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Development of RAPD Markers and SCAR Markers Linked to Bentazon Susceptible Lethality Gene in Rice 被引量:2
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作者 向太和 杨剑波 +6 位作者 李莉 倪大虎 杨前进 朱启升 汪秀峰 张毅 黄大年 《Acta Botanica Sinica》 CSCD 2003年第2期223-228,共6页
Rice cultivar Norin 8 and its mutant Norin 8m harbour bentazon resistance trait and bentazon susceptibility trait respectively. A total of 360 arbitrary 10-mer oligonucleotide primers were screened on the genomic DNA ... Rice cultivar Norin 8 and its mutant Norin 8m harbour bentazon resistance trait and bentazon susceptibility trait respectively. A total of 360 arbitrary 10-mer oligonucleotide primers were screened on the genomic DNA of Norin 8 and Norin 8m with RAPD technique. Among which, five primers produced seven polymorphic RAPD bands between Norin 8 and Norin 8m. Amplified RAPD polymorphic products were cloned and sequenced. The sequences were used to design primers for PCR. Five SCAR markers, SCAR/G18/883, SCAR/G18/890, SCAR/G18/919/948, SCAR/D10/1237 and SCAR/F03/1186, were developed from OPG18/943, OPG18/972, OPD10/1248 and OPF03/1198. F-2 progeny of 320 individuals was analyzed to map SCAR markers in relationship to ben or Ben genes. SCAR markers of SCAR/G18/883, SCAR/G18/890, SCAR/G18/919/948 were shown to cosegregate with ben or Ben genes, and SCAR/D10/1237 to be linked of Ben gene with a distance of (14.8 +/- 2.1) cM. The genetic linkage to ben gene and SCAR markers was identified by a pair of near isogenic lines H121 and Hben121. Southern blotting analysis and segregation ratio of F-2 progeny revealed that OPG18/943 and OPG18/972 were single-copy in genome, and locus of OPG18/943 and OPG18/972 were allelic and sequence tagged sites. It is the first report on molecular markers linked to ben or Ben genes. The markers are useful to marker-assisted selection for the breeding and tag ben gene with map-based cloning. 展开更多
关键词 rice ( Oryza saliva ) bentazon susceptible lethality gene RAPD marker SCAR marker
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Effects of gas supersaturation on lethality and avoidance responses in juvenile rock carp(Procypris rabaudi Tchang) 被引量:13
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作者 Xiang HUANG Ke-feng LI +1 位作者 Jun DU Ran LI 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2010年第10期806-811,共6页
Laboratory experiments were conducted to determine the effects of total dissolved gas (TDG) supersaturation on acute lethality and avoidance responses in juvenile rock carp (Procypris rabaudi Tchang). The juvenile... Laboratory experiments were conducted to determine the effects of total dissolved gas (TDG) supersaturation on acute lethality and avoidance responses in juvenile rock carp (Procypris rabaudi Tchang). The juvenile rock carp were exposed to water with different levels of supersaturation (105%, 115%, 120%, 125%, 130%, 135%, 140%, and 145%) and depth of 0.20 m at 25℃ for 60 h. Median lethal time (LT50) was used to assess the lethal responses corresponding to different levels of gas supersaturation. The results show that half of the juvenile rock carp died at the 120%, 125%, 130%, 135%, 140%, and 145% levels of supersaturation, and the LT50 corresponding to different levels of supersaturation was 18.7, 15.4, 8.2, 6.6, 3.5, and 1.7 h. When the level of supersaturated water is below 115%, the mortality is negligible. Avoidance responses were observed 5 min after the fish were put into equilibrated water (99%, 0.08 m deep) and water with different supersaturated levels (105%, 115%, 125%, 135%, and 145%, 0.08 m deep) at 25 ℃. The fish exhibited strong avoidance responses in supersaturated water when the gas supersaturation was above 135%. However, they exhibited an obvious preference to supersaturated water when the gas supersaturation was below 115%. Thus, the juvenile rock carp can likely survive in water with a supersaturated level of 115%. 展开更多
关键词 Gas supersaturation lethality AVOIDANCE Juvenile rock carp (Procypris rabaudi Tchang)
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Anti-bacterial activity and brine shrimp lethality bioassay of methanolic extracts of fourteen different edible vegetables from Bangladesh 被引量:5
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作者 M.Obayed Ullah Mahmuda Haque +4 位作者 Kaniz Fatima Urmi Abu Hasanat Md.Zulfiker Elichea Synthi Anita Momtaj Begum Kaiser Hamid 《Asian Pacific Journal of Tropical Biomedicine》 SCIE CAS 2013年第1期1-7,共7页
