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A Transformer-Assisted Cascade Learning Network for Choroidal Vessel Segmentation

Journal of Computer Science & Technology 2024年第2期39卷 286-304页

作者：温阳吴依林毕磊石武祯刘潇骁许毓鹏许迅曹文明冯大淦 Guangdong Provincial key laboratory of Intelligent Information Processing School of Electronics and Information EngineeringShenzhen UniversityShenzhen 518060China Institute of Translational medicine Shanghai Jiao Tong UniversityShanghai 200240China Department of Ophthalmology Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China School of Information Technologies The University of SydneySydney 2006Australia

As a highly vascular eye part,the choroid is crucial in various eye disease diagnoses.However,limited research has focused on the inner structure of the choroid due to the challenges in obtaining sufficient accurate label data,particularly for the choroidal vessels.Meanwhile,the existing direct choroidal vessel segmentation methods for the intelligent diagnosis of vascular assisted ophthalmic diseases are still unsatisfactory due to noise data,while the synergistic segmentation methods compromise vessel segmentation performance for the choroid layer segmentation tasks.Common cascaded structures grapple with error propagation during training.To address these challenges,we propose a cascade learning segmentation method for the inner vessel structures of the choroid in this paper.Specifically,we propose TransformerAssisted Cascade Learning Network(TACLNet)for choroidal vessel segmentation,which comprises a two-stage training strategy:pre-training for choroid layer segmentation and joint training for choroid layer and choroidal vessel segmentation.We also enhance the skip connection structures by introducing a multi-scale subtraction connection module designated as MSC,capturing differential and detailed information simultaneously.Additionally,we implement an auxiliary Transformer branch named ATB to integrate global features into the segmentation process.Experimental results exhibit that our method achieves the state-of-the-art performance for choroidal vessel segmentation.Besides,we further validate the significant superiority of the proposed method for retinal fluid segmentation in optical coherence tomography(OCT)scans on a publicly available dataset.All these fully prove that our TACLNet contributes to the advancement of choroidal vessel segmentation and is of great significance for ophthalmic research and clinical application.

关键词： choroidal vessel segmentation optical coherence tomography(OCT) Transformer-assisted cascade learning retinal fluid segmentation multi-scale feature extraction

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Oxidative cyclization of allyl compounds and isocyanide: A facile entry to polysubstituted 2-cyanopyrroles

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Chinese Chemical Letters 2024年第4期35卷 330-335页

作者： Yaping Zhang Wei Zhou Mingchun Gao Tianqi Liu Bingxin Liu Chang-Hua Ding Bin Xu Department of Chemistry Affiliated Nantong Hospital of Shanghai University(The Sixth People's Hospital of Nantong)Shanghai Engineering Research Center of Organ RepairInnovative Drug Research CenterSchool of MedicineShanghai UniversityShanghai 200444China State key laboratory of Organometallic Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai 200032China

A facile Tf OH-catalyzed oxidative cyclization of allyl compounds and isocyanide has been developed with the assistance of DDQ, where isocyanide is used as the crucial "N" and "CN" sources. Highly functionalized 2-cyanopyrroles are constructed efficiently through a new formal [3 + 2] mode, demonstrating diverse reactivity and synthetic utility in organic chemistry. 2-Cyanopyrrole is converted into a nucleobase analogue of Remdesivir and 5H-pyrrolo[2,1-a]isoindole through a three-step or a two-step sequence, respectively. This protocol features broad substrate scope, operational simplicity and good functional group tolerance.

关键词： Isocyanide Cyanopyrrole Insertion Allyl compound Bronsted acid catalysis

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Lactate regulates major zygotic genome activation by H3K18 lactylation in mammals

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National Science Review 2024年第2期11卷 124-134页

作者： Jingyu Li Weibo Hou Qi Zhao Wei Han Hongdi Cui Songling Xiao Ling Zhu Jiadan Qu Xiaoyu Liu Weitao Cong Jingling Shen Yuzheng Zhao Shaorong Gao Guoning Huang Qingran Kong Chongqing key laboratory of Human Embryo Engineering Center for Reproductive Medicine Chongqing Health Center for Women and ChildrenWomen and Children's Hospital of Chongqing Medical University Oujiang laboratory Zhejiang Provincial Key Laboratory of Medical Genetics Key Laboratory of Laboratory MedicineMinistry of EducationSchool of Laboratory Medicine and Life Sciences Wenzhou Medical University Frontier Science Center for Stem Cell Research School of Life Sciences and Technology Tongji University School of Pharmaceutical Science Wenzhou Medical University Institute of Life Sciences College of Life and Environmental Sciences Wenzhou University Optogenetics&Synthetic Biology Interdisciplinary Research Center State Key Laboratory of Bioreactor Engineering Shanghai Frontiers Science Center of Optogenetic Techniques for Cell Metabolism School of Pharmacy East China University of Science and Technology

