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B cell-derived anti-beta 2 glycoprotein I antibody mediates hyperhomocysteinemia-aggravated hypertensive glomerular lesions by triggering ferroptosis

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Signal Transduction and Targeted Therapy 2023年第4期8卷 1926-1941页

作者： Xing Du Xiaolong Ma ying Tan Fangyu Shao Chun Li Yang Zhao Yutong Miao Lulu Han Guohui Dang Yuwei Song Dongmin Yang Zhenling Deng yue wang Changtao Jiang Wei Kong Juan Feng Xian wang Department of Physiology and Pathophysiology School of Basic Medical SciencesKey Laboratory of Molecular Cardiovascular ScienceMinistry of EducationPeking University100191 BeijingP.R.China Department of Nephrology Peking University First Hospital100034 BeijingP.R.China Department of Rheumatology and Immunology Peking University People’s HospitalBeijingChina Department of Laboratory Medicine Peking University Third Hospital100083 BeijingP.R.China Department of Nephrology Peking University Third Hospital100083 BeijingP.R.China

Hyperhomocysteinemia(HHcy)is a risk factor for chronic kidney diseases(CKDs)that affects about 85%CKD *** stimulates B cells to secrete pathological antibodies,although it is unknown whether this pathway mediates kidney *** HHcytreated 2-kidney,1-clip(2K1C)hypertensive murine model,HHcy-activated B cells secreted anti-beta 2 glycoprotein I(β2GPI)antibodies that deposited in glomerular endothelial cells(GECs),exacerbating glomerulosclerosis and reducing renal ***,HHcy 2K1C mice increased phosphatidylethanolamine(PE)(18:0/20:4,18:0/22:6,16:0/20:4)in kidney tissue,as determined by *** oxidative lipidomics validated the increase of oxidized phospholipids upon Hcy-activated B cells culture medium(Hcy-B CM)treatment,including PE(18:0/20:4+3[O],PE(18:0a/22:4+1[O],PE(18:0/22:4+2[O]and PE(18:0/22:4+3[O]).PE synthases ethanolamine kinase 2(etnk2)and ethanolamine-phosphate cytidylyltransferase 2(pcyt2)were increased in the kidney GECs of HHcy 2K1C mice and facilitated polyunsaturated PE synthesis to act as lipid peroxidation *** HHcy 2K1C mice and Hcy-B CM-treated GECs,the oxidative environment induced by iron accumulation and the insufficient clearance of lipid peroxides caused by transferrin receptor(TFR)elevation and down-regulation of SLC7A11/glutathione peroxidase 4(GPX4)contributed to GECs ferroptosis of the *** vivo,pharmacological depletion of B cells or inhibition of ferroptosis mitigated the HHcy-aggravated hypertensive renal ***,our findings uncovered a novel mechanism by which B cell-derived pathogenic anti-β2GPI IgG generated by HHcy exacerbated hypertensive kidney damage by inducing GECs *** B cells or ferroptosis may be viable therapeutic strategies for ameliorating lipid peroxidative renal injury in HHcy patients with hypertensive nephropathy.

关键词： hypertensive glomerular peroxidation

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外阴Paget病8例临床分析

中国妇产科临床杂志 2025年第1期26卷 27-29页

作者：杨莹超张艺环王悦李广学王益勤郝娟北京大学人民医院妇产科北京100044 西藏自治区人民医院妇产科拉萨850010 北京大学人民医院医疗美容科北京100044

目的外阴Paget病(PDV)是一种罕见的恶性肿瘤,常被误认为是其他良性疾病。本文回顾性分析北京大学人民医院收治的外阴Paget病患者的临床特点,探讨治疗方式。方法本研究对2013年1月至2023年12月在北京大学人民医院妇科治疗的PDV患者进行... 详细信息

