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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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Metagenomic insights into microorganisms and antibiotic resistance genes of waste antibiotic fermentation residues along production,storage and treatment processes

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Journal of Environmental Sciences 2024年第2期136卷 45-55页

作者： Ziming Han Xiao Luan Haodi Feng Yanqin Deng Min Yang Yu Zhang State Key Laboratory of Environmental Aquatic Chemistry Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China National Engineering Research center of Industrial Wastewater Detoxication and Resource Recovery Beijing 100085China Wuhan Agricultural Inspection center Wuhan 430016China University of Chinese Academy of Sciences Beijing 100049China

Antibiotic fermentation residue(AFR)is nutrient-rich solid waste generated from fermentative antibiotic production process.It is demonstrated that AFR contains high-concentration of remaining antibiotics,and thus may promote antibiotic resistance development in receiving environment or feeding farmed animals.However,the dominate microorganisms and antibiotic resistance genes(ARGs)in AFRs have not been adequately explored,hampering understanding on the potential antibiotic resistance risk development caused by AFRs.Herein,seven kinds of representative AFRs along their production,storage,and treatment processes were collected,and multiple methods including amplicon sequencing,metagenomic sequencing,and bioinformatic approaches were adopted to explore the biological characteristics of AFRs.As expected,antibiotic fermentation producer was found as the predominant species in raw AFRs,which were collected at the outlet of fermentation tanks.However,except for producer species,more environment-derived species persisted in stored AFRs,which were temporarily stored at a semi-open space.Lactobacillus genus,classified as Firmicutes phylum and Bacilli class,became predominant bacterial taxa in stored AFRs,which might attribute to its tolerance to high concentration of antibiotics.Results from metagenomic sequencing together with assembly and binning approaches showed that these newly-colonizing species(e.g.,Lactobacillus genus)tended to carry ARGs conferring resistance to the remaining antibiotic.However,after thermal treatment,remaining antibiotic could be efficiently removed from AFRs,and microorganisms together with DNA could be strongly destroyed.In sum,the main risk from the AFRs was the remaining antibiotic,while environment-derived bacteria which tolerate extreme environment,survived in ARFs with high content antibiotics,and may carry ARGs.Thus,hydrothermal or other harmless treatment technologies are recommended to remove antibiotic content and inactivate bacteria before recycling of AFRs in pharmaceutical industry.

关键词： Pharmaceutical manufacturing Antibiotic mycelia residue Antibiotic resistance bacteria Thermal treatment Solid waste

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Magnetism and Superconductivity in the t–J Model of La_(3)Ni_(2)O_7 Under Multiband Gutzwiller Approximation

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Chinese Physics Letters 2024年第5期41卷 97-106页

作者：薛洁然王垡 International center for Quantum Materials School of PhysicsPeking UniversityBeijing 100871China Collaborative Innovation center of Quantum Matter Beijing 100871China

The recent discovery of possible high temperature superconductivity in single crystals of La_(3)Ni_(2)O_(7) under pressure renews the interest in research on nickelates.The density functional theory calculations reveal that both d_(z^(2)) and d_(x^(2)-y^(2)) orbitals are active,which suggests a minimal two-orbital model to capture the low-energy physics of this system.In this work,we study a bilayer two-orbital t–J model within multiband Gutzwiller approximation,and discuss the magnetism as well as the superconductivity over a wide range of the hole doping.Owing to the inter-orbital super-exchange process between d_(z^(2)) and d_(x^(2)-y^(2)) orbitals,the induced ferromagnetic coupling within layers competes with the conventional antiferromagnetic coupling,and leads to complicated hole doping dependence for the magnetic properties in the system.With increasing hole doping,the system transfers to A-type antiferromagnetic state from the starting G-type antiferromagnetic(G-AFM)state.We also find the inter-layer superconducting pairing of d_(x^(2)-y^(2)) orbitals dominates due to the large hopping parameter ofd_(z^(2)) along the vertical inter-layer bonds and significant Hund’s coupling between d_(z^(2)) and d_(x^(2)-y^(2)) orbitals.Meanwhile,the G-AFM state and superconductivity state can coexist in the low hole doping regime.To take account of the pressure,we also analyze the impacts of inter-layer hopping amplitude on the system properties.

