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RARRES2 regulates lipid metabolic reprogramming to mediate the development of brain metastasis in triple negative breast cancer

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Military Medical Research 2024年第1期11卷 34-49页

作者： Yi-Qun Li fang-zhou sun Chun-Xiao Li Hong-Nan Mo Yan-Tong zhou Dan Lv Jing-Tong Zhai Hai-Li Qian Fei Ma Department of Medical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

Background Triple negative breast cancer(TNBC),the most aggressive subtype of breast cancer,is characterized by a high incidence of brain metastasis(BrM)and a poor prognosis.As the most lethal form of breast cancer,BrM remains a major clinical challenge due to its rising incidence and lack of effective treatment strategies.Recent evidence suggested a potential role of lipid metabolic reprogramming in breast cancer brain metastasis(BCBrM),but the underlying mechanisms are far from being fully elucidated.Methods Through analysis of BCBrM transcriptome data from mice and patients,and immunohistochemical validation on patient tissues,we identified and verified the specific down-regulation of retinoic acid receptor responder 2(RARRES2),a multifunctional adipokine and chemokine,in BrM of TNBC.We investigated the effect of aberrant RARRES2 expression of BrM in both in vitro and in vivo studies.Key signaling pathway components were evaluated using multi-omics approaches.Lipidomics were performed to elucidate the regulation of lipid metabolic reprogramming of RARRES2.Results We found that downregulation of RARRES2 is specifically associated with BCBrM,and that RARRES2 deficiency promoted BCBrM through lipid metabolic reprogramming.Mechanistically,reduced expression of RARRES2 in brain metastatic potential TNBC cells resulted in increased levels of glycerophospholipid and decreased levels of triacylglycerols by regulating phosphatase and tensin homologue(PTEN)-mammalian target of rapamycin(mTOR)-sterol regulatory element-binding protein 1(SREBP1)signaling pathway to facilitate the survival of breast cancer cells in the unique brain microenvironment.Conclusions Our work uncovers an essential role of RARRES2 in linking lipid metabolic reprogramming and the development of BrM.RARRES2-dependent metabolic functions may serve as potential biomarkers or therapeutic targets for BCBrM.

关键词： RARRES2 Lipid metabolic reprogramming Brain metastasis(BrM) Breast cancer

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A New Method for Solving Nonlinear Partial Differential Equations Based on Liquid Time-Constant Networks

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Journal of Systems Science & Complexity 2024年第2期37卷 480-493页

作者： sun Jiuyun DONG Huanhe fang Yong College of Mathematics and Systems Science Shandong University of Science and TechnologyQingdao 266590China

In this paper,physics-informed liquid networks(PILNs)are proposed based on liquid time-constant networks(LTC)for solving nonlinear partial differential equations(PDEs).In this approach,the network state is controlled via ordinary differential equations(ODEs).The significant advantage is that neurons controlled by ODEs are more expressive compared to simple activation functions.In addition,the PILNs use difference schemes instead of automatic differentiation to construct the residuals of PDEs,which avoid information loss in the neighborhood of sampling points.As this method draws on both the traveling wave method and physics-informed neural networks(PINNs),it has a better physical interpretation.Finally,the KdV equation and the nonlinear Schr¨odinger equation are solved to test the generalization ability of the PILNs.To the best of the authors’knowledge,this is the first deep learning method that uses ODEs to simulate the numerical solutions of PDEs.

