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Elevated peripheral levels of receptor-interacting protein kinase 1(RIPK1)and IL-8 as biomarkers of human amyotrophic lateral sclerosis

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Signal Transduction and Targeted Therapy 2024年第1期9卷 271-278页

作者： Jun Wei Min Li Zhi Ye Xinqian Hu Xiaoyan He Jia Wang Gaofeng Chen Chengyu Zou Daichao Xu Hongbing Zhang Junying Yuan Yunhong Zha Institute of Neural Regeneration and Repair and Department of Neurology The First College of Clinical Medical ScienceYichang Central HospitalCollege of Basic Medical ScienceChina Three Gorges UniversityHubei Province Clinical Medical Research Center for Rare Diseases of Nervous SystemYichang 443000China interdisciplinary research Center on Biology and Chemistry Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai Key Laboratory of Aging StudiesShanghai 201210China State Key Laboratory of Common Mechanism research for Major Diseases Haihe Laboratory of Cell EcosystemDepartment of PhysiologyInstitute of Basic Medical Sciences and School of Basic MedicineChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

Amyotrophic lateral sclerosis(ALS)is a devastating fatal neurodegenerative disease with no cure.Receptor-interacting protein kinase 1(RIPK1)has been proposed to mediate pathogenesis of ALS.Primidone has been identified as an old drug that can also inhibit RIPK1 kinase.We conducted a drug-repurposing biomarker study of primidone as a RIPK1 inhibitor using SOD1G93A mice and ALS patients.SOD1G93A mice treated with primidone showed significant delay of symptomatic onset and improved motor performance.One-hundred-sixty-two ALS participants dosed daily with primidone(62.5 mg)completed 24-week follow-up.A significant reduction was showed in serum levels of RIPK1 and IL-8,which were significantly higher in ALS patients than that of healthy controls(P<0.0001).Serum RIPK1 levels were correlated positively with the severity of bulbar symptoms(P<0.05).Our study suggests that serum levels of RIPK1 and IL-8 in peripheral can be used as clinical biomarkers for the activation of RIPK1 in central nervous system in human ALS patients.Repurposing primidone may provide a promising therapeutic strategy for ALS.The effect of primidone for the treatment of other inflammatory diseases may also be considered,since the activation of RIPK1 has been implicated in mediating a variety of inflammatory diseases including COVID-19-associated cytokine release syndrome(CRS).(ChiCTR2200060149).

关键词： RIPK1 diseases Serum

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Study of Complex Nitrogen and Oxygen-bearing Molecules toward the High-mass Protostar IRAS 18089–1732

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research in Astronomy and Astrophysics 2024年第6期24卷 83-95页

作者： Arijit Manna Sabyasachi Pal Tapas Baug Sougata Mondal Department of Physics Midnapore City CollegePaschim Medinipur S.N.Bose National centre for basic sciences

The observation of oxygen （O）-and nitrogen （N）-bearing molecules gives an idea about the complex prebiotic chemistry in the interstellar medium.Recent millimeter and submillimeter wavelength observations have shown the presence of complex O-and N-bearing molecules in the star formation regions.So,the investigation of those molecules is crucial to understanding the chemical complexity in the star-forming regions.In this article,we present the identification of the rotational emission lines of N-bearing molecules ethyl cyanide （C2H5CN） and cyanoacetylene （HC3N）,and O-bearing molecule methyl formate （CH3OCHO） toward high-mass protostar IRAS18089–1732 using the Atacama Compact Array.We also detected the emission lines of both the N-and O-bearing molecule formamide （NH2CHO） in the envelope of IRAS 18089–1732.We have detected the v=0 and 1 state rotational emission lines of CH3OCHO.We also detected the two vibrationally excited states of HC3N （v7=1 and v7=2）.The estimated fractional abundances of C2H5CN,HC3N （v7=1）,HC3N （v7=2）,and NH2CHO toward IRAS 18089–1732 are （1.40±0.5）×10-10,（7.5±0.7）×10-11,（3.1±0.4）×10-11,and （6.25±0.82）×10-11respectively.Similarly,the estimated fractional abundances of CH3OCHO （v=0） and CH3OCHO （v=1） are（1.90±0.9）×10-9and （8.90±0.8）×10-10,respectively.We also created the integrated emission maps of the detected molecules,and the observed molecules may have originated from the extended envelope of the protostar.We show that C2H5CNand HC3N are most probably formed via the subsequential hydrogenation of the CH2CHCNand the reaction between C2H2and CN on the grain surface of IRAS 18089–1732.We found that NH2CHO is probably produced due to the reaction between NH2and H2CO in the gas phase.Similarly,CH3OCHO is possibly created via the reaction between radical CH3O and radical HCO on the grain surface of IRAS 18089–1732.