关键词： properties doping orbital

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Lithiophilic Li-Si alloy-solid electrolyte interface enabled by high-concentration dual salt-reinforced quasi-solid-state electrolyte

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Journal of Energy Chemistry 2024年第8期95卷 216-230页

作者： Yuanxing Zhang Ling Zhang Zhiguang Zhao Yuxiang Zhang Jingwen Cui Chengcai Liu Daobin Mu Yuefeng Su Borong Wu Feng Wu School of Materials Science and Engineering Beijing Institute of Technology Chongqing Innovation center Beijing Institute of Technology Collaborative Innovation center of Electric Vehicles in Beijing

Solid polymer electrolytes（SPEs） are urgently required to achieve practical solid-state lithium metal batteries（LMBs） and lithium-ion batteries（LIBs）,Herein,we proposed a mechanism for modulating interfacial conduction and anode interfaces in high-concentration SPEs by LiDFBOP.Optimized electrolyte exhibits superior ionic conductivity and remarkable interface compatibility with salt-rich clusters:（1）polymer-plastic crystal electrolyte（P-PCE,TPU-SN matrix） dissociates ion pairs to facilitate Li+transport in the electrolyte and regulates Li+diffusion in the SEI.The crosslinking structure of the matrix compensates for the loss of mechanical strength at high-salt concentrations;（2） dual-anion TFSI-_n-DFBOP-min the Li+solvation sheath facilitates facile Li+desolvation and formation of salt-rich clusters and is conducive to the formation of Li conductive segments of TPU-SN matrix;（3） theoretical calculations indicate that the decomposition products of LiDFBOP form SEI with lower binding energy with LiF in the SN system,thereby enhancing the interfacial electrochemical redox kinetics of SPE and creating a solid interface SEI layer rich in LiF.As a result,the optimized electrolyte exhibits an excellent ionic conductivity of9.31 × 10-4S cm-1at 30℃ and a broadened electrochemical stability up to 4.73 V.The designed electrolyte effectively prevents the formation of Li dendrites in Li symmetric cells for over 6500 h at0.1 mA cm-2.The specific Li-Si alloy-solid state half-cell capacity shows 711.6 mAh g-1after 60 cycles at 0.3 A g-1. Excellent rate performance and cycling stability are achieved for these solid-state batteries with Li-Si alloy anodes and NCM 811 cathodes.NCM 811‖ Prelithiated silicon-based anode solid-state cell delivers a discharge capacity of 195.55 mAh g-1and a capacity retention of 97.8% after 120 cycles.NCM 811‖Li solid-state cell also delivers capacity retention of 84.2% after 450 cycles.

关键词： Li-Si alloy anode Prelithiation SEI layer Solid-state electrolyte

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New insights into the therapeutic approaches for the treatment of tauopathies

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Neural Regeneration Research 2024年第5期19卷 1020-1026页

作者： Himanshi Singh Asmita Das Mohammad Moshahid Khan Tayebeh Pourmotabbed Department of Microbiology Immunology and BiochemistryUniversity of Tennessee Health Science CenterMemphisTNUSA Department of Biotechnology Delhi Technological UniversityShahbad DaulatpurDelhiIndia Department of Neurology College of MedicineUniversity of Tennessee Health Science CenterMemphisTNUSA Neuroscience Institute University of Tennessee Health Science CenterMemphisTNUSA center for Muscle Metabolism and NeuropathologyDivision of Regenerative and Rehabilitation Sciences and Department of Physical TherapyCollege of Health ProfessionsUniversity of Tennessee Health Science CenterMemphisTNUSA

Tauopathies are a group of neurological disorders,including Alzheimer’s disease and frontotemporal dementia,which involve progressive neurodegeneration,cognitive deficits,and aberrant tau protein accumulation.The development of tauopathies cannot currently be stopped or slowed down by treatment measures.Given the significant contribution of tau burden in primary tauopathies and the strong association between pathogenic tau accumulation and cognitive deficits,there has been a lot of interest in creating therapies that can alleviate tau pathology and render neuroprotective effects.Recently,small molecules,immunotherapies,and gene therapy have been used to reduce the pathological tau burden and prevent neurodegeneration in animal models of tauopathies.However,the major pitfall of the current therapeutic approach is the difficulty of drugs and gene-targeting modalities to cross the blood-brain barrier and their unintended side effects.In this review,the current therapeutic strategies used for tauopathies including the use of oligonucleotide-based gene therapy approaches that have shown a promising result for the treatment of tauopathies and Alzheimer’s disease in preclinical animal models,have been discussed.

