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A circular single-stranded DNA mycovirus infects plants and confers broad-spectrum fungal resistance

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Molecular Plant 2024年第6期17卷 955-971页

作者： Xianhong Wang Ioly Kotta-Loizou Robert H.A.Coutts Huifang Deng Zhenhao Han Ni Hong Karim Shafik Liping Wang Yashuang Guo Mengmeng Yang Wenxing Xu Guoping Wang National Key laboratory for Germplasm Innovation&Utilization of Horticultural Crops Wuhan 430070China Hubei Hongshan laboratory Wuhan 430070China College of Plant Science and Technology Huazhong Agricultural UniversityWuhan 430070China Key lab of Plant pathology of Hubei Province Wuhan 430070China Department of Life Sciences Faculty of Natural SciencesImperial College LondonLondon SW72AZUK Department of Clinical Pharmaceutical and Biological ScienceSchool of Life and Medical SciencesUniversity of HertfordshireHatfield AL109ABUK Department of Plant pathology Faculty of AgricultureAlexandria UniversityAlexandria 21526Egypt

Circular single-stranded DNA(ssDNA)viruses have been rarely found in fungi,and the evolutionary and ecological relationships among ssDNA viruses infecting fungi and other organisms remain *** this study,a novel circular ssDNA virus,tentatively named Diaporthe sojae circular DNA virus 1(DsCDV1),was identified in the phytopathogenic fungus Diaporthe sojae isolated from pear ***1 has a monopartite genome(3185 nt in size)encapsidated in isometric virions(21-26 nm in diameter).The genome comprises seven putative open reading frames encoding a discrete replicase(Rep)split by an intergenic region,a putative capsid protein(CP),several proteins of unknown function(P1-P4),and a long intergenic ***,the two split parts of DsCDV1 Rep share high identities with the Reps of Geminiviridae and Genomoviridae,respectively,indicating an evolutionary linkage with both *** analysis based on Rep or CP sequences placed DsCDV1 in a unique cluster,supporting the establishment of a new family,tentatively named Gegemycoviridae,intermediate to both ***1 significantly attenuates fungal growth and nearly erases fungal virulence when transfected into the host ***,DsCDV1 can systematically infect tobacco and pear seedlings,providing broad-spectrum resistance to fungal *** localization analysis revealed that DsCDV1 P3 is systematically localized in the plasmodesmata,while its expression in trans-complementation experiments could restore systematic infection of a movement-deficient plant virus,suggesting that P3 is a movement ***1 exhibits unique molecular and biological traits not observed in other ssDNA viruses,serving as a link between fungal and plant ssDNA viruses and presenting an evolutionary connection between ssDNA viruses and *** findings contribute to expanding our understanding of ssDNA virus diversity and evolution,offering potential biocontrol applications for managing crucial plant d

关键词： circular single-stranded DNA virus mycovirus virus evolution Genomoviridae Gegemycoviridae Diaporthe sojae circular DNA virus 1

3D bioprinting of in vitro porous hepatoma models:establishment,evaluation,and anticancer drug testing

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Bio-Design and Manufacturing 2024年第2期7卷 137-152页

作者： Xiaoyuan Wang Zixian Liu Qianqian Duan Boye Zhang Yanyan Cao Zhizhong Shen Meng Li Yanfeng Xi Jianming Wang Shengbo Sang Shanxi Key laboratory of Micro Nano Sensors and Artificial Intelligence Perception College of Electronic Information and Optical EngineeringTaiyuan University of TechnologyTaiyuan 030024China Key lab of Advanced Transducers and Intelligent Control System of the Ministry of Education Taiyuan University of TechnologyTaiyuan 030024China Shanxi Institute of 6D Artificial Intelligence Biomedical Science Taiyuan 030031China Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering Taiyuan 030024China Department of pathology Shanxi Provincial Cancer HospitalTaiyuan 030024China General Hospital of Taiyuan Iron and Steel Company Taiyuan 030809China

