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散发性早发阿尔茨海默病中磷酸化tau蛋白的高负荷和特异性楔前叶萎缩:一项前瞻性队列研究

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Science Bulletin 2023年第22期68卷 2817-2826,M0006页

作者：吕心怡程昭昭王琼高峰戴林斌杜琛刘畅谢强申勇施炯 Department of Neurology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Neurodegenerative Disorder Research Center Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Radiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Department of Nuclear medicine The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China Anhui Province Key Laboratory of Biomedical Aging Research University of Science and Technology of ChinaHefei 230001China

早发性阿尔茨海默病(EOAD)是阿尔茨海默病(AD)的罕见且严重的亚型,于65岁之前发病,占所有AD病例的5%~10%.以往关于EOAD的研究主要集中在家族性遗传人群,而对于占EOAD病例85%~90%的散发性EOAD(sEOAD)的研究则较为有限.在这项前瞻性队列... 详细信息

早发性阿尔茨海默病(EOAD)是阿尔茨海默病(AD)的罕见且严重的亚型,于65岁之前发病,占所有AD病例的5%~10%.以往关于EOAD的研究主要集中在家族性遗传人群,而对于占EOAD病例85%~90%的散发性EOAD(sEOAD)的研究则较为有限.在这项前瞻性队列研究中,共纳入sEOAD110例,晚发性AD(LOAD)89例,年龄匹配对照组75例.研究对象排除了家族性EOAD患者,所有纳入AD患者均符合基于ATN框架下的生物标志物证据的诊断标准.对纳入患者进行了患病危险因素分析、多维度认知功能评估、多模态分子影像学评估及脑脊液/外周血生物标记物检测.结果显示,与LOAD患者相比,sEOAD患者没有表现出特定的危险因素,但表现出更严重的执行功能损害和双侧楔前叶萎缩.在sEOAD患者中的脑脊液和血浆中磷酸化tau181(P-tau181)水平较LOAD组显著升高.本研究探讨了散发性EOAD人群的临床特征,发现了tau蛋白磷酸化在sEOAD发生和进展中的重要性,有助于全面了解AD的病因、发病年龄决定因素和疾病进展,并为潜在的治疗策略提供了重要思路.

关键词： Alzheimer’s disease Early-onset Alzheimer’s disease Familial hereditary Phosphorylated tau Precuneus

Intrapartum and early postpartum glycemic profiles in women with gestational diabetes mellitus:an observational study

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Chinese Medical Journal 2022年第21期135卷 2547-2553页

作者： Yu Ding Xueying Zheng Yujie Liu Tian Wei Tong Yue Siqi Wang Suyu Chen Jianping Weng Sihui Luo Department of Endocrinology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Department of Obstetrics and Gynecology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China Institute of Endocrine and Metabolic Diseases The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001China

Background: Data on the glycemic profile of pregnant women with gestational diabetes mellitus (GDM) during the perinatal period are sparse. This study described the intrapartum and early postpartum glucose profiles among pregnant women with GDM, and analyzed factors potentially affecting glycemic parameters during the period.Methods: This was a prospective observational study conducted from March 2020 to November 2021. Pregnant women with GDM receiving lifestyle interventions alone during pregnancy and matched women with non-diabetic pregnancies (NDPs) were enrolled from among patients admitted to the obstetrics department for childbirth. Glucose monitoring was performed via a flash glucose monitoring (FGM) system on admission, and glucose readings during labor and early postpartum were analyzed. The clinical characteristics and FGM-based parameters of participants in the two groups were compared.Results: A total of 124 participants (mean age: 29.5 ± 3.5 years, 92 [74.2%] primipara) were included in the final analysis. A total of 17,571 glucose readings were retrieved. There were no significant differences in clinical characteristics between the GDM (n = 60) and NDP (n = 64) groups. The average glucose level was 92.2 mg/dL, and the level was higher in the GDM group (95.5 ± 12.1 mg/dLvs. 89.1 ± 13.4 mg/dL,P = 0.008) during the intrapartum and early postpartum periods. The data were split into the intrapartum period (from the start of labor to delivery of the placenta) and the early postpartum period (within 24 h after placental delivery) for analysis. During intrapartum, women with GDM exhibited glycemic profiles and fluctuations similar to those in the NDP group. However, women with GDM had higher postpartum glucose levels (97.7 ± 13.4 mg/dLvs. 90.8 ± 15.3 mg/dL,P = 0.009), a longer time spent >140 mg/dL (8.7 ± 9.3%vs. 5.9 ± 10.3%,P = 0.011), and greater glycemic fluctuations than those with NDP. Postpartum hyperglycemia in GDM might be associated with high parity and postprandial glucose abnormalities in GDM scr

关键词： Blood glucose Flash glucose monitoring Gestational diabetes mellitus Glycemic profiles

Neutrophil-to-lymphocyte ratio or platelet-to-lymphocyte ratio is a predictive factor of pancreatic cancer patients with type 2 diabetes

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Hepatobiliary & Pancreatic Diseases International 2022年第2期21卷 202-204页

作者： Bao Dong Rong-Rong Wu The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230031China

To the Editor:Pancreatic cancer (PC) is one of the most deadly cancers due to the difficulty of its early diagnosis.Most patients have developed an unresectable PC when diagnosed [1].According to GLOBOCAN2018 estimates,PC ranked the 11th most common cancer in the world counting 458 918 new cases and causing 432 242 deaths(4.5%of all deaths caused by cancer) in 2018 [2].

