The main mechanism of toxicity of organophosphate (OP) and carbamate (CB) insecticides is their irreversible binding and inhibition of acetylcholinestrase (AChE), encoded by ace1 (acetylcholinestrase gene 1), leading to eventual death of insects. Mutations in AChE may significantly reduce insects susceptibility to these pesticides. Bombyx mori is an important beneficial insect, and no OP- or CB-resistant strains have been generated. In this study, wild-type ace1 (wace1) and mutant ace1 (mace1) were introduced into BmN cells, confirmed by screening and identification. The expression of wace1 and mace1 in the cells was confirmed by Western blot and their expression levels were about 21-fold higher than the endogenous ace1 level. The activities of AChE in wace1 and mace1 transgenic cells were 10.6 and 20.2% higher compared to control cells, respectively. mace1 transgenic cells had higher remaining activity than wace1 transgenic cells under the treatment of physostigmine (a reversible cholinesterase inhibitor) and phoxim (an OP acaricide). The results showed that ace1 transgene can significantly improve ace1 expression, and ace1 mutation at a specific site can reduce the sensitivity to AChE inhibitors. Our study provides a new direction for the exploration of the relationship between AChE mutations and drug resistance.
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Front Immunol
January 2025
Integrative Immunobiology Department, Duke University, Durham, NC, United States.
Introduction: The regulation of expression during T-cell development and immune responses is essential for proper lineage commitment and function in the periphery. However, the mechanisms of genetic and epigenetic regulation are complex, and their interplay not entirely understood. Previously, we demonstrated the need for CD4 upregulation during positive selection to ensure faithful commitment of MHC-II-restricted T cells to the CD4 lineage.
View Article and Find Full Text PDFCancer Res Commun
January 2025
Candel Therapeutics, Needham, MA, United States.
CAN-2409 is a replication-defective adenovirus that delivers the herpes simplex virus (HSV)-thymidine kinase gene to infected cells. Intratumoral administration of CAN-2409 followed by prodrug results in the formation of a toxic metabolite able to induce immunogenic cell death, exposure of tumor-associated antigens, and activation of local and systemic immune responses. We used a dynamic labeling model with MC38 tumor cells implanted in photoconvertible Kaede mice.
View Article and Find Full Text PDFSci Rep
January 2025
International Joint Research Laboratory for Recombinant Pharmaceutical Protein Expression System of Henan, Xinxiang Medical University, Xinxiang, China.
To meet the requirements of the biopharmaceutical industry, improving the yield of recombination therapeutic protein (RTP) from Chinese hamster ovary (CHO) cells is necessary. The human cytomegalovirus (CMV) promoter is widely used for RTP expression in CHO cells. To further improve RTP production, we truncated the human CMV intron and further evaluated the effect of four synthetic introns, including ctEF-1α first, EF-1α first, chimeric, and β-globin introns combined with the CMV promoter on recombinant expression levels in transient and stably recombinant CHO cells.
View Article and Find Full Text PDFJ Nat Prod
January 2025
School of Pharmacy, Nantong University, 9 Seyuan Road, Nantong 226019, People's Republic of China.
Ten new resin glycosides, controlins I-X (-), were isolated from the seeds of . Their structures were established by spectroscopic analysis as well as by chemical means. Compounds were identified as glycosidic acid methyl esters, considered as artifacts generated via transesterification with MeOH from natural resin glycosides.
View Article and Find Full Text PDFCell Rep Med
January 2025
Biomaterials Research Center, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; Department of Cardiology, Guangzhou Institute of Cardiovascular Disease, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou 510260, China; Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China; School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 510182, P.R. China. Electronic address:
C-C chemokine receptor type 2 (CCR2) cardiac-resident macrophages (CCR2 cRMs) are known to promote cardiac repair after myocardial infarction (MI). However, the substantial depletion and slow recovery of CCR2 cRMs pose significant barriers in cardiac recovery. Here, we construct a functional conductive cardiac patch (CCP) that can provide exogenously elastic conductive microenvironment and induce endogenously reparative microenvironment mediated by CCR2 cRMs for MI repair.
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