SEARCH · Search PubMed

Results for “Olfactory receptor (OR) gene”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 451 records · Page 25Linked to original sources

PubMed2026

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals↗

PubMed2026

Emerging techniques of CRISPR/Cas system in antiviral therapy and diagnostics: Applications, limitations, and translational perspectives.

The CRISPR/Cas (clustered regularly interspaced short palindromic repeats) system is a versatile technology for developing antiviral medicines and editing viral genomes in both diagnostics and vaccine synthesis. Emerging insights into class 2 effectors, such as Cas9, Cas12, and Cas13, which target viral DNA and RNA, have revolutionized vaccines against viruses such as HIV, HPV, HBV, and EBV. Innovative diagnostic techniques such as SHERLOCK, DETECTR, and FELUDA have demonstrated system's diversity and accuracy in detecting the virus markers, supporting clinical decision-making, indicating adaptability and precision of CRISPR. This review critically evaluates CRISPR's role in RNA editing, emphasizing its importance for functional genomics and development of recombinant vaccines. Translational challenges are critically discussed, including off-target effects, delivery limitations, and ethical issues, for which unique approaches such as high-fidelity Cas variants, non-viral delivery systems, and bioethical frameworks are evaluated to address these limitations. This review also covers other social implications, such as accessibility and biosecurity risks, associated with CRISPR technologies Collectively, these advances underscore the transformative potential of CRISPR technologies in shaping next-generation antiviral diagnostics and therapeutics.

CRISPR-Cas Systems↗

PubMed2026

Ramu stunt virus genome reveals previously unreported segments and nucleocapsid domain duplication in Mechlorovirus.

Ramu stunt virus (RmSV), a member of the genus Mechlorovirus within the family Phenuiviridae, was previously described as a six-segmented RNA virus infecting sugarcane. In this study, we re-examined type material and additional isolates using high-throughput sequencing and RT-PCR validation, revealing that RmSV possesses a nine-segmented genome, making it the largest reported in the Phenuiviridae. This expanded architecture includes duplicated RNA segments (RNA 2a and RNA 2b) encoding nucleocapsid-like proteins and two novel segments (RNA 7 and RNA 8). Comparative analysis showed that RNA 2a and 2b share about 84% amino acid identity, while RNA 5 encodes a third nucleocapsid homolog, indicating unprecedented domain redundancy. Structural modeling confirmed that all three nucleocapsid proteins maintain a conserved fold despite low sequence identity, with electrostatic mapping suggesting differential RNA-binding potential. Additionally, RNA 6 encodes a hypothetical protein structurally similar to the rice stripe virus disease-specific S-protein, implicating a role in symptom development. Transcript abundance analysis revealed RNA 6 as the most highly expressed segment across isolates. These findings revise the genomic composition of RmSV, highlight mechanisms of genome plasticity and adaptive evolution in plant-infecting bunyaviruses, and underscore practical implications for diagnostic assay design, resistance breeding, and biosecurity surveillance.

Genome, Viral↗

PubMed2026

Insights into the regulation of the HOTAIR proximal promoter.

HOTAIR (HOX transcript antisense RNA) is a HOXC-cluster long intervening non-coding RNA (lincRNA) whose cancer relevance is tightly coupled to how its transcription is wired into hormone, hypoxia, inflammatory, and developmental signaling. HOTAIR is known to associate with cancer cell proliferation, motility, tumor invasion, and metastasis. The present mini-review focuses on the regulatory architecture and mechanistic complexity of HOTAIR transcriptional regulation, with emphasis on three organizing principles. First, we consider the impact of promoter choice between a canonical proximal promoter (P1), which supports the 2.2-2.4 kb transcript, and an alternative upstream promoter/TSS (P2), which contributes to context-dependent transcription initiation. Second, we examine the long-distance enhancer-promoter communication between HOTAIR distal enhancer and P1/P2. Third, we summarize the recent epigenetic and epi-transcriptomic mechanisms involved in HOTAIR transcript initiation and elongation. A combination of these events determines isoform-specific transcription to govern cell-type-, context-, and cancer specific modulation of HOTAIR expression that promotes tumor formation and cancer progression. Finally, the review proposes how large-scale RNA datasets, long-read sequencing, and isoform-specific studies can refine our understanding of this versatile lincRNA's regulation.