Objective:To investigate the antibacterial and cytotoxic activity of fourteen different edible vegetables methanolic extract from Bangladesh.Methods:The antibacterial activity was evaluated using disc diffusion assay ... Objective:To investigate the antibacterial and cytotoxic activity of fourteen different edible vegetables methanolic extract from Bangladesh.Methods:The antibacterial activity was evaluated using disc diffusion assay method against 12 bacteria(both gram positive and gram negative).The plant extracts were also screened for cytotoxic activity using the brine shrimp lethality bioassay method and the lethal concentrations(LC_(50))were determined at confidence intervals by analyzing the data on a computer loaded with"Finney Programme??Results:All the vegetable extracts showed low to elevated levels of antibacterial activity against most of the tested strains(zone of inhibition=5-28 mm).The most active extract against all bacterial strains was from Xanthium indicum which showed remarkable antibacterial activity having the diameter of growth inhibition zone ranging from 12 to 28 mm followed by Alternanthera sessilis(zone of inhibition=6-21 mm).All extracts exhibited considerable general toxicity towards brine shrimps.The LC_(50)value of the tested extracts was within the range of 8.447 to 60.323μg/mL with respect to the positive control(vincristine sulphate)which was 0.91μg/mL.Among all studied extracts,Xanthium indicum displayed the highest cytotoxic effect with LC_(50)value of 8.447μg/mL.Conclusions:The results of the present investigation suggest that most of the studied plants are potentially good source of antibacterial and anticancer agents. 展开更多
关键词 BANGLADESHI VEGETABLES Antibacterial Disc diffusion BRINE SHRIMP lethality
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The acute lethality and endocrine effect of 1,2,3,7,8-PeCDD in juvenile goldfish (Carassius auratus) in vivo 被引量:2
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作者 YANG Yongbin LIU Zhengtao +4 位作者 ZHENG Minghui ZHAO Yanyan WANG Liang SUN Wei XIAO Feng 《Journal of Environmental Sciences》 SCIE EI CAS CSCD 2008年第2期240-245,共6页
1,2,3,7,8-PeCDD was administrated to juvenile goldfish (Carassius auratus) by peritoneal injections to explore the acute lethality and endocrine effects of 1,2,3,7,8-PeCDD in vivo. The value of acute median lethal d... 1,2,3,7,8-PeCDD was administrated to juvenile goldfish (Carassius auratus) by peritoneal injections to explore the acute lethality and endocrine effects of 1,2,3,7,8-PeCDD in vivo. The value of acute median lethal dosage (LD50) of 1,2,3,7,8-PeCDD was determined in acute lethality tests. The endocrine effect of 1,2,3,7,8-PeCDD, whose exposed concentrations were determined based on the LD50 (1.84 mg/kg), was studied by measuring the plasma vitellogenin (Vtg) content in juvenile male goldfish with enzyme-linked immunosorbent assays (ELISA). Due to its significant induction of the plasma Vtg after one week's exposure in vivo in the 1/2 LD50 and LD30 groups, 1,2,3,7,8-PeCDD might be one of the important contributors to the estrogenic effect of PCDDs in the environment. The values of 1/2 LD50 and LD30 were within the range of the effective dosages of 1,2,3,7,8-PeCDD, indicating that there was a certain relationship between the estrogenic effective dosages and the LD50. 展开更多
关键词 1 2 3 7 8-PeCDD GOLDFISH endocrine effect vitellogenin (Vtg) acute lethality ELISA
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DNA repair and synthetic lethality 被引量:2
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作者 Gong-she Guo Feng-mei Zhang +3 位作者 Rui-jie Gao Robert Delsite Zhi-hui Feng Simon N. Powell 《International Journal of Oral Science》 SCIE CAS CSCD 2011年第4期176-179,共4页
Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particu... Tumors often have DNA repair defects, suggesting additional inhibition of other DNA repair pathways in tumors may lead to synthetic lethality. Accumulating data demonstrate that DNA repair-defective tumors, in particular homologous recombination (HR), are highly sensitive to DNA-damaging agents. Thus, HR-defective tumors exhibit potential vulnerability to the synthetic lethality approach, which may lead to new therapeutic strategies. It is well known that poly (adenosine diphosphate (ADP)-ribose) polymerase (PARP) inhibitors show the synthetically lethal effect in tumors defective in BRCA1 or BRCA2 genes encoded proteins that are required for efficient HR. In this review, we summarize the strategies of targeting DNA repair pathways and other DNA metabolic functions to cause synthetic lethality in HR-defective tumor cells. 展开更多
关键词 DNA repair homologous recombination synthetic lethality BRCA Rad52
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SCAR Markers Assisted Selection for a Bentazon Susceptible Lethality Gene (ben) in Rice 被引量:1
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作者 XIANGTai-he YANGJian-bo +3 位作者 YANGQian-jin ZHUQi-sheng LILi HUANGDa-niant 《Rice science》 SCIE 2003年第1期6-10,共5页
