Cell Reports Methods
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2024
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IF 4.3
Jinli Geng,Yaxiong Yang,Boying Li,Zhen Yu,Shuang Qiu,Wen Zhang,Shixin Gao,Nan Liu,Yi Liu,Bo Wang,Yubo Fan,Chengfen Xing,Xiaodong Liu
Genetically encoded inhibitors of Ca V 1 channels that operate via C-terminus-mediated inhibition (CMI) have been actively pursued. Here, we advance the design of CMI peptides by proposing a membrane-anchoring tag that is sufficient to link the inhibitory modules to the target channel as well as chemical and optogenetic modes of system control. We designed and implemented the constitutive and inducible CMI modules with appropriate dynamic ranges for the short and long variants of Ca V 1.3, both naturally occurring in neurons. Upon optical (near-infrared-responsive nanoparticles) and/or chemical (rapamycin) induction of FRB/FKBP binding, the designed peptides translocated onto the membrane via FRB-Ras, where the physical linkage requirement for CMI could be satisfied. The peptides robustly produced acute, potent, and specific inhibitions on both recombinant and neuronal Ca V 1 activities, including Ca 2+ influx-neuritogenesis coupling. Validated through opto-chemogenetic induction, this prototype demonstrates Ca 2+ channel modulation via membrane-assisted molecular linkage, promising broad applicability to diverse membrane proteins.
研究领域:
神经科学
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分子生物学
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生物工程
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DOI
PubMed
高影响因子
CHEMICO-BIOLOGICAL INTERACTIONS
·
2024
·
IF 4.7
Yingying Hu,Zhize Ye,Hualu Wu,Xiaohai Chen,Hailun Xia,Jian-ping Cai,Guo-xin Hu,Ren-ai Xu
Clothianidin , classified as a second-generation neonicotinoid , has achieved extensive application due to its high efficacy against insect pests . This broad-spectrum usage has resulted in its frequent detection in environmental surveys. CYP2C19 and CYP3A4 are crucial for converting clothianidin to desmethyl-clothianidin (dm-clothianidin). The expression of these CYP450s can be significantly influenced by genetic polymorphisms . The objective of our research was to examine the catalytic effects of 27 CYP3A4 variants and 31 CYP2C19 variants on the metabolism of clothianidin within recombinant insect microsomes . These variants were assessed through a well-established incubation procedure. In addition, the concentration of its metabolite dm-clothianidin was quantified by employing an ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Lastly, the kinetic parameters of these CYP3A4 and CYP2C19 variants were calculated by applying Michaelis-Menten kinetic analysis to fit the data. The observed changes in enzyme activity were related to the metabolic transformation of clothianidin to dm-clothianidin. In the CYP2C19 metabolic pathway, one variant (CYP2C19.23) showed no notable change in intrinsic clearance (CL int ), four variants (CYP2C19.29, .30, .31 and L16F) demonstrated a marked increase in CL int (110.86–183.46 %), and the remaining 25 variants exhibited a considerable decrease in CL int (26.38–89.79 %), with a maximum decrease of 73.62 % (CYP2C19.6). In the CYP3A4 metabolic pathway, 26 variants demonstrated significantly reduced CL int (10.54–52.52 %), with a maximum decrease of 89.46 % (CYP3A4.20). Our results suggested that most variants of CYP3A4 and CYP2C19 significantly altered the enzymatic activities associated with clothianidin metabolism to various degrees. This study provides new insights into assessing the metabolic behavior of pesticides and delivers crucial data that can guide clinical detoxification strategies.