目的外阴Paget病(PDV)是一种罕见的恶性肿瘤,常被误认为是其他良性疾病。本文回顾性分析北京大学人民医院收治的外阴Paget病患者的临床特点,探讨治疗方式。方法本研究对2013年1月至2023年12月在北京大学人民医院妇科治疗的PDV患者进行回顾性分析。8例均接受手术,4例行带蒂皮瓣转移术,2例补充光动力治疗。结果5例切缘呈阳性。1例创面裂开二次手术恢复良好。8例患者随访的平均时间为53个月(13~130个月),随访期间观察到1例皮损,目前均存活,无疾病相关死亡。结论PDV病程较长,皮损范围大,恶性程度低,有远期复发倾向。应及早诊断,以避免大手术对局部外阴结构和功能破坏,可配合光动力等后续补充治疗提高治愈率。

关键词：外阴Paget病带蒂皮瓣转移术光动力治疗

A chromosome-level genome assembly of anesthetic drug–producing Anisodus acutangulus provides insights into its evolution and the biosynthesis of tropane alkaloids

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Plant Communications 2024年第1期5卷 231-244页

作者： Wei Zhou Can wang Xiaolong Hao Fei Chen Qikai Huang Tingyao Liu Jiang Xu Shuai Guo Baosheng Liao Zhixiang Liu yue Feng Yao wang Pan Liao Jiayu Xue Min Shi Itay Maoz Guoyin Kai Zhejiang Provincial International S&T Cooperation Base for Active Ingredients of Medicinal and Edible Plants and Health Zhejiang Provincial Key TCM Laboratory for Chinese Resource Innovation and TransformationSchool of Pharmaceutical SciencesJinhua AcademyZhejiang Chinese Medical UniversityHangzhouZhejiang 310053China Sanya Nanfan Research Institute from Hainan University Hainan Yazhou Bay Seed LaboratorySanya 572025China Institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Department of Biology Hong Kong Baptist UniversityKowloon TongHong KongChina College of Horticulture Academy for Advanced Interdisciplinary StudiesNanjing Agricultural UniversityNanjing 210095China Department of Postharvest Science Agricultural Research OrganizationVolcani CenterP.O.Box 15159HaMaccabim Road 68Rishon LeZion 7505101Israel

Tropane alkaloids(TAs),which are anticholinergic agents,are an essential class of natural compounds,and there is a growing demand for TAs with anesthetic,analgesic,and spasmolytic *** acutan-gulus(Solanaceae)is a TA-producing plant that was used as an anesthetic in ancient *** this study,we assembled a high-quality,chromosome-scale genome of *** with a contig N50 of 7.4 Mb.A recent whole-genome duplication occurred in *** after its divergence from other Solanaceae species,which resulted in the duplication of ADC1 and UGT genes involved in TA *** catalytic activities of H6H enzymes were determined for three Solanaceae *** the basis of evolution and co-expressed genes,AaWRKY11 was selected for further analyses,which revealed that its encoded tran-scription factor promotes TA biosynthesis by activating AaH6H1 *** provide useful insights into genome evolution related to TA biosynthesis and have potential implications for genetic manipulation of TA-producing plants.

关键词： Anisodus acutangulus tropane alkaloid biosynthesis hyoscyamine 6 b-hydroxylase AaWRKY11

Phospho-proteomics identifies a critical role of ATF2 in pseudorabies virus replication

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Virologica Sinica 2022年第4期37卷 591-600页

作者： Fang-Fang Jiang Ren-Qi wang Chao-yue Guo Ke Zheng Hai-Long Liu Le Su Sheng-Song Xie Huan-Chun Chen Zheng-Fei Liu State Key Laboratory of Agricultural Microbiology Hongshan Laboratory and Key laboratory of Preventive Veterinary Medicine in Hubei ProvinceCollege of Veterinary MedicineHuazhong Agricultural UniversityWuhan430070China Key Lab of Agricultural Animal Genetics Breedingand Reproduction of Ministry of EducationHuazhong Agricultural UniversityWuhan430070China

