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Advances in functional MRI research in bipolar disorder:from the perspective of mood states

General Psychiatry 2024年第1期37卷 33-43页

作者： Yankun Wu Yun-Ai Su Linlin Zhu Jitao Li Tianmei Si Department of Clinical Psychopharmacology Peking University Sixth HospitalPeking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)BeijingChina peking university Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratoryof Mental Health(Peking University)National Clinical Research Centerfor Mental Disorders(Peking University Sixth Hospital)BeijingChina

Bipolar disorder is characterised by recurrent and alternating episodes of mania/hypomania and depression.Current breakthroughs in functional MRI techniques have uncovered the functional neuroanatomy of bipolar disorder.However,the pathophysiology underlying mood instability,mood switching and the development of extreme mood states is less well understood.This reviewpresents a comprehensive overviewof current evidence from functional MRI studies from the perspective of mood states.We first summarise the disrupted brain activation patterns and functional connectivity that have been reported in bipolar disorder,irrespective of the mood state.We next focus on research that solely included patients in a single mood state for a better understanding of the pathophysiology of bipolar disorder and research comparing patients with different mood states to dissect mood state-related effects.Finally,we briefly summarise current theoretical models and conclude this review by proposing potential avenues for future research.A comprehensive understanding of the pathophysiology with consideration of mood states could not only deepen our understanding of how acute mood episodes develop at a neurophysiological level but could also facilitate the identification of biological targets for personalised treatment and the development of new interventions for bipolar disorder.

关键词： anatomy bipolar functional

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Curcumin Interferes with TGF-β1-Induced Fibrosis in NRK-49F Cells by Reversing ADAMTS18 Gene Methylation

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Chinese Journal of Integrative Medicine 2024年第7期30卷 600-607页

作者： XU Ben ZHANG Jia-en YE Lin YUAN Chang-wei Department of Urology Peking University First Hospital and Institute of Urology Peking UniversityNational Urological Cancer Center

Objective: To explore the molecular mechanism by which curcumin affects renal interstitial fibrosis（RIF） progression by regulating ADAM metallopeptidase with thrombospondin type 1 motif 18（ADAMTS18） methylation. Methods: NRK-49F cells RIF model were induced with transforming growth factor β1（TGF-β1）. Effects of different concentrations of curcumin（0, 10, 20, and 30 μmol/L） on cell proliferation, cell cycle, cell apoptosis as well as cyclin D1 expression were analyzed by cell counting kit-8, flow cytometry and Western blot, respectively. ADAMTS18 methylation levels were determined by methylation-specific polymerase chain reaction. ADAMTS18, fibronectin（FN）, type Ⅰ collagen（Col-Ⅰ） and alpha-smooth muscle actin（α-SMA） mRNA and protein expressions were analyzed by real-time PCR（RT-PCR） and Western blot, respectively. Meanwhile, cells were treated with 50 mmol/L 5-aza-2'-deoxycytidine（5-aza-dC, demethylation agent） for 72 h. Effect of curcumin on extracellular matrix（ECM） deposition was evaluated by immunochemical staining and Western blot. NRK-49F cells were transfected with ADAMTS18 small interfering RNA and grouped into a normal control, ADAMTS18-knock-out（KO）, and ADAMTS18-KO+ 30 μmol/L curcumin groups, and whether curcumin can reverse the effect of ADAMTS18 knockdown on RIF was evaluated. Results: Compared with the control group, TGF-β1 significantly inhibited the proliferation of NRK-49F cells, blocked the G1/G0phase, promoted cell apoptosis and inhibited cyclin D1 expression（P<0.01）. Among the different concentrations of curcumin, 30 μmol/L curcumin significantly reversed these processes（P<0.01）. Immunochemical staining and Western blot results showed that curcumin significantly inhibited the deposition of FN, Col-Ⅰ and α-SMA（P<0.01）. Curcumin and 5-zaz-dC had synergistic effects, promoting ADAMTS18 expression, removing ADAMTS18 methylation, and reducing ECM deposition. ADAMTS18 knockdown promoted ECM accumulation, and curcumin reversed this process（P<0.01）. Conclusion: TGF-β1 induced fibrosis in NRK-49F cells.