Humans↗

PubMed2026

Loss, persistence and reversal of phenotypic traits.

The irreversibility of complex trait loss has long been a tenet of evolutionary biology. However, this idea is increasingly at odds with the numerous documented exceptions across the Tree of Life. We synthesise this growing body of evidence across a diverse array of taxa and traits, exploring the evolutionary conditions that enable evolutionary reversal. By integrating macroevolutionary, genetic, and developmental information, we argue that trait reversal is commonly fostered by some form of persistence in the generative developmental pathway of the lost trait. We identify three overarching modes of trait reversal and support them with multiple case studies: by pleiotropy (the involvement of the same generative components in other traits and/or functions), by plasticity (environment-dependent expression of the trait) and by hemiplasy (persistence in another lineage, followed by reticulate evolution). We also examine important affinities between trait reversal and evolutionary novelties, undermining a neat distinction between what is old and what is new in evolution. This survey may provide a useful framework for future explorations of the developmental mechanisms underlying these still overlooked macroevolutionary dynamics.

Phenotype↗

PubMed2026

Phenotypic and transcriptomic characterization of biallelic RNU2-2 developmental and epileptic encephalopathy.

OBJECTIVE: A significant proportion of individuals with suspected genetic developmental and epileptic encephalopathies (DEEs) remain unsolved following whole genome sequencing (WGS). Here we describe biallelic RNU2-2 variants causing a recently reported, severe, recessive DEE. METHODS: We screened individuals who have received WGS analyses at the Genomic Medicine Centre Karolinska for Rare Diseases for biallelic RNU2-2 variants. Deep phenotyping was performed through reviewing entire medical histories and phenotypic traits were transcribed to their corresponding Human Phenotype Ontology (HPO) term. HPO terms were used to generate pairwise phenotypic similarity scores and assess for significantly shared phenotype enrichment in the RNU2-2 sub-cohort. RNA sequencing analyses were performed in fibroblast and blood tissues to compare splicing events between RNU2-2 individuals and two independent control groups. RESULTS: We identified 14 individuals from nine families with 12 ultra-rare biallelic RNU2-2 variants clustering in the conserved 5' domains. Genotype data from 13 of 14 individuals has been reported previously as part of a larger cohort. All individuals presented with a highly concordant, severe DEE, characterized by severe to profound intellectual disability, inability to walk or communicate, hyperkinesia, and refractory seizures. Infantile spasms and tonic seizures were the predominant seizure types and a Lennox-Gastaut syndrome-like phenotype was common. These individuals had a significantly similar phenotypic signature when compared with 703 individuals with complex pediatric epilepsies (two-sided Monte Carlo permutation test, p = .005). RNA sequencing analyses showed aberrant splicing, with the most pronounced effects in fibroblast tissues in mutually exclusive exon and alternate 3' splice-site events, which were not detectable in blood. SIGNIFICANCE: We present deep phenotyping data and transcriptomic analyses that provide support for rare, 5' clustering biallelic RNU2-2 variants causing this novel, severe DEE. We propose an RNA sequencing methodology on fibroblast tissue for future validation of RNU2-2 variants.

autosomal recessive disease↗

PubMed2026

CRISPR-Cas and Infectious Diseases: A Decade of Translational Advances in Molecular Biotechnology.

CRISPR-Cas systems have emerged as a versatile tool for diagnosing, treating, and preventing infectious diseases. This review highlights translational advancements in CRISPR-Cas-based applications, concentrating on the past decades in diagnostics, therapeutic genome editing, and vaccine development. The article highlights key platforms like DETECTR and SHERLOCK, which enable rapid, sensitive pathogen detection, and explores CRISPR-Cas9 systems in therapeutic strategies for directly targeting viral genomes and combating antimicrobial resistance. It also examines the role of CRISPR-Cas9 in engineering live-attenuated and personalized neoantigen vaccines. Principal findings demonstrate a clear progression from experimental proof-of-concept to preclinical applications primarily in CRISPR-based diagnostics and the engineering of live-attenuated vaccine candidates, whereas translation in CRISPR-based therapeutics and personalized neoantigen vaccines for infectious diseases remains at earlier, more exploratory stages. CRISPR-based diagnostics have progressed further toward clinical evaluation than therapeutics due to delivery and safety constraints, while personalized neoantigen vaccines are included mainly as an emerging, comparative concept for infectious diseases rather than a mature application. This review uniquely integrates CRISPR-based diagnostics, therapeutics, and vaccine development within a single infectious disease framework, critically assesses their current maturity, and systematically highlights technical, regulatory, and ethical barriers alongside realistic future priorities. The review concludes that while CRISPR-Cas holds transformative potential for infectious disease management, significant challenges in delivery efficiency, off-target effects, and ethical regulation must be addressed to ensure safe and equitable clinical translation.