In progenies resulting from crosses involving rice cultivar Norin 8m susceptible to bentazon as the donor of ben gene, SCARs tightly linked to ben were utilized for selection of ben. The homozygous and heterozygous ge... In progenies resulting from crosses involving rice cultivar Norin 8m susceptible to bentazon as the donor of ben gene, SCARs tightly linked to ben were utilized for selection of ben. The homozygous and heterozygous genotypes with ben could be identified with the SCARs. The molecular markers offer a powerful tool for indirect selection of ben and can accelerate the introgression of ben into current rice cultivars. 展开更多
关键词 RICE bentazon susceptible lethality gene molecular marker assisted selection breeding
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Early lethality of shRNA-transgenic pigs due to saturation of microRNA pathways
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作者 Zhen DAI Rong WU +8 位作者 Yi-cheng ZHAO Kan-kan WANG Yong-ye HUANG Xin YANG Zi-cong XIE Chang-chun TU Hong-sheng OUYANG Tie-dong WANG Da-xin PANG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2014年第5期466-473,共8页
RNA interference (RNAi) is considered as a potential modality for clinical treatment and anti-virus animal breeding. Here, we investigate the feasibility of inhibiting classical swine fever virus (CSFV) replicatio... RNA interference (RNAi) is considered as a potential modality for clinical treatment and anti-virus animal breeding. Here, we investigate the feasibility of inhibiting classical swine fever virus (CSFV) replication by short hairpin RNA (shRNA) in vitro and in vivo. We generate four different shRNA-positive clonal cells and two types of shRNA-transgenic pigs. CSFV could be effectively inhibited in shRNA-positive clonal cells and tail tip fibroblasts of shRNA-transgenic pigs. Unexpectedly, an early lethality due to shRNA is observed in these shRNA-transgenic pigs. With further research on shRNA-positive clonal cells and transgenic pigs, we report a great induction of interferon (IFN)-responsive genes in shRNA-positive clonal cells, altered levels of endogenous microRNAs (miRNA), and their processing enzymes in shRNA-positive cells. What is more, abnormal expressions of miRNAs and their processing enzymes are also observed in the livers of shRNA-transgenic pigs, indicating saturation of miRNNshRNA pathways induced by shRNA. In addition, we investigate the effects of shRNAs on the development of somatic cell nuclear transfer (SCNT) embryos. These results show that shRNA causes adverse effects in vitro and in vivo and shRNA- induced disruption of the endogenous miRNA pathway may lead to the early lethality of shRNA-transgenic pigs. We firstly report abnormalities of the miRNA pathway in shRNA-transgenic animals, which may explain the early lethality of shRNA-transgenic pigs and has important implications for shRNA-transgenic animal preparation. 展开更多
关键词 MicroRNA pathway shRNA-transgenic pigs Classical swine fever virus (CSFV) Blastocyst formation Early lethality
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Progression of Frequency and Lethality of Severe Malaria from 2017 to 2020 in the Pediatric Unit of CHUD-Parakou (Benin)
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作者 Honorat Francis Lalya Alphonse Noudamadjo +4 位作者 Falilatou Agbeille-Mohamed Mèdétinmè Gérard Kpanidja Zinsou Rodrigue Ahodègnon Julien Didier Adédémy Joseph Agossou 《Open Journal of Pediatrics》 2021年第4期551-558,共8页
<strong>Background:</strong><span style="font-family:""><span style="font-family:Verdana;"> The latest WHO report shows a decline in the performances achieved concernin... <strong>Background:</strong><span style="font-family:""><span style="font-family:Verdana;"> The latest WHO report shows a decline in the performances achieved concernin</span><span style="font-family:Verdana;">g the fight against malaria since 2017. This research work aimed to investigate the progression of frequency and lethality due to severe malaria from 2017 to 2020 in the pediatric unit of the Borgou University Teaching Hospital in Parakou (CHU</span></span><span style="font-family:Verdana;">D</span><span style="font-family:""><span style="font-family:Verdana;">-Parakou). </span><b><span style="font-family:Verdana;">Patients and Methods:</span></b><span style="font-family:Verdana;"> This research work is a descriptive and analytical case-control study focused on all the children aged 1 month and more, hospitalized in the pediatric unit of CHU</span></span><span style="font-family:Verdana;">D-</span><span style="font-family:""><span style="font-family:Verdana;">Parakou from January 1, 2017, to December 31, 2020. Recruitment criteria were the following: be admitted to hospital during the period specified above;have a usable medical record containing the diagnosis and type of discharge, and the findings of thick smear examination and/or of a rapid diagnostic test. Sampling was complete and takes into account all the medical records of children meeting the inclusion criteria. Epi Info 7.2.2 was the software used to perform data processing. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">The frequencies of severe malaria in the unit were estimated at 19.89%, 22.65%, 29.65% and 27.51% respectively in 2017, </span></span><span style="font-family:Verdana;">2018, 2019 and 2020. Lethality rates varied from 7.76% to 8.68 from 2017 through 2020. The death risk associated with severe malaria was 3.08 times</span><span style="font-family:""><span style="font-family:Verdana;"> higher in children suffering from severe acute undernutrition. </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">Despite all the efforts made by the health authorities and the technical and financial part</span><span style="font-family:Verdana;">ners, the frequency and lethality of severe malaria are increasing in the pediatric</span><span style="font-family:Verdana;"> unit of the B/A Regional University Teaching Hospital (CHUD-B/A).</span><span style="font-family:Verdana;"> It is therefore worth investigating the determinants of this situation.</span></span> 展开更多
关键词 Severe Malaria CHILDREN FREQUENCY lethality BENIN
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Effects of total dissolved gas supersaturated water on lethality and catalase activity of Chinese sucker(Myxocyprinus asiaticus Bleeker) 被引量:11
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作者 Shi-chao CHEN Xiao-qing LIU +4 位作者 Wen JIANG Ke-feng LI Jun DU Dan-zhou SHEN Quan GONG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2012年第10期791-796,共6页
Total dissolved gas(TDG) supersaturation caused by dam sluicing can result in gas bubble trauma(GBT) in fish and threaten their survival.In the present study,Chinese suckers(Myxocyprinus asiaticus Bleeker) were expose... Total dissolved gas(TDG) supersaturation caused by dam sluicing can result in gas bubble trauma(GBT) in fish and threaten their survival.In the present study,Chinese suckers(Myxocyprinus asiaticus Bleeker) were exposed to TDG supersaturated water at levels ranging from 120% to 145% for 48 h.The median lethal concentration(LC 50) and the median lethal time(LT 50) were determined to evaluate acute lethal effects on Chinese suckers.The results showed that the LC 50 values of 4,6,8,and 10 h were 142%,137%,135%,and 130%,respectively.The LT 50 values were 3.2,4.7,7.8,9.2,and 43.4 h,respectively,when TDG supersaturated levels were 145%,140%,135%,130%,and 125%.Furthermore,the biological responses in Chinese suckers were studied by assaying the catalase(CAT) activities in gills and muscles at the supersaturation level of 140% within LT 50.The CAT activities in the gills and muscle tissues exhibited a regularity of a decrease after an increase.CAT activities in the muscles were increased significantly at 3/5LT 50(P<0.05) and then came back to the normal level.However,there were no significant differences between the treatment group(TDG level of 140%) and the control group(TDG level of 100%) on CAT activities in the gills before 3/5LT 50(P>0.05),but the activities were significantly lower than the normal level at 4/5LT 50 and LT 50(P<0.05). 展开更多
关键词 Total dissolved gas supersaturation Median lethal time(LT 50) Median lethal concentration(LC 50) Chinese sucker CATALASE
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Synthetic Lethality Induced by Toxic Polyglutamine Tract II: A Survey in Drosophila
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作者 Ping Zhang Daniel Camacho +2 位作者 Shashank Vodapally Shanado Williams Kavitha Kannan 《Open Journal of Genetics》 2015年第2期58-70,共13页
Mutant proteins containing an expanded polyglutamine tract induce cell death and cause neurodegenerative diseases. These toxic proteins interfere with a variety of physiological pathways, but the key interactions betw... Mutant proteins containing an expanded polyglutamine tract induce cell death and cause neurodegenerative diseases. These toxic proteins interfere with a variety of physiological pathways, but the key interactions between the toxins and cellular factors remain unclear. To model the diseases in Drosophila, the GMR-Gal4/UAS gene expression system has been used extensively, which operates in the eyes. By using the system, genome-wide studies have resulted in the isolation of functionally diverse groups of Drosophila genes that interact with the disease proteins. We previously reported that coexpressing the Drosophila Dikar gene and an expanded polyglutamine tract by GMR-Gal4/UAS induced a synthetic lethality. We carried out follow-up experiments to isolate additional synthetic lethal alleles. Our data provide evidence that synthetic lethality associated with expressing an expanded polyglutamine tract is more common than thought to be and could have escaped the conventional genetic screens. Our results also suggest that 1) the gene expression system is leaky, allowing expression outside of the primary target eye cell types;2) expressing an expanded polyglutamine tract is extremely toxic to cells;and 3) combining the leaky expression and the toxicity results in a lethal-prone condition. Thus, genetic modifications to the disease proteins’ acute toxicity could frequently lead to synthetic lethality. However, synthetic lethal alleles are excluded from most conventional screens, necessitating alternative approaches such as a two-step method used in this study to isolate the modifiers. Since synthetic lethality reflects essential genetic buffering networks, studying these alleles may hold the keys to identify the critical interactions in the disease development between the toxic proteins and the physiological pathways. 展开更多