关键词： renal fibrosis curcumin Chinese medicine ADAMTS18 methylation modification

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Evolution of artificial ion channels

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National Science Review 2024年第1期11卷 72-73页

作者： Yugang Wang School of Physics Peking University

Protein ion channels on a cell membrane generate action potentials for cellular signal transduction, and regulate biological activities during life. Since the discovery of the asymmetric ion transport phenomenon in quartz nanopipettes by Bard and colleagues [1], synthetic nanofluidic materials and devices have attracted a lot of research interests from the scientific community,

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Pancreatic ductal adenocarcinoma chemoresistance:From metabolism reprogramming to novel treatment

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Chinese Medical Journal 2024年第4期137卷 408-420页

作者： Jingcheng Zhang Yutong Wang Lejunzi Wang Lei You Taiping Zhang Department of General Surgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China peking Union Medical College Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Anaesthesia Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Clinical Immunology Centre Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China

As pancreatic cancer(PC)is highly malignant,its patients tend to develop metastasis at an early stage and show a poor response to conventional chemotherapies.First-line chemotherapies for PC,according to current guidelines,include fluoropyrimidine-and gemcitabine-based regimens.Accumulating research on drug resistance has shown that biochemical metabolic aberrations in PC,especially those involving glycolysis and glutamine metabolism,are highly associated with chemoresistance.Additionally,lipid metabolism is a major factor in chemoresistance.However,emerging compounds that target these key metabolic pathways have the potential to overcome chemoresistance.This review summarizes how PC develops chemoresistance through aberrations in biochemical metabolism and discusses novel critical targets and pathways within cancer metabolism for new drug research.

关键词： Pancreatic cancer Drug resistance Drug development Signal transduction

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Clinical manifestations,diagnosis and long-term prognosis of adult autoimmune enteropathy:Experience from peking Union Medical College Hospital

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World Journal of Gastroenterology 2024年第19期30卷 2523-2537页

作者： Mu-Han Li Ge-Chong Ruan Wei-Xun Zhou Xiao-Qing Li Sheng-Yu Zhang Yang Chen Xiao-Yin Bai Hong Yang Yu-Jie Zhang Peng-Yu Zhao Ji Li Jing-Nan Li Department of Gastroenterology Chinese Academy of Medical Sciences&Peking Union Medical College HospitalBeijing 100730China Department of Pathology Chinese Academy of Medical Scinences&Peking Union Medical College HospitalBeijing 100730China Department of Pathology Tianjin First Central HospitalNankai UniversityTianjin 300192China Affairs Office Chinese Academy of Medical Sciences&Peking Union Medical College Hospital(West campus)Beijing 100032China

BACKGROUND Autoimmune enteropathy(AIE)is a rare disease whose diagnosis and long-term prognosis remain challenging,especially for adult AIE patients.AIM To improve overall understanding of this disease’s diagnosis and prognosis.METHODS We retrospectively analyzed the clinical,endoscopic and histopathological characteristics and prognoses of 16 adult AIE patients in our tertiary medical center between 2011 and 2023,whose diagnosis was based on the 2007 diagnostic criteria.RESULTS Diarrhea in AIE patients was characterized by secretory diarrhea.The common endoscopic manifestations were edema,villous blunting and mucosal hyperemia in the duodenum and ileum.Villous blunting(100%),deep crypt lymphocytic infiltration(67%),apoptotic bodies(50%),and mild intraepithelial lymphocytosis(69%)were observed in the duodenal biopsies.Moreover,there were other remarkable abnormalities,including reduced or absent goblet cells(duodenum 94%,ileum 62%),reduced or absent Paneth cells(duodenum 94%,ileum 69%)and neutrophil infiltration(duodenum 100%,ileum 69%).Our patients also fulfilled the 2018 diagnostic criteria but did not match the 2022 diagnostic criteria due to undetectable anti-enterocyte antibodies.All patients received glucocorticoid therapy as the initial medication,of which 14/16 patients achieved a clinical response in 5(IQR:3-20)days.Immunosuppressants were administered to 9 patients with indications of steroid dependence(6/9),steroid refractory status(2/9),or intensified maintenance medication(1/9).During the median of 20.5 months of followup,2 patients died from multiple organ failure,and 1 was diagnosed with non-Hodgkin’s lymphoma.The cumulative relapse-free survival rates were 62.5%,55.6%and 37.0%at 6 months,12 months and 48 months,respectively.CONCLUSION Certain histopathological findings,including a decrease or disappearance of goblet and Paneth cells in intestinal biopsies,might be potential diagnostic criteria for adult AIE.The long-term prognosis is still unsatisfactory despite corticosteroid and immunosuppressan

