CORE PATTERN-INDUCED ENHANCER 35(CPIE35),which is rapidly activated upon pathogenic elicitation and negatively regulates antifungal resistance through modulating WRKY15 *** immune activation,CPIE35 activates the transcription of WRKY15 by forming chromatin loops with the promoter of WRKY15 in a WRKY18/40/60-,WRKY33-,and MYC2-dependent ***15 directly binds to the promoters of PAD3 and GSTU4,suppressing their expression and leading to reduced camalexin synthesis and ***,CPIE35 region is evolutionarily conserved among Brassicaceae plants,and the CPIE35-WRKY15 module exerts similar functions in Brassica napus to negatively regulate antifungal *** work reveals the“enhancer–promoter-transcription factor”regulatory mechanism in maintenance of immune homeostasis,highlighting the importance and conserved role of enhancers in fine-tuning immune gene expression in plants.

关键词： plant innate immunity enhancers antifungal resistance transcriptional regulation cis-regulatory elements transcription factors

Recent advances in exploring new blood-based biomarkers for the early diagnosis of gastric cancer

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Science China Chemistry 2025年第1期68卷 35-45页

作者： Xinyu Peng Qian Ma Da Han School of Life Science Shanghai UniversityShanghai 200444China institute of Molecular medicine Shanghai Key Laboratory for Nucleic Acid Chemistry and NanomedicineState Key Laboratory of Oncogenes and Related GenesRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200025China Department of Research and Development Intellinosis Biotechnologies Co.Ltd.Shanghai 201112China

Gastric cancer(GC)is a prevalent and lethal malignancy worldwide,and the 5-year survival rate is less than 30%.The absence of distinctive symptoms often leads to late-stage diagnosis,contributing to a grim *** detection is pivotal for improving the survival rates and outcomes of GC *** diagnostic methods,including gastroscopy and histopathological examination,are restricted in the early diagnosis of *** protein biomarkers,such as carcinoembryonic antigen(CEA),carbohydrate antigen 19-9(CA19-9),and carbohydrate antigen 72-4(CA72-4),exhibit insufficient sensitivity and specificity for GC screening,which diminishes their clinical ***,novel circulating biomarkers,such as circulating tumor cells(CTCs),circulating tumor cell DNA(ct DNA),and circulating free RNA(cf RNA),have emerged as promising candidates in the burgeoning field of liquid biopsy due to their superior sensitivity and *** review focuses on the latest research on blood-based biomarkers for GC diagnosis and examines the clinical potentials and challenges associated with these emerging biomarkers.

关键词： gastric cancer early diagnosis blood

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Ribosome profiling and single-cell RNA sequencing identify the unfolded protein response as a key regulator of pigeon lactation

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Zoological Research 2025年第01期 54-74页

作者： Jing Liu San-Feng Liu Hui-Rong Mao Hong-Xia Jiang Shui-Bing Liu Xiao-Fei Xu Jin-Tao Wu Xun Liu Wen-Tao Zhang Xiao-Long Hu Biao Chen College of Animal Science and Technology Jiangxi Agricultural University Poultry institute Jiangxi Agricultural University Zhongshan Shiqi Pigeon Breeding Limited Company National Key Laboratory for Swine genetic Improvement and Germplasm Innovation Ministry of Science and Technology of ChinaJiangxi Agricultural University

Pigeons and certain other avian species produce a milklike secretion in their crop sacs to nourish offspring, yet the detailed processes involved are not fully elucidated. This study investigated the crop sacs of 225-day-old unpaired non-lactating male pigeons(MN) and males initiating lactation on the first day after incubation(ML). Using RNA sequencing,ribosomeprofiling,andsingle-cell transcriptome sequencing(scRNA-seq), we identified a significant up-regulation of genes associated with ribosome assembly and protein synthesis in ML compared to MN. Results from scRNA-seq analysis identified 12distinct cell types and 22 clusters, with secretory epithelial cells(SECs) exhibiting marked expression of plasma cell markers, including IGLL1 and MZB1. RNA fluorescence in situ hybridization(RNA FISH) and IgY quantification confirmed the critical role of SECs in producing endogenous IgY during lactation. We propose that fibroblast-derived BAFF signals activate SECs, mimicking B cell transformation and enhancing protein production through the unfolded protein response(UPR). These findings shed light on the cellular dynamics of pigeon milk production and contribute to a broader understanding of avian biology.