Lactate is present at a high level in the microenvironment of mammalian preimplantation embryos in vivo and in vitro. However, its role in preimplantation development is unclear. Here, we report that lactate is highly enriched in the nuclei of early embryos when major zygotic genome activation(ZGA) occurs in humans and mice. The inhibition of its production and uptake results in developmental arrest at the 2-cell stage, major ZGA failure, and loss of lactate-derived H3K18lac, which could be rescued by the addition of Lac-Co A and recapitulated by overexpression of H3K18R mutation. By profiling the landscape of H3K18lac during mouse preimplantation development, we show that H3K18lac is enriched on the promoter regions of most major ZGA genes and correlates with their expressions. In humans, H3K18lac is also enriched in ZGA markers and temporally concomitant with their expressions. Taken together, we profile the landscapes of H3K18lac in mouse and human preimplantation embryos, and demonstrate the important role for H3K18lac in major ZGA, showing that a conserved metabolic mechanism underlies preimplantation development of mammalian embryos.

关键词： mammalian preimplantation development lactate epigenetic remodeling histone lactylation zygotic genome activation

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Effectiveness of Histopathological Examination of Ultrasound-guided Puncture Biopsy Samples for Diagnosis of Extrapulmonary Tuberculosis

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Biomedical and Environmental Sciences 2024年第2期37卷 170-177页

作者： GU Wen Fei SHI Xia MA Xin YU Jun Lei XU Jin Chuan QIAN Cheng Cheng HU Zhi Dong ZHANG Hui shanghai Public Health Clinical Center Fudan UniversityShanghai 201508China School of laboratory medicine and Life Science Wenzhou Medical UniversityWenzhou 325000ZhejiangChina Department of laboratory medicine Zhejiang Putuo HospitalZhoushan 316100ZhejiangChina Zhongshan Hospital Fudan UniversityShanghai 200032China

Objective To evaluate the diagnostic value of histopathological examination of ultrasound-guided puncture biopsy samples in extrapulmonary tuberculosis(EPTB).Methods This study was conducted at the shanghai Public Health Clinical Center.A total of 115patients underwent ultrasound-guided puncture biopsy,followed by MGIT 960 culture(culture),smear,Gene Xpert MTB/RIF(Xpert),and histopathological examination.These assays were performed to evaluate their effectiveness in diagnosing EPTB in comparison to two different diagnostic criteria:liquid culture and composite reference standard(CRS).Results When CRS was used as the reference standard,the sensitivity and specificity of culture,smear,Xpert,and histopathological examination were(44.83%,89.29%),(51.72%,89.29%),(70.11%,96.43%),and(85.06%,82.14%),respectively.Based on liquid culture tests,the sensitivity and specificity of smear,Xpert,and pathological examination were(66.67%,72.60%),(83.33%,63.01%),and(92.86%,45.21%),respectively.Histopathological examination showed the highest sensitivity but lowest specificity.Further,we found that the combination of Xpert and histopathological examination showed a sensitivity of 90.80%and a specificity of 89.29%.Conclusion Ultrasound-guided puncture sampling is safe and effective for the diagnosis of EPTB.Compared with culture,smear,and Xpert,histopathological examination showed higher sensitivity but lower specificity.The combination of histopathology with Xpert showed the best performance characteristics.

关键词： Extrapulmonary tuberculosis Diagnosis Biopsy Histopathological examination Puncture samples

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HIF-1αpromotes virus replication and cytokine storm in H1N1 virus-induced severe pneumonia through cellular metabolic reprogramming

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Virologica Sinica 2024年第1期39卷 81-96页

作者： Xiaoxiao Meng Yong Zhu Wenyu Yang Jiaxiang Zhang Wei Jin Rui Tian Zhengfeng Yang Ruilan Wang Department of Critical Care medicine Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China Precision Research Center for Refractory Diseases Shanghai General HospitalShanghai Jiaotong UniversitySchool of MedicineShanghai201620China