关键词： Autoimmune enteropathy Clinical manifestations Diagnostic criteria Pathological features Long-term prognosis

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Versatile photonic molecule switch in multimode microresonators

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Light(Science & Applications) 2024年第3期13卷 498-509页

作者： Zihan Tao Bitao Shen Wencan Li Luwen Xing Haoyu Wang Yichen Wu Yuansheng Tao Yan Zhou Yandong He Chao Peng Haowen Shu Xingjun Wang State Key Laboratory of Advanced Optical Communications System and Networks School of ElectronicsPeking UniversityBeijing 100871China College of Engineering Peking UniversityBeijing 100871China School of Integrated Circuits Peking University100871 BejingChina peking university Yangtze Delta Institute of Optoelectronics Nantong 226010China Frontiers Science Center for Nano-optoelectronics Peking UniversityBeijing 100871China Peng Cheng Laboratory Shenzhen 518055China

Harnessing optical supermode interaction to construct artificial photonic molecules has uncovered a series of fundamental optical phenomena analogous to atomic physics.Previously,the distinct energy levels and interactions in such two-level systems were provided by coupled microresonators.The reconfigurability is limited,as they often require delicate external field stimuli or mechanically altering the geometric factors.These highly specific approaches also limit potential applications.Here,we propose a versatile on-chip photonic molecule in a multimode microring,utilizing a flexible regulation methodology to dynamically control the existence and interaction strength of spatial modes.The transition between single/multi-mode states enables the“switched-off/on”functionality of the photonic molecule,supporting wider generalized applications scenarios.In particular,“switched-on”state shows flexible and multidimensional mode splitting control in aspects of both coupling strength and phase difference,equivalent to the a.***.and d.c.Stark effect.“Switched-off”state allows for perfect low-loss single-mode transition(Qi~10 million)under an ultra-compact bend size(FSR~115 GHz)in a foundry-based silicon microring.It breaks the stereotyped image of the FSR-Q factor trade-off,enabling ultra-wideband and high-resolution millimeter-wave photonic operations.Our demonstration provides a flexible and portable solution for the integrated photonic molecule system,extending its research scope from fundamental physics to real-world applications such as nonlinear optical signal processing and sixth-generation wireless communication.

关键词： switched multimode millimeter

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Progress in the generation of spinal cord organoids over the past decade and future perspectives

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Neural Regeneration Research 2024年第5期19卷 1013-1019页

作者： Gang Zhou Siyuan Pang Yongning Li Jun Gao Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina Department of International Medical Service Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingChina

Spinal cord organoids are three-dimensional tissues derived from stem cells that recapitulate the primary morphological and functional characteristics of the spinal cord in vivo.As emerging bioengineering methods have led to the optimization of cell culture protocols,spinal cord organoids technology has made remarkable advancements in the past decade.Our literature search found that current spinal cord organoids do not only dynamically simulate neural tube formation but also exhibit diverse cytoarchitecture along the dorsal-ventral and rostral-caudal axes.Moreover,fused organoids that integrate motor neurons and other regionally specific organoids exhibit intricate neural circuits that allows for functional assessment.These qualities make spinal cord organoids valuable tools for disease modeling,drug screening,and tissue regeneration.By utilizing this emergent technology,researchers have made significant progress in investigating the pathogenesis and potential therapeutic targets of spinal cord diseases.However,at present,spinal cord organoid technology remains in its infancy and has not been widely applied in translational medicine.Establishment of the next generation of spinal cord organoids will depend on good manufacturing practice standards and needs to focus on diverse cell phenotypes and electrophysiological functionality evaluation.