关键词： astrochemistry ISM: abundances ISM: individual objects (IRA 18089-1732) (except) ISM: kinematics and dynamics stars: formation

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Characteristics and quality of clinical practice guidelines for diabetic kidney disease: a systematic review

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Journal of Traditional Chinese Medicine 2024年第3期44卷 609-619页

作者： WANG Yuhuang ZHANG Le ZHANG Zhengshan YAO Zhi LI Xiyao SUN Luying LIAO Xing Department of Nephropathy and Endocrine Dongzhimen HospitalBeijing University of Chinese Medicine centre for Evidence-Based Chinese Medicine Institute of Basic Research in Clinical MedicineChina Academy of Chinese Medical Sciences Department of Endocrine One Zone Fangshan HospitalBeijing University of Chinese Medicine

OBJECTIVE: To assess the quality of Clinical practice guidelines(CPGs) in the context of diabetic kidney disease(DKD) and determine whether any factors affect the quality. METHODS: We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of ***. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for research and Evaluation Ⅱ(AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1(lowest possible quality) to 7(highest possible quality). Moreover, an overall recommendation for use was also assigned(“recommended”, “recommended with modifications” or “not recommended”). RESULTS: A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development(33%), followed by application(36%), and stakeholder involvement(51%). The highest average score was for scope and purpose(79%), followed by clarity of presentation(75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. CONCLUSIONS: According to the AGREE II evaluation, more than one in four CPGs for DKD had poor methodolo

关键词： appraisal of guidelines for research and evaluation II diabetic nephropathies practice guideline quality assessment systematic review

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Blockade of CD300A enhances the ability of human NK cells to lyse hematologic malignancies

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Cancer Biology & Medicine 2024年第4期21卷 331-346页

作者： Shuangcheng Li Tianci Wang Xinghui Xiao Xiaodong Zheng Haoyu Sun Rui Sun Hongdi Ma Zhigang Tian Xiaohu Zheng Hefei National research Center for Physical sciences at Microscale The CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesCenter for Advanced Interdisciplinary Science and Biomedicine of IHMDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Immunology University of Science and Technology of ChinaHefei 230027China Hefei TG ImmunoPharma Corporation Limited Hefei 230601China research Unit of NK Cell Study Chinese Academy of Medical SciencesBeijing 100864China Key Laboratory of Quantitative Synthetic Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China

Objective: The human cluster of differentiation(CD)300A, a type-I transmembrane protein with immunoreceptor tyrosine-based inhibitory motifs, was investigated as a potential immune checkpoint for human natural killer(NK) cells targeting hematologic malignancies(HMs).Methods: We implemented a stimulation system involving the CD300A ligand, phosphatidylserine(PS), exposed to the outer surface of malignant cells. Additionally, we utilized CD300A overexpression, a CD300A blocking system, and a xenotransplantation model to evaluate the impact of CD300A on NK cell efficacy against HMs in in vitro and in vivo settings. Furthermore, we explored the association between CD300A and HM progression in patients.Results: Our findings indicated that PS hampers the function of NK cells. Increased CD300A expression inhibited HM lysis by NK cells. CD300A overexpression shortened the survival of HM-xenografted mice by impairing transplanted NK cells. Blocking PS–CD300A signals with antibodies significantly amplified the expression of lysis function-related proteins and effector cytokines in NK cells, thereby augmenting the ability to lyse HMs. Clinically, heightened CD300A expression correlated with shorter survival and an “exhausted” phenotype of intratumoral NK cells in patients with HMs or solid tumors.Conclusions: These results propose CD300A as a potential target for invigorating NK cell-based treatments against HMs.

