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Expanding the targeting scope of CRISPR/Cas9-mediated genome editing by Cas9 variants in Brassica

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aBIOTECH 2024年第2期5卷 202-208页

作者： Wenjing Li Xuan Li Chunyang Wang Guanzhong Huo Xinru Zhang Jintai Yu Xiaoxiao Yu Jing Li Chao Zhang Jianjun Zhao Yan Li Jun Li State Key Laboratory of North China Crop Improvement and Regulation College of Life SciencesHebei Agricultural UniversityBaoding 071001China Hebei Key Laboratory of Plant Physiology and molecular pathology Hebei Agricultural UniversityBaoding 071001China Key Laboratory of Vegetable Germplasm Innovation and Utilization of Hebei Collaborative Innovation Center of Vegetable Industry in HebeiCollege of HorticultureHebei Agricultural UniversityBaoding 071001China College of Modern Science and Technology Hebei Agricultural UniversityBaoding 071001China

CRISPR/Cas9,presently the most widely used genome editing technology,has provided great potential for functional studies and plant ***,the strict requirement for a protospacer adjacent motif(PAM)has hindered the application of the CRISPR/Cas9 system because the number of targetable genomic sites is ***,the engineered variants Cas9-NG,SpG,and SpRY,which recognize non-canonical PAMs,have been successfully tested in plants(mainly in rice,a monocot).In this study,we evaluated the targeted mutagenesis capabilities of these Cas9 variants in two important Brassica vegetables,Chinese cabbage(Brassica rapa ***)and cabbage(Brassica oleracea ***).Both Cas9-NG and SpG induced efficient mutagenesis at NGN PAMs,while SpG outperformed Cas9-NG at NGC and NGT *** achieved efficient editing at almost all PAMs(NRN>NYN),albeit with some self-targeting activity at transfer(T)-DNA *** SpRY-induced mutants were detected in cabbage plants in a PAM-less ***,an adenine base editor was developed using SpRY and TadA8e deaminase that induced A-to-G conversions within target sites using non-canonical ***,the toolboxes developed here induced successful genome editing in Chinese cabbage and *** work further expands the targeting scope of genome editing and paves the way for future basic research and genetic improvement in Brassica.

关键词： Brassica Cas9 variants CRISPR Genome editing Non-canonical PAM

Early gastric composite tumor comprising signet-ring cell carcinoma and mucosa-associated lymphoid tissue lymphoma:A case report

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World Journal of Gastroenterology 2024年第38期30卷 4232-4238页

作者： Yi-Fan Jia Fei-Fan Chen Li Yang Yun-Xia Ye Yi-Zhu Gao Wen-Yan Zhang Jin-Lin Yang Department of Gastroenterology and Hepatology University of Oxford Huaxi Joint Centre for Gastrointestinal CancerFrontiers Science Center for Disease-Related Molecular NetworkWest China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of pathology West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina Department of Emergency West China HospitalSichuan UniversityChengdu 610041Sichuan ProvinceChina

BACKGROUND Composite tumors are neoplasms comprising two distinct,yet intermingling,cell *** paper reports a rare phenomenon where early gastric signet-ring cell carcinoma(SRCC)and gastric mucosa-associated lymphoid tissue(MALT)lymphoma coexist within the same *** SUMMARY A 40-year-old woman presented to the West China Hospital for examination,which revealed a whitish,shallow,and uneven mucosal lesion in the *** lesion was diagnosed as a poorly differentiated adenocarcinoma,including SRCC with atypical lymphoid hyperplasia associated with Helicobacter pylori infection,based on histopathological examination of the biopsy *** lesion was excised using segmental ***,histological exami-nation of the surgical specimen confirmed that it was a poorly differentiated gastric adenocarcinoma with features of SRCC and MALT *** two entities were stage I and coexisted in the same *** It is uncommon for gastric SRCC and MALT lymphoma to coexist without distinct *** resection is effective for these lesions.

关键词： Gastric cancer Composite tumors Early stage Signet-ring cell carcinoma Mucosa-associated lymphoid tissue lymphoma Case report

Calcium channels caught in peripheral glia’s tug-of-war on axon regeneration in Drosophila

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Neural Regeneration Research 2025年第2期20卷 475-476页

作者： Jackson Powell Tobias Steinschaden Rose Horowitz Yuanquan Song Raymond G.Perelman Center for Cellular and molecular Therapeutics The Children’s Hospital of PhiladelphiaPhiladelphiaPAUSA The Neuroscience Graduate Group University of PennsylvaniaPhiladelphiaPAUSA Department of pathology and Laboratory Medicine University of PennsylvaniaPhiladelphiaPAUSA Medical University of Vienna Center for Brain ResearchDepartment of NeuroimmunologyViennaAustria

