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Neoadjuvant nivolumab with or without platinum-doublet chemotherapy based on PD-L1 expression in resectable NSCLC(CTONG1804):a multicenter open-label phase II study

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Signal Transduction and Targeted Therapy 2024年第1期9卷 249-258页

作者： Si-Yang Liu Song Dong Xue-Ning Yang Ri-Qiang Liao Ben-Yuan Jiang Qun Wang Xiao-Song Ben Gui-Bin Qiao Jun-Tao Lin Hong-Hong Yan Li-Xu Yan Qiang Nie Hai-Yan Tu Bin-Chao Wang Jin-Ji Yang Qing Zhou Hong-Rui Li Ke Liu Wendy Wu Si-Yang Maggie Liu Wen-Zhao Zhong Yi-Long Wu guangdong Lung Cancer Institute Guangdong Provincial Key Laboratory of Translational Medicine in Lung CancerGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Thoracic Surgery Zhongshan HospitalFudan UniversityShanghaiChina Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouChina Fujian key laboratory of Advanced Technology for Cancer Screening and Early Diagnosis FuzhouChina Berry Oncology Corporation FuzhouChina Chinese Thoracic Oncology Group(CTONG) GuangzhouChina Department of Hematology The First Affiliated HospitalJinan UniversityGuangzhouChina

This prospective multicenter phase II study evaluated the clinical efficacy of neoadjuvant nivolumab-exclusive(N)and nivolumab–chemotherapy(N/C)combinations based on PD-L1 *** patients exhibited resectable clinical stage IIA–IIIB(AJCC 8th edition)NSCLC without EGFR/ALK *** received either mono-nivolumab(N)or nivolumab+nabpaclitaxel+carboplatin(N/C)for three cycles based on PD-L1 *** primary endpoint was the major pathological response(MPR).key secondary endpoints included the pathologic complete response(pCR),objective response rate(ORR),and event-free survival(EFS).Baseline PD-L1 expression and perioperative circulating tumor DNA(ctDNA)status were correlated with pCR and ***-two patients were enrolled,with 46 undergoing *** MPR was 50.0%(26/52),with 25.0%(13/52)achieving pCR,and 16.7%and 66.7%for patients with PD-L1≥50%in N and N/C groups,***(25.0%)patients experienced grade 3 or higher immune-related adverse events during neoadjuvant *** with post-neoadjuvant ctDNA negativity was more likely to have pCR(39.1%)compared with those remained positive(6.7%,odds ratio=6.14,95%CI 0.84-Inf,p=0.077).With a median follow-up of 25.1 months,the 18-month EFS rate was 64.8%(95%CI 51.9–81.0%).For patients with ctDNA–***+,the 18m-EFS rate was 93.8%vs 47.3%(HR,0.15;95%CI 0.04,0.94;p=0.005).Immunochemotherapy may serve as an optimal neoadjuvant treatment even for patients with PD-L1 expression≥50%.ctDNA negativity following neoadjuvant treatment and surgery could help identify superior pathological and survival benefits,which requires further confirmation in a prospective clinical trial(NCT04015778).

关键词： chemotherapy NSCLC treatment

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Artificial intelligence-based analysis of tumor-infiltrating lymphocyte spatial distribution for colorectal cancer prognosis

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Chinese Medical Journal 2024年第4期137卷 421-430页

作者： Ming Cai Ke Zhao Lin Wu Yanqi Huang Minning Zhao Qingru Hu Qicong Chen Su Yao Zhenhui Li Xinjuan Fan Zaiyi Liu Department of Radiology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China guangdong provincial key laboratory of Artificial Intelligence in Medical Image Analysis and Application GuangzhouGuangdong 510080China guangdong Cardiovascular Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Third Affiliated Hospital of Kunming Medical UniversityYunnan Cancer HospitalYunnan Cancer CenterKunmingYunnan 650118China The Second School of clinical Medicine Southern Medical UniversityGuangzhouGuangdong 510515China Institute of Computing Science and Technology Guangzhou UniversityGuangzhouGuangdong 510006China Department of Pathology Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China Department of Pathology The Sixth Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510655China

