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PubMed1999

Phylogenetic analysis of the apolipoprotein B mRNA-editing region. Evidence for a secondary structure between the mooring sequence and the 3' efficiency element.

Apolipoprotein (apo) B mRNA editing is the deamination of C(6666) to uridine, which changes the codon at position 2153 from a genomically encoded glutamine (CAA) to an in-frame stop codon (UAA). The apoB mRNA-editing enzyme complex recognizes the editing region of the apoB pre-mRNA with exquisite precision. Four sequence elements spanning 139 nucleotides (nt) on the apoB mRNA have been identified that specify this precision. In cooperation with the indispensable mooring sequence and spacer element, a 5' efficiency element and a 3' efficiency element enhance editing in vitro. A phylogenetic comparison of 32 species showed minor differences in the apoB mRNA sequence, and the apoB mRNA from 31 species was robustly edited in vitro. However, guinea pig mRNA was poorly edited. Compared with the consensus sequences of these 31 species, guinea pig apoB mRNA has three variations in the 3' efficiency element, and the conversion of these to the consensus sequence increased editing to the levels in the other species. From this information, a model for the secondary structure was formulated in which the mooring sequence and the 3' efficiency element form a double-stranded stem. Thirty-one mammalian apoB mRNA sequences are predicted to form this stem positioning C(6666) two nucleotides upstream of the stem. However, the guinea pig apoB mRNA has a mutation in the 3' efficiency element (C(6743) to U) that predicts an extension of the stem and hence the lower editing efficiency. A test of this model demonstrated that a single substitution at 6743 (U to C) in the guinea pig apoB mRNA, that should reduce the stem, enhanced editing, and mutations in the 3' efficiency element that extended the stem for three base pairs dramatically reduced editing. Furthermore, the addition of a 20-nucleotide 3' efficiency element RNA, to a 58-nucleotide guinea pig apoB mRNA lacking the 3' efficiency element more than doubled the in vitro editing activity. Based on these results, a model is proposed in which the mooring sequence and the 3' efficiency element form a double-stranded stem, thus suggesting a mechanism of how the 3' efficiency element enhances editing.

Animals↗
PubMed1990

A model for RNA editing in kinetoplastid mitochondria: "guide" RNA molecules transcribed from maxicircle DNA provide the edited information.

A class of small RNA molecules possibly involved in RNA editing is present in the mitochondrion of Leishmania tarentolae. These "guide" RNA (gRNA) molecules are encoded in intergenic regions of the mitochondrial maxicircle DNA and contain sequences that represent precise complementary versions of the mature mRNAs within the edited regions. In addition, the 5' portions of several gRNAs can form hybrids with mRNAs just 3' of the preedited region. A model is presented in which a partial hybrid formed between the gRNA and preedited mRNA is substrate for multiple cycles of cleavage, addition or deletion of uridylates, and religation, eventually resulting in a complete hybrid between the gRNA and the mature edited mRNA.

Animals↗
PubMed1991

Modification of Trypanosoma brucei mitochondrial rRNA by posttranscriptional 3' polyuridine tail formation.

Trypanosoma brucei mitochondrial transcripts can be posttranscriptionally processed by uridine addition or deletion. With editing of mRNAs, uridine addition and deletion create precisely altered reading frames. The addition of nonencoded uridines to mitochondrial guide RNAs results in a less precise modification. Although uridines are specifically added to the 3' termini, their number varies, which results in heterogeneous oligo(U) tails on guide RNAs. In this paper, we show that the mitochondrial 9S and 12S rRNAs are also modified by uridine addition. These modifications appear to have aspects in common with both RNA editing and oligo(U) tail formation. Metabolic labeling studies with intact mitochondria and [alpha-32P]UTP, in the absence of transcription, demonstrated the posttranscriptional timing of the event. T1 RNase comparison analyses of cytidine 3',5'-[5'-32P]biphosphate 3'-end-labeled and [alpha-32P]UTP metabolically labeled rRNAs, along with direct RNA sequencing of the 3' termini, identified the site of uridine addition and revealed the creation of an oligo(U) tail for both rRNAs. 12S and 9S rRNAs hybrid selected from total cell RNA exhibited the same modification, demonstrating the presence of this processing in vivo. Moreover, only 3'-poly(U)-tailed 9S and 12S rRNAs were detected in total cellular and mitochondrial RNAs, which suggests that they are the most abundant and probable mature forms. The 12S and 9S rRNA oligo(U) tails differed significantly from each other, with the 12S having a heterogeneous tail of 2 to 17 uridines and the 9S having a tail of precisely 11 uridines. The mechanism of formation and the function of the rRNA poly(U) tails remain to be determined.