Humans↗

PubMed2026

Promoter Methylation of HOXA5 and NDRG2 in Multiple Myeloma Patients with Renal Impairment.

Renal impairment (RI) is frequently caused by multiple myeloma (MM), which makes clinical care more difficult if renal function deteriorates or renal failure develops. Thus, in this investigation, we looked at the relationship between HOXA5&NDRG2 promoter methylation in MM patients and evaluated their prognostic potential in predicting RI risk in MM patients. This study included 60 control volunteers and 120 MM patients. The promoter methylations of HOXA5&NDRG2 were quantitatively evaluated by real-time PCR (qPCR) after the extraction of gDNA from whole blood and then treated with bisulfite. The promoter methylation percentages of HOXA5&NDRG2 were significantly increased in MM patients (77.16 ± 2.43&45.49 ± 2.16;p < 0.05) when compared to controls (4.47 ± 0.61&3.33 ± 0.31,respectively), in stage II&III patients when compared to stage I patients and in patients with age ≥ 60 years when compared to patients with age < 60 years. While only the methylation percentage of NDRG2 promoter was significantly increased in MM patients with RI (53.61 ± 3.21,p < 0.05) when compared to MM patients without RI (37.37 ± 2.04). Results obtained from ROC curve revealed that both HOXA5&NDRG2 promoter methylation were good diagnostic tools for MM. The NDRG2 promoter methylation was good prognostic biomarker could predict renal while HOXA5 promoter in the prediction of MM staging. The Kaplan-Meier survival test showed that patients with higher HOXA5&NDRG2 promoter methylation had a shorter OS and a worse prognosis. Only NDRG2 promoter hypermethylation was significantly associated with the risk of RI development in MM patients. HOXA5&NDRG2 promoter hypermethylation may have roles in the molecular etiology of MM and could be used as a treatment regimen.

Humans↗

PubMed2026

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12 cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B) ≈ 9, coefficient of variance (CV) < 10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus↗

PubMed2026

Pcgf5 controls the exit from totipotency in mouse embryonic stem cells.

Mouse embryonic stem cell (ESC) cultures contain a rare subpopulation of two-cell-like cells (2CLCs) that transiently reactivate a two-cell embryo-like transcriptional program characteristic of zygotic genome activation (ZGA), including the endogenous retrovirus MERVL and Zscan4, and thereby regain a totipotent-like state. Polycomb repressive complex 1 (PRC1)-mediated H2AK119ub1 has been implicated in restraining entry into the 2C-like state through Pcgf6, yet the factors governing exit from this state and loss of totipotency remain poorly defined. Here, we show that among the six Pcgf paralogs, Pcgf5, which is most prominently upregulated in 2CLCs and forms an MERVL-driven chimeric transcript (Pcgf5MT2C_Mm) during ZGA in 2-cell embryos, controls exit from the 2C-like state in mouse ESCs. Using a reporter ESC line carrying MERVL-tdTomato and Zscan4c-EGFP (MtZG), we manipulated Pcgf5 dosage bidirectionally. Doxycycline (Dox)-inducible overexpression (OE) of Pcgf5 reduced the double-positive (DP) 2C-like population. Conversely, CRISPR-mediated knockout (KO) of Pcgf5 by targeting a common exon shared by all Pcgf5 variants (hereafter, total Pcgf5) increased the DP population. Time-lapse imaging directly confirmed that these changes reflected genuine differences in duration of the 2C-like state: OE shortened, whereas KO prolonged, the time cells spent in this state. These findings reveal that a Polycomb group factor controls not only entry into but also exit from the 2C-like state.

