Skin biology is commonly framed through signaling pathways that reprogram transcription in response to inflammatory and environmental cues. Here, a complementary perspective is proposed: epidermal homeostasis and disease recurrence may also depend on the physical organization of the genome within the nucleus. HNRNPU/SAF-A has emerged as an RNA-dependent architectural factor that links RNA binding to chromatin topology, while architectural long non-coding RNAs provide precedents for how RNA can scaffold nuclear compartments and influence higher-order genome organization. Building on these concepts, the Epidermal Differentiation Complex is considered as a tractable epidermal locus in which RNA-dependent nuclear tethering may help stabilize barrier gene programs. This framework further suggests that chronic inflammation could remodel chromatin architecture in ways that persist after apparent resolution, generating a "structural scar" that biases future responses. Although this model remains hypothetical, it is now experimentally testable. By integrating architectural RNA biology with epidermal differentiation and inflammatory memory, this Perspective provides a roadmap for investigating how nuclear structure may contribute to epithelial state stability and how it may be altered in inflammatory skin disease.
Ependymoma (EPN) is the third most common pediatric brain tumor with no targeted therapies available to patients. In supratentorial ependymoma, the most frequent driver alteration is a gene fusion between ZFTA and RELA (denoted ZR), leads to constitutive localization of ZR in the nucleus. Because ZR is not currently druggable, we tested whether ZR expression leads to aberrant protein interactions that could represent therapeutic vulnerabilities. Using CRISPR-Cas9 pooled screening, we identified many novel druggable ZR interacting proteins including XPO1, CARM1, SMARCA4, and CDK1. We focused on the nuclear export protein (XPO1), given the ability of most XPO1 inhibitors (i.e. Selinexor) to cross the blood brain barrier, FDA approval, and documented safety profiles in children. We found that specific nuclear ZR levels are needed for cell proliferation and are regulated by XPO1. Increased ZR accumulation in the nucleus does not increase oncogenic gene expression but drives tumor cells out of cell cycle, as compared to a defective ZR DNA binding mutant. Treatment of ZR driven patient-derived mouse models with Selinexor impairs cell growth and extends survival of animals in vivo. The combination of Selinexor treatment with Gemcitabine and Ribociclib (used in a clinical trial for relapsed EPN at St Jude Children's Research Hospital (SJDAWN)) further extends mouse survival. Our findings demonstrate that ZR interacting proteins constitute therapeutic leads, and that XPO1 is critical for titrating 'goldilocks' levels of ZR nuclear expression. We identify a novel combination therapy of Selinexor, Gemcitabine, and Ribociclib that may be immediately translated into clinical trials for EPN patients that are currently without targeted treatments. XPO1 inhibition is an effective therapeutic strategy against ZFTA-RELA ependymoma.
Understanding the subcellular localization of RNA and proteins is critical to dissecting gene regulation in eukaryotic organisms. However, this task is elusive as existing fractionation methods often rely on protoplast isolation or commercial kits, that are labor-intensive, costly, and can introduce stress-induced transcriptomic and proteomic changes. Here, we present a simple, rapid, and cost-effective protocol for the fractionation of nuclear and cytoplasmic components directly from diverse plant tissues, that does not require protoplastization. This Subcellular-fractionation protocol in 3 steps (a.k.a. "bueno, bonito y barato" -spanish for "good, nice and cheap"-), referred to as "SuB3", yields nuclear- and cytoplasmic- enriched subcellular fractions suitable for downstream applications such as RT-PCR, RNA/cDNA sequencing, and Western blotting. The procedure is based on sequential detergent-assisted extraction and centrifugation and enables the simultaneous isolation of RNA and protein from the same biological material. Due to its simplicity, speed, and broad compatibility, this protocol is a valuable tool for plant molecular biology laboratories investigating subcellular dynamics of gene expression.