关键词 POLYGLUTAMINE Diseases DROSOPHILA Genetic Screen GMR-Gal4/UAS System Synthetic LETHAL Mutations
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Synthetic Lethality Induced by a Strong <i>Drosophila</i>Enhancer of Expanded Polyglutamine Tract
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作者 Ping Zhang Qiming Wang +1 位作者 Hannah Hughes Gino Intrieri 《Open Journal of Genetics》 2014年第4期300-315,共16页
Proteins containing an expanded polyglutamine tract are neurotoxins. The expanded polyglutamine proteins influence a variety of cellular functions. In Drosophila the GMR-Gal4/UAS expression system has been widely used... Proteins containing an expanded polyglutamine tract are neurotoxins. The expanded polyglutamine proteins influence a variety of cellular functions. In Drosophila the GMR-Gal4/UAS expression system has been widely used in an eye-based model to study human neurodegenerative diseases. This system has facilitated the isolation and characterization of abundant Drosophilagenes that interact with the expanded polyglutamine proteins. We used the GMR-Gal4/UAS system to express three proteins containing an expanded polyglutamine tract, or an expanded polyglutamine tract alone. Doubling the dose of these proteins resulted in pupal lethality, indicating that these toxic proteins induced a sensitized condition that is prone to synthetic lethality. By using the GMR-Gal4/UAS system, we showed that a Drosophilagene interacts with three expanded polyglutamine proteins to induce a synthetic lethal phenotype. We further demonstrated that the synthetic lethality was mediated through the toxic expanded polyglutamine tract. Our study raises a possibility that conventional genetic screens may not recover synthetic lethal alleles, which are presumably stronger interacting alleles than the currently known modifiers of an expanded polyglutamine tract, due to synthetic lethality. 展开更多
关键词 POLYGLUTAMINE Diseases DROSOPHILA Genetic Screen GMR-Gal4/UAS System Synthetic LETHAL Mutations
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Targeting synthetic lethality in colorectal cancer
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作者 Pingting Chen Junsha An +3 位作者 Jianbo Zhou Jiayu Zou Cheng Peng Fu Peng 《Chinese Medical Journal》 2025年第14期1752-1754,共3页
To the Editor:Synthetic lethality(SL)occurs when the simultaneous perturbation of two genes results in cellular death,whereas the perturbation of an individual gene alone is compatible.Colorectal cancer(CRC)is one of ... To the Editor:Synthetic lethality(SL)occurs when the simultaneous perturbation of two genes results in cellular death,whereas the perturbation of an individual gene alone is compatible.Colorectal cancer(CRC)is one of the leading malignancy,ranking third in global incidence and second in mortality.It is widely believed that most CRCs arise from the accumulations of genetic and epigenetic changes.This tumorigenic process,from normal to dysplastic epithelium to carcinoma,along with multiple genetic alterations,is referred to as the adenoma–carcinoma sequence. 展开更多
关键词 genetic epigenetic changesthis genetic changes genetic alterationsi dysplastic epithelium synthetic lethality perturbation two genes adenoma carcinoma sequence epigenetic changes
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Graph based recurrent network for context specific synthetic lethality prediction
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作者 Yuyang Jiang Jing Wang +5 位作者 Yixin Zhang ZhiWei Cao Qinglong Zhang Jinsong Su Song He Xiaochen Bo 《Science China(Life Sciences)》 2025年第2期527-540,共14页