The mortality of patients with severe pneumonia caused by H1N1 infection is closely related to viral replication and cytokine storm.However,the specific mechanisms triggering virus replication and cytokine storm are still not fully elucidated.Here,we identified hypoxia inducible factor-1α(HIF-1α)as one of the major host molecules that facilitates H1N1 virus replication followed by cytokine storm in alveolar epithelial cells.Specifically,HIF-1αprotein expression is upregulated after H1N1 infection.Deficiency of HIF-1αattenuates pulmonary injury,viral replication and cytokine storm in vivo.In addition,viral replication and cytokine storm were inhibited after HIF-1αknockdown in vitro.Mechanistically,the invasion of H1N1 virus into alveolar epithelial cells leads to a shift in glucose metabolism to glycolysis,with rapid production of ATP and lactate.Inhibition of glycolysis significantly suppresses viral replication and inflammatory responses.Further analysis revealed that H1N1-induced HIF-1αcan promote the expression of hexokinase 2(HK2),the key enzyme of glycolysis,and then not only provide energy for the rapid replication of H1N1 virus but also produce lactate,which reduces the accumulation of the MAVS/RIG-I complex and inhibits IFN-α/βproduction.In conclusion,this study demonstrated that the upregulation of HIF-1αby H1N1 infection augments viral replication and cytokine storm by cellular metabolic reprogramming toward glycolysis mainly through upregulation of HK2,providing a theoretical basis for finding potential targets for the treatment of severe pneumonia caused by H1N1 infection.

关键词： H1N1 Severe pneumonia Virus replication Hypoxia inducible factor-1α Glycolysis

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Current Mycoplasma pneumoniae epidemic among children in shanghai:unusual pneumonia caused by usual pathogen

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World Journal of Pediatrics 2024年第1期20卷 5-10页

作者： Xiao-Bo Zhang Wen He Yong-Hao Gui Quan Lu Yong Yin Jian-Hua Zhang Xiao-Yan Dong Ying-Wen Wang Ying-Zi Ye Hong Xu Jia-Yu Wang Bing Shen Dan-Ping Gu Li-Bo Wang Yi Wang Department of Respiratory medicine Children's Hospital of Fudan University399 Wanyuan RoadShanghai 201102China State key laboratory of Genetic Engineering at School of Life Sciences Institute of Reproduction&DevelopmentChildren's Hospital of Fudan UniversityShanghaiChina Department of Respiratory medicine Children's Hospital of Shanghai Jiao Tong UniversityShanghaiChina Department of Respiratory medicine Shanghai Children's Medical CenterAffiliated to Shanghai Jiaotong University School of MedicineShanghaiChina Department of Pediatric Respiratory Xinhua HospitalAffiliated to Shanghai Jiaotong University School of MedicineShanghaiChina Department of Nursing Children's Hospital of Fudan UniversityShanghaiChina Department of Infectious Diseases Children's Hospital of Fudan UniversityShanghaiChina Department of Nephrology Children's Hospital of Fudan UniversityShanghaiChina NHC key laboratory of Neonatal Diseases Children's Hospital of Fudan UniversityShanghaiChina shanghai Shenkang Hospital Development Center ShanghaiChina Center for Medical Quality Control Management of shanghai ShanghaiChina Department of Neurology Children's Hospital of Fudan University399Wanyuan RoadShanghai 201102China

Mycoplasma pneumoniae(M.pneumoniae),primarily transmitted through respiratory droplets when infected individuals cough or sneeze,is a common cause of communityacquired pneumonia,especially among school-age children and adolescents.The infection occurs endemically with an epidemic peak every few years.The worldwide incidence confirmed by direct test methods was reported to be 8.61%between 2017 and 2020 across all age groups[1].

关键词： pneumonia epidemic respiratory

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DNA bridging of FOXP3 ladder-like multimer: Unveiling a novel transcriptional regulation paradigm

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The Innovation 2024年第3期5卷 15-16页

作者： Ying Lu Lanfang Li Hanting Yang Bin Li Zuoyun Wang key laboratory of Metabolism and Molecular medicine of the Ministry of Education Shanghai Xuhui Central Hospital and School of Basic Medical SciencesFudan UniversityShanghai 200032China Institute for Translational Brain Research State Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceDepartment of NeurologyZhongshan HospitalFudan UniversityShanghai 200032China Center for Immune-Related Diseases at shanghai Institute of Immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China

In the latest issue of Nature,Zhang et al.characterized a novel ladder-like structure of FOXP3-DNA interaction involving FOXP3 multimerization and remote DNA bridging through a combination of biochemistry,structural biology,cell biology,and bioinformatics analyses.1 In this commentary,we highlight their key findings and provide our insights into the research paradigm for further exploration of a novel transcriptional regulation mode as well as a therapeutic strategy from the structural aspects of the FOXP3 complex(Figure 1).

关键词： FOXP3 bridging

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Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus

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Acta Pharmaceutica Sinica B 2024年第2期14卷 437-454页

作者： Jiamei Le Yilong Chen Wei Yang Ligong Chen Jianping Ye shanghai key laboratory of Molecular Imaging Zhoupu HospitalShanghai University of Medicine and Health SciencesShanghai 201318China School of Health Science and Engineering University of Shanghai for Science and TechnologyShanghai 200093China Metabolic Disease Research Center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450007China School of Pharmaceutical Sciences Tsinghua UniversityBeijing 100084China Research Center for Basic medicine Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China

Solute carriers(SLCs) constitute the largest superfamily of membrane transporter proteins.These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions.They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake(e.g., SLC2A4/GLUT4), glucose reabsorption(e.g., SLC5A2/SGLT2), thermogenesis(e.g., SLC25A7/UCP-1), and ATP production(e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus(T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone(SLCO1B1/OATP1B1) and metformin(SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.

