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Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway

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Science China(Life Sciences) 2024年第7期67卷 1427-1440页

作者： Hongfeng Guo Qihang Sun Xiaoli Huang Xiaohao Wang Feng Zhang Wenzheng Qu Jinling Liu Xuejun Cheng qiang Zhu Wen Yi qiang shu Xuekun Li The Children’s Hospital National Clinical Research Center for Child HealthSchool of MedicineZhejiang UniversityHangzhou 310052China The Institute of Translational Medicine School of MedicineZhejiang UniversityHangzhou 310029China College of Life Sciences Zhejiang UniversityHangzhou 310058China Binjiang Institute of Zhejiang University Hangzhou 310053China Zhejiang University Cancer Center Zhejiang UniversityHangzhou 310029China

Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy metabolism.However,the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown.We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells(aNSPCs)and postnatal brain development.Fut8 depletion reduces the proliferation of a NSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo,respectively.Additionally,Fut8 deficiency impairs learning and memory in mice.Mechanistically,Fut8 directly interacts with integrinα6(Itga6),an upstream regulator of the PI3kAkt signaling pathway,and catalyzes core fucosylation of Itga6.Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6.Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway.Moreover,the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency.In summary,our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.

关键词： Fut8 adult neural stem/progenitor cells neurogenesis Itga6 PI3K/Akt

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Coinfection of SARS-CoV-2 Omicron variant and other respiratory pathogens in children

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World Journal of Pediatrics 2024年第1期20卷 92-96页

作者： Wei Li Bing-Han Wang Bao-Hai Chen Yi Sun Lin Li Wen-Qing Xiang Ahmed Faisal Ali Lin-Xuan Su Hai-Yan Mao Hong-qiang Shen qiang shu Department of Clinical Laboratory Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina School of Public Health Zhejiang University School of MedicineHangzhouChina Department of Information Center Children's HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial Center for Disease Control and Prevention HangzhouChina Department of Thoracic&Cardiovascular Surgery Children's HospitalNational Clinical Research Center for Child HealthZhejiang University School of MedicineHangzhouChina

Since the outbreak of coronavirus disease 2019(COVID-19),the entire world has been affected by the epidemic[1,2].On November 9,2021,a variant of the novel coronavirus B.1.1.529 was detected for the first time from case samples in South Africa.The Omicron strain spread and mutated significantly fast.This variant has the characteristics of escape immunity,which can induce relatively extreme disease and reduce the neutralization of antibodies in vaccinators,and is more likely to be reinfected[3,4].The clinical presentation of severe acute respiratory syndrome coronavirus 2(SARSCoV-2)in children has mild symptoms and a lower risk of hospitalization and death.

关键词： respiratory immunity acute

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Severe pediatric COVID‑19:a review from the clinical and immunopathophysiological perspectives

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World Journal of Pediatrics 2024年第4期20卷 307-324页

作者： Yi‑Kan Sun Can Wang Pei‑Quan Lin Lei Hu Jing Ye Zhi‑Gang Gao Ru Lin Hao‑Min Li qiang shu Li‑Su Huang Lin‑Hua Tan Children's Hospital Zhejiang University School f MedicineHangzhou 310052China The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310030China Surgical Intensive Care Unit Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of General Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiopulmonary and Extracorporeal Life Support Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Clinical Data Center Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiac Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China National Clinical Research Center for Child Health Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Infectious Diseases Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background Coronavirus disease 2019(COVID-19)tends to have mild presentations in children.However,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from clinicians.Meanwhile,the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely understood.Data sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang databases.Searched keywords included“COVID-19 in children”,“severe pediatric COVID-19”,and“critical illness in children with COVID-19”.Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated status.Acute respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be seen.Multiple immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways,whose dysregulation in severe and critical diseases translates into adverse clinical manifestations.Multisystem inflammatory syndrome in children(MIS-C),a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure,denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric immunity.Despite the considerable dissimilarities between the pediatric and adult immune systems,clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult guidelines.Conclusions Severe pediatric COVID-19 can affect multiple organ systems.The dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the pediatric immune system and highlight the immun

关键词： Immunopathophysiology MIS-C Pediatric critical care Severe pediatric COVID-19

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NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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World Journal of Pediatrics 2024年第2期20卷 153-164页

作者： Bo Shi Cheng-Jie Lyu Zhen-Kai Le Hao-Sen Ji Yi Xiao Yuan-Yuan Zhang Shou-Jiang Huang Lin-Jun Yu qiang shu Jin-Fa Tou Deng-Ming Lai Department of Neonatal Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Pulmonology Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Department of Thoracic and Cardiovascular Surgery Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China

Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3^(-/-))model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Macrophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut“healthy”patients,the intestinal lamina propria of NEC patients had high macrophage infiltration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3^(-/-)NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.