Quantum key distribution (QKD), a cryptographic method grounded in the laws of quantum mechanics rather than computational hardness, promises provably secure communications. Its integration into critical infrastructure offers a pathway to secure resilient operation of next-generation control systems, from power-intensive data centers to remotely operated microreactors located in energy-deprived remote communities. While QKD has been demonstrated in laboratory and network settings, its use in safety-critical control systems remains unexplored where requirements on latency, key availability, and operational stability pose unique challenges. Here, we introduce a QKD-secured data acquisition and control framework for embedding quantum cybersecurity directly into safety-critical cyber-physical systems and report the first end-to-end experimental demonstration in a nuclear reactor. The framework establishes the conditions necessary to achieve secure, low-latency, real-time operation in safety-critical environments. Using a phase-encoding decoy-state BB84 system deployed on Purdue's 10 kWth fully digital research reactor (PUR-1) we validate the model and achieve real-time encryption and decryption of 2,000 reactor signals. Experiments demonstrated a stable secret-key rate of 320 kbps with a quantum bit error rate of 3.8% at 54 km, and maximum optical-fiber distances of 82 km with One-Time Pad (OTP) encryption and 140 km with AES-256. We further evaluated compliance with latency and key availability conditions using three cryptographic schemes (OTP, AES-256, ASCON), finding that all variants supported real-time operation at typical data reporting rates. Our results establish a universal framework for quantum-cybersecurity in safety-critical systems, demonstrating that quantum communication technologies can enable secure, low-latency, real-time operation of nuclear reactors and other critical infrastructure.
Fuping goat milk powder is a kind of geographical indication protected food in China. To realize a rapid and accurate identification of Fuping goat milk, in this paper, an identification method was proposed based on nuclear magnetic resonance and machine learning to accurately distinguish Fuping goat milk on small scale geographical authenticity. Deuterated chloroform was selected as extraction solvent, partial least squares discriminant analysis (PLSDA), random forest (RF) and support vector machine (SVM) models were constructed using seven different geographical origin goat milk samples in Shaanxi Province. The identification based on PLS-DA model was unsatisfactory, the RF model performed better, and the SVM model showed best performance with accuracy rate reached 100% based on selected 17 features, and the 5-fold cross-validation accuracy was 94.7% ± 7.2%. It is disclosed that different geographic samples have different chemical compositions, particularly unsaturated fatty acids, such as conjugated linoleic acid.
Healthcare systems will be overwhelmed in the case of a large-scale nuclear incident, not only by members of the exposed population, but also by non-exposed ("worried-well") individuals. Current methods of biodosimetry are time-consuming and resource-intensive for use in a large-scale triage operation. We present a rapid blood smear-based assay utilizing a modified γH2AX assay and a new calculation system (test score) to identify non- or low-exposed individuals within 1 h and 24 h after radiation exposure. Venous blood from seven healthy donors was irradiated, in vitro (0-4 Gy) and blood smears were prepared 1 and 24 h postirradiation. Smears were fixed and γH2AX immunostaining was performed. Fifty round nuclei were evaluated by a minimum of seven operators for the presence of γH2AX foci. The proportion of γH2AX foci-positive nuclei, called test score, was used to discriminate between irradiated and non-irradiated samples. Blood smears from non-exposed venous blood were correctly identified as non-exposed within 1 h against a minimum exposure of 0.1 Gy. After 24 h, the smears from non-exposed blood were identified as non-exposed against a minimum exposure of 1 Gy. This result was also validated with blinded samples irradiated at a partner institute. This established protocol was adapted for blood smears generated with capillary blood from three donors, which eliminates the need for a trained professional to draw venous blood and enables the use in field conditions. A discrimination of irradiated and non-irradiated blood was also possible, but thresholds established for venous blood have to be adjusted in future experiments. Together, this fast, operator-friendly assay will allow effective triage in radiological emergencies by reliable exclusion of non-exposed individuals within 6 h of sample arrival, using minimal resources and specialized equipment.