Traditional tumor models do not tend to accurately simulate tumor growth in vitro or enable personalized treatment and are particularly unable to discover more beneficial targeted *** address this,this study describes the use of threedimensional(3D)bioprinting technology to construct a 3D model with human hepatocarcinoma SMMC-7721 cells(3DP-7721)by combining gelatin methacrylate(GelMA)and poly(ethylene oxide)(PEO)as two immiscible aqueous phases to form a bioink and innovatively applying fluorescent carbon quantum dots for long-term tracking of *** GelMA(10%,mass fraction)and PEO(1.6%,mass fraction)hydrogel with 3:1 volume ratio offered distinct pore-forming characteristics,satisfactorymechanical properties,and biocompatibility for the creation of the 3DP-7721 *** analysis and quantitative real-time fluorescence polymerase chain reaction(PCR)were used to evaluate the biological properties of the *** with the two-dimensional culture cell model(2D-7721)and the 3D mixed culture cell model(3DM-7721),3DP-7721 significantly improved the proliferation of cells and expression of tumor-related proteins and ***,we evaluated the differences between the three culture models and the effectiveness of antitumor drugs in the three models and discovered that the efficacy of antitumor drugs varied because of significant differences in resistance proteins and genes between the three *** addition,the comparison of tumor formation in the three models found that the cells cultured by the 3DP-7721 model had strong tumorigenicity in nude *** evaluation of the levels of biochemical indicators related to the formation of solid tumors showed that the 3DP-7721 model group exhibited pathological characteristics of malignant tumors,the generated solid tumors were similar to actual tumors,and the deterioration was *** research therefore acts as a foundation for the application of 3DP-7721 models in drug devel

关键词： 3D bioprinting Hepatoma tumor models Drug screening Antitumor drug development

The big data challenge-and how polypharmacology supports the translation from pre-clinical research into clinical use against neurodegenerative diseases and beyond

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Neural Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel Stefan Muhammad Rafehi Drug Development and Chemical Biology Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of pathology Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School of Medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Clinical Pharmacology University Medical Center GöttingenGöttingenGermany Department of Medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and validation of disease-modifying proteins are fundamental aspects in drug ***,the m ultifactority of n eurodegen era tive diseases poses a real challenge for targeted ***,the behavior of individually(over-)expressed to rget proteins in vitro is likely to differ from their actual functional behavior when embedded in cascades and pathways in vivo.

关键词： translation beyond likely

Schistosoma infection,KRAS mutation status,and prognosis of colorectal cancer

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Chinese Medical Journal 2024年第2期137卷 235-237页

作者： Xinyi Li Hongli Liu Bo Huang Ming Yang Jun Fan Jiwei Zhang Mixia Weng Zhecheng Yan Li Liu Kailin Cai Xiu Nie Xiaona Chang Department of pathology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Hubei Key laboratory of Precision Radiation Oncology WuhanHubei 430022China Institute of Radiation Oncology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Epidemiology and Biostatistics The Ministry of Education Key Lab of Environment and HealthSchool of Public HealthHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Gastrointestinal Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China

To the Editor:Colorectal cancer(CRC)is a major cause of cancer-related death worldwide,and several pathogens with carcinogenic potential,such as Schistosoma,have been associated with an increased risk of *** a frequently mutated gene in CRC patients,kirsten rat sarcoma viral oncogene homolog(KRAS)helps to determine the selection of CRC ***,we aimed to elucidate the association among Schistosoma infection,KRAS mutation status,and the prognosis of CRC in this study.

关键词： Schistosoma KRAS prognosis

Tunable THz spectrum analyzer with hyperspectral resolution

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Chinese Optics Letters 2024年第7期 116-121页

作者：何欣姚铭家钱城薇孟雷欣刘小威唐文豪沈小明 Paul Beckett 肖铎刘旭殷锐 School of Information and Electrical Engineering Hangzhou City University Research Center for Humanoid Sensing Zhejiang Lab State Key laboratory of Modern Optical Instrumentation College of Optical Science and Engineering Zhejiang University Research Center for Intelligent Chips and Devices Zhejiang Lab STEM College RMIT University

We present a tunable terahertz （THz） spectrum analyzer with hyperspectral resolution formed from electrically tunable metamaterial and plasmonic *** few as eight encoders based on four detectors are needed to recover 396spectral *** incident spectra in the range of 1–5 THz can be reconstructed with a localization precision of0.3 GHz and a minimum average mean squared error （MSE） of 6.9×*** proposed analyzers are faster and more portable than those based on frequency combs and power meters,and more accurate than existing Fourier transform techniques,showing promising applications in pathology,biomedical imaging,and many other areas.