Background:Artificial intelligence(AI)technology represented by deep learning has made remarkable achievements in digital pathology,enhancing the accuracy and reliability of diagnosis and prognosis *** spatial distribution of CD3^(+)and CD8^(+)T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer(CRC).This study aimed to investigate CD3_(CT)(CD3^(+)T cells density in the core of the tumor[CT])prognostic ability in patients with CRC by using AI ***:The study involved the enrollment of 492 patients from two distinct medical centers,with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation *** facilitate tissue segmentation and T-cells quantification in whole-slide images(WSIs),a fully automated workflow based on deep learning was *** the completion of tissue segmentation and subsequent cell segmentation,a comprehensive analysis was ***:The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3_(CT) and CD3-CD8(the combination of CD3^(+)and CD8^(+)T cells density within the CT and invasive margin)in predicting mortality(C-index in training cohort:0.65 vs.0.64;validation cohort:0.69 vs.0.69).The CD3_(CT) was confirmed as an independent prognostic factor,with high CD3_(CT) density associated with increased overall survival(OS)in the training cohort(hazard ratio[HR]=0.22,95%confidence interval[CI]:0.12–0.38,Pclinical settings.

关键词： Colorectal cancer Artificial intelligence Deep learning Digital pathology Prognosis Immune cells CD3 CD8 TME

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Biomimetic Phosphohydrolase Nanozyme Based on Defect-Engineered Metal-Organic Framework

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CCS Chemistry 2024年第7期6卷 1821-1835页

作者： Xiaoxue Kou Yuhong Lin Yong Shen Linjing Tong Rui Gao Suya Liu Siming Huang Fang Zhu Guosheng Chen Gangfeng Ouyang MOE key laboratory of Bioinorganic and Synthetic Chemistry School of ChemistrySun Yat-sen UniversityGuangzhou 510006 Shanghai NanoPort Thermo Fisher ScientificPudong DistrictShanghai 200120 Guangzhou Municipal and guangdong provincial key laboratory of Molecular Target and clinical pharmacology The NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and The Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436

Phosphodiester bonds are the backbone linkages of all the nucleic acids which store and transfer biological *** hydrolysis of phosphodiester bonds is of great importance to the replication,recombination,and damage repair of DNA as well as the maturation and processing of ***,the spontaneous scission of individual phosphodiester linkages is kinetically challenging under physiological conditions,with an estimated half-life of 30 million ***,we discover a defect-engineered Zr-metal-organic framework(Zr-MOF)nanozyme containing cluster-missing reo defects,named UiO-66 REO,that possesses intrinsic phosphodiesterase-like activity that allows for the cleavage of the phosphodiester bond in physiological condition(pH=7.4 and 37℃),outperforming the activityrecording *** atomic-level structure of the UiO-66 REO nanozyme has been directly identified by the synchrotron radiation absorption spectrum and integrated differential phase contrast-scanning transmission electron *** find that both the defective boundary regions and unusual Zr6-clusters formed in the reo phase of the UiO-66 REO nanozyme contribute to the improvement in efficiency of phosphodiesterase-like hydrolysis,which realizes the cleavage of DNA in mild *** work offers a new insight into biomimetic enzymology using crystal and defect engineering and opens up new possibilities for the development of low-cost,structurally stable and sustainable phosphodiesterase nanozymes for different biological applications.