Neural damage or degeneration is at the crux of many diseases,and treatment of these diseases will require the development of therapeutics to enhance and guide neural *** intrinsic and extrinsic factors dictate a neuron’s ability to regenerate,and the combination of these factors results in the great regenerative capacity of the peripheral nervous system(PNS)and the poor regenerative capacity of the central nervous system(CNS)following *** the core of a neuron’s function is its ability to relay electrochemical signals,and a neuron’s excitability is a key factor in its ability to *** works have focused on the changes in neuronal electrophysiological properties,firing patterns,and ion flux after injury,which differentially activate signaling pathways at the core of *** role of glia in neuron regeneration has long been studied.

关键词： degeneration firing system

Aldh2 deficiency plays a dual role in lung tumorigenesis and tumor progression

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Genes & Diseases 2024年第3期11卷 144-147页

作者： Hongjia Zhang Xueqian Sun Zhanming Li Tingting Liu Fang Zhang Xinyu Meng Kaimi Li Jianhua Xu Wei He Bo Jing Tong Wang Na Ni Beibei Sun Feng Yao Yadi Wu Qi Wang Jing Du Eugene Y.Chin Binhua P.Zhou Ping Jiang Lishun Wang Jiong Deng Key Laboratory of Cell Differentiation and Apoptosis of Chinese Minister of Education Department of PathophysiologyShanghai Jiao Tong University School of MedicineShanghai 200025China Shanghai Key Laboratory for Tumor Microenvironment and Inflammation Shanghai Jiao Tong University School of MedicineShanghai200025China Department of pathology Kunming Medical UniversityKunmingYunnan 650500China Medical Research Center Binzhou Medical University HospitalBinzhouShandong 256600China Center for Traditional Chinese Medicine and Gut Microbiota Minhang HospitalFudan UniversityShanghai 201100China Department of Radiation Oncology Yantai Affiliated Hospital of Binzhou Medical UniversityYantaiShandong 264100China Department of pathology Molecular Pathology Research CenterPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Laboratory Medicine Shanghai Pulmonary Hospital Affiliated Tongji UniversityShanghai 200080China Department of Physiology School of Basic Medical SciencesWeifang Medical UniversityWeifangShandong 261021China Department of Thoracic Surgery Shanghai Chest HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of molecular and Celular Biochemistry Markey Cancer CenterUniversity of Kentucky College of MedicineLexingtonKY40506USA Department of Respiratory Medicine The Second Affiliated HospitalDalian Medical UniversityDalianLiaoning116023China Peninsular Cancer Center Binzhou Medical UniversityYantaiShandong 264003China

Alcohol consumption contributes to global mortality and cancer ***(ACE),the oxidized metabolite of alcohol,is highly reactive towards DNA,resulting in DNA *** can be detoxified to acetate by acetaldehyde dehydrogenase... 详细信息

关键词： mortality damage ALDH2

Suppression of hepatic steatosis in non-alcoholic steatohepatitis model by modified Xiaoyao San formula:Evidence,mechanisms and perspective

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World Journal of Hepatology 2024年第10期16卷 1208-1212页

作者： Nabil Eid Payal Bhatnagar Li-Li Chan Marina Garcia-Macia Department of Anatomy Division of Human BiologySchool of MedicineIMU UniversityKuala Lumpur 57000Malaysia Department of Pharmaceutical Technology School of pharmacyIMU UniversityKuala Lumpur 57000Malaysia Department of pathology and Pharmacology School of MedicineIMU UniversityKuala Lumpur 57000Malaysia Institute of Functional Biology and Genomics Department of Biochemistry and Molecular BiologyUniversity of SalamancaSalamanca 37007Spain

In this letter,we comment on a recent publication by Mei et al,in the World Journal of Hepatology,investigating the hepatoprotective effects of the modified Xiaoyao San(MXS)formula in a male rat model of non-alcoholic steatohepatitis(NASH).The authors found that MXS treatment mitigated hepatic steatosis and inflam-mation in the NASH model,as evidenced by the reduction in lipid droplets(LDs),fibrosis markers and lipogenic ***,these hepatoprotective effects were associated with androgen upregulation(based on metabolomics analysis of male steroid hormone metabolites),adenosine 5’-monophosphate-activated protein kinase(AMPK)activation,and restoration of phosphatase and tensin homolog(PTEN)***,the authors did not clearly discuss the relationships between MXS-induced hepatic steatosis reduction in the NASH model,and androgen upregulation,AMPK activation,and restoration of PTEN *** editorial emphasizes the reported mechanisms and explains how they act or interact with each other to reduce hepatic steatosis and inflammation in the NASH *** a perspective,we propose additional mechanisms(such as autophagy/lipophagy activation in hepatocytes)for the clearance of LDs and suppression of hepatic steatosis by MXS in the NASH model.A proper understanding of the mechanisms of MXS-induced reduction of hepatic steatosis might help in the treatment of NASH and related diseases.