关键词： development organoid-on-a-chip pluripotent stem cells progress spinal cord diseases spinal cord organoids vascularization

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Targeting LTA4H facilitates the reshaping of the immune microenvironment mediated by CCL5 and sensitizes ovarian cancer to Cisplatin

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Science China(Life Sciences) 2024年第6期67卷 1226-1241页

作者： Zhengyang Guo Jiaqi Huang Xiao Huo Chen Huang Xiaotong Yu Yan Sun Yanfang Li Tianhui He Hongyan Guo Jianling Yang Lixiang Xue Cancer Center of peking university Third Hospital Beijing 100191China Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third HospitalBeijing 100191China peking university Third Hospital Cancer Center Department of Radiation OncologyPeking University Third HospitalBeijing 100191China Department of Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China

Ovarian cancer is the most lethal and aggressive gynecological cancer with a high recurrence rate and is often diagnosed late.In ovarian cancer,multiple metabolic enzymes of lipid metabolism are abnormally expressed,resulting in metabolism disorder.As a characteristic pathway in polyunsaturated fatty acid(PUFA)metabolism,arachidonic acid(AA)metabolism is disturbed in ovarian cancer.Therefore,we established a 10-gene signature model to evaluate the prognostic risk of PUFA-related genes.This 10-gene signature has strong robustness and can play a stable predictive role in datasets of various platforms(TCGA,ICGC,and GSE17260).The high association between the risk subgroups and clinical characteristics indicated a good performance of the model.Our data further indicated that the high expression of LTA4H was positively correlated with poor prognosis in ovarian cancer.Deficiency of LTA4H enhanced sensitivity to Cisplatin and modified the characteristics of immune cell infiltration in ovarian cancer.Additionally,our results indicate that CCL5 was involved in the aberrant metabolism of the AA/LTA4H axis,which contributes to the reduction of tumor-infiltrating CD8+T cells and immune escape in ovarian cancer.These findings provide new insights into the prognosis and potential target of LTA4H/CCL5 in treating ovarian cancer.

关键词： ovarian cancer polyunsaturated fatty acids prognostic risk model LTA4H tumor immunity CCL5

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Post-layout simulation driven analog circuit sizing

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Science China(Information Sciences) 2024年第4期67卷 289-300页

作者： Xiaohan GAO Haoyi ZHANG Siyuan YE Mingjie LIU David Z.PAN Linxiao SHEN Runsheng WANG Yibo LIN Ru HUANG School of Integrated Circuits Peking University School of Computer Science Peking University Department of Electrical and Computer Engineering University of Texas at Austin Institute of Electronic Design Automation Peking University

Post-layout simulation provides accurate guidance for analog circuit design, but post-layout performance is hard to be directly optimized at early design stages. Prior work on analog circuit sizing often utilizes pre-layout simulation results as the optimization objective. In this work, we propose a post-layoutsimulation-driven(post-simulation-driven for short) analog circuit sizing framework that directly optimizes the post-layout simulation performance. The framework integrates automated layout generation into the optimization loop of transistor sizing and leverages a coupled Bayesian optimization algorithm to search for the best post-simulation performance. Experimental results demonstrate that our framework can achieve over 20% better post-layout performance in competitive time than manual design and the method that only considers pre-layout optimization.

关键词： analog EDA transistor sizing Bayesian optimization post-layout simulation

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Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo Department of Pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China Department of General Surgery Peking University Third HospitalBeijing 100191China Department of Medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin overexpression.MUC1 has been identified as a critical oncogene in the progression of CCA.However,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still incomplete.AIM To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA patients.METHODS Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic analyses.Subse-quent validations were conducted through spatial transcriptomics and immuno-histochemistry.The construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data types.RESULTS CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased invasiveness.MUC5AC-high cells were found to promote CCA progression through WNT signaling.MUC5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral treatments.MUC13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor immunity.MUC16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with neutrophils.Utilizing the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple cohorts.CCA samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer prognosis.CONCLUSION Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis

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