Animals↗
PubMed2025

Fluorinated Ionizable Lipids for Efficient Spleen-Targeted mRNA Delivery in Cancer Immunotherapy.

Efficient and selective mRNA delivery to immune-related organs, particularly the spleen, remains a major barrier to the broader clinical translation of mRNA therapeutics. Here, leveraging the clinically approved SM-102/ALC-0315 ionizable lipid scaffold, we rationally designed a combinatorial library of fluorinated ionizable lipids (FILs) by systematically modulating hydrophobic tails and fluorine stoichiometry. Through synthesis and evaluation of 74 candidate FILs, we identify SSC6F5 lipid nanoparticles (LNPs) as a lead formulation with exceptional spleen-targeting specificity (>90%) across intravenous, intramuscular, and subcutaneous administrations. Compared to clinically approved SM102 LNPs and spleen-tropic SM102/18PA (SORT) LNPs, intravenously administered SSC6F5 LNPs achieve 10.6-fold and 63.1-fold higher splenic mRNA transfection, respectively. Proteomic analysis of protein corona on SSC6F5 LNPs reveals significant enrichment of apolipoprotein D (Apod) and reduction in apolipoprotein H (Apoh), implicating a novel endogenous recognition pathway driving enhanced spleen targeting. Functionally, SSC6F5 LNPs enable efficient genome editing in splenic macrophages, dendritic cells, T cells, and B cells in Ai9 mice, and elicit potent CD8+ T cell and humoral responses in a B16-OVA murine melanoma model, resulting in significant tumor growth inhibition. These findings establish fluorinated lipids as a mechanistically distinct and translationally versatile platform for precision spleen-targeted mRNA delivery in gene editing and cancer immunotherapy.

Animals↗
PubMed2005

Protein splicing: its discovery and structural insight into novel chemical mechanisms.

Protein splicing is a posttranslational cellular process, in which an intervening protein sequence (intein) is self-catalytically excised out from a nascent protein precursor and the two flanking sequences (N- and C-exteins) are ligated to produce two mature enzymes. This unique reaction was first discovered from studies of the structure and expression of the VMA1 gene in Saccharomyces cerevisiae. VMA1 consists of a single open reading frame and yet comprises two independent genetic information for Vma1p (a catalytic 70-kDa subunit of the vacuolar H+-ATPase) and VDE (a 50-kDa DNA endonuclease) as an in-frame spliced insert in the gene. Subsequent studies have demonstrated that protein splicing is not unique for the VMA1 precursor and there are many operons in nature, which implement genetic information editing at protein level. To elucidate its precise reaction mechanisms from a viewpoint of structure-directed chemistry, a series of crystal structural studies has been carried out with the use of splicing-inactive and slowly spliceable precursors of VMA1 recombinants. One precursor structure revealed that the N-terminal junction of the introduced extein polypeptide forms an intermediate containing a five-membered thiazolidine ring. The other precursor structures showed spliced products with a linkage between the N- and C-extein segments. This article summarizes biochemical and structural studies on a self-catalytic mechanism for protein splicing that is triggered and terminated solely via thiazolidine intermediates with tetrahedral configurations formed within the splicing sites where proton ingress and egress are driven by balanced protonation and deprotonation.

Amino Acid Sequence↗
PubMed2026

Hormone priming and metabolic engineering of phytohormone crosstalk in rice under combined biotic and abiotic stresses: a multi-omics perspective for climate-resilient crop development.