研究领域:
毒理学
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药理学
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环境科学
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产品关联
DOI
PubMed
高影响因子
CROP PROTECTION
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2011
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IF 1.517
B. Sarath Babu,S.R. Pandravada,R.D.V.J. Prasada Rao,K. Anitha,S.K. Chakrabarty,K.S. Varaprasad
Today India is the main producer of peppers especially the hot peppers , albeit mostly for domestic use. The thrips and mites, and the virus diseases transmitted by them along with fungal diseases like fruit rot, powdery mildew , bacterial wilt and leaf spots are the limiting factors in pepper productivity. The solution for managing these pests on a sustained basis exists in adopting eco-friendly approaches like using resistant cultivars. Fortunately huge natural genetic diversity exists in pepper and therefore, essential research efforts in finding out resistant sources and their utilization have been by and large dynamic and successful. Despite continuous scientific efforts there is a dire need for new cultivars with resistant traits for various pests suitable to varied climatic conditions, consumption and quality preferences all over the world. Efforts need to be intensified to find out useful genetic material and to introduce genes of resistance against insects, fungal and virus diseases into commercial cultivars. Genetic resources that have been used intensively in pepper breeding are for developing sweet peppers, hot peppers, bell peppers in various shapes, sizes and colors. Germplasm repositories at the World Vegetable Research Center (AVRDC) and United States Department of Agriculture (USDA) do possess number of genotypes resistant to insect pests , nematode, fungi, bacteria and virus diseases. At AVRDC resistant genotypes originating from several pepper growing countries to most virus diseases like Tobacco mosaic virus , Cucumber mosaic virus , Pepper veinal mottle virus , Chilli veinal mottle virus , Peanut bud necrosis virus etc., were identified from its rich pepper diversity. Exploitation of rich genetic diversity resulted in the development of new cultivars encompassing resistance to various pests and good agronomical traits. This has eventually resulted in meeting the demanding situations of diverse domestic as well as global production requirements. The chile database ( Chile Database, 2010 ) highlights the exemplary utilization of germplasm and development of large number of cultivars and hybrids resistant to most diseases and nematodes around the world. This paper also depicts information on Indian sources of resistance to thrips, mites, leaf curl complex, nematodes and diseases, while presenting the scope for exploitation of diversity available in the Indian National Gene Bank and other repositories all over the world. An attempt is also made to identify the gaps in the genetic diversity and cultivars against the biotic constraints and the augmentation efforts required to be initiated toward enrichment of the gene pool for domestic as well as global use.
研究领域:
植物学
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遗传学
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农业科学
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DOI
高影响因子
Frontiers in Pharmacology
·
2025
·
IF 4.8
Ruibing Wu,Hengye Yuan,Yuehua Wang,Xianggang Gou,Wanhua Hou,Zhongzheng Zhou,Xinran Wang,Xiuling Deng,Changshan Wang,Haisheng Wang,Jia Yan
Background: Norcantharidin (NCTD), a bioactive compound derived from traditional Chinese medicine, has demonstrated promising anticancer activity against multiple malignancies, particularly hepatocellular carcinoma (HCC). However, its epigenetic regulatory mechanisms and associated transcriptional consequences remain poorly characterized.Methods: In this study, we integrated biochemical assays with a panel of cellular analyses assessing cell viability, proliferation, colony formation, and migratory capacity to investigate NCTD’s therapeutic potential in HCC progression. Potential molecular targets of NCTD were systematically identified through integrated network pharmacology approaches. Chromatin immunoprecipitation quantitative PCR (ChIP-qPCR) was performed to quantify H3K27me3 enrichment level at the TOP2A locus in NCTD-treated HCC cells. Molecular docking simulations were employed to examine structural interactions between NCTD and EZH2 (enhancer of zeste homolog 2), while co-immunoprecipitation assays were further conducted to validate protein-protein interactions between EZH2 and protein phosphatase 1 (PP1).Results: We identified topoisomerase IIα (TOP2A) as a critical molecular target mediating NCTD’s anti-HCC effects. Functional characterization revealed that NCTD significantly attenuated HCC cell proliferation and induced G2/M phase cell cycle arrest through disruption of the TOP2A-p53 signaling axis. Mechanistic investigations demonstrated that NCTD epigenetically suppresses TOP2A transcription via PRC2 (Polycomb Repressive Complex 2)-mediated deposition of the repressive histone mark H3K27me3 at the TOP2A promoter. Structural biology analyses confirmed direct binding of NCTD to EZH2 protein, consequently impairing PP1-mediated dephosphorylation and enhancing PRC2 complex stability.Conclusion: Our findings establish that NCTD exerts anticancer effects in HCC through epigenetic silencing of TOP2A. This work not only elucidates a novel pharmacoepigenetic mechanism underlying NCTD’s antitumor activity but also provides translational rationale for developing PRC2-targeted therapeutic strategies in HCC management.