Animals↗

PubMed2026

Novel splice site variants in GBA1 are associated with Gaucher disease and genotype-phenotype correlations.

BACKGROUND: Variants in GBA1 are associated with neurodegenerative disease. This study aimed to explore pathogenic GBA1 variants. METHODS: Four patients with progressive myoclonic epilepsy (PME) and extremely low β-glucosidase levels were recruited. Whole-exome sequencing and long-range PCR were performed to identify GBA1 variants. Bioinformatic analyses were used to predict the impact of the identified variants. A literature review was performed to explore the genotype-phenotype correlations. GBA1 expression data across different brain regions and developmental stages were analyzed using the BrainSpan database. RT-PCR was performed to verify the splicing effects. RESULTS: Compound heterozygous GBA1 variants were identified in four patients. Five distinct variants were detected, including two novel splice site variants (c.308-2A>G and c.762-2A>C) and three previously reported variants. All identified variants were rare or absent in gnomAD. Splice site variants c.308-2A>G and c.762-2A>C were predicted to cause aberrant splicing. Minigene-based splicing assays coupled with RT-PCR and Sanger sequencing confirmed that both variants cause complete exon skipping (exon 4 and exon 7, respectively). All patients presented with PME onset in childhood/adolescence, intellectual regression, low β-glucosidase, and diffuse brain atrophy and were subsequently diagnosed with Gaucher disease type 3. GBA1 expression in the brain showed two distinct peaks: one in infancy and another after five years of age. The onset age of PME aligned with the second GBA1 expression peak (after five years of age). CONCLUSION: This study identified compound heterozygous GBA1 variants, including two novel candidate pathogenic splice site variants, in Gaucher disease type 3 patients, expanding the known mutational spectrum.

Humans↗

PubMed2026

Comparative genomic and proteomic analysis reveals orthogroup structured evolution of tick protease inhibitors.

Protease inhibitors (PIs) play central roles in regulating endogenous proteolysis and host-parasite interactions in ticks. However, the evolutionary architecture underlying their diversification across tick lineages remains insufficiently resolved. Here, we performed a genome-wide comparative analysis of predicted proteomes from 14 tick species to systematically characterize PI repertoires. In total, 4931 putative PIs were identified and grouped into 20 families using the MEROPS classification system. Further, PI families such as Antistasin, WAP-type, and Pacifastin, which have not previously been systematically reported in tick genomes, were classified. Orthogroup inference demonstrated that PI expansion is structured at the level of evolutionary lineages rather than uniformly across families. By stratifying orthogroups according to duplication burden and taxonomic conservation, we identified a broadly conserved single-copy core under strong purifying selection. Motif level analysis of serpin reactive center loops further revealed conservation of inhibitory specificity within single copy orthogroups and diversification of key functional residues in duplication-associated lineages. Integration of secretion prediction and tissue-resolved proteomics from Hyalomma anatolicum and Rhipicephalus microplus demonstrated that evolutionary stratification is reflected at the protein level. Together, these findings provide an orthogroup-resolved evolutionary framework linking duplication dynamics, molecular evolution, and tissue-level protein deployment. This integrative approach offers a systematic basis for prioritizing conserved and diversified PI lineages for future functional and anti-tick intervention studies.

Animals↗

PubMed2026

Identification and characterization of G protein-coupled receptors in the nocturnal halictid bee Megalopta genalis.

