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Clinical and molecular significance of homologous recombination deficiency positive non-small cell lung cancer in Chinese population:An integrated genomic and transcriptional analysis

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Chinese Journal of cancer Research 2024年第3期36卷 282-297页

作者： Yifei Wang Yidan ma Lei He Jun Du Xiaoguang Li Peng Jiao Xiaonan Wu Xiaomao Xu Wei Zhou Li Yang Jing Di Changbin Zhu Liming Xu Tianlin Sun Lin Li Dongge Liu Zheng Wang Department of Pathology Department of Minimally Invasive Tumor Therapies Center Department of Thoracic Surgery Department of oncology Department of Respiratory and Critical care Medicine Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Amoy Diagnostics Co. Ltd.Xiamen 361027China

objective:The clinical significance of homologous recombination deficiency(HRD)in breast cancer,ovarian cancer,and prostate cancer has been established,but the value of HRD in non-small cell lung cancer(NSCLC)has not been fully *** study aimed to systematically analyze the HRD status of untreated NSCLC and its relationship with patient prognosis to further guide clinical ***:A total of 355 treatment-naïve NSCLC patients were retrospectively *** status was assessed using the AmoyDx Genomic Scar Score(GSS),with a score of≥50 considered ***,transcriptomic,tumor microenvironmental characteristics and prognosis between HRD-positive and HRDnegative patients were ***:of the patients,25.1%(89/355)were *** to HRD-negative patients,HRDpositive patients had more somatic pathogenic homologous recombination repair(HRR)mutations,higher tumor mutation burden(TMB)(Pons(Pore,HRD-positive NSCLC had more amplifications in PI3K pathway and cell cycle genes,MET and MYC in epidermal growth factor receptor(EGFR)/anaplastic lymphoma kinase(ALK)mutant NSCLC,and more PIK3ca and AURKA in EGFR/ALK wild-type ***-positive NSCLC displayed higher tumor proliferation and immunosuppression ***-negative NSCLC showed activated signatures of major histocompatibility complex(MHC)-II,interferon(IFN)-γand effector memory CD8+T ***-positive patients had a worse prognosis and shorter progressionfree survival(PFS)to targeted therapy(first-and third-generation EGFR-TKIs)(P=0.042).Additionally,HRDpositive,EGFR/ALK wild-type patients showed a numerically lower response to platinum-free immunotherapy ***:Unique genomic and transcriptional characteristics were found in HRD-positive *** prognosis and poor response to EGFR-TKIs and immunotherapy were observed in HRD-positive *** study highlights potential actionable alterations in HRD

关键词： Non-small cell lung cancer homologous recombination deficiency genetic alterations transcriptional analysis tumor microenvironment prognosis

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Corrigendum to“Active components of Dengzhan Shengmai ameliorate cognitive impairment by facilitating hippocampal long-term potentiation via the NMDA receptor-mediated ca^(2+)/caMKII pathway”[***.14(2024)435–438]

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Journal of Pharmaceutical Analysis 2024年第6期14卷 933-933页

作者： Congyu ma Ning Sheng Jun Wu Lulu Wang Jiandong Jiang Haibo Yu Jinlan Zhang State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Institute of Medicinal Biotechnology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China

The authors regret there was an unfortunate error in the reproduction of Fig.1I in the *** the original figure,the fluorescence picture of the positive control drug-ifenprodil was *** authors have corrected Fig.1I and provided the original fluorescence pictures of all groups(seven groups,n=5 for each group)to the editorial ***,the corrected Fig.1I is shown *** authors declare that this correction does not affect the description,interpretation,or the original conclusions of the article.