研究领域:
肿瘤学
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分子生物学
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药理学
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产品关联
DOI
PubMed
高影响因子
INDUSTRIAL CROPS AND PRODUCTS
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2023
·
IF 5.9
Ningning Zhang,Lili Yang,Yongpeng Ma,Jinyong Huang,Shixin Zhu,Hao Dong,Zhuang Zhao,Yang Lu
Cornus officinalis Siebold & Zucc. is an important Chinese herbal medicine with traditional clinical applications, a long history of cultivation and high economic value in China. C. officinalis is distributed mainly in the Shaanxi, Henan, and Zhejiang provinces of China, which are also historically the main production areas, and which still provide 90% of the medicinal material of this species for the contemporary market. In this study, we investigated the main germplasm resources of C. officinalis across its distribution, based on fruit morphology, the concentrations of selected medicinally active ingredients, and molecular population genetic analysis. The results indicated that the C. officinalis populations sampled had abundant variation in fruit morphology and chemical component content, and showed high genetic diversity , as revealed by microsatellite markers. Clustering results based on morphology, active ingredient concentration and microsatellite markers supported the idea that populations from Zhejiang province were distinct from those in Shaanxi and Henan. The fruit and molecular data suggested that the Shaanxi and Henan populations were mixed, which could be attributed to their close geographical distance and frequent germplasm exchange . Most of the C. officinalis populations had relatively weak genetic differentiation from others sampled, and most of the individuals sampled showed extensive admixture. We suggest that artificial gene flow caused by intensive cultivation and widespread trading is responsible for the observed admixture of genetic components and blurred genetic boundaries between C. officinalis populations, especially in the Shaanxi and Henan populations. We also propose some suggestions for the efficient utilization and conservation of C. officinalis germplasm. These findings provide valuable information on the genetic resources of C. officinalis and offer guidelines for breeding programs and scientific management of C. officinalis .
研究领域:
植物学
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遗传学
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药理学
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植物育种
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产品关联
DOI
高影响因子
Frontiers in Microbiology
·
2024
·
IF 4
Yuanyuan Li,Tao Jiang,Jianfeng Mao,Fangyi Xu,Rong Zhang,Jing Yan,Jiachang Cai,Yanjun Xie
Linezolid-resistant enterococci have increased in recent years due to the worldwide spread of acquired resistance genes (cfr, optrA, and poxtA) in clinical, animal, and environmental settings. This study investigated the carriage of optrA-positive enterococci among patients in the anorectal surgery ward in Hangzhou, China, and characterized the genetic context of optrA. A total of 173 wound secretion samples were obtained to screen optrA-positive enterococci. Of the 173 samples, 15 (8.67%) were positive for optrA, including 12 Enterococcus faecalis, two E. faecium, and one E. hirae. Multilocus sequence type analysis revealed that 12 optrA-positive E. faecalis isolates belonged to eight different sequence types (STs), of which ST16 was the main type. Eight optrA variants were identified, whose optrA flanking regions with a fexA gene downstream were bounded by different mobile genetic elements. Furthermore, the optrA gene in 8 out of 15 optrA-positive enterococci could be successfully transferred through conjugation. The findings revealed a high carriage rate of optrA in enterococci from one anorectal surgery ward in China. The dissemination of optrA-positive enterococci isolates in clinical settings should be continually monitored.