Rice (Oryza sativa L.) is the caloric backbone for more than half of humanity, yet it remains one of the most vulnerable crops to the simultaneous biotic and abiotic stresses exacerbated by climate change. Phytohormone priming and the complex crosstalk networks governed by transcription factor hubs like WRKY, MYB, and NAC serve as the central adaptive mechanism for stress resilience. This review synthesizes how multi-omics integration, including spatial and single-cell transcriptomics, is resolving the molecular architecture of hormonal priming and epigenetic stress memory. We critically evaluate advanced metabolic engineering and genome-editing strategies such as CRISPR-Cas9, base/prime editing, and synthetic gene circuits that enable precision modifications to decouple stress tolerance from historical yield penalties. Furthermore, we discuss the emerging roles of microbiome-assisted priming via synthetic consortia and the application of artificial intelligence and digital twins (continuously updated computational models of crop physiology) for predictive stress management. By integrating these diverse technological pillars, we propose a systems-level roadmap for developing climate-resilient rice cultivars capable of maintaining yield stability across a volatile combinatorial stress landscape. This synthesis provides a framework for translating mechanistic hormonal insights into field-applicable cultivars to ensure global food security.

CRISPR↗
PubMed2003

[Ventricular tachycardia "in salvoes"].

The term of ventricular tachycardia "in salvoes" describes electrophysiographic appearances of several consecutive ectopic ventricular beats without interposition of sinus rhythm. This is an intermediate arrhythmic state between isolated ventricular extrasystoles and sustained ventricular tachycardia. The generally accepted definition of the term "sustained" implies a duration of over 30 seconds or poor haemodynamic tolerance. Strictly speaking, the term "salvoe" has no precise definition in cardiology. In the 1996 edition of the Petit Robert French dictionary, the term is defined as the simultaneous discharge of guns or successive blasts of canons. The Delaware medical dictionary does not provide a French definition of the term "salvoe". In practice, we use the term tachycardia in salvoes in the same meaning as ventricular tachycardia. Schematically, in clinical practice, two situations may be encountered. In the first case, salvoes of VT are recorded in apparently normal hearts; they are not life-threatening and, though often nearly asymptomatic, they may pose therapeutic problems. In the second case, the arrhythmia occurs in a diseased heart, with a low ejection fraction, in which the essential problem is the vital prognosis.

Electrocardiography↗
PubMed2026

Targeted Nanoparticle Delivery CRISPR/Cas9: overcoming biological barriers, enhancing stability, and improving therapeutic precision.

Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) has emerged as a promising gene-editing platform for genetic disorders; however, its in vivo application remains limited by low delivery efficiency and biological barriers. Many CRISPR payloads fail to reach target sites due to extracellular degradation, immune clearance, and intracellular trafficking limitations. This review examines the interplay between biological barriers and nanoparticle engineering strategies for CRISPR/Cas9 delivery. A barrier-oriented engineering approach is proposed as a central framework, encompassing ligand-based surface modification for enhanced targeting and uptake, improved circulation stability via PEGylation and biomimetic coatings, and optimized payload release through endosomal escape strategies. Stimulus-responsive nanoparticle systems further enable spatiotemporal control over payload release. Nuclear targeting strategies, including optimization of nuclear localization signals (NLS) and exploitation of endogenous trafficking pathways, are highlighted as key factors for improving genome-level editing efficiency. Despite these advances, major challenges-including limited intracellular delivery efficiency, insufficient targeting precision, and safety concerns-continue to hinder clinical translation. Future directions highlight artificial intelligence-driven nanoparticle design, personalized delivery systems, and next-generation CRISPR platforms. Overall, an integrated, barrier-oriented engineering strategy is essential for advancing CRISPR/Cas9 delivery toward clinical applications, ultimately advancing global good health and well-being.

CRISPR/Cas9↗
PubMed2025

CRISPR RNP-Mediated Transgene-Free Genome Editing in Plants: Advances, Challenges and Future Directions for Tree Species.