关键词： correction Active picture

Compound heterozygous mutation of AFG3L2 causes autosomal recessive spinocerebellar ataxia through mitochondrial impairment and MICU1 mediated caoverload

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Science China Life Sciences 2024年

作者： Hongyu Li Qingwen ma Yan Xue Linlin cai Liwen Bao Lei Hong Yitao Zeng Shuzhen Huang Richard H.Finnell Fanyi Zeng Shanghai Institute of Medical Genetics Shanghai Children's Hospital Shanghai Jiao Tong University School of Medicine Department of Histo-Embryology Genetics and Developmental Biology Shanghai Jiao Tong University School of Medicine NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology Shanghai Key Laboratory of Embryo and Reproduction Engineering Center for Precision Environmental Health Baylor College of Medicine School of Pharmacy Macau University of Science and Technology

Autosomal recessive spinocerebellar ataxias（ScaRs） are one of the most common neurodegenerative diseases characterized by progressive ataxia. Although ScaRs are known to be caused by mutations in multiple genes, there are still many cases that go undiagnosed or are misdiagnosed. In this study, we presented a ScaR patient, and identified a probable novel pathogenic mutation（c.1A>G, p.M1V） in the AFG3L2 start codon. The proband's genotype included heterozygous mutations of the compound AFG3L2(p.[M1V]; [R632X]（c.[1A>G];[1894.C>T]）), which were inherited from the father（c.1A>G, p.M1V） and mother（c.1894C>T, p.R632X）. Functional studies performed on hiPSCs（human induced pluripotent stem cells） generated from the patients and HEK293T cells showed that the mutations impair mitochondrial function and the unbalanced expression of AFG3L2 mRNA and protein levels. Furthermore, this novel mutation resulted in the degradation of the protein and the reduction of the stability of the AFG3L2 protein, and MCU（mitochondrial calcium uniporter） complex mediated ca2+overload.

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Competitive effect, but not competitive response, varies along a climatic gradient depending on tree species identity

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Forest Ecosystems 2024年第2期11卷 142-151页

作者： Teresa Valor Lluís Coll David I.Forrester Hans Pretzsch Miren del Río Kamil Bielak Bogdan Brzeziecki Franz Binder Torben Hilmers Zuzana Sitková Roberto Tognetti Aitor Ameztegui Department of Agricultural and Forest Sciences and Engineering(DCEFA) University of LleidaAv.Alcalde Rovira Roure 191E25198 LleidaSpain Joint Research Unit CTFC-AGRoTECNIo-CERca Ctra.Sant LlorençKm.225280SolsonaSpain Swiss Federal Institute of Forest Snow and Landscape Research WSLZürcherstrasse 1118903BirmensdorfSwitzerland CSIRo Land and Water GPO Box 1700CanberraACT2601Australia Chair of Forest Growth and Yield Science School of Life Sciences WeihenstephanTechnical University of MunichHans-Carl-Von-Carlowitz-Platz 285354FreisingGermany Forest Research Center INIA-CSICCtra.A Coruña Km 7.528040MadridSpain IuFoR Sustainable Forest Management Research InstituteUniversity of Valladolid&INIASpain Department of Silviculture Institute of Forest SciencesWarsaw University of Life SciencesNowoursynowska 159/3402776WarsawPoland Bavarian State Institute of Forestry(LWF) Hans-Carl-von-Carlowitz-Platz 1D-85354FreisingGermany National Forest Centre Forest Research InstituteT.G.Masaryka 2296001ZvolenSlovakia Faculty of Agricultural Environmental and Food SciencesFree University of Bozen-Bolzano Piazza Università1 I-39100Bolzano