关键词： dementia gene therapies immunotherapy neurodegeneration oligonucleotides tau tauopathies therapies

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High-grade pancreatic intraepithelial neoplasia diagnosed based on changes in magnetic resonance cholangiopancreatography findings:A case report

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World Journal of Clinical Cases 2024年第8期12卷 1487-1496页

作者： Nao Furuya Atsushi Yamaguchi Naohiro Kato Syuhei Sugata Takuro Hamada Takeshi Mizumoto Yuzuru Tamaru Ryusaku Kusunoki Toshio Kuwai Hirotaka Kouno Kazuya Kuraoka Yoshiyuki Shibata Sho Tazuma Takeshi Sudo Hiroshi Kohno Shiro Oka Department of Gastroenterology National Hospital Organization Kure Medical Center and Chugoku Cancer CenterKure 737-0023HiroshimaJapan Department of Gastroenterology Hiroshima University HospitalHiroshima 734-8551HiroshimaJapan Department of Pathology National Hospital Organization Kure Medical Center and Chugoku Cancer CenterKure 737-0023HiroshimaJapan Department of Surgery National Hospital Organization Kure Medical Center and Chugoku Cancer CenterKure 737-0023HiroshimaJapan

BACKGROUND High-grade pancreatic intraepithelial neoplasia(PanIN)exhibits no mass and is not detected by any examination modalities.However,it can be diagnosed by pancreatic juice cytology from indirect findings.Most previous cases were diagnosed based on findings of a focal stricture of the main pancreatic duct(MPD)and caudal MPD dilatation and subsequent pancreatic juice cytology using endoscopic retrograde cholangiopancreatography(ERCP).We experienced a case of high-grade PanIN with an unclear MPD over a 20-mm range,but without caudal MPD dilatation on magnetic resonance cholangiopancreatography(MRCP).CASE SUMMARY A 60-year-old female patient underwent computed tomography for a follow-up of uterine cancer post-excision,which revealed pancreatic cysts.MRCP revealed an unclear MPD of the pancreatic body at a 20-mm length without caudal MPD dilatation.Thus,course observation was performed.After 24 mo,MRCP revealed an increased caudal MPD caliber and a larger pancreatic cyst.We performed ERCP and detected atypical cells suspected of adenocarcinoma by serial pancreatic juice aspiration cytology examination.We performed a distal pancreatectomy and obtained a histopathological diagnosis of high-grade PanIN.Pancreatic parenchyma invasion was not observed,and curative resection was achieved.CONCLUSION High-grade Pan-IN may cause MPD narrowing in a long range without caudal MPD dilatation.

关键词： Pancreatic cancer Pancreatic intraepithelial neoplasm High-grade pancreatic intraepithelial neoplasm Magnetic resonance cholangiopancreatography Carcinoma in situ Case report

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Non-improvement of atrophic gastritis in cases of gastric cancer after successful Helicobacter pylori eradication therapy

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World Journal of Clinical Cases 2024年第14期12卷 2342-2349页

作者： Yuto Suzuki Yasumi Katayama Yo Fujimoto Ikuhiro Kobori Masaya Tamano Department of Gastroenterology Dokkyo medical University Saitama Medical CenterKoshigayaSaitama 343-8555Japan Endoscopy center Dokkyo Medical University Saitama Medical CenterKoshigayaSaitama 343-8555Japan

BACKGROUND Helicobacter pylori(H.pylori)infection is closely related to the development of gastric cancer(GC).However,GC can develop even after H.pylori eradication.Therefore,it would be extremely useful if GC could be predicted after eradication.The Kyoto classification score for gastritis(GA)is closely related to cancer risk.However,how the score for GC changes after eradication before onset is not well understood.AIM To investigate the characteristics of the progression of Kyoto classification scores for GC after H.pylori eradication.METHODS Eradication of H.pylori was confirmed in all patients using either the urea breath test or the stool antigen test.The Kyoto classification score of GC patients was evaluated by endoscopy at the time of event onset and three years earlier.In ad-dition,the modified atrophy score was evaluated and compared between the GC group and the control GA group.RESULTS In total,30 cases of early GC and 30 cases of chronic GA were evaluated.The pathology of the cancer cases was differentiated adenocarcinoma,except for one case of undifferentiated adenocarcinoma.The total score of the Kyoto classifi-cation was significantly higher in the GC group both at the time of cancer onset and three years earlier(4.97 vs 3.73,P=0.0034;4.2 vs 3.1,P=0.0035,respectively).The modified atrophy score was significantly higher in the GC group both at the time of cancer onset and three years earlier and was significantly improved only in the GA group(5.3 vs 5.3,P=0.5;3.73 vs 3.1,P=0.0475,respectively).CONCLUSION The course of the modified atrophy score is useful for predicting the onset of GC after eradication.Patients with severe atrophy after H.pylori eradication require careful monitoring.