The concept of synthetic lethality(SL)has been successfully used for targeted therapies.To further explore SL for cancer therapy,identifying more SL interactions with therapeutic potential are essential.Recently,graph... The concept of synthetic lethality(SL)has been successfully used for targeted therapies.To further explore SL for cancer therapy,identifying more SL interactions with therapeutic potential are essential.Recently,graph neural network-based deep learning methods have been proposed for SL prediction,which reduce the SL search space of wet-lab based methods.However,these methods ignore that most SL interactions depend strongly on genetic context,which limits the application of the predicted results.In this study,we proposed a graph recurrent network-based model for specific context-dependent SL prediction(SLGRN).In particular,we introduced a Graph Recurrent Network-based encoder to acquire a context-specific,low-dimensional feature representation for each node,facilitating the prediction of novel SL.SLGRN leveraged gate recurrent unit(GRU)and it incorporated a context-dependent-level state to effectively integrate information from all nodes.As a result,SLGRN outperforms the state-of-the-arts models for SL prediction.We subsequently validate novel SL interactions under different contexts based on combination therapy or patient survival analysis.Through in vitro experiments and retrospective clinical analysis,we emphasize the potential clinical significance of this context-specific SL prediction model. 展开更多
关键词 synthetic lethality graph recurrent network context-specific graph combination therapy
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DNMT3A loss drives a HIF-1-dependent synthetic lethality to HDAC6 inhibition in non-small cell lung cancer
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作者 Jiayu Zhang Yingxi Zhao +12 位作者 Ruijuan Liang Xue Zhou Zhonghua Wang Cheng Yang Lingyue Gao Yonghao Zheng Hui Shao Yang Su Wei Cui Lina Jia Jingyu Yang Chunfu Wu Lihui Wang 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2024年第12期5219-5234,共16页
DNMT3A encodes a DNA methyltransferase involved in development,cell differentiation,and gene transcription,which is mutated and aberrant-expressed in cancers.Here,we revealed that loss of DNMT3A promotes malignant phe... DNMT3A encodes a DNA methyltransferase involved in development,cell differentiation,and gene transcription,which is mutated and aberrant-expressed in cancers.Here,we revealed that loss of DNMT3A promotes malignant phenotypes in lung cancer.Based on the epigenetic inhibitor library synthetic lethal screening,we found that small-molecule HDAC6 inhibitors selectively killed DNMT3A-defective NSCLC cells.Knockdown of HDAC6 by siRNAs reduced cell growth and induced apoptosis in DNMT3A-defective NSCLC cells.However,sensitive cells became resistant when DNMT3A was rescued.Furthermore,the selectivity to HDAC6 inhibition was recapitulated in mice,where an HDAC6 inhibitor retarded tumor growth established from DNMT3A-defective but not DNMT3A parental NSCLC cells.Mechanistically,DNMT3A loss resulted in the upregulation of HDAC6 through decreasing its promoter CpG methylation and enhancing transcription factor RUNX1 binding.Notably,our results indicated that HIF-1 pathway was activated in DNMT3A-defective cells whereas inactivated by HDAC6 inhibition.Knockout of HIF-1 contributed to the elimination of synthetic lethality between DNMT3A and HDAC6.Interestingly,HIF-1 pathway inhibitors could mimic the selective efficacy of HDAC6 inhibition in DNMT3A-defective cells.These results demonstrated HDAC6 as a HIF-1-dependent vulnerability of DNMT3A-defective cancers.Together,our findings identify HDAC6 as a potential HIF-1-dependent therapeutic target for the treatment of DNMT3A-defective cancers like NSCLC. 展开更多
关键词 DNMT3A NSCLC Synthetic lethal HDAC6 HIF-1
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Enhancing the stability and ecological safety of mass-reared transgenic strains for field release by redundant conditional lethality systems 被引量:2
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作者 Alfred M. Handler 《Insect Science》 SCIE CAS CSCD 2016年第2期225-234,共10页
The genetic manipulation of agriculturally important insects now allows the development of genetic sexing and male sterility systems for more highly efficient biologically-based population control programs, most notab... The genetic manipulation of agriculturally important insects now allows the development of genetic sexing and male sterility systems for more highly efficient biologically-based population control programs, most notably the Sterile Insect Technique (SIT), for both plant and animal insect pests. Tetracycline-suppressible (Tet-off) conditional lethal systems may function together so that transgenic strains will be viable and fertile on a tetracycline-containing diet, but female-lethal and male sterile in tetracycline-free condi- tions. This would allow their most efficacious use in a unified system for sterile male-only production for SIT. A critical consideration for the field release of such transgenic insect strains, however, is a determination of the frequency and genetic basis of lethality revertant survival. This will provide knowledge essential to evaluating the genetic stability of the lethality system, its environmental safety, and provide the basis for modifications ensur- ing optimal efficacy. For Tet-off lethal survival determinations, development of large-scale screening protocols should also allow the testing of these modifications, and test the ability of other conditional lethal systems to fully suppress propagation of rare Tet-off survivors. If a dominant temperature sensitive (DTS) pupal lethality system proves efficient for sec- ondary lethality in Drosophila, it may provide the safeguard needed to support the release of sexing/sterility strains, and potentially, the release of unisex lethality strains as a form of genetic male sterility. Should the DTS Prosβ21 mutation prove effective for redundant lethality, its high level of structural and functional conservation should allow host-specific cognates to be created for a wide range of insect species. 展开更多