CRISPR ribonucleoprotein (RNP)-mediated genome editing offers a transgene-free platform for precise genetic modification in diverse herbaceous and tree species, including rice, wheat, apple, poplar, oil palm, rubber tree and grapevine. However, its application in woody plants faces distinct challenges, notably inefficient delivery and regeneration difficulties, particularly in species such as bamboo. While some of these issues also occur in herbaceous plants, they are often significantly more complex in woody species due to factors such as intricate cell wall architecture, widespread recalcitrant genotypes and inherent limitations of current delivery platforms. This review presents the first in-depth, critical re-evaluation of recent advancements in RNP-mediated editing in woody plants, highlighting these obstacles that warrant focused attention. Unlike plasmid-based CRISPR systems, RNP editing utilises Cas9/Cas12a protein-guide RNA complexes without integrating foreign DNA. This enables a DNA-free editing strategy that simplifies regulatory approval and minimises off-target effects due to the transient presence and rapid degradation of RNPs within plant cells. While PEG-mediated protoplast transfection and particle bombardment remain the primary reported methods for RNP delivery in trees, we evaluate promising alternative strategies such as lipofection, electroporation, cell-penetrating peptides and nanoparticle-based systems for targeted RNP delivery. Despite their promise, these advanced methods remain largely untested in woody species. Finally, we outline future research directions, including the development of tree-specific RNP delivery systems and regeneration protocols to enhance efficiency and minimise cytotoxicity. These innovations are essential for unlocking the full potential of RNP-mediated genome editing in long-lived tree species. This review provides a focused and timely roadmap for expanding the application of RNP technology across diverse woody plants.

Gene Editing↗
PubMed2025

Transitioning from native to synthetic receptors: broadening T-cell engineering and beyond.

T-cell immunotherapy has progressed rapidly, evolving from native T-cell receptor biology to the development of innovative synthetic receptors that extend therapeutic applications beyond cancer. This review explores engineering strategies, ranging from natural TCRs to synthetic receptors, that increase T-cell activation and therapeutic potential. We begin by highlighting the foundational role of native receptors in the T-cell response, emphasizing how these structural and functional insights inform the design of next-generation synthetic receptors. Comparisons between CAR and TCR-like synthetic receptors underscore their respective advantages in specificity, efficacy, and safety, as well as potential areas for further improvement. In addition, gene editing technologies such as CRISPR-Cas9 enable precise modifications to the T-cell genome, enhancing receptor performance and minimizing immunogenic risks. In addition to tumors, these engineered T cells can be directed against viral infections, autoimmune disorders, and other diseases. We also explore advanced strategies that engage multiple immune cell types to achieve synergistic, durable responses. By demonstrating how native and synthetic receptors collectively drive innovation, this review aims to inspire new research directions and ultimately expand the scope of T-cell engineering for universal therapeutic applications.

Humans↗
PubMed2006

[Surveys of the consumption of nutritional antioxidants in inflammatory bowel diseases].

The redox homeostasis of patients with inflammatory bowel disease is not balanced because of malnutrition and malabsorption. The seriousness of this illness often hinders the intake and use of bioactive agents. We have just a small amount of knowledge about how patients can get access to these important materials. The authors' aim was to edit a questionnaire, which can estimate, with large precision, the amount of fruit and vegetable consumption among a random-chosen group of IBD patients. We also thought that the measuring of tea, fruit-juice and wine consumption is also important in order to see whether the intake of these can help the intake of natural polyphenol, vitamin and trace elements. For this study 50 IBD patients (25 male, 25 female, 35-67 years) and 50 healthy people (35 male, 15 female, 25-47 years) were asked. During the completion of the questionnaire in 8 cases (5 male, 3 female) the provided data could not be accepted, because of inaccuracy. During this study, it became obvious that the intake of polyphenols was not enough if we focus on the average daily consumption of fruits and vegetables. Red wine cannot be considered efficient for replacing polyphenols, because more than the half of patients doesn't drink it at all, or drink it once or twice a month. From the aspect of drinking tea or eating fruits, the situation is much better. The participants' (92 people) consumption of vegetables and fruits is reduced to a small variety, which is not beneficial. Mostly used plants often caused different disorders, and that is why a controlled recommendation of polyphenol, vitamin, trace element and fiber would be favorable.