Pseudorabies virus(PRV),an etiological agent of pseudorabies in livestock,has negatively affected the porcine industry all over the *** cells are reported as the first site of PRV ***,the role of host proteins and its related signaling pathways in PRV replication is largely *** this study,we performed a quantitative phosphoproteomics screening on PRV-infected porcine kidney(PK-15)epithelial *** 5723phosphopeptides,corresponding to 2180 proteins,were obtained,and the phosphorylated states of 810 proteins were significantly different in PRV-infected cells compared with mock-infected cells(P<0.05).GO and KEGG analysis revealed that these differentially expressed phosphorylated proteins were predominantly related to RNA transport and MAPK signaling *** functional studies of NF-κB,transcription activator factor-2(ATF2),MAX and SOS genes in MAPK signaling pathway were analyzed using RNA interference(RNAi)*** showed that only ATF2-knockdown reduces both PRV titer and viral genome copy *** pathway inhibition and CRISPR/Cas9 gene knockout showed that ATF2 was required for the effective replication of PRV,especially during the biogenesis of viral genome ***,by overexpression of the ATF2 gene and point mutation of the amino acid positions 69/71 of ATF2,it was further demonstrated that the phosphorylation of ATF2 promoted PRV *** findings suggest that ATF2 may provide potential therapeutic target for inhibiting PRV infection.

关键词： Pseudorabies virus(PRV) Transcription activator factor-2(ATF2) iTRAQ Proteomics Phosphorylation

Dietary supplementation of 25-hydroxycholecalciferol increases tibial mass by suppression bone resorption in meat ducks

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Animal Nutrition 2020年第4期6卷 467-479页

作者： Huaiyong Zhang Qiufeng Zeng Shiping Bai Jianping wang Xuemei Ding yue Xuan Zhuowei Su Gergory S.Fraley Bing Yao Keying Zhang Institute of Animal Nutrition Key Laboratory for Animal Disease-Resistance Nutrition of ChinaMinistry of EducationSichuan Agricultural UniversityChengduSichuan611130China Biology Department Hope CollegeHolland49423USA DSM(China)Ltd. PuDong New AreaShanghai201203China

Leg problems often result from the rapid weight gain and poor bone quality in modern ducks,leading to a high risk of fractures and continuous *** hypothesized that improving bone quality in combination with delaying weight gain via a low nutrient density(LND)diet probably reverses these skeletal *** indicated that 25-hydroxycholecalciferol(25-OH-D3),a vitamin D3 metabolite,is effective in treating bone-related ***,Exp.1 evaluated the effects of 25-OH-D3 on tibial mass of meat *** meat ducklings were fed a standard nutrient density diet(containing a regular vitamin regimen)without or with 25-OH-D3 at 0.069 mg/kg for 35 *** results showed that 25-OH-D3 supplementation improved the mineral content,microarchitecture and mechanical properties of tibias,and this companied by a decreased serum bone resorption marker and a concomitant decrement in osteoclast-specific marker genes ***,Exp.2 was conducted to examine the impacts of 25-OH-D3 incorporating an LND diet on tibial quality of ducks under 2 different vitamin regimens(regular and high).Ducklings were allocated to a 2*2 factorial arrangement with 2 kinds of vitamin premixes and without or with 25-OH-D3 at 0.069 mg/kg in LND *** high premix had higher levels of all vitamins except biotin than the regular *** results demonstrated that high vitamin diets exhibited more significant effects than regular vitamin diets on inhibiting bone turnover and increasing minerals *** mineral content,microarchitecture,and strength of birds under the regular vitamin regimen were increased by 25-OH-D3 supplementation;However,these positive effects were not observed in ducks under the high vitamin *** conclude,25-OH-D3 supplementation improves tibial mass by suppressing osteoclast-mediated bone resorption in meat ducks,and this positive impact only was observed in regular but not high vitamin regimen when birds fed an LND diet.

关键词： Vitamin D_(3)metabolites Vitamin Bone turnover Tibial mass Meat duck

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/m TOR Signaling Pathway

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Chinese Journal of Integrative Medicine 2024年第3期30卷 251-259页

作者： YAO Jun-peng FENG Xiu-mei wang Lu LI Yan-qiu ZHU Zi-yue YAN Xiang-yun YANG Yu-qing LI ying ZHANG Wei Acupuncture and Tuina School Chengdu University of Traditional Chinese MedicineChengdu611137China Department of Rehabilitation Medicine Guanghan People’s HospitalGuanghanSichuan Province618399China Academic Affairs Office Chengdu University of Traditional Chinese MedicineChengdu611137China