关键词： NK cell CD300A phosphatidylserine immune checkpoint hematologic malignancy

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An effective pharmacological hydrogel induces optic nerve repair and improves visual function

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Science China(Life sciences) 2024年第3期67卷 529-542页

作者： Lipeng Wang Shan Zhang Yawen Han Shuo Tang Jiarui Li Lina Bu Dongyu Zhao Hongkui Deng Department of Cell Biology Schoolof Basic Medical SciencesPeking University Stem Cell Research CenterStateKey Laboratoryof Naturaland Biomimetic DrugsPeking University Health Science Center Beijing 100191China MOE Key Laboratory of Cell Proliferation and Differentiation College of Life SciencesPeking-Tsinghua Center for Life SciencesPeking UniversityBeijing 100871China Academy for Advanced interdisciplinary Studies Peking UniversityBeijing 100871China Changping Laboratory Beijing 102206China Department of Ophthalmology Peking University People's Hospital Eye Diseases and Optometry InstituteBeijing 100871China Department of Biomedical Informatics School of Basic Medical SciencesPeking UniversityBeijing 100191China

Irreversible eye lesions, such as glaucoma and traumatic optic neuropathy, can cause blindness;however, no effective treatments exist. The optic nerve, in particular, lacks the capacity to spontaneously regenerate, requiring the development of an effective approach for optic nerve repair, which has proven challenging. Here, we demonstrate that a combination of the small molecules 3BDO and trichostatin A(TSA)—which regulate mTOR and HDAC, respectively—packaged in thermosensitive hydrogel for 4-week-sustained release after intravitreal injection, effectively induced optic nerve regeneration in a mouse model of optic nerve crush injury. Moreover, this combination of 3BDO and TSA also protected axon projections and improved visual responses in an old mouse model(11 months old) of glaucoma. Taken together, our data provide a new, local small molecule-based treatment for the effective induction of optic nerve repair, which may represent a foundation for the development of pharmacological methods to treat irreversible eye diseases.

关键词： retinal ganglion cell axon regeneration old-age glaucoma small molecules pharmacological hydrogel visual function repair

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Decreased LDHB expression in breast tumor cells causes NK cell activation and promotes tumor progression

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Cancer Biology & Medicine 2024年第6期21卷 513-540页

作者： Zhihong Luo Xiaohua Huang Xinyi Xu Kefeng Wei Yi Zheng Ke Gong Wenhua Li Hubei Key Laboratory of Cell Homeostasis College of Life Sciences Wuhan University Wuhan University Shenzhen research Institute Central Laboratory University of Chinese Academy of Sciences-Shenzhen Hospital Hubei Province Key Laboratory of Allergy and Immunology and Department of Immunology School of Basic Medical Sciences Wuhan University

Objective: Abnormal metabolism is the underlying reason for breast cancer progression. Decreased lactate dehydrogenase B(LDHB) has been detected in breast cancer but the function of LDHB remains unknown.Methods: Western blot was used to analyze LDHB expression in breast cancer cells. The impact of LDHB on tumor cell migration and invasion was determined using Transwell assays, wound healing assays, and a mouse lung metastasis model. Subcutaneous tumor formation, a natural killer(NK) cell cytotoxicity assay, and flow cytometry evaluated NK cell activation. Immunofluorescence and quantitative real-time PCR detected NK cell activation markers. Kaplan-Meier analysis evaluated the effect of immune cell infiltration on prognosis. Single-sample gene set enrichment analysis determined NK cell activation scores. A support vector machine predicted the role of LDHB in NK cell activation.Results: In this study we showed that LDHB inhibits the breast cancer cell metastasis and orchestrates metabolic reprogramming within tumor cells. Our results revealed that LDHB-mediated lactic acid clearance in breast cancer cells triggers NK cell activation within the tumor microenvironment. Our findings, which were confirmed in a murine model, demonstrated that LDHB in tumor cells promotes NK cell activation and ultimately results in the eradication of malignant cells. Clinically, our study further validated that LDHB affects immune cell infiltration and function. Specifically, its expression has been linked to enhanced NK cell-mediated cytotoxicity and improved patient survival. Furthermore, we identified LDHB expression in tumors as an important predictor of NK cell activation, with strong predictive ability in some cancers.Conclusions: Our results suggest that LDHB is a promising target for activating the tumor immune microenvironment in breast cancer, where LDHB-associated lactic acid clearance leads to increased NK cell activity. This study highlights the critical role of LDHB in regulating immune responses and its potential as a the