关键词： nanozyme metal-organic framework biomimetic catalysis hydrolase-like activity defective engineering

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The role of cAMP-dependent protein kinase A in the formation of long-term memory in Bactrocera dorsalis

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Journal of Integrative Agriculture 2024年第2期23卷 605-620页

作者： Jinxin Yu Yanmin Hui Jiayi He Yinghao Yu Zhengbing Wang Siquan Ling Wei Wang Xinnian Zeng Jiali Liu National key laboratory of Green Pesticides/guangdong Engineering Research Center for Insect Behavior Regulation/College of Plant Protection South China Agricultural UniversityGuangzhou 510642China College of Life Science and Agronomy Zhoukou Normal UniversityZhoukou 466001China guangdong provincial key laboratory of Silviculture Protection and UtilizationGuangdong Academy of ForestryGuangzhou 510520China

The cAMP-dependent protein kinase A(PKA)signaling pathway has long been considered critical for long-term memory(LTM)*** studies have mostly focused on the role of PKA signaling in LTM induction by multiple spaced conditioning with less attention to LTM induction by a single ***,we conducted behavioral-pharmacology,enzyme immunoassay and RNA interference experiments to study the role of the PKA signaling pathway in LTM formation in the agricultural pest Bactrocera dorsalis,which has a strong memory capacity allowing it to form a two-day memory even from a single conditioning *** found that either blocking or activating PKA prior to conditioning pretreatment affected multiple spaced LTM,and conversely,they did not affect LTM formed by single *** was further confirmed by enzyme-linked immunosorbent assay(ELISA)and silencing of the protein kinase regulatory subunit 2 and catalytic subunit *** together,these results suggest that activating PKA during memory acquisition helps to induce the LTM formed by multiple spaced conditioning but not by a single *** findings challenge the conserved role of PKA signaling in LTM,which provides a basis for the greater diversity of molecular mechanisms underlying LTM formation across species,as well as possible functional and evolutionary implications.

关键词： Bactrocera dorsalis LTM multiple spaced PKA single

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Cdc42 deletion yielded enamel defects by disrupting mitochondria and producing reactive oxygen species in dental epithelium

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Genes & Diseases 2024年第5期11卷 335-349页

作者： Jinxuan Zheng Rongcheng Yu Yiqi Tang Sihui Su Sainan Wang Chenxi Liao Xuecong Li Jiabin Liao Dongsheng Yu Tingting Ai Wei Zhao Vicky Yau Chufeng Liu Liping Wu Yang Cao Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-sen UniversityGuangzhouGuangdong 510055China guangdong provincial key laboratory of Oral Diseases GuangzhouGuangdong 510055China Department of Cariology and Endodontology Peking University School and Hospital of Stomatology&National Center for Stomatology&National Clinical Research Center for Oral Diseases&National Engineering Research Center of Oral Biomaterials and Digital Medical DevicesBeijing 100081China Department of Oral and Maxillofacial Surgery University at BuffaloBuffaloNY 14214USA Department of Orthodontics Stomatological HospitalSouthern Medical UniversityGuangzhouGuangdong 510280China

Developmental defects of enamel are common due to genetic and environmental factors before and after ***42,a Rho family small GTPase,regulates prenatal tooth development in ***,its role in postnatal tooth development,especially enamel formation,remains ***,we investigated Cdc42 functions in mouse enamel development and tooth repair after ***42 showed highly dynamic temporospatial patterns in the developing incisors,with robust expression in ameloblast and odontoblast ***,epithelium-specific Cdc42 deletion resulted in enamel defects in *** differentiation was inhibited,and hypomineralization of enamel was observed upon epithelial Cdc42 *** analysis showed that abnormal mitochondrial components,phosphotransferase activity,and ion channel regulator activity occurred in the Cdc42 mutant dental *** oxygen species accumulation was detected in the mutant mice,suggesting that abnormal oxidative stress occurred after Cdc42 ***,Cdc42 mutant mice showed delayed tooth repair and generated less calcified *** dysfunction and abnormal oxygen consumption were evidenced by reduced Apool and Timm8a1 expression,increased Atp5j2 levels,and reactive oxygen species overproduction in the mutant repair ***-specific Cdc42 deletion attenuated ERK1/2 signaling in the labial cervical *** Sox2 expression in the mutant labial cervical loop after clipping might lead to delayed tooth *** findings suggested that mitochondrial dysfunction,up-regulated oxidative stress,and abnormal ion channel activity may be among multiple factors responsible for the observed enamel defects in Cdc42 mutant ***,Cdc42 exerts multidimensional and pivotal roles in enamel development and is particularly required for ameloblast differentiation and enamel matrix formation.