关键词： Nonlinear partial differential equations numerical solutions physics-informed liquid networks physics-informed neural networks

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Evolutionary mechanisms and practical significance of reproductive success and clonal diversity in unisexual vertebrate polyploids

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Science China(Life Sciences) 2024年第3期67卷 449-459页

作者： Meng Lu Li zhou Jian-fang Gui State Key Laboratory of Freshwater Ecology and Biotechnology Hubei Hongshan Laboratorythe Innovation Academy of Seed DesignInstitute of HydrobiologyChinese Academy of SciencesWuhan 430072China University of Chinese Academy of Sciences Beijing 100049China

Unisexual reproduction is generally relevant to polyploidy, and unisexual vertebrates are often considered an evolutionary “dead end” due to the accumulation of deleterious mutations and absence of genetic diversity. However, some unisexual polyploids have developed strategies to avoid genomic decay, and thus provide ideal models to unveil unexplored evolutionary mechanisms, from the reproductive success to clonal diversity creation. This article reviews the evolutionary mechanisms for overcoming meiotic barrier and generating genetic diversity in unisexual vertebrates, and summarizes recent research advancements in the polyploid Carassius complex. Gynogenetic gibel carp(Carassius gibelio) is a unique amphitriploid that has undergone a recurrent autotriploidy and has overcome the bottleneck of triploid sterility via gynogenesis. Recently, an efficient strategy in which ploidy changes, including from amphitriploid to amphitetraploid, then from amphitetraploid to novel amphitriploid, drive unisexual-sexual-unisexual reproduction transition and clonal diversity has been revealed.Based on this new discovery, multigenomic reconstruction biotechnology has been used to breed a novel strain with superior growth and stronger disease resistance. Moreover, a unique reproduction mode that combines both abilities of ameiotic oogenesis and sperm-egg fusion,termed as ameio-fusiongensis, has been discovered, and it provides an efficient approach to synthesize sterile allopolyploids. In order to avoid ecological risks upon escape and protect the sustainable property rights of the aquaculture seed industry, a controllable fertility biotechnology approach for precise breeding is being developed by integrating sterile allopolyploid synthesis and gene-editing techniques.This review provides novel insights into the origin and evolution of unisexual vertebrates and into the attempts being made to exploit new breeding biotechnologies in aquaculture.

关键词： unisexual vertebrates polyploidy reproduction transition clonal diversity precise breeding genomic reconstruction controllable fertility

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Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis

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World Journal of Emergency Medicine 2024年第1期15卷 35-40页

作者： Wei zhou Maiying Fan Xiang Li fang Yu En zhou Xiaotong Han Department of Emergency Medicine the First Affi liated Hospital of Hunan Normal University/Hunan Provincial People’s HospitalChangsha 410005China Department of Otolaryngology-head and Neck Surgery the First Affi liated Hospital of Hunan Normal University/Hunan Provincial People’s HospitalChangsha 410005China

BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.

关键词： Xuebijing injection Pyogenic liver abscess Sepsis

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Primary acinic cell carcinoma of the breast: A case report and review of literature

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World Journal of Clinical Cases 2024年第1期12卷 196-203页

作者： Jia-Sheng Ding Min Zhang fang-fang zhou Department of Intensive Care Unit Lishui Central HospitalThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000Zhejiang ProvinceChina Department of Pathology Lishui Central HospitalThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000Zhejiang ProvinceChina Department of Ultrasound Lishui Central HospitalThe Fifth Affiliated Hospital of Wenzhou Medical UniversityLishui 323000Zhejiang ProvinceChina

BACKGROUND In the current World Health Organization classification,acinic cell carcinoma(AcCC)of the breast is considered a rare histological subtype of triple-negative breast cancer.Because of the few reports in the literature,data concerning clinical outcomes are limited.Here,we report a case of AcCC of the breast in a 48-year-old woman.A 48-year-old woman with a mass in her right breast came to our hospital for further diagnosis.Mammography and an ultrasound(US)scan showed a mass in the upper inner side of the right breast.She then underwent surgery to resect the mass in her right breast.Postoperative pathological examination revealed that the tumor had abundant acinar-like structures formed by tumor cells with prominent eosinophilic granules in the cytoplasm,consistent with acinar cell carcinoma.The results of immunohistochemical analysis supported the diagnosis of breast acinar cell carcinoma.Two months later,she underwent breast-conserving surgery and sentinel lymph node biopsy.The pTNM stage was T2N0M0.After surgery,the patient received 30 radiotherapy sessions.The patient was followed up for a period of one year,and no recurrence was found.AcCC of the breast is a rare type of malignant tumor.Because it is usually asym-ptomatic and can be detected by imaging studies,routine breast US or mamm-ograms are important.However,there are no characteristic diagnostic imaging findings or clinical manifestations,so immunohistochemical examination is critical for an accurate diagnosis of AcCC of the breast.