Accurate chromosome segregation during meiosis depends on precise homolog pairing. This process is driven by a series of specialized proteins that link chromosomes to cytoskeletal motors and coordinate chromosome movement for homolog recognition and alignment. Here, we identified RBPL-1, the Caenorhabditis elegans homolog of RBBP6, as a germline-expressed regulator essential for proper homolog pairing and associated nuclear reorganization. Depletion of RBPL-1 impaired the formation of clusters of the LINC complex and CHK-2 kinase within the nuclear periphery. Furthermore, we showed that RBPL-1 regulates the protein abundance of ZIM/HIM-8-family proteins and PLK-2 kinase, two critical mediators of homolog pairing. Notably, RBPL-1's role in homolog pairing is independent of the RING finger domain and Zn knuckle motif, which are proposed to mediate ubiquitination and alternative polyadenylation (APA)/mRNA processing respectively. Instead, we reveal that the evolutionarily conserved yet functionally enigmatic DWNN domain is essential for RBPL-1's function in homolog pairing. In summary, our findings demonstrate that RBPL-1 contributes to meiotic homolog pairing through its DWNN domain, by mediating nuclear reorganization and controlling the abundance of essential pairing factors.
Central nervous system (CNS) injury is a leading cause of death and long-term disability worldwide. Neurological deficits reflect disruption of central neural circuits. A major barrier to circuit repair is the intrinsically low regenerative potential of adult CNS neurons-linked in part to failure of injury-induced nuclear export of class IIa histone deacetylases (notably HDAC5)-together with a hostile post-injury microenvironment. Here we present a multifunctional nanosystem, encapsulating the class IIa HDAC4/5-selective inhibitor LMK-235 and featuring an electroactive polyaniline coating with asymmetrically distributed 5-hydroxytryptamine moieties. Upon reaching the lesion, our nanosystem assembles into large-pore scaffolds that (i) inhibit the activity of nuclear-retained class IIa HDACs in neurons and thereby reactivate intrinsic regenerative programs, (ii) regulate microglial activation to mitigate neuroinflammation, and (iii) provide an electroactive interface promoting activity-dependent synaptic reconnection. This multi-pronged approach illustrates an integrated platform with translational potential for CNS disorders in which circuit disconnection constrains recovery.
Ferroptosis contributes to myocardial infarction (MI) pathogenesis. However, the role of nuclear receptor subfamily 1 group D member 2 (NR1D2) in MI-associated ferroptosis and its potential interaction with nuclear factor erythroid 2-related factor 2 (Nrf2) pathway remains unclear. We sought to determine whether NR1D2 regulates ferroptosis in MI through the Nrf2 pathway and to evaluate the therapeutic potential of NR1D2 knockdown. Bioinformatic analyses of GEO datasets identified NR1D2 as a key ferroptosis-related gene in MI. In vitro, NR1D2 expression was silenced in HL-1 cardiomyocytes subjected to hypoxia/reoxygenation (H/R) injury. Nrf2 inhibitor ML385 was used to verify pathway involvement. A mouse model of MI was established, and cardiac function was assessed following NR1D2 knockdown with or without ML385 co-treatment. NR1D2 expression was significantly upregulated in MI. Its knockdown in H/R-injured cardiomyocytes reduced cell death, inflammation, and ferroptosis, as indicated by decreased Fe²⁺ and malondialdehyde levels and elevated GSH/GSSG ratio. These protective effects were abolished by ML385, confirming Nrf2 dependence. Mechanistically, NR1D2 knockdown activated the Nrf2/HO-1 signaling axis, leading to the upregulation of downstream effectors glutathione peroxidase 4and SLC7A11. In MI mice, NR1D2 knockdown improved cardiac function (increased EF and FS), decreased infarct size, and inhibited ferroptosis-effects that were also negated by ML385. NR1D2 aggravates MI injury by suppressing the Nrf2 pathway and promoting ferroptosis. Targeting NR1D2 activates Nrf2 signaling and alleviates ferroptotic damage, revealing a novel regulatory mechanism and identifying NR1D2 as a promising therapeutic target for MI. A heart attack occurs when blood flow to the heart is blocked, causing heart muscle cells to die. We studied a specific type of cell death, ferroptosis, which is dependent on iron and worsens heart attack damage. Although ferroptosis is known to be important, how it is regulated remains unclear. Our data on heart attack identified NR1D2 as a protein that was significantly increased after a heart attack. To assess its importance, we reduced NR1D2 levels in isolated heart cells and in mice experiencing a heart attack. We discovered that lowering NR1D2 provided strong protection by reducing cell death and harmful inflammation and, crucially, preventing ferroptosis. We then sought to clarify the underlying mechanism. The protective effects of lowering NR1D2 were associated with activation of a well-known cellular defense pathway regulated by a protein called Nrf2. When we blocked the Nrf2 pathway, the benefits of reducing NR1D2 disappeared, confirming that NR1D2 acts by suppressing this natural protective system. In summary, our findings show that the NR1D2 protein aggravates heart attack injury by blocking the protective Nrf2 pathway and promoting ferroptosis. This suggests that therapies designed to target NR1D2 may offer a novel strategy to limit tissue damage and improve patient recovery after a heart attack.