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MET receptor tyrosine kinase promotes the generation of functional synapses in adult cortical circuits

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Neural Regeneration Research 2025年第5期20卷 1431-1444页

作者： Yuehua Cui Xiaokuang Ma Jing Wei Chang Chen Neha Shakir Hitesch Guirram Zhiyu Dai Trent Anderson Deveroux Ferguson Shenfeng Qiu Basic Medical Sciences University of Arizona College of Medicine-PhoenixPhoenixAZUSA Department of medicine University of Arizona College of Medicine-PhoenixPhoenixAZUSA

Loss of synapse and functional connectivity in brain circuits is associated with aging and neurodegeneration,however,few molecular mechanisms are known to intrinsically promote synaptogenesis or enhance synapse *** have previously shown that MET receptor tyrosine kinase in the developing cortical circuits promotes dendritic growth and dendritic spine *** investigate whether enhancing MET in adult cortex has synapse regenerating potential,we created a knockin mouse line,in which the human MET gene expression and signaling can be turned on in adult(10–12 months)cortical neurons through doxycycline-containing *** found that similar to the developing brain,turning on MET signaling in the adult cortex activates small GTPases and increases spine density in prefrontal projection *** findings are further corroborated by increased synaptic activity and transient generation of immature silent *** MET signaling resulted in an increasedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-Daspartate(AMPA/NMDA)receptor current ratio,indicative of enhanced synaptic function and *** data reveal that enhancing MET signaling could be an interventional approach to promote synaptogenesis and preserve functional connectivity in the adult *** findings may have implications for regenerative therapy in aging and neurodegeneration conditions.

关键词： aging circuit connectivity cortical circuits molecular mechanisms neural regeneration neurodegeneration synapses

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Network pharmacology and animal experiments revealed the protective effects of Guilong prescription(归龙方) on chronic prostatitis and its possible mechanisms

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Journal of Traditional Chinese medicine 2025年第1期45卷 89-99页

作者： ZHU Peixuan SU Zeqi FAN Qiongyin ZHANG Cai WANG Ting School of Chinese medicine Beijing University of Chinese Medicine Beijing Research institute of Chinese medicine Beijing University of Chinese Medicine State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of NeuropsychopharmacologyBeijing Institute of Pharmacology and Toxicology

OBJECTIVE: To investigate the protective effects of Guilong prescription(归龙方, GL) on chronic prostatitis(CP) and unravel the underlying mechanisms of its pharmacological effects. METHODS: The composition of GL was determined via linear ion trap/electrostatic field orbital trap tandem highresolution mass spectrometry, and the identified compounds were performed network pharmacological analysis to predict possible pathways of the effects of GL on CP. A CP rat model was established by carrageenan, and rats were randomly assigned into a Control group, Sham group, CP group, GL low dose(3.5 g/kg) group, GL medium dose(7 g/kg) group, and GL high dose(14 g/kg) group. Hematoxylin-eosin staining of the prostate, and prostate blood-perfusion measured by laser speckle contrast analysis were used to evaluate the efficacy of GL. Expression of intercellular cell adhesion molecule-1(ICAM-1) and induce nitric oxide synthase(i NOS) were determined by immunohistochemistry, and the content of interferon-γ(IFN-γ), interleukin-1β(IL-1β), interleukin-4(IL-4), interleukin-10(IL-10), chemokine ligand 1(CXCL1) and tumor necrosis factor-α(TNF-α) were determined by electro-chemiluminescence assays. The expression of p38 mitogen-activated protein kinase(p38 MAPK), phosphatidylinositol 3-kinase(PI3K), ribosomeassociated complex-alpha serine/threonine-protein kinase(Akt), nuclear factor-κ-gene binding p65(NF-κB p65), inhibitor of NF-κB-α(IκBα), glycogen synthase kinase-3β(GSK-3β), and their phosphorylated forms were tested by Western blot. RESULTS: In GL, a total of 48 compounds were identified, including 14 flavonoids, 14 alkaloids, 11 carboxylic acids, 4 lactones, 2 glycosides, 2 terpenoids and 1 aldehyde. Network pharmacological analysis suggested that the mechanism of GL may be related to PI3K-Akt signaling pathway and cytokine expression. After treatment with GL, inflammatory pathological changes in the prostate of rats were significantly improved, and blood perfusion of the prostate was sig