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Efficacy and safety of PD-1 blockade plus long-course chemoradiotherapy in locally advanced rectal cancer(NECTAR):a multi-center phase 2 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1721-1729页

作者： Zhengyang Yang Jiale Gao Jianyong Zheng Jiagang Han Ang Li Gang Liu Yi Sun Jie Zhang Guangyong Chen Rui Xu Xiao Zhang Yishan Liu Zhigang Bai Wei Deng Wei He Hongwei Yao Zhongtao Zhang Department of General Surgery Beijing Friendship HospitalCapital Medical UniversityState Key Lab of Digestive HealthNational Clinical Research Center for Digestive DiseasesBeijingChina Department of Gastrointestinal Surgery The First Affiliated Hospital of Air Force Medical UniversityXi'anChina Department of General Surgery Beijing Chaoyang HospitalCapital Medical UniversityBeijingChina Department of General Surgery Beijing Xuanwu HospitalCapital Medical UniversityBeijingChina Department of General Surgery Tianjin Medical University General HospitalTianjinChina Department of Anorectal Tianjin People's HospitalTianjinChina Department of Radiology Beijing Friendship Hospital Capital Medical UniversityBeijingChina Department of pathology Beijing Friendship HospitalCapital Medical UniversityBeijingChina Department of Thoracic Surgery/Institute of Thoracic Oncology West China HospitalSichuan UniversityChengduChina

Adding PD-1 blockade in the neoadjuvant regimens for locally advanced rectal cancer(LARC)patients with microsatellite stable(MsS)/mismatch repair-proficient(pMMR)tumors is an attractive,but debatable *** phase 2,multicenter,prospective,single-arm study enrolled patients from 6 centers from June 2021 to November *** advanced rectal cancer(LARC,cT_(3-4a)N_(0)M_(0) and cT_(1-4a)N_(1-2)M_(0))patients aged≥18 years with the distance from distal border of tumor to anal verge≤10 cm(identified by Magnetic Resonance Imaging)were qualifed for *** patients received long-course radiotherapy(50 Gy/25 fractions,2 Gy/fraction,5 days/week)and three 21-day cycles capecitabine(850-1000 mg/m2,bid,po,day1-14)and three 21-day cycles tislelizumab(200 mg,***,day8)as *** mesorectal excision(TME)was 6-12 weeks after the end of radiotherapy to achieve radical resection.A total of 50 patients were enrolled in this *** pathological complete response rate was 40.0%[20/50,95%confidence interval(CI):27.61-53.82%],while 15(30.0%,95%CI:19.1-43.75%),9(18.0%,95%CI:9.77-30.8%),2(4.0%,95%CI:1.10-13.46%)patients respectively achieved grade 1,2,and 3 tumor ***-related adverse events(TRAEs)occurred in 28(56.0%)LARC patients,including 26(52.0%)with grade I-II and 2(4.0%)with grade II(1 with grade 3 immune-related colitis and 1 with grade 3 rash).PD-1 blockade plus long-course chemoradiotherapy(CRT)showed promising therapeutic effects according to pathological complete response rate and is well-tolerated in LARC patients.A larger randomized controlled study is desired to further validate the above findings.

关键词： rectal cancer phase

Clinical efficacy and identification of factors confer resistance to afatinib(tyrosine kinase inhibitor)in EGFR-overexpressing esophageal squamous cell carcinoma

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3130-3140页

作者： Yanni Wang Chang Liu Huan Chen Xi Jiao Yujiao Wang Yanshuo Cao Jian Li Xiaotian Zhang Yu Sun Na Zhuo Fengxiao Dong Mengting Gao Fengyuan Wang Liyuan Dong Jifang Gong Tianqi Sun Wei Zhu Henghui Zhang Lin Shen Zhihao Lu Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Genecast Biotechnology Co. LtdWuxiPR China State Key laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDepartment of Gastrointestinal OncologyPeking University Cancer Hospital and InstituteBeijingChina Key laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijingChina Precision Scientific(Beijing)Co. Ltd.BeijingChina Generulor Company Bio-X lab ZhuhaiGuangdongChina Biomedical Innovation Center Beijing Shijitan HospitalCapital Medical UniversityBeijingChina Beijing Key laboratory for Therapeutic Cancer Vaccines Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