G protein-coupled receptors (GPCRs) are one of the largest families of membrane proteins in insects, regulating vision, neural signal transduction, and various physiological behaviors. Megalopta genalis exhibits a unique facultatively eusocial lifestyle and possesses adaptations for nocturnal activity; however, its GPCR family has not yet been systematically characterized. In this study, we performed genome-wide identification, phylogenetic analysis, and expression profiling of GPCRs in M. genalis by integrating genomic annotation and transcriptomic analysis. The results showed that a total of 99 GPCRs were identified in the genome of M. genalis, which were classified into four major families. Here, we show that M. genalis has undergone lineage-specific GPCR repertoire remodeling, marked by the expansion of novel orphan receptors and the systematic loss of multiple receptor subtypes, such as the neuropeptide receptors MIP-R and NPFR. Moreover, opsins have formed a diverse array of combinations and non-GPCR odorant receptors have undergone significant expansion via tandem duplication. Together, these features may represent part of the molecular repertoire associated with the adaptation of M. genalis to a nocturnal lifestyle. Furthermore, transcriptomic analysis revealed distinct spatiotemporal expression divergence within each of the Mth/Mthl and Fz GPCR families, suggesting functional specialization across development and adult tissues. This study provides the first systematic identification and initial functional characterization of GPCRs in M. genalis, revealing an evolutionary pattern characterized by the coexistence of contraction and expansion within the GPCR family. These findings lay a foundation for further studies aimed at elucidating the roles of these GPCRs in regulating M. genalis physiology and behavior.

Animals↗

PubMed2026

Unraveling the c-Myc-CASC19/HDAC1-NPM1 epigenetic axis: A novel regulatory circuitry and therapeutic target in gastric carcinogenesis.

Mounting evidence implicates long non-coding RNA cancer susceptibility candidate 19 (CASC19) in the pathogenesis of diverse malignancies. However, its functional role and molecular mechanisms in gastric cancer (GC) remain elusive. Herein, we identified a novel 717-bp transcript isoform of CASC19 in GC cells. This study aimed to delineate the biological functions and underlying mechanisms of this novel CASC19 transcript in GC pathogenesis. CASC19 was significantly upregulated in GC tissues and cell lines, correlating with adverse clinicopathological features and poor prognosis in GC patients. Functional investigations demonstrated that CASC19 overexpression potentiated GC cell proliferation, metastasis, and epithelial-mesenchymal transition, whereas CASC19 knockdown attenuated these malignant phenotypes and suppressed tumorigenesis in xenograft models. Mechanistically, CASC19 functioned as a molecular scaffold by recruiting histone deacetylase 1 (HDAC1) to the nucleophosmin 1 (NPM1) promoter. This recruitment sustained H3K27 deacetylation, thereby transcriptionally repressing NPM1 promoter activity and accelerating gastric carcinogenesis. Crucially, Depletion of HDAC1 or NPM1 partial rescued CASC19-mediated oncogenic effects. Intriguingly, the transcription factor c-Myc was found to transcriptionally activate CASC19 through direct binding to its promoter region. Collectively, our findings indicate that the c-Myc-CASC19/HDAC1-NPM1 axis acts as a potential prognostic biomarker candidate for GC and may represent a therapeutic vulnerability worthy of future investigation.

Humans↗

PubMed2026

Compound muscle action potential amplitudes in newborn screen positive spinal muscular atrophy.

OBJECTIVE: To evaluate the utility of compound muscle action potential (CMAP) amplitudes as biomarkers of disease severity in newborn screening (NBS)-positive infants with spinal muscular atrophy (SMA). METHODS: We conducted a retrospective review of 21 infants identified through SMA NBS (11 with 2 SMN2 copies and 10 with 3 SMN2 copies). Baseline and serial right median, ulnar, and fibular motor nerve CMAP amplitudes (millivolts, mV) were obtained during the study. Functional outcomes were assessed using the Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND). RESULTS: At baseline, infants with 2 SMN2 copies demonstrated significantly lower median, ulnar, and fibular CMAP amplitudes compared with infants with 3 SMN2 copies (p < 0.05). In contrast, baseline CHOP-INTEND scores did not differ significantly between the two groups. Prior to genetic confirmation, a right median CMAP amplitude ≥3.2 mV predicted ≥3 SMN2 copies. Following treatment, right median and fibular CMAP amplitudes demonstrated significant improvement over time, including in analyses accounting for SMN2 copies number. CONCLUSION: CMAP amplitudes obtained from multiple upper- and lower-extremity motor nerves provided objective electrophysiological measures that distinguished infants with two versus three SMN2 copies, despite similar baseline CHOP-INTEND scores. Furthermore, CMAP abnormalities were detectable in some cases before confirmatory genetic testing results became available. Serial CMAP measurements demonstrated significant longitudinal changes following treatment, whereas functional assessments approached ceiling values, supporting the potential value of electrophysiological monitoring in the era of disease-modifying therapies. SIGNIFICANCE: CMAP assessment is a useful adjunct in the evaluation of infants identified through SMA NBS.