关键词： Steatosis Liver Xiaoyao San Inflammation Androgen Adenosine 5’-monophosphate-activated protein kinase Phosphatase and tensin homolog Autophagy Lipophagy Alpha smooth muscle actin

Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1637-1650页

作者： Yuanliang Yan Shangjun Zhou Xi Chen Qiaoli Yi Songshan Feng Zijin Zhao Yuanhong Liu Qiuju Liang Zhijie Xu Zhi Li Lunquan Sun Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of pathology Xiangya HospitalCentral South UniversityChangsha 410008China Xiangya Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of molecular Radiation Oncology Hunan Province Changsha 410008China institute of Cancer Research National Clinical Research Center for Geriatric Disorders(Xiangya)Xiangya HospitalCentral South UniversityChangsha 410008China

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant *** specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to ***,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug *** investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were *** Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent *** through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma *** TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to ***,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ***,in turn,elevated ITPKB stability and impaired ROS ***,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse *** findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

关键词： TMZ homeostasis impaired

Evaluating genetic insights into ulcerative colitis and anxiety:Limitations and future directions

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World Journal of Gastroenterology 2024年第37期30卷 4156-4159页

作者： Ying Peng Xi-Dai Long Department of pathology The First Affiliated HospitalGuangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of pathology Shenzhen Qianhai Shekou Free Trade Zone HospitalShenzhen 518000Guangdong ProvinceChina Department of pathology The Affiliated Hospital of Youjiang Medical University for NationalitiesBaise 533000Guangxi Zhuang Autonomous RegionChina Department of Liver Surgery Ren Ji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai 200000China

We reviewed the study by He et al,which investigates the genetic correlation between ulcerative colitis(UC)and anxiety using bidirectional Mendelian *** study reveals a genetic link between UC and anxiety,diverging from prior research associating higher anxiety with Crohn’s *** the study's use of large-scale genome-wide association studies data is commendable,it faces limitations such as single nucleotide polymorphism selection biases,lack of multiple testing corrections,and a reliance on European *** research should address these limitations,incorporate diverse populations,and explore psychotherapeutic interventions to improve UC management and patient outcomes.

关键词： Ulcerative colitis Anxiety Mendelian randomization Genome-wide association study Gut-brain axis Instrumental variables Genetic epidemiology Pleiotropy

New insights into astrocyte diversity from the lens of transcriptional regulation and their implications for neurodegenerative disease treatments

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Neural Regeneration Research 2024年第11期19卷 2335-2336页

作者： Ibrahim Olabayode Saliu Guoyan Zhao Department of Genetics Washington University School of MedicineSt.LouisMOUSA Department of Neurology Department of Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA

Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to *** addition to these roles,they play crucial roles in modulating synaptic functions,development,and pruning(Brandebura et al.,2023).Astrocytes become reactive(activated)by undergoing morphological,molecular,and functional alterations in response to neuropathology such as in injuries and neurodegenerative diseases(NDs)(Escartin et al.,2021).

关键词： degenerative injuries

Oomycete Nudix effectors display WY-Nudix conformation and mRNA decapping activity

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Journal of Integrative Plant Biology 2024年第8期66卷 1548-1552页

作者： Baodian Guo Qinli Hu Bangwei Wang Deqiang Yao Haonan Wang Guanghui Kong Chenyang Han Suomeng Dong Fengquan Liu Weiman Xing Yuanchao Wang Department of Plant pathology Nanjing Agricultural UniversityNanjing 210095China Institute of Plant Protection Jiangsu Academy of Agricultural SciencesNanjing 210014China Department of molecular Genetics University of Texas Southwestern Medical CenterDallasTexas 75390USA Institute of Aging&Tissue Regeneration Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200127China College of Horticulture Nanjing Agricultural UniversityNanjing 210095China College of Agriculture Guizhou UniversityGuiyang 550025China College of Life Sciences Shanghai Normal UniversityShanghai 200234China

Phytopathogens secrete effectors to promote colonization of their host *** effectors modulate host immune responses by interfering with various pathways,but little is known about their biochemical *** recent reports indicate that some phytopathogen effectors have Nudix hydrolase activity,including Avr3b from Phytophthora sojae(Dong et al.,2011),AvrM14 from Melampsora lini (McCombe et al.,2023),and RipN from Ralstonia solanacearum (Sun et al.,2019).

关键词： plants Phytophthora biochemical