Adult↗
PubMed2001

Internet user profile in the field of parasitology.

This study determined a profile of current Internet users in parasitology, their use patterns on the Internet for parasitologic purposes, and the Web sites they would recommend. In a European survey, 689 parasitologically engaged scientists were asked to fill out a questionnaire about Internet access, current problems, current and future use, and which Web sites they would recommend as well as about the use of e-mail. In all, 153 (22.2%) of the interviewees returned the questionnaire. Only one participant had no access to the Internet. Time expenditure was considered the main problem involved in use of the Internet. The Internet was mainly used for e-mail (96.1%); for literature research (93.5%); for reading of electronic journals (51.6%); and for gathering of information, e.g., about institutes and colleagues (58.2%) and about congresses (49.7%). In the future, 71.9% of the respondents would like to read electronic journals more often and 49.7% would like to use the web more intensively for acquisition of information about congresses, universities, and institutions. Requests for the future included an easier application of the browser software (33%) and a shorter response time (47.7%). The survey demonstrates that the Internet has assumed a definite place in the lives of researchers in the field of parasitology. Survey responses indicate a need for electronic journals. In our opinion, universities and parasitology societies should be urged to publish journals electronically on the Web. To diminish current problems involved in the finding of relevant information on the Internet, we strongly recommend careful reading of the instructions regarding the search engines used. Web pages with clear structures, small file sizes, precise HTML (hypertext markup language) key-word editing, and page titles would facilitate more accurate discovery of specific sites. In addition, there seems to be a need for regular publication of reviewed parasitology-link collections.

Computer Literacy↗
PubMed2025

Advances in Cytoplasmic Male Sterility in Sugar Beet from Mitochondrial Genome Structural Dynamics and Nuclear-Cytoplasmic Coordination.

Sugar beet (Beta vulgaris L.) is a globally important sugar crop whose hybrid breeding system relies heavily on cytoplasmic male sterility (CMS) lines. Recent advances in sugar beet genomics, particularly the release of high-quality reference genomes and the characterization of organellar genomes, have provided a foundation for elucidating the molecular genetic mechanisms of CMS. Furthermore, innovations in gene editing technologies are enabling transformative functional studies in this field. The precise targeting of CMS-associated mitochondrial genes and nuclear restorer-of-fertility genes not only allows for direct investigation of theoretical models governing fertility regulation through nuclear-cytoplasmic interactions but also holds promise for the targeted development of sterile and restorer lines. This review systematically summarizes progresses in sugar beet genomics, the development of gene editing tools, and the current understanding of the molecular genetics of CMS and fertility restoration in sugar beet. Although challenges remain-such as efficient delivery of editing tools into mitochondria and coordinated editing of multiple genes-the integration of genomic and gene editing technologies is expected to accelerate multi-omics-guided dissection of CMS mechanisms. These advances will facilitate the precise design of high-yield, high-sugar, and stress-resistant sugar beet hybrids, thereby providing core scientific and technological support for the sustainable development of the global sugar industry.

Beta vulgaris↗
PubMed2006

ApoB mRNA editing is mediated by a coordinated modulation of multiple apoB mRNA editing enzyme components.