研究领域:
微生物学
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分子生物学
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临床医学
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遗传学
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产品关联
DOI
PubMed
高影响因子
DEVELOPMENT
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2025
·Vol. 152
·期 6
·
IF 3.6
Lin Zhen,Rong Bowen,Wu Meixia,Yan Junyi,Hong Tong,Hou Linjun,Tang Xinzhe,Liu Qiang,Peng Xiaozhong,Chen Yao,Lan Fei,Tong Ming-Han
ASH2L is a core component of KMT2 complexes, crucial for H3K4 trimethylation. However, its role in spermatogenesis remains elusive. Here, we demonstrate an essential role of Ash2l for meiotic prophase but dispensable for mitosis in differentiated spermatogonia. Using a germ cell-specific Ash2l knockout mouse model, we reveal that Ash2l deficiency leads to meiotic arrest and sterility in both sexes. Ash2l -deficient spermatocytes exhibit failures in chromosomal synapsis associated with persistent DMC1 foci and γH2AX, resulting in meiocyte loss due to apoptosis. Conversely, Ash2l -deficient differentiated spermatogonia show normal development. Mechanistically, Ash2l deficiency results in a global loss of H3K4me3 in promoter regions and significantly decreases expression of thousands of genes. Among these are genes involved in epigenetic silencing pathways, such as H3K9 di-methylation, DNA methylation and piRNA pathways, that are crucial for transposon repression during meiotic prophase I progression. Supporting this, we observe that Ash2l mutant spermatocytes display ectopic expression of LINE1-ORF1P. Our findings therefore reveal the previously unappreciated role of ASH2L-dependent H3K4me3 modification in spermatogenesis and provide clues to the molecular mechanisms in epigenetic disorders underlying male infertility.
研究领域:
分子生物学
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生殖生物学
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遗传学
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DOI
PubMed
高影响因子
Agronomy-Basel
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2025
·Vol. 15
·期 8
·1807
·
IF 3.4
Tao Shen,Jianping Li,Chao Wang,Haihong Fan,Yunxiao Zheng,Yifan Liu,Shuzhen Zhang,Liying Zhu,Xiaoyan Jia,Yongfeng Zhao,Wei Song,Jinjie Guo
Kernel test weight (KTW) is one of the important assessment indexes of maize quality grade and one of the important influencing factors of yield. This study analyzed 12 traits related to KTW in 321 maize inbred lines using multivariate methods. The principal component analysis (PCA) indicated that the four PCs covered 78.176% of the information of the 12 traits in 321 maize inbred lines. Cluster analysis categorized the maize lines into six groups, identifying 16 elite inbred lines with the highest KTW. A stepwise regression model for KWT evaluation was developed using four PCA traits: starch content, amylopectin content, 100-kernel weight, and kernel circumference. The findings of this study serve as a valuable reference point for the genetic improvement of maize germplasm re-sources in kernel test weight and the creation of high kernel test weight maize resources.
研究领域:
作物遗传学
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植物育种学
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数量性状分析
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产品关联
DOI
高影响因子
IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-PLANT
·
2023
·Vol. 59
·期 1
·1-13
·
IF 2.6
Xiao Xu,Zhang Chunling,Liu Yang,Wang Xiaofei,You Chunxiang
Agrobacterium-mediated genetic transformation is inefficient in apple, which limits the development of apple-related research and industry . Using molecular methods to create a new and more efficient method of genetic transformation has become the focus of research, and improving the efficiency of the three key steps of transformation, regeneration, and rooting has become an effective means of achieving this goal. Baby Boom (BBM) is widely used in plant biotechnology as an important transcription factor regulating adventitious shoot regeneration and somatic embryogenesis. A homologous gene, MDP0000125317 , with high amino acid sequence similarity to AtBBM was cloned in this study, and it was identified from the Royal Gala apple genome ( Malus × domestica Borkh.), which was named as MdBBM . The qRT-PCR analysis revealed that MdBBM was expressed at higher levels in the ovary, roots, and seeds. Agrobacterium -mediated transformation of pRI101- MdBBM significantly improved the shoot regeneration efficiency in apples. In the experiment, 33 of the MdBBM-OE transformants were obtained. Compared with the control, only adventitious shoots were formed on the regeneration shoot medium. In vitro leaves of MdBBM-OE transformants were regenerated in three forms: adventitious shoots, adventitious roots, and somatic embryos. Overexpression of MdBBM promoted somatic embryogenesis under 2,4-dichlorophenoxyacetic acid (2,4-D) induction.