Background: Understanding the role of species identity in interactions among individuals is crucial for assessing the productivity and stability of mixed forests over time. However, there is limited knowledge concerning the variation in competitive effect and response of different species along climatic gradients. In this study, we investigated the importance of climate, tree size, and competition on the growth of three tree species: spruce(Picea abies), fir(Abies alba), and beech(Fagus sylvatica), and examined their competitive response and effect along a climatic ***: We selected 39 plots distributed across the European mountains with records of the position and growth of 5,759 individuals. For each target species, models relating tree growth to tree size, climate and competition were proposed. Competition was modelled using a neighbourhood competition index that considered the effects of inter-and intraspecific competition on target trees. Competitive responses and effects were related to *** methods and information theory were used to select the best ***: our findings revealed that competition had a greater impact on target species growth than tree size or climate. Climate did influence the competitive effects of neighbouring species, but it did not affect the target species? response to competition. The strength of competitive effects varied along the gradient, contingent on the identity of the interacting species. When the target species exhibited an intermediate competitive effect relative to neighbouring species, both higher inter-than intraspecific competitive effects and competition reduction occurred along the gradient. Notably, species competitive effects were most pronounced when the target species' growth was at its peak and weakest when growing conditions were far from their ***: Climate modulates the effects of competition from neighbouring trees on the target tree and not the susceptibility of th

关键词： Competition coefficient Competition reduction Interspecific competition Intraspecific competition Mixing effects Mixed species forest Neighbourhood models Plant-plant interactions

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Investigation multi-target synergistic mechanism of Choerospondias axillaris in the treat of cerebral ischemia based on systems pharmacology and experimental verification

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Natural Therapy Advances 2024年第3期7卷 37-47页

作者： Yang ma Min-Chun Chen Zuo-Yan Zhang Kang-Kang Yan Yi Ding Department of Pharmacy Xi'an No.3 Hospital the affiliated Hospital of Northwest UniversityXi’an 710000China Department of Pharmacy Xijing HospitalFourth Military Medical UniversityXi’an 71000China

Background:Choerospondias axillaris(ca)is a traditional Mongolian medicine that has been proven to have a good therapeutic effect on cerebrovascular *** Ischemia(CI)is a severe and life-threatening cerebrovascular ***,the specific mechanism of action of ca in the treatment of CI is still ***:In this study,the related targets and pathways of ca in the treatment of CI were first predicted by system pharmacology and then verified by relevant ***:The results showed that 12 active ingredients and 208 targets were *** validation through protein-protein interaction(PPI)network analysis and active ingredients-target-pathway(A-T-P)network analysis has confirmed the pivotal roles of the main bioactive constituents,including quercetin,kaempferol,naringin,β-sitosterol,and gallic *** components exert their anti-ischemic effects by modulating key targets such as IL6,TNF,maPK3,and caSP3,thereby regulating the PI3K-Akt,HIF-1,and maPK signaling pathways,which are integral to processes like inflammation,apoptosis,and oxidative *** importantly,through experimental verification,this study confirmed our prediction that caE significantly reduced neurological function scores,infarct volume,and the percentage of apoptosis ***:This indicates that ca acts on CI through multi-target synergistic mechanism,and this study provides theoretical basis for the clinical application of ca.

关键词： systems pharmacology Choerospondias axillaris cerebral ischemia multi-target synergistic mechanism middle cerebral artery occlusion

Attenuation of the Activation of NLRP3 Inflammasome in Fibroblast Like Synoviocytes of Rheumatoid Arthritis by Baicalin through Regulating the Let-7i-3p/PI3K/Akt/NF-κB Signaling Axis

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Medicinal Plant 2024年第2期15卷 69-73,76页

作者： Wei ZHANG Li WANG Yuxin YANG Rui ma Li WANG Ling HUANG Qiaofeng WAN Department of Pathogenic Biology and Immunology School of Basic MedicineNingxia Medical UniversityYinchuan 750004China Department of Rheumatology Ningxia Medical University General HospitalYinchuan 750003China School of Clinical Medicine Ningxia Medical UniversityYinchuan 750004China