关键词： Caspase-1 Interleukin-1β Macrophage Necrotizing enterocolitis NLRP3

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Indian monsoon drove the dispersal of the thoracica group of Scytodes spitting spiders

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Zoological Research 2024年第1期45卷 152-159页

作者： Yu-Fa Luo shu-qiang Li School of Life and Environmental Sciences Shaoxing UniversityShaoxingZhejiang 312000China Key Laboratory of Zoological Systematics and Evolution Institute of ZoologyChinese Academy of SciencesBeijing 100101China Southeast Asia Biodiversity Research Institute Chinese Academy of SciencesYezinNay Pyi Taw 05282Myanmar

We examined the global biogeography of the Scytodes thoracica group of spitting spiders based on 23 years of sampling at the species level(61 species in the thoracica group and 84 species of Scytodes)using DNA data from six loci.Our results indicated that the thoracica group initially dispersed from Southeast Asia to East Africa between 46.5 and 33.0 million years ago,and dispersal events intensified between Southeast/South Asia and East/South Africa from the early to late Miocene.The timing of these events indicates that Asian-African faunal exchange of the thoracica group was driven by the Indian monsoon,and the pattern of dispersal suggests that colonialization took root when the Indian monsoon shifted from a North-South direction to an East-West direction from the middle Eocene.

关键词： Geological event Climate change Ballooning organism Faunal exchange Species distribution

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Response to the outbreak of severe acute hepatitis of unknown origin in children

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World Journal of Pediatrics 2022年第8期18卷 525-528页

作者： Jie Chen qiang shu Zheng‑Yan Zhao National Clinical Research Center for Child Health National Children’s Regional Medical CenterChildren’s HospitalZhejiang University School of MedicineHangzhou 310052China

During October 2021 and February 2022,nine pediatric patients with acute hepatitis of unknown origin were identifed in Children’s of Alabama[1].These patients were tested negative for hepatitis viruses;and several other etiologies of hepatitis in children including autoimmune hepatitis were ruled out[1].In a short period of time,the number of cases has surged in many countries;importantly,the rate has exceeded past annual incidence in various regions[2–4].On 23 April 2022,World Health Organization(WHO)has issued a warning on severe hepatitis of unknown origin in children[5].As of May 18,575 suspected cases have been identifed in Europe,United States of American(USA),Israel,India,Japan,and other countries;35 children required liver transplantation and 11 died[6].

关键词： hepatitis acute origin

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Sex-specific differences in ossification patterns of the atlas and axis:a computed tomography study

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World Journal of Pediatrics 2022年第4期18卷 263-270页

作者： Wei-Liang Wu Xiao-Bo Shao Yi-Guo Shen Jian-Song Chen qiang shu Department of Orthopedic Surgery Children’s HospitalZhejiang University School of MedicineHangzhouChina Department of Cardiac Surgery Children’s HospitalZhejiang University School of MedicineAdministrative BuildingNo.3333 Binsheng RoadHangzhou 310052China

Background We investigated the sex-specific differences in ossification patterns of the first two cervical vertebrae in Chinese children.Methods A retrospective computed tomography(CT)study was performed between June 2016 and December 2020.Patients younger than 16 years with cervical CT images acquired<1.5 mm slice thickness were included.All eligible patients were stratified into 2 sex groups and 16 age groups based on 1-year intervals.The ossification status of each synchondrosis and ossification variants were evaluated.Results A total of 910 subjects(518 males and 392 females)were included in the study.For the Cl vertebra,the neurocentral synchondroses closed at a median age of 8 years in males and 6.3 years in females,and the posterior synchondrosis fused at 5.4 years in males and at 4.4 years in females.Multifocal anterior arch ossification centers were present in 74 of 411(18%)subjects,whereas posterior arch variants were observed in 18 of 258(7%)subjects.For the C2 vertebra,the sequence of complete fusion was as follows:posterior synchondrosis,neurocentral synchondroses,and dentoneural synchondrosis.Uniquely,a fusion line was observed in the dentocentral synchondrosis through adolescence.Anterior arch variants of the C2 vertebra occurred in 17 of 248(6.9%)subjects.There was no significant difference between the sexes in ossification variants.Conclusions All synchondroses of the first two cervical vertebrae fuse slightly earlier in females.The sequence of fusion follows a posterior-to-anterior and caudal-to-cephalad pattern in both sexes.Congenital variants are not rare and should not be confused with trauma.