关键词： patients cancer diabetes

Decoding transcriptional regulation via a human gene expression predictor

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Journal of Genetics and Genomics 2023年第5期50卷 305-317页

作者： Yuzhou Wang Yu Zhang Ning Yu Bingyan Li Jiazhen Gong Yide Mei Jianqiang Bao Shisong Ma The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230027China MOE Key Laboratory for Cellular Dynamics School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaInnovation Academy for Seed DesignChinese Academy of SciencesHefeiAnhui 230027China School of Data Science University of Science and Technology of ChinaHefeiAnhui 230027China

Transcription factors(TFs)regulate cellular activities by controlling gene expression,but a predictive model describing how TFs quantitatively modulate human transcriptomes is lacking.We construct a universal human gene expression predictor named EXPLICIT-Human and utilize it to decode transcriptional regulation.Using the expression of 1613 TFs,the predictor reconstitutes highly accurate transcriptomes for samples derived from a wide range of tissues and conditions.The broad applicability of the predictor indicates that it recapitulates the quantitative relationships between TFs and target genes ubiquitous across tissues.Significant interacting TF-target gene pairs are extracted from the predictor and enable downstream inference of TF regulators for diverse pathways involved in development,immunity,metabolism,and stress response.A detailed analysis of the hematopoiesis process reveals an atlas of key TFs regulating the development of different hematopoietic cell lineages,and a portion of these TFs are conserved between humans and mice.The results demonstrate that our method is capable of delineating the TFs responsible for fate determination.Compared to other existing tools,EXPLICIT-Human shows a better performance in recovering the correct TF regulators.

关键词： Gene expression predictor Gene regulatory network Graphical Gaussian model Gene module Human Mouse

Injectable bone marrow microniches by co-culture of HSPCs with MSCs in 3D microscaffolds promote hematopoietic reconstitution from acute lethal radiation

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Bioactive Materials 2023年第4期22卷 453-465页

作者： Haiwei Liang Yanxiao Ao Wenjing Li Kaini Liang Baixue Tang Junyang Li Jianwei Wang Xiaoyu Zhu Yanan Du Department of Biomedical Engineering School of MedicineTsinghua-PekingCenter for Life SciencesTsinghua UniversityBeijing100084China School of Pharmaceutical sciences Tsinghua UniversityBeijing100084China Department of Hematology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina

Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limited to medication-assisted treatment,while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure.Our study aimed to assemble biomimetic three-dimensional(3D)BM microniches by co-culture of hematopoietic stem and progenitor cells(HSPCs)and mesenchymal stem cells(MSCs)in porous,injectable and viscoelastic microscaffolds in vitro.The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS.We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84μm in pore diameter and 11.2 kPa in Young’s modulus compared with 2D co-culture system.Besides,the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS,which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs.Furthermore,the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs,while the Jagged1 expression of the co-cultured MSCs was upregulated,indicating the significance of Notch signaling pathway in maintenance of HSPCs.Collectively,our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs,promote hematopoiesis regeneration and alleviate post-radiation injury,which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.

关键词： Hematopoietic syndrome of acute radiation syndrome Bone marrow Hematopoietic stem cells Mesenchymal stem cells 3D microscaffolds

Microbial sensing in the intestine

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Protein & Cell 2023年第11期14卷 824-860页

作者： Tingting Wan Yalong Wang Kaixin He Shu Zhu Division of Life Sciences and Medicine The CAS Key Laboratory of Innate Immunity and Chronic DiseaseInstitute of ImmunologySchool of Basic Medical SciencesUniversity of Science and Technology of ChinaHefei 230027China Department of Digestive Disease Division of Life Sciences and MedicineThe First Affiliated Hospital of USTCUniversity of Science and Technology of ChinaHefei 230001China Institute of Health and medicine Hefei Comprehensive National Science CenterHefei 230601China

The gut microbiota plays a key role in host health and disease,particularly through their interactions with the immune system.Intestinal homeostasis is dependent on the symbiotic relationships between the host and the diverse gut microbiota,which is influenced by the highly co-evolved immune-microbiota interactions.The first step of the interaction between the host and the gut microbiota is the sensing of the gut microbes by the host immune system.In this review,we describe the cells of the host immune system and the proteins that sense the components and metabolites of the gut microbes.We further highlight the essential roles of pattern recognition receptors(PRRs),the G protein-coupled receptors(GPCRs),aryl hydrocarbon receptor(AHR)and the nuclear receptors expressed in the intestinal epithelial cells(IECs)and the intestine-resident immune cells.We also discuss the mechanisms by which the disruption of microbial sensing because of genetic or environmental factors causes human diseases such as the inflammatory bowel disease(IBD).