关键词： Acinic cell carcinoma Breast Malignant tumor Immunohistochemical Surgery Case report

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Natural polysaccharide-based smart CXCR4-targeted nano-system for magnified liver fibrosis therapy

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Chinese Chemical Letters 2024年第2期35卷 341-346页

作者： Liqiong sun Xinping Luo Chenxi zhou Zhanwei zhou Minjie sun College of Horticulture Nanjing Agricultural UniversityNanjing 210095China NMPA Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients State Key Laboratory of Natural MedicinesDepartment of PharmaceuticsChina Pharmaceutical UniversityNanjing 210009China

Activated hepatic stellate cells(aHSCs),the main source of extracellular matrix deposition,are key targets in liver fibrosis.However,no effective drug specific to aHSCs has been clinically applied due to poor drug delivery efficiency.Herein,we designed a CXC chemokine receptor 4(CXCR4)-targeted reactive oxygen species(ROS)-responsive platform AMD-Dex-ROS-responsive-sorafenib(ARS)based on natural polysaccharide and thioctic acid frame,which can deliver anti-fibrosis drug represented by sorafenib specifically to aHSCs on account of CXCR4 over-expression on aHSCs,and smartly disassemble via ROS-responsive thioketal rupture relying on high intracellular ROS in HSCs,realized on-demand drug release and effective liver fibrosis reversion.Notably,in this platform,the CXCR4 antagonist AMD3100 not only enhanced aHSCs targeting efficiency of sorafenib but also effectively magnified the aHSCs elimination of sorafenib by blocking stroma cell derived factor-1(SDF-1)/CXCR4-induced aHSCs protection,resulting in synergistic anti-fibrosis effect.The platform provided a new approach for drug delivery system design and liver fibrosis treatment.

关键词： Nanoparticle CXCR4 antagonism ROS-responsive Hepatic stellate cells Liver fibrosis

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Physical informed memory networks for solving PDEs:implementation and applications

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Communications in Theoretical Physics 2024年第2期76卷 51-61页

作者： Jiuyun sun Huanhe Dong Yong fang College of Mathematics and Systems Science Shandong University of Science and TechnologyQingdao 266590China

With the advent of physics informed neural networks(PINNs),deep learning has gained interest for solving nonlinear partial differential equations(PDEs)in recent years.In this paper,physics informed memory networks(PIMNs)are proposed as a new approach to solving PDEs by using physical laws and dynamic behavior of PDEs.Unlike the fully connected structure of the PINNs,the PIMNs construct the long-term dependence of the dynamics behavior with the help of the long short-term memory network.Meanwhile,the PDEs residuals are approximated using difference schemes in the form of convolution filter,which avoids information loss at the neighborhood of the sampling points.Finally,the performance of the PIMNs is assessed by solving the Kd V equation and the nonlinear Schr?dinger equation,and the effects of difference schemes,boundary conditions,network structure and mesh size on the solutions are discussed.Experiments show that the PIMNs are insensitive to boundary conditions and have excellent solution accuracy even with only the initial conditions.