Objective:To explore the mechanism of electroacupuncture(EA) in promoting recovery of the facial function with the involvement of autophagy,glial cell line-derived neurotrophic factor(GDNF),and phosphatidylinositol-3-kinase(PI3K)/mammalian target of rapamycin(mTOR) signaling ***:Seventy-two male Sprague-Dawley rats were randomly allocated into the control,sham-operated,facial nerve injury(FNI),EA,EA+3-methyladenine(3-MA),and EA+GDNF antagonist groups using a random number table,with 12 rats in each *** FNI rat model was established with facial nerve crushing *** intervention was conducted at Dicang(ST 4),Jiache(ST 6),yifeng(SJ 17),and Hegu(LI 4) acupoints for 2 *** Simone’s 10-Point Scale was utilized to monitor the recovery of facial *** histopathological evaluation of facial nerves was performed using hematoxylin-eosin(HE) *** levels of Beclin-1,light chain 3(LC3),and P62 were detected by immunohistochemistry(IHC),immunofluorescence,and reverse transcriptionpolymerase chain reaction,***,IHC was also used to detect the levels of GDNF,Rai,PI3K,and ***:The facial functional scores were significantly increased in the EA group than the FNI group(P<0.05 or P<0.01).HE staining showed nerve axons and myelin sheaths,which were destroyed immediately after the injury,were recovered with EA *** expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats(P<0.01);however,EA treatment reversed these abnormal changes(P<0.01).Meanwhile,EA stimulation significantly increased the levels of GDNF,Rai,PI3K,and mTOR(P<0.01).After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist,the repair effect of EA on facial function was attenuated(P<0.05 or P<0.01).Conclusions:EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of *** may exert this neuroreparative effect through

关键词： electroacupuncture facial nerve injury autophagy glial cell line-derived neurotrophic factor phosphatidylinositol-3-kinase/mammalian target of rapamycin Chinese medicine

Hybrid-augmented intelligence： collaboration and cognition

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Frontiers of Information Technology & Electronic Engineering 2017年第2期18卷 153-179页

作者： Nan-ning ZHENG Zi-yi LIU Peng-ju REN Yong-qiang MA Shi-tao CHEN Si-yu YU Jian-ru XUE Ba-dong CHEN Fei-yue wang Institute of Artificial Intelligence and Robotics Xi ' an Jiaotong University Xi ' an 710049 China National Engineering Laboratory of Visual Information Processing Applications Xi 'an Jiaotong University Xi'an 710049 China State Key Laboratory of Management and Control for Complex Systems Institute of Automation Chinese Academy of Sciences Beijing 100190 China

The long-term goal of artificial intelligence （AI） is to make machines learn and think like human beings. Due to the high levels of uncertainty and vulnerability in human life and the open-ended nature of problems that humans are facing, no matter how intelligent machines are, they are unable to completely replace humans. Therefore, it is necessary to introduce human cognitive capabilities or human-like cognitive models into AI systems to develop a new form of AI, that is, hybrid-augmented intelligence. This form of AI or machine intelligence is a feasible and important developing model. Hybrid-augmented intelligence can be divided into two basic models： one is human-in-the-loop augmented intelligence with human-computer collaboration, and the other is cognitive computing based augmented intelligence, in which a cognitive model is embedded in the machine learning system. This survey describes a basic framework for human-computer collaborative hybrid-augmented intelligence, and the basic elements of hybrid-augmented intelligence based on cognitive computing. These elements include intuitive reasoning, causal models, evolution of memory and knowledge, especially the role and basic principles of intuitive reasoning for complex problem solving, and the cognitive learning framework for visual scene understanding based on memory and reasoning. Several typical applications of hybrid-augmented intelligence in related fields are given.