关键词 conditional lethality ecological safety redundant lethality Sterile InsectTechnique transgenic insects
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Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy 被引量:6
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作者 Kailin Li Jieqiong You +5 位作者 Qian Wu Wen Meng Qiaojun He Bo Yang Chengliang Zhu Ji Cao 《Acta Pharmaceutica Sinica B》 SCIE CAS CSCD 2021年第9期2738-2748,共11页
Synthetic lethality is a proven effective antitumor strategy that has attracted great attention.Large-scale screening has revealed many synthetic lethal genetic phenotypes,and relevant smallmolecule drugs have also be... Synthetic lethality is a proven effective antitumor strategy that has attracted great attention.Large-scale screening has revealed many synthetic lethal genetic phenotypes,and relevant smallmolecule drugs have also been implemented in clinical practice.Increasing evidence suggests that CDKs,constituting a kinase family predominantly involved in cell cycle control,are synthetic lethal factors when combined with certain oncogenes,such as MFC,TP53,and RAS,which facilitate numerous antitumor treatment options based on CDK-related synthetic lethality.In this review,we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future. 展开更多
关键词 Synthetic lethality Cyclin-dependent kinase Antitumor therapy ONCOGENES MYC P53 RAS PARP
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Targeting“undruggable”c-Myc protein by synthetic lethality 被引量:2
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作者 Chen Wang Hui Fang +1 位作者 Jiawei Zhang Ying Gu 《Frontiers of Medicine》 SCIE CSCD 2021年第4期541-550,共10页
Synthetic lethal screening,which exploits the combination of mutations that result in cell death,is a promising method for identifying novel drug targets.This method provides a new avenue for targeting Uundruggable,9 ... Synthetic lethal screening,which exploits the combination of mutations that result in cell death,is a promising method for identifying novel drug targets.This method provides a new avenue for targeting Uundruggable,9 proteins,such as c-Myc.Here,we revisit current methods used to target c-Myc and discuss the important functional nodes related to c-Myc in non-oncogene addicted network,whose inhibition may cause a catastrophe for tumor cell destiny but not for normal cells.We further discuss strategies to identify these functional nodes in the context of synthetic lethality.We review the progress and shortcomings of this research field and look forward to opportunities offered by synthetic lethal screening to treat tumors potently. 展开更多
关键词 synthetic lethality undruggable transcription factor C-MYC
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Evaluation of Effects of Copper Sulphate and Ferrocene on Nile Tilapia Oreochromis niloticus(L.)Fingerlings
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作者 Oriaku Ugonma Isdore-Rufus Chioma Nwakanma 《Journal of Agricultural Science and Technology(A)》 2025年第1期31-50,共20页
This study was carried out to evaluate the response of Nile tilapia(Oreochromis niloticus)fingerlings to acute copper sulphate and ferrocene toxicity.Nile tilapia fingerlings weighing 2.3±0.2 g were acclimated an... This study was carried out to evaluate the response of Nile tilapia(Oreochromis niloticus)fingerlings to acute copper sulphate and ferrocene toxicity.Nile tilapia fingerlings weighing 2.3±0.2 g were acclimated and randomly distributed at a rate of 10 fish per 30 L aquarium.Fish were exposed to a range of copper sulphate and ferrocene concentrations of 4 mg/L,8 mg/L,12 mg/L,16 mg/L and 2.5 mg/L,5 mg/L,7.5 mg/L,10 mg/L respectively.Fish not exposed to any toxicant served as control.Mortality was assessed and median lethal concentration(LC50)and median lethal time(LT50)were calculated.The 96-h LC50 values obtained for copper sulphate and ferrocene were 7.49 mg/L(confidence interval CI:6.35 to 8.57 mg/L)and 3.55 mg/L(CI:0.98 to 5.17 mg/L)respectively.The LC50 decreased with time of exposure implying that toxicity increased over time,however,LT50 decreased as concentration increased.The safe concentration for copper sulphate derived was 1.913 mg/L and 1.196 mg/L for ferrocene.Histological analyses were carried out on fish gills and skin.The skin histomorphology showed marked and widespread epidermal loss and widespread mycocytic degeneration in treatments with high concentration for both toxicants.The gill morphology showed moderate to severe hyperplasia of the primary gill epithelia leading to partial or complete loss of the secondary lamellae. 展开更多