关键词： Helicobacter pylori Kyoto classification Gastritis Eradication therapy Gastric cancer

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Sinonasal Polyposis: About 60 Cases at Fann University Hospital center, Senegal

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International Journal of Otolaryngology and Head & Neck Surgery 2024年第1期13卷 53-61页

作者： Mame Sanou Diouf Moustapha Ndiaye Ahmadou Dembele Evelyne Siga Diom Ciré Ndiaye Amadou Thiam Richard E. A. Deguenonvo Abdou Sy Malick Ndiaye Abdourahmane Tall Issa Cheikh Ndiaye Raymond Diouf HOGIP Hospital center Dakar Senegal Fann University Hospital center Dakar Senegal Ourossogui Hospital center Matam Senegal La Paix Hospital center Ziguinchor Senegal Children Hospital center of Diamniadio Dakar Senegal

Introduction: Sinonasal polyposis (SNP) is a chronic inflammatory disease of the mucosa of the nasal cavities and facial sinuses. It is characterized by an oedematous, multifocal and bilateral degeneration of the nasosinus mucosa, which originates in the lateral masses of the ethmoid, where it causes the formation of smooth, gelatinous, translucent and pyriform polyp lesions. The objective of this study was to review epidemiological, clinical, paraclinical data and evaluate the results of endoscopic surgical treatment. Patients and Methods: This is a retrospective study on 60 patients followed at the ENT department of the Fann National University Hospital center, from January 2010 to December 2015. All patients with sinonasal polyposis were included in the study. Results: The average age of our patients was 38 years and the sex ratio (M/F) was 0.8. In the patients’ histories, we found 18% asthma and 10% Widal’s disease. The average consultation time was 8.5 years. All patients had consulted for nasal obstruction;rhinorrhea was bilateral and found in 67.7% of cases, with olfactory disorders accounting for 50%. The CT scan performed in 58% of cases made it possible to specify the extent of the lesions;the involvement of the ethmoidal sinus was constant and extended to the other sinuses except in 2 cases. All patients had received medical treatment with local corticosteroids. Endoscopic surgical treatment was initiated in 43% of cases after failure of corticosteroid-based medical treatment. The evolution under treatment marked by the reappearance of symptoms that increased each month. At one month postoperatively, all clinical symptomatology had improved with the exception of olfactory disorders, which persisted in 3 patients. At 12 months we noted 12 cases of reappearance of nasal obstruction. Conclusion: SNP is a disease of little known etiology. The diagnosis is almost always clinical. Endoscopic surgery remains a recourse to medical treatment. For good local control, patients should be more respectful of good co

关键词： Sinonasal Polyposis Endonasal Endoscopic Surgery CHNU Fann

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Apoer2/Lrp8:the undercover cop of synaptic homeostasis

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Neural Regeneration Research 2024年第12期19卷 2563-2564页

作者： Gordon C.Werthmann Joachim Herz Department of Molecular Genetics and center for Translational Neurodegeneration Research University of Texas Southwestern Medical Center at DallasDallasTXUSA Department of Neuroscience Department of Neurology University of Texas Southwestern Medical center at Dallas DallasTXUSA

Apolipoprotein E receptor 2(ApoER2)is a receptor for the protein ApoE,the most common genetic risk factor for late-onset Alzheimer's disease(AD).It is also a key modulator of syna ptic homeostasis,in part through its effect on the expression of neuronal genes including those implicated in AD and other neuropsychiatric disorders.In this perspective,we highlight several genes affected by ApoER2 and its alternatively spliced forms and how aberrant expression can be rescued by the reintroduction of the ApoER2 intracellular domain in the mouse hippocampus.

关键词： homeostasis ApoE Alzheimer

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Imprints of ultralight axions on the gravitational wave and pulsar timing measurement

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Science China(Physics,Mechanics & Astronomy) 2024年第1期67卷 23-29页

作者： Ning Xie Fa Peng Huang MOE Key Laboratory of TianQin Mission TianQin Research Center for Gravitational Physics&School of Physics and AstronomyFrontiers Science Center for TianQinGravitational Wave Research Center of CNSASun Yat-sen University(Zhuhai Campus)Zhuhai 519082China

The axion or axion-like particle motivated from a natural solution of strong CP problem or string theory is a promising dark matter candidate.We study the new observational effects of ultralight axion-like particles by the space-borne gravitational wave detector and the radio telescope.Taking the neutron star-black hole binary as an example,we demonstrate that the gravitational waveform could be obviously modified by the slow depletion of the axion cloud around the black hole formed through the superradiance process.We compare these new effects on the binary with the well-studied effects from dynamical friction with dark matter and dipole radiation in model-independent ways.Finally,we discuss the constraints from LIGO/Virgo and study the detectability of the ultralight axion particles at LISA and TianQin.

关键词： gravitational wave axion dark matter

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