关键词： Guilong prescription Prostatitis anti-inflammatory agents carrageenan cytokines network pharmacology

Identification of novel rodent and shrew orthohepeviruses sheds light on hepatitis E virus evolution

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Zoological Research 2025年第01期 103-121页

作者： Fu-Li Li Bo Wang Pei-Yu Han Bei Li Hao-Rui Si Yan Zhu Hong-Min Yin Li-Dong Zong Yi Tang Zheng-Li Shi Ben Hu Xing-Lou Yang Yun-Zhi Zhang institute of Preventive medicine School of Public Health Dali University Yunnan Key Laboratory of Screening and Research on Antipathogenic Plant Resources from Western Yunnan Yunnan Key Laboratory of Zoonotic Disease Cross-border Prevention and Quarantine Second People's Hospital of Qujing Programme in Emerging Infectious Diseases Duke-NUS Medical School CAS Key Laboratory of Special Pathogens Wuhan Institute of Virology Chinese Academy of Sciences Key Laboratory of genetic Evolution & Animal Models Yunnan International Joint Laboratory of Zoonotic Viruses Yunnan Key Laboratory of Biodiversity Information Kunming Institute of Zoology Chinese Academy of Sciences

The family Hepeviridae has seen an explosive expansion in its host range in recent years, yet the evolutionary trajectory of this zoonotic pathogen remains largely unknown. The emergence of rat hepatitis E virus(HEV)has introduced a new public health threat due to its potential for zoonotic transmission. This study investigated2 ?464 wild small mammals spanning four animal orders,eight families, 21 genera, and 37 species in Yunnan Province, China. Using broadly reactive reverse transcription-polymerase chain reaction(RT-PCR), we systematically screened the presence and prevalence of Orthohepevirus and identified 192 positive specimens from10 species, corresponding to an overall detection rate of7.79%. Next-generation sequencing enabled the recovery of 24 full-length genomic sequences from eight host species, including Bandicota bengalensis, Eothenomys eleusis, and Episoriculus caudatus, representing newly reported host species for Orthohepevirus *** and sequence analyses revealed extensive genetic diversity within orthohepeviruses infecting rodents and shrews. Notably, among the identified strains, 20 were classified as Rocahepevirus ratti C1, two as C3, and one as Rocahepevirus eothenomi, while the remaining strain exhibited significant divergence, precluding *** analyses highlighted close associations between orthohepeviruses and their respective host taxa,with distinct phylogenetic clustering patterns observed across different host orders. These findings emphasize the critical roles of co-speciation and cross-species transmission in shaping the evolutionary trajectories of the genera Paslahepevirus and Rocahepevirus.

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Assembly and network of Rhei Radix et Rhizoma surface microbiome shaped by processing methods and sampling locations

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Chinese Herbal medicines 2025年第1期17卷 189-199页

作者： Guangfei Wei Xiao Chen Guozhuang Zhang Conglian Liang Zhaoyu Zhang Bo Zhang Shilin Chen Linlin Dong State Key Laboratory for Quality Ensurance and Sustainable Use of Dao-di Herbs Institute of Chinese Materia Medica China Academy of Chinese Medical Sciences School of Biomedicine Beijing City University Shandong University of Traditional Chinese medicine School of Pharmacy Linyi University institute of Herbgenomics Chengdu University of Traditional Chinese Medicine