[objectives]To study the effect and mechanism of baicalin on the activation of NLRP3 inflammasome in human fibroblast like synoviocytes of rheumatoid arthritis(HFLS-RA).[Methods]To confirm that baicalin alleviated the activation of NLRP3 inflammasome in HFLS-RA,the expression of NLRP3 before and after baicalin treatment was observed by *** blot was used to detect the protein expression of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1 after baicalin treatment for 48 h,and the contents of IL-1 and IL-18 in the supernatents were detected by *** order to explore the mechanism of baicalin alleviating the activation of NLRP3 inflammasome,the corresponding relationship between let-7i-3p and PIK3ca was verified by double luciferin and Westen blot *** expression of let-7i-3p and PI3K before and after baicalin intervention was detected by ***-7i-3p interference was used to verify whether baicalin mitigated the activation of enhanced NLRP3 inflammasome.[Results]Baicalin(50 and 100 mg/L)significantly reduced the activation of NLRP3 inflammasome,inhibited the protein expressions of p-PI3K,p-Akt,NF-κB p65,NLRP3,ASC and caspase-1,and the secretion of IL-1 and ***-7i-3p and PIK3ca had a targeted correspondence,and baicalin up-regulated the expression of let-7i-3p and down-regulated the expression of *** attenuated the activation of NLRP3 inflammasome enhanced by let-7i-3p interference.[Conclusions]Baicalin can up-regulate let-7i-3p expression,inhibit PI3K/Akt/NF-κB signal transduction,and thus reduce the activation of NLRP3 inflammasome in HFLS-RA.

关键词： Baicalin Rheumatoid arthritis Human fibroblast like synoviocytes of rheumatoid arthritis NLRP3 inflammasome miRNA Dual-luciferase

Serum bile acid and unsaturated fatty acid profiles of non-alcoholic fatty liver disease in type 2 diabetic patients

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World Journal of Diabetes 2024年第5期15卷 898-913页

作者： Su-Su Feng Si-Jing Wang Lin Guo Pan-Pan ma Xiao-Long Ye Ming-Lin Pan Bo Hang Jian-Hua mao Antoine M Snijders Yi-Bing Lu Da-Fa Ding Department of Endocrinology The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210011Jiangsu ProvinceChina Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720United States

BACKGRoUND The understanding of bile acid(BA)and unsaturated fatty acid(UFA)profiles,as well as their dysregulation,remains elusive in individuals with type 2 diabetes mellitus(T2DM)coexisting with non-alcoholic fatty liver disease(NAFLD).Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in *** To identify potential metabolite biomarkers capable of distinguishing between NAFLD and *** A training model was developed involving 399 participants,comprising 113 healthy controls(HCs),134 individuals with T2DM without NAFLD,and 152 individuals with T2DM and *** validation encompassed 172 *** patients were divided based on liver fibrosis *** analytical approach employed univariate testing,orthogonal partial least squares-discriminant analysis,logistic regression,receiver operating characteristic curve analysis,and decision curve analysis to pinpoint and assess the diagnostic value of serum *** Compared to HCs,both T2DM and NAFLD groups exhibited diminished levels of specific *** UFAs,particular acids exhibited a positive correlation with NAFLD risk in T2DM,while theω-6:ω-3 UFA ratio demonstrated a negative *** ofα-linolenic acid andγ-linolenic acid were linked to significant liver fibrosis in *** validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM *** This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM,proposing their potential as biomarkers in the pathogenesis of NAFLD.

关键词： Bile acid Non-alcoholic fatty liver disease Type 2 diabetes mellitus Unsaturated fatty acid

Physical manipulation of ultrathin-film optical interference for super absorption and two-dimensional heterojunction photoconversion

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Chinese Physics B 2018年第12期27卷 64-70页

作者： Guo-Yang ca Cheng Zhang Shao-Long Wu Dong ma Xiao-Feng Li School of optoelectronic Science and Engineering &Collaborative Innovation Center ofSuzhou Nano Science and Technology Soochow University Suzhou 215006China Key Laboratory of Advanced optical manufacturing Technologies of Jiangsu Province Key Laboratory of Modern Optical Technologies of the Education Ministry of ChinaSoochow UniversitySuzhou 215006China School of Rail Transportation Soochow UniversitySuzhou 215131China