关键词： Cdc42 Enamel defects Mitochondrial dysfunction Rho GTPase Tooth repair

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Dcalycinumines A-E,Alkaloids with Cytotoxic Activities of Nasopharyngeal Carcinoma Cells from Daphniphyllum calycinum

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Chinese Journal of Chemistry 2024年第1期42卷 35-42页

作者： Qing Tang Xiao-Yong Dai Qiang Lin Zhi-Peng Ling Yi-Kun Hao Tian-Xi Zhu Ji-Hui Zhang Yi-Bo Hou Yao-Lan Li Lai-Qiang Huang Jing-Hao Wang Guo-Cai Wang Yu-Bo Zhang guangdong clinical Translational Centerfor Targeted Drug Department of PharmacologySchoolof MedicineJinan University GuangzhouGuangdong 510632China Institute of Traditional Chinese Medicine&Natural Products Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs ResearchCollegeof PharmacyJinan UniversityGuangzhouGuangdong511443China Institute of Biopharmaceutical and Health Engineering Shenzhen Key Laboratory of Gene and Antibody TherapyState Key Laboratory of Chemical OncogenomicsShenzhen International Graduate SchoolTsinghua UniversityShenzhenGuangdong 518055China The Guangzhou key laboratoryof Basic and Translational Research on Chronic Disease Department of PharmacyThe First Affiliated HospitalJinan UniversityGuangzhouGuangdong 510630China

Fivenovel Daphniphyllum alkaloids,named dcalycinumines A-E(1-4,6),andeight previously described Daphniphyllum alkaloids(5,7-13)were isolated from Daphniphyllum *** 1 is the first Daphniphyllum alkaloid possessing a highly rearranged 6/6/6/7/5/6 hexacyclic architecture with a unique 3-methyl-1-azabicyclo[4,4,0]decane ring *** 2 represents a rare diamino Daphniphyllum alkaloid with an unprecedented 6/5/5/6/6/5 carbon skeleton featuring a unique 1-aza-6-azaspiro[4,5]decane unit,whereas 3 also represents a rare diamino Daphniphyllum alkaloid as a possible precursor of *** 4 is the second example of c-22-nor yuzurimine-type *** structures and absolute configurations were elucidated by HRESIMS,NMR spectroscopic analyses,EcD calculations,and single-crystal X-ray ***,compound 1 showed remarkable antitumor activities,which could inhibit the proliferation,migration and invasion of nasopharyngeal carcinoma cells,and promoted nasopharyngeal carcinoma cells apoptosis.

关键词： Daphniphyllum calycinum Natural products Daphniphyllum alkaloid Structural elucidation Biological activity Apoptosis Nasopharyngealcarcinoma

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Single-base editing in IGF2 improves meat production and intramuscular fat deposition in Liang Guang Small Spotted pigs

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Journal of Animal Science and Biotechnology 2024年第1期15卷 108-126页

作者： Tianqi Duo Xiaohong Liu Delin Mo Yu Bian Shufang Cai Min Wang Ruiqiang Li Qi Zhu Xian Tong Ziyun Liang Weilun Jiang Shiyi Chen Yaosheng Chen Zuyong He State key laboratory of Biocontrol School of Life SciencesSun Yat-Sen UniversityGuangzhou 510275GuangdongChina Department of pharmacology(the State‑Province key Laboratories of Biomedicine‑Pharmaceutics of China Key Laboratory of Cardiovascular ResearchMinistry of Education)College of PharmacyHarbin Medical UniversityHarbin 150081China Hunan provincial key laboratory for Genetic Improvement of Domestic Animal College of Animal Science and TechnologyHunan Agricultural UniversityChangsha 410128China