Spin ensembles are central to quantum science, from fundamental physics searches to magnetic resonance spectroscopy and quantum sensing. The standard quantum limit for their performance is ultimately posed by spin projection noise, yet solid-state implementations have so far been limited by significantly larger photon shot noise. Here, we demonstrate a direct quantum non-demolition readout of a mesoscopic ensemble of nitrogen-vacancy (NV) centers in diamond that surpasses the photon shot-noise limit and approaches the intrinsic spin projection noise. By stabilizing the intrinsic 14N nuclear spin bath at high magnetic fields and employing a repetitive nuclear-assisted spin readout, we achieve a noise reduction of 3.8 dB below the thermal projection noise level. This enables direct access to the intrinsic fluctuations of the spin ensemble, allowing us to directly observe the signatures of correlated spin states. Our results establish projection noise-limited readout as a practical tool for solid-state quantum sensors, opening pathways to quantum-enhanced metrology, direct detection of many-body correlations, and the implementation of spin squeezing in mesoscopic solid-state ensembles.
IntroductionNUT carcinoma (NC) is a rare, aggressive squamous-lineage malignancy characterized by NUTM1 gene rearrangement and distinctive nuclear NUT expression by immunohistochemistry. Ocular adnexal involvement is exceptional.Patient presentationA 26-year-old woman presented with redness, pruritus, and a large nasal canthal mass obstructing vision in the left eye. Examination showed a 4 × 3 cm lacrimal mass extending into the extraconal orbit with extraocular muscle compression. Histology showed nests of small round blue cells with crush artifact and abrupt keratinization. Immunohistochemistry demonstrated diffuse pan-keratin, p63, p40, and speckled nuclear NUTM1 positivity; CD99 and NKX2.2 were negative-confirming NC.ConclusionLacrimal sac/gland NC should be considered in rapidly enlarging medial canthal masses in young patients. Prompt biopsy with IMMUNOHISTOCHEMISTRY for NUT and early multidisciplinary management are critical.
The histopathologic distinction between patch-stage mycosis fungoides (MF) and benign inflammatory dermatoses (BID) remains a persistent diagnostic challenge, often due to overlapping clinical and immunophenotypic features. GATA binding protein 3 (GATA3), a transcription factor critical in T-helper 2 cell differentiation, has emerged as a potential immunohistochemical marker in T-cell neoplasms. This study aimed to evaluate GATA3 expression in patch-stage MF compared with BID to assess its diagnostic value. Sixty formalin-fixed, paraffin-embedded skin biopsies were retrospectively analyzed, including 30 cases of patch-stage MF and 30 cases of BID (psoriasis, chronic dermatitis, and lichen planus). Immunohistochemical staining for GATA3 was performed, and lymphocytic nuclear staining was assessed in dermal and epidermal compartments. GATA3 expression > 50% in dermal lymphocytes was observed in 20% of MF cases and 6.7% of BID cases, yielding high specificity (93.3%) but low sensitivity (20%) for MF diagnosis. Epidermal GATA3 expression was uniformly low across both groups. No significant correlations were found between GATA3 expression and key histopathologic or immunophenotypic features of MF. Although elevated dermal GATA3 expression may support the diagnosis of MF in some cases, its substantial overlap with BID and low sensitivity limit its utility as a reliable standalone diagnostic marker for early-stage MF. GATA3 can be incorporated into broader immunohistochemical panels alongside more specific markers to improve diagnostic accuracy.