Apolipoprotein (apo)B mRNA editing is accomplished by a large multiprotein complex. How these proteins interact to achieve the precise single-nucleotide change induced by this complex remains unclear. We investigated the relationship between altered apoB mRNA editing and changes in editing enzyme components to evaluate their roles in editing regulation. In the mouse fetal small intestine, we found that the dramatic developmental upregulation of apoB mRNA editing from approximately 3% to 88% begins with decreased levels of inhibitory CUG binding protein 2 (CUGBP2) expression followed by increased levels of apoB mRNA editing enzyme (apobec)-1 and apobec-1 complementation factor (ACF) (4- and 8-fold) and then by decreased levels of the inhibitory components glycine-arginine-tyrosine-rich RNA binding protein (GRY-RBP) and heterogeneous nuclear ribonucleoprotein (hnRNP)-C1 (75% and 56%). In contrast, the expression of KH-type splicing regulatory protein (KSRP), apobec-1 binding protein (ABBP)1, ABBP2, and Bcl-2-associated athanogene 4 (BAG4) were unaltered. In the human intestinal cell line Caco-2, the increase of apoB mRNA editing from approximately 1.7% to approximately 23% was associated with 6- and 3.2-fold increases of apobec-1 and CUGBP2, respectively. In the mouse large intestine, the editing was 48% and had a 2.7-fold relatively greater CUGBP2 level. Caco-2 and the large intestine thus have increased instead of decreased CUGBP2 and a lower level of editing, suggesting that inhibitory CUGBP2 may play a critical role in the magnitude of editing regulation. Short interfering RNA-mediated gene-specific knockdown of CUGBP2, GRY-RBP, and hnRNP-C1 resulted in increased editing in Caco-2 cells, consistent with their known inhibitory function. These data suggest that a coordinated expression of editing components determines the magnitude and specificity of apoB mRNA editing.

Animals↗
PubMed2004

Simple statistical models predict C-to-U edited sites in plant mitochondrial RNA.

BACKGROUND: RNA editing is the process whereby an RNA sequence is modified from the sequence of the corresponding DNA template. In the mitochondria of land plants, some cytidines are converted to uridines before translation. Despite substantial study, the molecular biological mechanism by which C-to-U RNA editing proceeds remains relatively obscure, although several experimental studies have implicated a role for cis-recognition. A highly non-random distribution of nucleotides is observed in the immediate vicinity of edited sites (within 20 nucleotides 5' and 3'), but no precise consensus motif has been identified. RESULTS: Data for analysis were derived from the the complete mitochondrial genomes of Arabidopsis thaliana, Brassica napus, and Oryza sativa; additionally, a combined data set of observations across all three genomes was generated. We selected datasets based on the 20 nucleotides 5' and the 20 nucleotides 3' of edited sites and an equivalently sized and appropriately constructed null-set of non-edited sites. We used tree-based statistical methods and random forests to generate models of C-to-U RNA editing based on the nucleotides surrounding the edited/non-edited sites and on the estimated folding energies of those regions. Tree-based statistical methods based on primary sequence data surrounding edited/non-edited sites and estimates of free energy of folding yield models with optimistic re-substitution-based estimates of approximately 0.71 accuracy, approximately 0.64 sensitivity, and approximately 0.88 specificity. Random forest analysis yielded better models and more exact performance estimates with approximately 0.74 accuracy, approximately 0.72 sensitivity, and approximately 0.81 specificity for the combined observations. CONCLUSIONS: Simple models do moderately well in predicting which cytidines will be edited to uridines, and provide the first quantitative predictive models for RNA edited sites in plant mitochondria. Our analysis shows that the identity of the nucleotide -1 to the edited C and the estimated free energy of folding for a 41 nt region surrounding the edited C are the most important variables that distinguish most edited from non-edited sites. However, the results suggest that primary sequence data and simple free energy of folding calculations alone are insufficient to make highly accurate predictions.

Arabidopsis↗
PubMed1997

Mitochondrial mRNA 3' cleavage/polyadenylation and RNA editing in Trypanosoma brucei are independent events.