研究领域:
植物学
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遗传学
·
分子生物学
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产品关联
DOI
高影响因子
JOURNAL OF FOOD SCIENCE
·
2025
·Vol. 90
·期 3
·e70075
·
IF 3.4
Xuefeng Qu,Qinxi Wang,Zemi Xie,Yuejin Wu,Yangjunna Zhang,Zhen Liu,Yin Wang
The Chlamydomonas reinhardtii (red) is a strain rich in protoporphyrin IX, which could be used as algal-derived novel sustainable nutritional sources. However, the safety research on C. reinhardtii (red) remains insufficient and further investigation is needed. In order to assess the safety of C. reinhardtii (red) and to expand its use in food applications, a series of toxicological safety evaluations were carried out to observe acute toxicity, subchronic toxicity and genotoxicity of C. reinhardtii (red). The C. reinhardtii (red) was administered to an acute oral toxicity test, mammalian micronucleus test, mouse chromosomal aberration test in Institute of Cancer Research (ICR) mice, and 90-day repeated-dose oral toxicity test in Sprague-Dawley (SD) rats. In the acute oral toxicological test, no mortality or abnormalities were observed in male and female rats, with an median lethal dose(Lethal Dose, 50%) (LD 50 ) exceeding 10.0 g/kg body weight (BW). Similarly, male and female mice exhibited no mortality or abnormalities, with an LD 50 surpassing 20.0 g/kg BW. The results of bacterial reverse mutation test, mammalian micronucleus test, and mouse chromosomal aberration test were all negative, suggesting that the C. reinhardtii (red) did not show mutagenicity under the conditions of this experiment. In a 90-day repeated-dose oral toxicity study, the SD rats were orally administered daily doses of 2.0 g/kg BW, 4.0 g/kg BW, and 8.0 g/kg BW without exhibiting any signs or symptoms of toxicity. Therefore, the no observed adverse effect level (NOAEL) of C. reinhardtii (red) was 8.0 g/kg BW/day. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food. Practical Application The aim of this study was to assess the safety of C. reinhardtii (red) and to expand its use in food applications. The major finding of this study is that the C. reinhardtii (red) did not show acute toxicity, subchronic toxicity and genotoxicity under the conditions of this experiment. This study contributes to information necessary to form a basis for safety for expanding the application range of C. reinhardtii (red) in food.