Objective:Rhei Radix et Rhizoma has five types of products,namely,raw rhubarb(RR),wine rhubarb(WR),vinegar rhubarb(VR),cooked rhubarb(CR),and rhubarb charcoal(RC).However,Rhei Radix et Rhizoma is easily contaminated with fungi and mycotoxins if not harvested or processed ***,we intend to analyze how microbiome assemblies and co-occurrence patterns are influenced by sampling locations and processing ***:High-throughput sequencing and internal transcribed spacer 2(ITS2) were carried out to study the diversities(α-and β-diversity),composition(dominant taxa and potential biomarkers),and network complexitity of surface fungi on RR, WR,VR,CR,and RC collected from Gansu and Sichuan provinces,***:The phyla Ascomycota and Basidiomycota;the genera Kazachstania,Malassezia,and Asterotremella;and the species Kazachstania exigua,Asterotremella pseudolonga,and Malassezia restricta were the dominant fungi and exhibited differences in the two provinces and the five processed *** α-diversity and network complexity were strongly dependent on processing *** 1,the Shannon index,and network complexity and connectivity were highest in the CR *** α-diversity and network complexity were influenced by sampling *** 1 and network complexity and connectivity were highest in the Gansu ***:The assembly and network of the surface microbiome on Rhei Radix et Rhizoma were shaped by processing methods and sampling *** paper offers a comprehensive understanding of microorganisms,which can provide early warning for potential mycotoxins and ensure the safety of drugs and consumers.

关键词： community assembly fungi processing methods Rhei Radix et Rhizoma sampling locations

Dysregulation of genes involved in the long-chain fatty acid transport in pancreatic ductal adenocarcinoma

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World Journal of Gastrointestinal Oncology 2025年第1期17卷 199-206页

作者： Radu Cristian Poenaru Elena Milanesi Andrei Marian Niculae Anastasia-Maria Dobre Catalina Vladut Mihai Ciocîrlan Daniel Vasile Balaban Vlad Herlea Maria Dobre Mihail Eugen Hinescu Faculty of medicine Carol Davila University of Medicine and PharmacyBucharest 050474Romania Department of Radiobiology Victor Babes National Institute of PathologyBucharest 050096Romania Department of Pathology Victor Babes National Institute of PathologyBucharest 050096Romania Department of Gastroenterology Prof.Dr.Agrippa Ionescu Clinical Emergency HospitalBucharest 011356Romania Department of Pathology Fundeni Clinical InstituteBucharest 022258Romania

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is an aggressive lethal malignancy with limited options for treatment and a 5-year survival rate of 11%in the United *** for other types of tumors,such as colorectal cancer,aberrant de novo lipid synthesis and reprogrammed lipid metabolism have been suggested to be associated with PDAC development and *** To identify the possible involvement of lipid metabolism in PDAC by analyzing in tumoral and non-tumoral tissues the expression level of the most relevant genes involved in the long-chain fatty acid(FA)import into *** A gene expression analysis of FASN,CD36,SLC27A1,SLC27A2,SLC27A3,SLC27A4,SLC27A5,ACSL1,and ACSL3 was performed by qRT-PCR in 24 tumoral PDAC tissues and 11 samples from non-tumoral pancreatic tissues obtained via fine needle aspiration or via surgical *** genes were considered significantly dysregulated between the groups when the p value was<0.05 and the fold change(FC)was≤0.5 and≥*** We found that three FA transporters and two long-chain acyl-CoA synthetases genes were significantly upregulated in the PDAC tissue compared to the non-tumoral tissue:SLC27A2(FC=5.66;P=0.033),SLC27A3(FC=2.68;P=0.040),SLC27A4(FC=3.13;P=0.033),ACSL1(FC=4.10;P<0.001),and ACSL3(FC=2.67;P=0.012).We further investigated any possible association between the levels of the analyzed mRNAs and the specific characteristics of the tumors,including the anatomic location,the lymph node involvement,and the presence of metastasis.A significant difference in the expression of SLC27A3(FC=3.28;P=0.040)was found comparing patients with and without lymph nodes involvement with an overexpression of this transcript in 17 patients presenting tumoral cells in the lymph *** Despite the low number of patients analyzed,these preliminary results seem to be *** lipid metabolism through a broad strategy could be a beneficial way to treat this *** in vitro and in vivo s

关键词： Carcinoma Pancreatic ductal Fatty acid transport Gene expression Biomarkers