The organization of the mitochondrial maxicircle genome of Trypanosoma brucei is unique in the close packing of the mRNA genes. For many of them, the 5' and 3' ends of adjacent transcripts overlap and formation of the proper 3' or 5' end can eliminate a portion of the coding sequence of the adjacent gene. Large, polycistronic transcripts have been detected. suggesting that mechanisms for precise cleavages at both 5' and 3' gene boundaries must exist. However, no common sequences near the ends of the mRNAs that could be candidates for control regions have been detected. In addition, nothing is known about how RNA editing interacts with and affects 5' and 3' processing and/or polyadenylation. Edited precursor transcripts have been detected, indicating that editing complexes can assemble prior to transcript cleavage. Because editing often initiates near the 3' end of the mRNA, the assembly of an editing complex in this region may influence the cleavage selection process. In order to determine the extent that RNA editing and 3' end-processing interact, RNAs were analyzed to determine the extent of editing in precursor RNAs and to determine if unedited transcripts can be cleaved and polyadenylated. Two overlapping RNA junctions were analyzed; the junction between NADH dehydrogenase (ND) subunit 7 and cytochrome oxidase (CO) subunit III, and the junction between CO subunit II and maxicircle unidentified reading frame (MURF) II. For both of these RNAs, editing affects restriction endonuclease recognition sequences, allowing us to analyze editing patterns by differential restriction digests. These analyses suggest that when the gRNA is supplied in trans, RNA editing and cleavage/polyadenylation are independent events and while they may influence one another, one event is not dependent on the other. Conversely, for the COII transcript, where the gRNA is located at the 3' end of the mRNA and appears to be supplied in cis, edited precursors were not detected. This suggests a requirement for a precise intramolecular interaction for COII editing that cannot form prior to 3' end-maturation.

Animals↗
PubMed2026

Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.

Macrophages are central regulators of the tumor microenvironment (TME), shaping immune suppression, angiogenesis, metabolism, and therapeutic resistance in solid cancers. While early strategies sought to deplete tumor-associated macrophages (TAMs) or block monocyte recruitment, limited efficacy and compensatory mechanisms revealed the need for functional reprogramming rather than elimination. Recent advances in viral vectors, CRISPR-Cas genome editing, and RNA-based delivery platforms have enabled precise genetic modification of macrophages, giving rise to chimeric antigen receptor macrophages (CAR-Ms) and related engineered products. Beyond antigen targeting, effective macrophage engineering requires stabilization of pro-inflammatory identity, resistance to tumor-induced repolarization, metabolic reinforcement, and integration of checkpoint modulation pathways. This review synthesizes current strategies across DNA, mRNA, and siRNA-based platforms, highlighting convergent design principles that connect TAM reprogramming with CAR-M development. We discuss reshaping phagocytosis checkpoints, metabolic and transcriptional stabilization, cytokine augmentation, and synthetic receptor architecture, emphasizing combinatorial and context-aware engineering, while proposing new candidate gene targets. Engineered macrophages are thus evolving from simple effector cells into programmable immune coordinators capable of converting immunologically "cold" tumors into inflamed, therapy-responsive niches.

CAR-M↗
PubMed1992

Uses of statistical editing of real-time ambulatory electrocardiographic recordings for quantitative ventricular ectopic beat counts.

Real-time ambulatory monitoring analyzes each heart beat, counts events, and stores ECG samples for later visual verification. Typically, a physician examines these to determine whether the computer algorithm accurately identified arrhythmias. Physician editing is performed using best clinical judgement. We developed a simple statistical editing procedure for adjusting false positive and false negative computer detections. In 20 subjects having 24-hr monitoring we compared statistically edited ventricular premature beat (VPB) counts and pair/run counts with the unedited monitor counts and with physician assessment using a visual counted gold standard. The agreement of the statistically edited count with the visual standard was 65% for total VPB, 85% for VPB pair/runs, and 90% for a risk score based on ventricular ectopy. Corresponding agreements for unedited monitor count were 15, 25, and 30%, respectively. Physician assessment was not sufficiently precise to allow quantitative count estimates. This study indicates a statistical editing procedure substantially increases the level of agreement between the visual standard and the monitor count of VPB frequency and complexity. Statistically edited data are suitable for quantitative counts of VPB and other arrhythmic events in research and in medical diagnosis and treatment. This editing procedure can be a useful adjunct to any ambulatory monitoring system.

Arrhythmias, Cardiac↗