关键词： nonlinear partial differential equations physics informed memory networks physics informed neural networks numerical solution

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Approaching the commercial threshold of solar water splitting toward hydrogen byⅢ-nitrides nanowires

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Frontiers in Energy 2024年第1期18卷 122-124页

作者： Baowen zhou Shuhui sun Key Laboratory for Power Machinery and Engineering of the Ministry of Education School of Mechanical EngineeringShanghai Jiao Tong UniveristyShanghai 200240China Institut National de la Recherche Scientifique(INRS)-CenterÉnergie Matériaux Télécommunications VarennesQuebec J3X 1P7Canada

In a recent article in Nature,Mi and coworkers from the University of Michigan reported a solar-to-hydrogen(STH)efficiency of>9%in converting water into hydrogen and oxygen[1],which represents an important breakthrough in this field due to the benchmarking leap in STH efficiency of photocatalytic overall water splitting under natural sunlight.

关键词： breakthrough splitting Michigan

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An aqueous magnesium-ion hybrid supercapacitor operated at-50℃

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Green Energy & Environment 2024年第4期9卷 702-712页

作者： Guoshen Yang Gangrui Qu Chi fang Jie Deng Xianqi Xu Yinghao Xie Tian sun Yachao Zhu Jiaxin Zheng Hang zhou School of Electronic and Computer Engineering Peking University Shenzhen Graduate SchoolShenzhen518055China School of Advanced Materials Peking University Shenzhen Graduate SchoolShenzhenChina College of Food and Biological Engineering Chengdu UniversityChengdu610106China Institute Charles Gerhardt Montpellier UMR 5253Universitae MontpellierMontpellierCC 1502France

The recent advances in aqueous magnesium-ion hybrid supercapacitor(MHSC)have attracted great attention as it brings together the benefits of high energy density,high power density,and synchronously addresses cost and safety issues.However,the freeze of aqueous electrolytes discourages aqueous MHSC from operating at low-temperature conditions.Here,a low-concentration aqueous solution of 4 mol L^(-1) Mg(ClO_(4))_(2) is devised for its low freezing point(-67℃)and ultra-high ionic conductivity(3.37 mS cm^(-1) at-50℃).Both physical characterizations and computational simulations revealed that the Mg(ClO_(4))_(2) can effectively disrupt the original hydrogen bond network among water molecules via transmuting the electrolyte structure,thus yielding a low freezing point.Thus,the Mg(ClO_(4))_(2) electrolytes endue aqueous MHSC with a wider temperature operation range(-50℃–25℃)and a higher energy density of 103.9 Wh kg^(-1) at 3.68 kW kg^(-1) over commonly used magnesium salts(i.e.,MgSO_(4) and Mg(NO_(3))_(2))electrolytes.Furthermore,a quasi-solid-state MHSC based on polyacrylamide-based hydrogel electrolyte holds superior low-temperature performance,excellentﬂexibility,and high safety.This work pioneers a convenient,cheap,and eco-friendly tactic to procure low-temperature aqueous magnesium-ion energy storage device.

关键词： Low-concentration aqueous electrolyte Anti-freezing property Magnesium-ion hybrid supercapacitor High energy density

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Enhancing sheepgrass through genomic exploration and targeted editing

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Science China(Life Sciences) 2024年第3期67卷 629-630页

作者： Miao sun Sanwen Huang Yao zhou Key Laboratory of Plant Molecular Physiology Institute of BotanyChinese Academy of SciencesBeijing 100093China State Key Laboratory of Tropical Crop Breeding Shenzhen BranchGuangdong Laboratory of Lingnan Modern AgricultureGenome Analysis Laboratory of the Ministry of Agriculture and Rural AffairsAgricultural Genomics Institute at ShenzhenChinese Academy of Agricultural SciencesShenzhen 518120China State Key Laboratory of Tropical Crop Breeding Chinese Academy of Tropical Agricultural SciencesHaikou 571101China

The growth of grass industry is essential for meeting human needs for proteins and sustaining grassland ecosystems(Bengtsson et al., 2019). Leymus chinensis, also known as sheepgrass, is a perennial Triticeae forage r... 详细信息

关键词： grassland sheep ecosystems

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