研究领域:
毒理学
·
食品安全
·
营养学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Cell and Developmental Biology
·
2022
·
IF 6.081
Zhou Tong,Chen Guobin,Chen Meng,Wang Yubin,Zou Guiwei,Liang Hongwei
Sex dimorphism is a key feature of Chinese soft-shelled turtle (Pelodiscus sinensis). The males (M) have higher econosmic value than females (F) due to wider calipash and faster growth. Exogenous hormones like estradiol and methyltestosterone can induce sexual reversal to form new phenotypes (pseudo-female, PF; pseudo-male, PM) without changing the genotype. The possibility of inducing sexual reversal is particularly important in aquaculture breeding, but the underlying biological mechanisms remain unclear. Here we applied a direct RNA sequencing method with ultralong reads using Oxford Nanopore Technologies to study the transcriptome complexity in P. sinensis. Nanopore sequencing of the four gender types (M, F, PF, and PM) showed that the distribution of read length and gene expression was more similar between same-sex phenotypes than same-sex genotypes. Compared to turtles with an M phenotype, alternative splicing was more pronounced in F turtles, especially at alternative 3′ splice sites, alternative 5′ splice sites, and alternative first exons. Furthermore, the two RNA methylation modifications m5C and m6A were differentially distributed across gender phenotypes, with the M type having more modification sites in coding sequence regions, but fewer modification sites in 3′UTR regions. Quantitative analysis of enriched m6A RNAs revealed that the N6-methylated levels of Odf2, Pacs2, and Ak1 were significantly higher in M phenotype individuals, while the N6-methylated levels of Ube2o were reduced after sexual reversal from both M and F phenotypes. Taken together, these findings reveal an important role of epigenetics during sexual reversal in Chinese soft-shelled turtles.
研究领域:
发育生物学
·
分子生物学
·
水产养殖学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Hailin Long,Xuehong Qiu,Li Cao,Guiqing Liu,Zhongchen Rao,Richou Han
Ethnopharmacological relevance The Chinese cordyceps, a parasitic Thitarodes insect- Ophiocordyceps sinensis fungus complex in the Qinghai-Tibet Plateau, is one of the most valuable traditional Chinese medicines and health food for ameliorating conditions associated with aging and for treating fatigue, night sweats, hyperglycemia, hyperlipidemia, respiratory, renal and liver diseases, and hyposexuality. The natural Chinese cordyceps resource is rare due to its harsh growing environment, limited geographical distribution and global climate warming. Artificial cultivation of Chinese cordyceps has been successfully established to meet its high demand in market. Aims of the study The present study aims to evaluate the toxicological safety of the cultivated Chinese cordyceps and provide scientific data for subsequent development and utilization of this valuable biological resource. Materials and methods The Chinese cordyceps was cultivated by mimicking the habitat environment in low-altitude areas and identified by morphological and microscopic characteristics. Its phytochemical profile was determined by the HPLC. Toxicological studies based on the cultivated Chinese cordyceps were conducted, including chromosomal aberration test of Chinese hamster lung (CHL) cells, Ames test, acute toxicity test and micronucleus (MN) test of bone marrow cells. Results The Chinese cordyceps successfully cultivated in low-altitude areas exhibited the same morphological and microscopic characteristics as natural Chinese cordyceps. The adenosine content was in accordance with the Chinese Pharmacopoeia (2015 Edition). The HPLC fingerprint was determined and five main chromatographic peaks representing uracil, uridine, inosine, guanosine and adenosine were identified. No dose-dependent increase in the rates of chromosomal aberration was detected in the presence or absence of metabolic activation system. Ames test also demonstrated no dose-dependent increase in the number of reversion mutation for five bacterial strains, with or without rat liver microsomal enzyme mixture (S9) metabolic activation, at a quantity range of 128–5000 μg cultivated Chinese cordyceps per plate. The acute toxicity test with mice showed that after 20 g/kg oral administration of cultivated Chinese cordyceps, neither animal death nor any abnormal change in general dissection of various tissues and organs of the animals were found within 14 days. The median lethal dose (LD 50 ) was greater than 5 g/kg, which is regarded as a non-toxic level, and maximum tolerable dose (MTD) of cultivated Chinese cordyceps in ICR mice was more than 20 g/kg. MN test of mouse bone marrow cells indicated no significant differences among each sample dose and the negative control. Conclusion Based on the results from four toxicological tests, it was concluded that the cultivated Chinese cordyceps was classified as non-toxic in one single administration at high doses by intragastric route in mice. This study provides scientific experimental basis for its safety.
研究领域:
药理学
·
毒理学
·
传统中药研究
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）