关键词： mucosal immunology pattern recognition receptors protein-coupled receptors intestinal epithelial cells immune cells gut microbiota enteric viruses inflammatory bowel disease

Panoramic comparison between NK cells in healthy and cancerous liver through single-cell RNA sequencing

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Cancer Biology & medicine 2022年第9期19卷 1334-1351页

作者： Huan Liu Ronghua Zhao Rongrong Qin Haoyu Sun Qiang Huang Lianxin Liu Zhigang Tian Björn Nashan Cheng Sun Rui Sun The First Affiliated Hospital of USTC Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001China The CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Immunology University of Science and Technology of ChinaHefei 230027China

Objective:NK cells play crucial roles in the immune defense mechanisms against viral infections and transformed cells.However,the developmental progression,transcriptomic landscape,and functional subtypes of liver NK cells are not well defined.Hepatocellular carcinoma(HCC)accounts for approximately 80%of primary liver cancer worldwide,yet the biological characteristics of NK cells in the HCC environment are unclear.Therefore,we aimed to determine these cells’roles in tumorigenesis and prognosis.Methods:We compared the single-cell RNA sequencing profiles of NK cells purified from blood(n=1),healthy liver tissues(n=3),HCC tumor tissues(n=4),and peritumor liver tissues(n=1)to identify NK cell subsets.Furthermore,we performed bioinformatics analysis by using The Cancer Genome Atlas(TCGA)data to identify prognostic biomarkers simultaneously overexpressed in the blood and tumor tissues of patients with HCC.Results:Transcriptomic analysis revealed 5 NK cell subsets(L1-NK-CD56bright,L2-NK-CD56dim,L3-NK-HLA,L4-LrNK-FCGR3A,and L5-LrNK-XCL1)in the healthy liver tissues.However,the transitional L3 subset and the CXCR6+CD16+L4 subset with strong anti-tumor activity were absent in the HCC and peritumor liver tissues.Furthermore,4 common prognosis-associated genes(RHOB,TALDO1,HLA-DPA1,and TKT)were significantly overexpressed in the paired tumor tissue and blood.Conclusions:Our study revealed 5 specific subsets of NK cells in healthy human liver tissues.However,only 3 of the 5 NK cell subsets were present in HCC and peritumor tissues.The cytotoxic NK cell subsets were absent in HCC tissues.Furthermore,we identified 4 potential non-invasive prognostic biomarkers in patients with HCC.

关键词： Hepatocellular carcinoma natural killer cell single-cell RNA sequencing heterogeneity prognosis

TMK:A crucial piece of the acid growth puzzle

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Molecular Plant 2021年第12期14卷 1982-1984页

作者： Yakun Peng Shutang Tan MOE Key Laboratory for Cellular Dynamics Division of Molecular&Cell BiophysicsHefei National Science Center for Physical Sciences at the Microscaleand School of Life SciencesDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Plant cells have relatively high turgor pressure driving cell expan-sion,which is restricted by the cell wall.How plant cells grow in an intrinsically controlled manner is an intriguing question,and the phytohormone auxin(indole-3-acetic acid,IAA)plays a vital reg-ulatory role.The auxin-mediated acid growth theory was pro-posed decades ago,whereas the underlying mechanisms were not fully elucidated.Plasma membrane(PM)H+-ATPases,also called Arabidopsis AUTOINHIBITED H+ATPASEs(AHAs),are proton pumps majorly responsible for regulating cell growth in plants.Based on our current understandings of the acid growth theory,auxin stimulates AHA proteins and thus promotes proton(H+)efflux,which thereby acidifies the apoplast to activate cell wall-modifying enzymes,such as expansins,eventually softening the cell wall to accommodate cell expansion(Duet al.,2020).Activated AHA proteins also cause PM hyperpolarization,enabling solute and water uptake to increase turgor pressure driving cell expansion(Duet al.,2020).Hence,how auxin activates PM H^(+)-ATPases is central to the acid growth theory.However,that was until now not fully understood.

关键词： driving eventually thereby

Shining more light on G protein signalling modules:a novel optogenetic tool for Gq activation

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Science China(life sciences) 2022年第12期65卷 2567-2568页

作者： Jing Ren Tian Xue Liping Wang division of Neurobiology MRC Laboratory of Molecular BiologyCambridge CB20QHUnited Kingdom School of life sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230026China Shenzhen Institutes of Advanced Technology Chinese Academy of SciencesShenzhen 518055China

The use of optogenetic and chemogenetic approaches to control cellular activities with high temporal,spatial and cell-type specific resolution has profoundly transformed the field of neuroscience.In addition to enabling the manipulation of neuronal excitability,there is a great need for targeting intracellular signalling proteins and secondary messengers precisely。

关键词： transformed precisely profound