Ultrathin optical interference in a system composed of absorbing material and metal reflector has attracted extensive attention due to its potential application in realizing highly efficient optical absorption by using extremely thin semiconductor material. In this paper, we study the physics behind the high absorption of ultrathin film from the viewpoint of destructive interference and admittance matching, particularly addressing the phase evolution by light propagation and interface reflection. The physical manipulations of the ultrathin interference effect by controlling the substrate material and semiconductor material/thickness are examined. We introduce typical two-dimensional materials — i.e., MoS2and WSe2— as the absorbing layer with thickness below 10 nm, which exhibits ～ 90% absorption in a large range of incident angle(0°～70°). According to the ultrathin interference mechanism, we propose the ultrathin(oS2/WSe2heterojunction for photovoltaic application and carefully examine the detailed optoelectronic responses by coupled multiphysics simulation. By comparing the same cells on Sio2substrate, both the short-circuit current density(up to 20 ma/cm~2) and the photoelectric conversion efficiency(up to 9.5%) are found to be increased by ～200%.

关键词： photovoltaic subwavelength structures interference coating

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Beyond ribosomal function:RPS6 deficiency suppresses cholangiocarcinoma cell growth by disrupting alternative splicing

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Acta Pharmaceutica Sinica B 2024年第9期14卷 3931-3948页

作者： Wenkang Fu Yanyan Lin Mingzhen Bai Jia Yao Chongfei Huang Long Gao Ningning Mi Haidong ma Liang Tian Ping Yue Yong Zhang Jinduo zhang Yanxian Ren Liyun Ding Lunzhi Dai Joseph WLeung Jinqiu Yuan Wenhua Zhang Wenbo Meng The First School of Clinical Medicne Lanzhou UniversityLanzhou 730030China Department of General Surgery the First Hospital of Lanzhou UniversityLanzhou 730030China Key Laboratory of Biotherapy and Regenerative Medicine of Gansu Province the First Hospital of Lanzhou UniversityLanzhou 730000China School of Physical Science and Technology Lanzhou UniversityLanzhou 730000China National Clinical Research Center for Geriatrics and Department of General Practice State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Division of Gastroenterology UC Davis Medical Center and Sacramento VA Medical CenterSacramentoCA 95817USA Clinical Research Center Big Data Centerthe Seventh Affiliated HospitalSun Yat-sen UniversityShenzhen 518107China School of Life Sciences Lanzhou UniversityLanzhou 730000China

Cholangiocarcinoma(Cca)is a bile duct malignancy with a dismal *** study systematically investigated the role of the ribosomal protein S6(RPS6)gene,which is dependent in *** found that RPS6 upregulation in Cca tissues was correlated with a poor *** investigations have shown that alterations in RPS6 expression,both gain-and loss-of function could affect the proliferation of Cca *** xenograft tumor models,RPS6 overexpression enhances tumorigenicity,whereas RPS6 silencing reduces *** analysis using RNA-seq and proteomics elucidated downstream signaling pathways of RPS6 depletion by affecting the cell cycle,especially DNA *** followed by mass spectrometry has identified numerous spliceosome complex proteins associated with *** profiling revealed that RPS6 affects numerous alternative splicing(AS)events,and combined with RNA immunoprecipitation sequencing,revealed that minichromosome maintenance complex component 7(MCM7)binds to RPS6,which regulates its AS and increases oncogenic activity in *** RPS6 with vivo phosphorodiamidate morpholino oligomer(V-PMo)significantly inhibited the growth of Cca cells,patient-derived organoids,and subcutaneous xenograft *** together,the data demonstrate that RPS6 is an oncogenic regulator in Cca and that RPS6-V-PMo could be repositioned as a promising strategy for treating Cca.

关键词： Cholangiocarcinoma Ribosomal protein S6 Alternative splicing p53 Minichromosome maintenance complex component 7 Vivo morpholino Patient-derived organoids