Humans↗

PubMed2026

Targeting ncRNA control networks with engineered exosomes to overcome therapy resistance in thyroid cancer.

Papillary thyroid cancer (PTC) is the most prevalent endocrine malignancy, accounting for over 90% of thyroid cancers. While differentiated thyroid cancers (DTCs) typically have favorable outcomes, a significant subset progresses to radioactive iodine-refractory (RAIR) disease, characterized by impaired iodine uptake and a 10-year survival rate below 10%. Genetic alterations and dysregulated signaling pathways underlie this transition. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), circular RNAs (circRNAs), and long non-coding RNAs (lncRNAs), play critical regulatory roles in tumor biology and may be transported via exosomes, facilitating intercellular communication and contributing to RAIR-PTC. This systematic review, conducted according to PRISMA 2020 guidelines, evaluated the role of exosomal ncRNAs in RAIR-PTC. A comprehensive search of PubMed, PubMed Central, and Google Scholar identified studies published within the past 15 years in English. Following stringent quality appraisal, studies with a non-bias score above 40% were included. Of 961 identified publications, 96 high-quality studies met inclusion criteria. Evidence indicates that therapy resistance in RAIR-PTC is driven by convergent ncRNA regulatory networks that suppress sodium-iodide symporter (NIS) expression and activate oncogenic pathways, most notably MAPK, PI3K/AKT/mTOR, and Wnt/β-catenin signaling. Multiple ncRNAs converge on key regulatory nodes, forming redundant circuits that sustain dedifferentiation, metabolic adaptation, and impaired iodide transport. Several consistently dysregulated ncRNAs directly or indirectly regulate NIS expression and trafficking, highlighting actionable targets. Exosomes emerge as biologically compatible, programmable delivery vehicles capable of transporting therapeutic ncRNA payloads independent of endogenous packaging mechanisms. These findings support a precision therapeutic paradigm in which engineered exosomes reprogram ncRNA networks to restore iodine-handling pathways and overcome therapy resistance in RAIR-PTC.

Humans↗

PubMed2026

Tracing the evolution and diversity of human parvovirus B19 across human history.

Human parvovirus B19 (B19V) is an ubiquitously spread, exclusively human pathogen, mainly posing risks to children, as well as pregnant and immunocompromised individuals. Despite evidence of B19V infection of human populations as far back as 7,000 years, the evolutionary history of B19V remains poorly understood. In this study, we present B19V genomic data from the remains of 53 globally distributed individuals spanning more than 8,000 years, including 7 children. Our findings suggest that the most recent common ancestor of all present B19V lineages existed around 12,000 years ago, at the end of the last Ice Age. Additionally, we identified an extinct Eurasian clade that participated in the recombination event that led to the emergence of B19V genotype 2 (GT-2). We date this event to ∼3,200-1,800 BP, potentially in the greater Mediterranean area. Our study shows aspects of how ancient parvovirus variants arose, disseminated, and impacted human health through time.

ancient DNA↗

PubMed2026

Decoding bipotency: a transient regulatory state bridging totipotency and lineage commitment.

Early mammalian embryogenesis entails a coordinated transition from totipotency to the first lineage bifurcation, giving rise to embryonic lineages and the extra-embryonic trophectoderm. The mechanisms by which totipotency is resolved into lineage-primed states remain incompletely understood. Emerging evidence supports a non-binary model in which cells traverse a continuum of potency states, passing through a transient bipotent intermediate that retains both embryonic and extra-embryonic potential while exiting totipotency. Here, we synthesize recent advances in the mechanisms that establish, maintain, and resolve bipotency. We emphasize the coordinated roles of transposable elements, transcription factors, and signaling pathways in regulating this transition. We also highlight newly developed bipotent stem cell models and their implications in generating advanced embryo models in vitro. Notably, current insights are largely derived from mouse systems; given key differences between mouse and human early embryogenesis, extending these findings to human models remains a critical next step.

Animals↗