关键词 Acute toxicity test Oreochromis niloticus copper sulphate FERROCENE median lethal concentration(LC50) median lethal time(LT50)
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Efficacy of Selected Botanical Powders to Control Maize Weevil, Sitophilus zeamais Motschulsky in Stored Sorghum Grain
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作者 Hamé Abdou Kadi Kadi Aissata Mamadou Ibrahim +1 位作者 Bonnie B. Pendleton Kadri Aboubacar 《Journal of Agricultural Chemistry and Environment》 2025年第1期23-36,共14页
Increasing concern over the amount of insecticide residues in food has encouraged research for ecologically sound strategies to effectively manage stored-product insect pests and protect living organisms and the envir... Increasing concern over the amount of insecticide residues in food has encouraged research for ecologically sound strategies to effectively manage stored-product insect pests and protect living organisms and the environment. Botanicals were evaluated as potential alternatives to control maize weevil, Sitophilus zeamais Motschulsky, in stored sorghum, Sorghum bicolor (L.) Moench. Beetles and moths of stored grain at farm and consumer levels damage 5 - 35% worldwide and >40% in tropical countries. Maize weevil is the most damaging storage insect of sorghum grain. Management of storage insects relies on insecticides that leave residues in food and the environment. Treatments were powders of neem bark, Azadirachta indica;mesquite pods, Prosopis glandulosa;milkweed leaves, Asclepias speciosa;and a check (no botanical powder). Eight newly emerged maize weevils were provided 5 g of Malisor-84 grain treated with three doses of each plant powder. Every 2 days, data were recorded on the number of adults killed by each treatment. Percentage killed was calculated by dose per treatment and compared with the check. Grain loss was calculated based on initial and final weights. LD50 was determined by probit analysis, and associations between variables were assessed by simple linear correlation. Powder of mesquite and milkweed at 0.2 g were more effective than neem or the check in killing S. zeamais (>90%) and reducing grain damage (34 - 35.2%) and weight loss (0.8%). Milkweed at 0.1 g and neem at 0.2 g killed 78.1% of weevils. Neem at 0.05 g was slow acting, resulting in 62.5% dead and more grain damage (59.5%) and weight loss (3.6%). Botanicals at low doses (LD50 = 0.2 - 0.4 g) showed efficacy in controlling maize weevils and are recommended alternatives to guarantee quantity and quality of stored cereal grains. 展开更多
关键词 SORGHUM GRAIN Botanical Plants Powder Maize Weevil Sitophilus zeamais Lethal Dose
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Antimicrobial,antityrosinase and brine shrimp lethality test of Bauhinia rufescens Lam(Fabaceae)
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作者 Aminu Muhammad Hasnah Mohd Sirat 《Journal of Coastal Life Medicine》 2013年第2期135-140,共6页
Objective:To evaluate leaves and stem bark extracts of Bauhinia rufescens for antimicrobial activities,tyrosinase enzyme inhibition potentials and lethality to brine shrimp larvae(Artemiasalina).Methods:The plant mate... Objective:To evaluate leaves and stem bark extracts of Bauhinia rufescens for antimicrobial activities,tyrosinase enzyme inhibition potentials and lethality to brine shrimp larvae(Artemiasalina).Methods:The plant materials were extracted based on polarity gradient of petroleum ether,ethyl acetate and methanol.The extracts were investigated for their antimicrobial,antityrosinase and cytotoxicity potentials.Results:The antimicrobial results indicated that the extracts inhibited the microbial growth in the range of 6.00-12.57 mm(450-1800μg/mL)for bacterial strains and 7.33-14.03 mm(225-1800μg/mL)for fungal strains.While the tyrosinase enzyme inhibition assay of the extracts showed that both the petroleum ether leaves and stem bark extracts exhibited a moderate inhibition(39.60%and 39.89%)towards the action of mushroom tyrosinase enzyme on L-DOPA.In the brine shrimp lethality assay,ethyl acetate and methanol extracts of the leaves of the plant were found toxic to the Artemia salina with IC_(50)values of 0.059 mg/mL and 0.389 mg/mL.However,both the petroleum ether and ethyl acetate extracts of the stem bark were nontoxic to the larvae.Conclusions:The result of the present study suggest the presence of phytochemicals possessing antimicrobial and antityrosinase activity as well as cytotoxic agents. 展开更多
关键词 ANTIMICROBIAL Antityrosinase Brine shrimp lethality Bauhinia rufescens
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