关键词： Cervical vertebra Fusion Ossification center Ossification variant Synchondrosis

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Analysis and comparison of failure causes of minimally invasive surgical closure of ventricular septal defects in children

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World Journal of Pediatric Surgery 2023年第1期6卷 48-54页

作者： Jin Yu Zhuo Shi Jingjing Qian Lianglong Ma Baofu Zhang Liyang Ying qiang shu Department of Ultrasound Diagnosis The Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina Department of Pediatric Surgery The Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina Department of Cardiac Surgery The Children’s HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhouChina

Objectives The aims of the present study were to explore the causes of minimally invasive surgical ventricular septal defect(VSD)closure failure under transesophageal echocardiography guidance and thus to improve the success rate of surgical VSD closure.Methods From January 2015 to December 2019,522 children with VSD underwent minimally invasive surgical closure.Nineteen procedures(3.64%)were unsuccessful.The failure causes,VSD locations and surgical incision approaches were retrospectively analyzed.Results Among the 19 patients(3.64%)with unsuccessful outcomes,18 were switched to cardiopulmonary bypass(CPB)surgery,and 1 was closed successfully using an occlusion device a year later.The causes of failure included occlusion device shedding or shifting(n=6),failure of the guidewire(or the sheath)to pass through a small defect(n=5),device-related valve regurgitation(n=4),significant residual shunt(n=2),ventricular fibrillation(n=1),and continuous sharp blood pressure decreases(n=1).Patients with high VSD had a slightly higher failure rate than those with perimembranous VSD(p=0.049),and its key reason is the high proportion of occlusion device shedding or shifting(p=0.005).No significant difference in the failure rate was found between patients with different surgical incision approaches.Conclusions Minimally invasive surgery has a high success rate for perimembranous VSDs.Occlusion device shedding or shifting is the most common cause of failure.The shedding or shifting risk of eccentric occlusion devices being used only for high VSDs is much greater than that of concentric occlusion devices being used for perimembranous VSDs,which increases the risk of conversion to CPB surgery for high VSDs.

关键词： surgical ventricular closure

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Integrative biogeography: Validating hypotheses of species distribution

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Zoological Research(Diversity and Conservation) 2024年第1期1卷 86-88页

作者： Zhong-E Hou shu-qiang Li Key Laboratory of Animal Biodiversity Conservation and Integrated Pest Management Institute of ZoologyChinese Academy of SciencesBeijing 100101China

DEAR EDITOR,Biogeography is a scientific field dedicated to the investigation of the origins and distribution patterns of organisms,as well as predicting future alterations in their geographical distributions(Cox&Moore,2005).However,the majority of conclusions drawn within the field of biogeography are hypothetical.Rigorous testing of these biogeographic hypotheses remains a considerable challenge.This paper presents the concept of“integrative biogeography”,which emphasizes the experimental testing of biogeographic hypotheses through studies on geological history,as well as biotic and abiotic factors(Figure 1).

关键词： biogeography distribution dating

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Extraskeletal Ewing sarcoma of the stomach:A rare case report

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World Journal of Clinical Cases 2023年第1期11卷 201-209页

作者： qiang shu Jia-Nong Luo Xiao-Ling Liu Min Jing Ting-Gang Mou Fei Xie Department of Hepatic-Biliary-Pancreatic Surgery Neijiang First People’s Hospital Affiliated to Chongqing Medical UniversityNeijiang 641000Sichuan ProvinceChina Department of Hospital Infection Management Neijiang Hospital of Traditional Chinese MedicineNeijiang 641000Sichuan ProvinceChina Department of Pathology Neijiang First People’s Hospital Affiliated to Chongqing Medical UniversityNeijiang 641000Sichuan ProvinceChina

BACKGROUND Extraskeletal Ewing sarcoma(EES)is a rare and highly malignant small round cell tumor associated with a poor clinical outcome.Ewing sarcoma(ES)involving the stomach is an uncommon presentation and can be easily confused with other small round cell tumors.We herein present a rare case of ES involving the gastric area.CASE SUMMARY We report a case of gastric ES in a 19-year-old female patient who initially presented with a complaint of a tender epigastric mass for 5 d.Contrast-enhanced abdominal computed tomography revealed a soft-tissue-density mass with a diameter of 8.5 cm between the liver and stomach;the mass was connected to the gastric antrum.Then,the mass was surgically excised completely.Upon histopathological,immunophenotype and molecular analysis,the mass was identified to be a primary gastric ES.CONCLUSION EES is an aggressive tumor with poor prognosis.Therefore,early diagnosis and timely intervention are essential for a good prognosis.It is imperative for us to raise awareness about this rare tumor.Surgical resection is still the best treatment option.

关键词： Stomach neoplasms Extraskeletal Ewing’s sarcoma CD99 FLI-1 Case report

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