Epidermal growth factor receptor(EGFR)is reportedly overexpressed in most esophageal squamous cell carcinoma(ESCC)patients,but anti-EGFR treatments offer limited survival *** preclinical data showed the promising antitumor activity of afatinib in EGFR-overexpressing *** proof-of-concept,phase II trial assessed the efficacy and safety of afatinib in pretreated metastatic ESCC patients(n=41)with EGFR overexpression(NCT03940976).The study met its primary endpoint,with a confirmed objective response rate(ORR)of 39%in 38 efficacy-evaluable patients and a median overall survival of 7.8 months,with a manageable toxicity *** analysis of pretreatment tumors revealed that neurotrophic receptor tyrosine kinase 2(NTRK2)was negatively associated with afatinib sensitivity and might serve as a predictive biomarker,irrespective of EGFR ***,knocking down or inhibiting NTRK2 sensitized ESCC cells to afatinib *** study provides novel findings on the molecular factors underlying afatinib resistance and indicates that afatinib has the potential to become an important treatment for metastatic ESCC patients.

关键词： esophageal squamous expressing

Gene replacement therapy in Bietti crystalline corneoretinal dystrophy:an open-label,single-arm,exploratory trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2275-2284页

作者： Jinyuan Wang Jinlu Zhang Shicheng Yu Hongyan Li Shaohong Chen Jingting Luo Haibo Wang Yuxia Guan Haihan Zhang Shiyi Yin Huili Wang Heping Li Junle Liu Jingyuan Zhu Qiong Yang Ying Sha Chuan Zhang Yuhang Yang Xuan Yang Xifang Zhang Xiuli Zhao Likun Wang Liping Yang Wenbin Wei Beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology&Visual Sciences Key LabMedical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information TechnologyBeijing Tongren HospitalCapital Medical University100730 BeijingChina School of Clinical Medicine Tsinghua University100084 BeijingChina Chigenovo Co. Ltd.102206 BeijingChina Department of Ophthalmology Peking University Third HospitalBeijing Key Laboratory of Restoration of Damaged Ocular NervePeking University Third Hospital100191 BeijingChina Department of Ophthalmology The Third People’s Hospital of Dalian116091 DalianChina Department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available ***,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 *** open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/***,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were *** with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the *** conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).

关键词： cor dystrophy crystalline

Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1

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Protein & Cell 2024年第6期15卷 419-440页

作者： Wei Ma Lu Zhang Weilong Chen Zhaoxia Chang Juchuanli Tu Yuanyuan Qin Yuwen Yao Mengxue Dong Jiajun Ding Siqin Li Fengkai Li Qiaodan Deng Yifei Yang Tingting Feng Fanrong Zhang Xiying Shao Xueyan He Lixing Zhang Guohong Hu Quentin Liu Yi-Zhou Jiang Shu Zhu Zhi Xiao Dan Su Tong Liu Suling Liu Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences State Key Laboratory of Genetic EngineeringCancer InstitutesDepartment of OncologyKey Laboratory of Breast Cancer in ShanghaiThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Key Laboratory of Radiation OncologyThe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghai Medical CollegeFudan UniversityShanghai 200032China Intelligent pathology Institute and Department of pathology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230071China Department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’an 710032China Institute of Immunology CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of pathology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast Medical Oncology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Shanghai Institute of Nutrition and Health University of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Department of Breast Surgery Xiangya HospitalChangsha 410008China Department of Breast Surgery Tumor Hospital of Harbin Medic

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant ***,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in ***,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis(ETBF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant ***,albeit at low biomass,secreted the toxic protein BFT-1 to promote breast cancer cell stemness and *** studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 ***1 was highly expressed on ALDH+breast cancer stem cells(BCSCs)and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation,thereby activating the NOTCH1-HEY1 signaling pathway to increase ***1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.

关键词： NOD1 breast chemotherapy