关键词： Solute carriers(SLCs) Energ ymetabolism ATP production Type 2 diabetes mellitus(T2DM) Glucose homeostasis Polymorphisms

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Relationship between plasma risperidone concentrations and clinical features in chronic schizophrenic patients in China

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World Journal of Psychiatry 2024年第4期14卷 523-532页

作者： Jing-Wen Xu Xiao-Bo Guan Xue-Ying Wang Yang Feng Qi Zhang Jun-Juan Zhu Jian-Hua Chen Department of medicine Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China The Fourth Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghai Key Laboratory of Psychotic DisordersShanghai 200030China The First Sick Ward Shanghai No.3 Mental Health Center of Civil AdministrationShanghai 200435China

BACKGROUND Prior studies have noted great variability in the plasma levels of risperidone(RIS).Plasma concentrations of RIS and its active moiety are highly variable and depend on absorption,metabolism,and other predictors of metabolic dysregulation;however,these factors are poorly understood and the association between metabolic change and change in psychopathology is uncertain.AIM To ascertain the characteristics of chronic schizophrenic patients treated with RIS,and to assess their relationship with plasma RIS levels.METHODS This was a descriptive cross-sectional study of 50 patients with a diagnosis of schizophrenic psychosis treated with RIS in a psychiatric service.The plasma concentrations of RIS and its metabolite 9-hydroxyrisperidone were determined by high performance liquid chromatography.The patients’demographic and clinical characteristics,and psychopathologies were assessed,and the associations between clinical variables and plasma levels of RIS were explored.RESULTS Male patients received higher doses of RIS than female ones,but plasma concentrations of RIS and risperidone+9-hydroxyrisperidone(active moiety)were higher in female patients.Age and the mean scores of the general psychopathology subscale of the Positive and Negative Syndrome Scale(PANSS)were significantly positively correlated with plasma concentrations of risperidone+9-hydroxyrisperidone adjusted for weight and dose in all 50 subjects.In male subjects,we found a statistically significant positive correlation between the concentrations of risperidone+9-hydroxyrisperidone in plasma/(dose×kg)and age,mean PANSS negative subscale scores,mean PANSS general psychopathology subscale scores,and mean PANSS total scores.CONCLUSION Long-term use of RIS should be closely monitored in older patients and females to minimize the risk of high concentrations which could induce side effects.

关键词： Antipsychotics Risperidone 9-hydroxyrisperidone Plasma drug concentration monitoring Chronic schizophrenia

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Developmental Impairments of Synaptic Refinement in the Thalamus of a Mouse Model of Fragile X Syndrome

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Neuroscience Bulletin 2024年第4期40卷 439-450页

作者： Xiaotong Wu Yali Liu Xiaomeng Wang Lu Zheng Libiao Pan Hao Wang Department of Neurosurgery of Second Affiliated Hospital and School of Brain Science and Brain medicine Key Laboratory for Biomedical Engineering of Education MinistryZhejiang University School of MedicineHangzhou310058China Nanhu Brain-computer Interface Institute Hangzhou311100China NHC and CAMS key laboratory of Medical Neurobiology MOE Frontier Science Center for Brain Research and Brain Machine IntegrationKey Laboratory of Precise Treatment and Clinical Translational Research of Neurological DiseasesSchool of Brain Science and Brain MedicineZhejiang UniversityHangzhou310058China Lingang laboratory Shanghai200031China

While somatosensory over-reactivity is a common feature of autism spectrum disorders such as fragile X syndrome(FXS),the thalamic mechanisms underlying this remain unclear.Here,we found that the developmental elimination of synapses formed between the principal nucleus of V(PrV)and the ventral posterior medial nucleus(VPm)of the somatosensory system was delayed in fragile X mental retardation 1 gene knockout(Fmr1 KO)mice,while the developmental strengthening of these synapses was disrupted.Immunohistochemistry showed excessive VGluT2 puncta in mutants at P12–13,but not at P7–8 or P15–16,confirming a delay in somatic pruning of PrV-VPm synapses.Impaired synaptic function was associated with a reduction in the frequency of quantal AMPA events,as well as developmental deficits in presynaptic vesicle size and density.Our results uncovered the developmental impairment of thalamic relay synapses in Fmr1 KO mice and suggest that a thalamic contribution to the somatosensory over-reactivity in FXS should be considered.

关键词： Fragile X syndrome Synaptic refinement VPm Sensory over-reactivity

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