关键词： Human-machine collaboration Hybrid-augmented intelligence Cognitive computing Intuitivereasoning Causal model Cognitive mapping Visual scene understanding Self-driving cars

Cardioprotective mechanism of SGLT2 inhibitor against myocardial infarction is through reduction of autosis

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Protein & Cell 2022年第5期13卷 336-359页

作者： Kai Jiang yue Xu Dandan wang Feng Chen Zizhuo Tu Jie Qian Sheng Xu yixiang Xu John Hwa Jian Li Hongcai Shang Yaozu Xiang Shanghai East Hospital School of Life Sciences and TechnologyTongji UniversityShanghai 200092China State Key Laboratory of Bioreactor Engineering Shanghai Key Laboratory of New Drug DesignEast China University of Science and TechnologyShanghai 200237China Section of Cardiovascular Medicine Department of Internal MedicineYale Cardiovascular Research CenterYale University School of MedicineNew HavenCT 06511USA Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing Dongzhimen Hospital Affiliated to Beijing University of Chinese MedicineBeijing 100700China

Sodium-glucose cotransporter 2(SGLT2)inhibitors reduce cardiovascular mortality in patients with diabetes mellitus but the protective mechanism remains *** we demonstrated that the SGLT2 inhibitor,Empagliflozin(EMPA),suppresses cardiomyocytes autosis(autophagic cell death)to confer cardioprotective *** myocardial infarction(Ml)mouse models with and without diabetes mellitus,EMPA treatment significantly reduced infarct size,and myocardial fibrosis,thereby leading to improved cardiac function and *** the context of ischemia and nutritional glucose deprivation where autosis is already highly stimulated,EMPA directly inhibits the activity of the Na^(+)/H^(+)exchanger 1(NHE1)in the cardiomyocytes to regulate excessive *** of NHE1 significantly rescued glucose deprivation-induced *** contrast,overexpression of NHE1 aggravated the cardiomyocytes death in response to starvation,which was effectively rescued by EMPA ***,in vitro and in vivo analysis of NHE1 and Beclin 1 knockout mice validated that EMPA s cardioprotective effects are at least in part through downregulation of autophagic *** findings provide new insights for drug development,specifically targeting NHE1 and autosis for ventricular remodeling and heart failure after Ml in both diabetic and non-diabetic patients.

关键词： myocardial infarction SGLT2 inhibitors empagliflozin cardioprotection NHE1 autosis

Phylotranscriptomics of Swertiinae(Gentianaceae)reveals that key floral traits are not phylogenetically correlated

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Journal of Integrative Plant Biology 2023年第6期65卷 1490-1504页

作者： Chunlin Chen Brad R.Ruhfel Jialiang Li Zefu wang Lushui Zhang Lei Zhang Xingxing Mao Ji wang Dashan He yue Luo Quanjun Hu Yuanwen Duan Xiaoting Xu Zhenxiang Xi Jianquan Liu Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education&State Key Laboratory of Hydraulics and Mountain River Engineering College of Life SciencesSichuan UniversityChengdu 610065China Department of Ecology and Evolutionary Biology University of MichiganAnn ArborMichigan 48109USA Institute Key Laboratory for Plant Diversity and Biogeography of East Asia Kunming Institute of BotanyChinese Academy of SciencesKunming 650201China

Establishing how lineages with similar traits are phylogenetically related remains critical for understanding the origin of biodiversity on *** traits in plants are widely used to explore phylogenetic relationships and to delineate taxonomic *** subtribe Swertiinae(Gentianaceae)comprises more than 350 species with high floral diversity ranging from rotate to tubular corollas and possessing diverse *** we performed phylogenetic analysis of 60 species from all 15 genera of the subtribe Swertiinae sensu Ho and Liu,representing the range of floral diversity,using data from the nuclear and plastid *** topological conflicts were present between the nuclear and plastome *** of the 15 genera represented by multiple species are polyphyletic in both *** floral traits including corolla type,absence or presence of lobe scales,nectary type,nectary position,and stigma type are randomly distributed in the nuclear and plastome trees without phylogenetic *** also revealed the likely ancient hybrid origin of one large clade comprising 10 genera with diverse floral *** results highlight the complex evolutionary history of this *** phylogenies constructed here provide a basic framework for further exploring the ecological and genetic mechanisms underlying both species diversification and floral diversity.

关键词： ancient hybridization floral diversity Gentianaceae phylogenomics Qinghai-Tibet Plateau subtribe Swertiinae