Pyridine quaternary amino disinfectants (PYRs) are extensively used as antimicrobial agents. However, the specific PYRs responsible for inhibition and their structure-activity relationship (SAR) for human 3β-hydroxysteroid dehydrogenase 2 (h3β-HSD2) and its homolog rat r3β-HSD1, the critical enzyme in gonadal steroidogenesis, remain poorly understood. This study evaluated eleven PYRs for their inhibitory effects on h3β-HSD2 and r3β-HSD1, determining potency (IC50), inhibition kinetics, cellular impact, binding interactions, and toxicology prediction via molecular docking, 3D-QSAR, and network toxicology analysis. Inhibitory potency (IC50) revealed C18 (8.68 μM) > C16 (15.45 μM) > C14 (21.70 μM) > C20 (36.10 μM) > C12 (57.83 μM) > C1-C8 PYRs (no inhibition at 100 μM) against h3β-HSD2 and C18 (1.61 μM) > C16 (2.54 μM) > C20 (5.56 μM) > C14 (7.91 μM) > C12 (38.06 μM) > C1-C8 PYRs (no inhibition at 100 μM) against r3β-HSD1. Mechanism of action revealed mixed/noncompetitive inhibition for both enzymes. Cellular suppression showed that C12-C18 PYRs effectively inhibited progesterone synthesis in human KGN granulosa tumor cells at 1 and 10 μM. Molecular docking and SAR showed that binding occurs at the NAD+/steroid interface via hydrogen bonds, hydrophobic interactions, and van der Waals forces, and lipophilicity (LogP), steric bulk (molecular weight, alkyl chain length and volume), Fsp3, and flexibility positively correlated with potency (pIC50), indicating that longer alkyl chains (up to C18) enhance inhibition, and 3D-QSAR confirmed the importance of hydrophobic regions in binding affinity due to long alkyl chain. Network toxicology analysis revealed common pathway (nuclear receptor signaling/steroidogenesis) in male hypospadias. In conclusion, PYRs inhibit gonadal 3β-HSD activity in a chain-length-dependent manner (C12-C18), with lipophilicity as a key determinant. These findings suggest that PYR disinfectants may act as potential endocrine disruptors by interfering with steroidogenesis.
Biomolecular condensates formed through liquid-liquid phase separation (LLPS) organize the intracellular environment and regulate diverse biochemical processes. Despite their importance, probing condensate composition, exchange dynamics, and internal organization remains challenging, particularly without external tags. Nuclear magnetic resonance (NMR) spectroscopy can provide a unique label-free window into these mesoscale assemblies, capturing both molecular motion and environmental heterogeneity. Two complementary NMR methodologies enable a comprehensive characterization of condensates directly within their biphasic state. For condensates which are dynamic enough to be observable by NMR, the diffusion-exchange approach, REstricted DIffusion of INvisible speciEs abbreviated as REDIFINE, utilizes the diffusion contrast with chemical exchange to quantify the fraction of molecules partitioned between condensed and dilute phases, determine droplet size and interface permeability, and extract molecular exchange rates across the phase boundary. For more rigid condensates that are NMR invisible, the water-detected semi-solid magnetization-transfer method, CONdensate DEtectioN by SEmi-solid Magnetization Transfer, or in short CONDENSE-MT, exploits the relaxation contrast and proton exchange between condensed biomolecules and dilute phase solvent to monitor condensates onto the bulk water protons, providing access to relative partitioning, molecular tumbling rates, hydration dynamics, and bound-water content. Together, these approaches deliver a multidimensional, quantitative view of condensate structure and dynamics under near-native biphasic conditions without fluorescent or detection tags. Their integration expands the NMR toolbox for studying biomolecular phase separation and establishes a foundation for connecting condensate physicochemical properties with their biological function and pathological misregulation.