关键词： Breast cancer NK cells lactate dehydrogenase B lactic acid tumor immunity

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Temporal-spatial Generation of Astrocytes in the Developing Diencephalon

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Neuroscience Bulletin 2024年第1期40卷 1-16页

作者： Wentong Hong Pifang Gong Xinjie Pan Zhonggan Ren Yitong Liu Guibo Qi Jun-Liszt Li Wenzhi Sun Woo-Ping Ge Chun-Li Zhang Shumin Duan Song Qin Department of Anatomy Histology and EmbryologySchool of Basic Medical SciencesFudan UniversityShanghai 200032China Academy for Advanced interdisciplinary Studies Peking UniversityBeijing 100871China Chinese Institute for Brain research Beijing 102206China School of basic Medical sciences Capital Medical UniversityBeijing 100069China Department of Molecular Biology University of Texas Southwestern Medical CenterDallasTexas 75390-9148USA Department of Neurobiology Key Laboratory of Medical Neurobiology of Ministry of Health of ChinaZhejiang University School of MedicineHangzhou 310058China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghai 200032China

tAstrocytes are the largest glial population in the mammalian brain.However,we have a minimal understanding of astrocyte development,especially fate specification in different regions of the brain.Through lineage tracing of the progenitors of the third ventricle(3V)wall via in-utero electroporation in the embryonic mouse brain,we show the fate specification and migration pattern of astrocytes derived from radial glia along the 3V wall.Unexpectedly,radial glia located in different regions along the 3V wall of the diencephalon produce distinct cell types:radial glia in the upper region produce astrocytes and those in the lower region produce neurons in the diencephalon.With genetic fate mapping analysis,we reveal that the first population of astrocytes appears along the zona incerta in the diencephalon.Astrogenesis occurs at an early time point in the dorsal region relative to that in the ventral region of the developing diencephalon.With transcriptomic analysis of the region-specific 3V wall and lateral ventricle(LV)wall,we identified cohorts of differentially-expressed genes in the dorsal 3V wall compared to the ventral 3V wall and LV wall that may regulate astrogenesis in the dorsal diencephalon.Together,these results demonstrate that the generation of astrocytes shows a spatiotemporal pattern in the developing mouse diencephalon.

关键词： Radial glia Astrocyte specification Lineage tracing Diencephalon Third ventricle

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Potential and progress of studying mountain biodiversity by means of butterfly genetics and genomics

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Journal of Genetics and Genomics 2024年第3期51卷 292-301页

作者： Shuting Wang Marco Girardello Wei Zhang State Key Laboratory of Protein and Plant Gene research School of Life SciencesPeking UniversityBeijing 100871China Peking-Tsinghua Center for Life sciences Academy for Advanced Interdisciplinary StudiesPeking UniversityBeijing 100871China cE3c-centre for Ecology Evolution and Environmental Changes/Azorean Biodiversity GroupFaculdade de Ciencias Agrarias e do AmbienteUniversidade dos Açores9700-042 Angra do HeroísmoTerceiraPortugal

Mountains are rich in biodiversity,and butterflies are species-rich and have a good ecological and evolutionary research foundation.This review addresses the potential and progress of studying mountain biodiversity using butterflies as a model.We discuss the uniqueness of mountain ecosystems,factors influencing the distribution of mountain butterflies,representative genetic and evolutionary models in butterfly research,and evolutionary studies of mountain biodiversity involving butterfly genetics and genomics.Finally,we demonstrate the necessity of studying mountain butterflies and propose future perspectives.This review provides insights for studying the biodiversity of mountain butterflies as well as a summary of research methods for reference.