Background Chinese indigenous pigs are popular with consumers for their juiciness,flavour and meat quality,but they have lower meat ***-like growth factor 2(IGF2) is a maternally imprinted growth factor that promotes skeletal muscle growth by regulating cell proliferation and differentiation.A single nucleotide polymorphism(SNP) within intron 3 of porcine IGF2 disrupts a binding site for the repressor,zinc finger BED-type containing 6(ZBED6),leading to up-regulation of IGF2 and causing major effects on muscle growth,heart size,and backfat *** favorable mutation is common in Western commercial pig populations,but absent in most Chinese indigenous pig *** improve meat production of Chinese indigenous pigs,we used cytosine base editor 3(CBE3)to introduce IGF2 intron3-C3071T mutation into porcine embryonic fibroblasts(PEFs) isolated from a male Liang Guang Small Spotted pig(LGSS),and single-cell clones harboring the desired mutation were selected for somatic cell nuclear transfer(SCNT) to generate the founder line of IGF2^(T/T) *** We found the heterozygous progeny IGF2^(C/T) pigs exhibited enhanced expression of IGF2,increased lean meat by 18%-36%,enlarged loin muscle area by 3%-17%,improved intramuscular fat(IMF) content by 18%-39%,marbling score by 0.75-1,meat color score by 0.53-1.25,and reduced backfat thickness by 5%-16%.The enhanced accumulation of intramuscular fat in IGF2^(C/T) pigs was identified to be regulated by the PI3K-AKT/AMPK pathway,which activated SREBP1 to promote *** We demonstrated the introduction of IGF2-intron3-C3071T in Chinese LGSS can improve both meat production and quality,and first identified the regulation of IMF deposition by IGF2 through SREBP1 via the PI3KAKT/AMPK signaling *** study provides a further understanding of the biological functions of IGF2and an example for improving porcine economic traits through precise base editing.

关键词： CBE3 IGF2 Intramuscular fat Meat production PI3K-AKT/AMPK ZBED6

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The key laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China guangdong provincial key laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China clinical Research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

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World Journal of Gastroenterology 2024年第6期30卷 607-609页

作者： Bai-Wei Zhao Ying-Jia Chen Ruo-Peng Zhang Yong-Ming Chen Bo-Wen Huang Department of Gastric Surgery Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaGuangdong Provincial Clinical Research Center for CancerGuangzhou 510060Guangdong ProvinceChina Health Science Center Peking UniversityBeijing 100191China

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

关键词： Angiotensin-converting enzyme 2 Hepatic stellate cells Liver fibrosis Angiotensin II Angiotensin 1-7 Renin-angiotensin system

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Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment

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Chinese Journal of Natural Medicines 2024年第6期22卷 501-514页

作者： CHEN Chiwei HUANG Renlun WANG Neng ZHENG Yifeng ZHOU Jianfu YANG Bowen WANG Xuan ZHANG Juping PAN Bo CHEN Zhiqiang WANG Shengqi WANG Zhiyu XIANG Songtao The Research Center of Integrative Cancer Medicine Discipline of Integrated Chinese and Western Medicinethe Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China The First clinical College of Guangzhou University of Chinese Medicine Guangzhou 510000China guangdong provincial key laboratory of clinical Research on Traditional Chinese Medicine Syndrome Guangdong Provincial Academy of Chinese Medical SciencesGuangdong Provincial Hospital of Chinese MedicineGuangzhou 510000China guangdong-Hong Kong-Macao Joint Lab on Chinese Medicine and Immune Disease Research Guangzhou University of Chinese MedicineGuangzhou 510000China The Research Center for Integrative Medicine School of Basic Medical SciencesGuangzhou University of Chinese MedicineGuangzhou 510000China State key laboratory of Dampness Syndrome of Chinese Medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000China

Prostate cancer(PCa)is the second most common malignancy among men *** Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of *** study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 *** conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their *** showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM ***,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by *** FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity *** studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture ***,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 ***,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

关键词： Traditional Chinese medicine Tumor-associated macrophages Prostate cancer stem cells CCL5 Tumor microenvironment

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