关键词： Mountain ecosystem Butterfly Biodiversity Adaptation Genomics Genetics

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Refinement ofα′Martensite by Oxygen in Selective Laser Melted Ti-6Al-4V

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Acta Metallurgica Sinica(English Letters) 2024年第5期37卷 777-792页

作者： Hasfi FNurly Jinhu Zhang Dechun Ren Yusheng Cai Haibin Ji Dongsheng Xu Zhicheng Dong Hao Wang Qingmiao Hu Jiafeng Lei Rui Yang School of Materials Science and Engineering University of Science and Technology of ChinaShenyang 110016China Shi-Changxu Innovation Center for Advanced Materials Institute of Metal ResearchChinese Academy of SciencesShenyang 110016China School of Materials and Chemistry/interdisciplinary centre for Additive Manufacturing University of Shanghai for Science and TechnologyShanghai 200093China centre for Adaptive System Engineering ShanghaiTech UniversityShanghai 201210China

Oxygen is crucial in influencing the microstructure evolution of selective laser melted(SLMed)Ti–6Al–4V,significantly impacting its applicability in various sectors.Therefore,this study investigates the influnce of oxygen on microstructure evolution,particularlyα′martensite transformation and refinement mechanisms.Four alloys,Ti–6Al–4V–xO(x=0.11,0.16,0.21,and 0.25 wt%),were fabricated by the SLM process.The martensite start temperature(M_(s))of Ti–6Al–4V,as evaluated by computation,is 656.8°C,and oxygen was found to increase the M_(s) by about 10°C per 0.1 wt%.The SLMed alloy samples exhibit[001]_(β)growth texture along the build direction.Crystallographic analysis of martensite morphology suggests internal twinning on{1011}planes as the lattice invariant strain,which becomes more predominant with increasing oxygen content.Refinement of α′martensite plates by oxygen is due to increased lattice distortion,reduced prior β grain size,and oxygen segregation toβgrain boundaries.Our findings contribute to improving the understanding of the effect of oxygen on the transformation mechanism ofα′martensite during SLM of Ti–6Al–4V.

关键词： Selective laser melting α′Martensite Martensite start temperature Oxygen Ti-6Al-4V

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Glacier area change (1993-2019) and its relationship to debris cover, proglacial lakes, and morphological parameters in the Chandra-Bhaga Basin, Western Himalaya, India

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Journal of Mountain Science 2024年第4期21卷 1287-1306页

作者： VATSAL Sarvagya AZAM Mohd Farooq BHARDWAJ Anshuman MANDAL Arindan BAHUGUNA Ishmohan RAMANATHAN Alagappan RAJU N.Janardhana TOMAR Sangita Singh Department of Civil Engineering Indian Institute of Technology IndoreSimrol 453552India School of Geosciences University of AberdeenKing’s CollegeAberdeen AB243FXUnited Kingdom interdisciplinary centre for Water research Indian Institute of ScienceBengaluru 560012India Space Application centre Ahmedabad 380015India School of Environmental sciences Jawaharlal Nehru UniversityNew Delhi 110067India Department of Geography Norwegian University of Science and TechnologyTrondheim No-7491Norway

Glacier inventories serve as critical baseline data for understanding the impacts of climate change on glaciers.The present study maps the outlines of glaciers in the Chandra-Bhaga Basin(western Himalaya)for the years 1993,2000,2010,and 2019 using Landsat Thematic Mapper(TM),Enhanced Thematic Mapper(ETM),and Operational Land Imager(OLI)datasets.A total of 251 glaciers,each having an area above 0.5 km^(2),were identified,which include 216 clean-ice and 35 debris-covered glaciers.Area changes are estimated for three periods:1993-2000,2000-2010,and 2010-2019.The total glacierized area was 996±62 km^(2) in 1993,which decreased to 973±70 km^(2) in 2019.The mean rate of glacier area loss was higher in the recent decade(2010-2019),at 0.036 km^(2),compared to previous decades(0.029 km^(2) in 2000-2010 and 0.025 km^(2) in 1993-2000).Supraglacial debris cover changes are also mapped over the period of 1993 and 2019.It is found that the supraglacial debris cover increased by 14.12±2.54 km^(2)(15.2%)during 1993-2019.Extensive field surveys on Chhota Shigri,Panchi II,Patsio,Hamtah,Mulkila,and Yoche Lungpa glaciers were carried out to validate the glacier outlines and supraglacial debris cover estimated using satellite datasets.Controls of various morphological parameters on retreat were also analyzed.It is observed that small,clean ice,south oriented glaciers,and glaciers with proglacial lakes are losing area at faster rates than other glaciers in the basin.

关键词： Glacier Area change Debris cover Morphology Proglacial lake

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