Retinal degenerative diseases range from rare inherited forms to common multifactorial disorders such as age-related macular degeneration, which is the leading cause of blindness in developed countries. Recent evidence identifies impaired autophagy as a key pathogenetic mechanism. In the disease process alterations of the outer retina start from the retinal pigment epithelium (RPE), to progress downstream in the inner retina leading to widespread whole retinal degeneration. Recent studies indicate that among autophagy-related proteins Beclin1 plays a relevant effect in sustaining retinal integrity, since it is induced by light exposure and it is placed at the intersection between mitophagy, lipophagy, and glycophagy, which are involved during retinal degeneration. The present study was carried out by profiting of BECN1 heterozygous aged mice (BECN+/-), where RT-PCR and western blotting analysis confirmed the loss of both the primary transcript (BECN1) and protein (Beclin1) in the whole retina. Multiple converging techniques indicate a marked degeneration of RPE and photoreceptor layer, where a dismantling of proteins forming tight junction was documented. Inner retinal degeneration was extended within outer and inner nuclear layer. In the inner retina the expression of the detrimental protein alpha synuclein was increased concomitantly with a defect of autophagy markers. The study indicates a seminal role of Beclin1 in maintaining retinal integrity and it defines the vulnerability of various retinal layers in the spreading of Beclin1-dependent retinal degeneration. The potential of increasing the expression of Beclin1 through photobiomodulation is discussed, since it supports retinal integrity when amber/red light-induced stimulation occurs.
Metal-liquid interfaces host partially charged adsorbates whose solvent reorganization and polarization strongly influence electron-transfer kinetics, yet these quantities are difficult to extract from ab initio calculations because strong hybridization broadens and shifts the electronic levels of an adsorbate. Here, we combine the implicit continuum solvation model and explicit atomistic water molecular dynamics, using a combination of machine-learned interatomic potentials trained to density functional theory (DFT) and explicit DFT calculations, to quantify solvation potentials and reorganization energies for a model Agδ+ adsorbate on an Au(111) slab. Continuum solvation model calculations along the adsorption pathway yield bulk-like solvation shifts for fully solvated Ag+ and constrain the solvent polarization potential acting on adsorbed Agδ+ to roughly half this value. To separate nuclear from electronic contributions at finite temperature, we fine-tuned a machine-learned interatomic potential to ab initio molecular dynamics trajectories and generated 200 ps of explicit-water dynamics for both bulk Ag+ and surface Agδ+, with hybrid-functional DFT (HSE06) sampling of instantaneous eigenvalues. Gerischer-Hopfield analysis gives a bulk reorganization energy of near 1.4 eV and a lower bound at ∼30% of this value upon interfacial reorganization. Analysis of the solvation potential, non-vanishing reorganization energy (through tracking adsorbate core-level fluctuations), and persistent dipole polarization upon adsorption suggests that partially solvated surface species can retain an appreciable fraction of bulk-like solvation properties. Altogether, the theoretical findings presented imply that sufficiently resolved spectroscopic probes of core-level fluctuations could be essential to quantifying these properties. This, in turn, could have broad implications for understanding interfacial kinetics within many practical electrochemical systems.
Metal chelates play a crucial role in diagnostic imaging and radiotherapy. While gadolinium-based chelates are widely used in MRI, radiometal chelates are increasingly used in nuclear medicine and theranostics. Despite their clinical importance, the extent to which the identity of the coordinated metal influences in vivo chelate pharmacology remains unclear. The goal of this work was to determine whether metal substitution alters transporter-mediated cellular uptake and pharmacological behavior of hepatospecific chelates. Apo-forms of the clinical hepatospecific MRI contrast agents EOB-DTPA and BOPTA were generated and re-chelated with eight different metals (Sc, Y, Pr, Eu, Gd, Tb, Dy, Ho). In vitro transport of these chelates was assessed in cells expressing rodent and human hepatic transporters. In vivo hepatic uptake was evaluated in mice expressing either wild-type or human hepatic transporters. Tissue distribution and clearance were quantified analytically. In vitro uptake of EOB-DTPA and BOPTA chelates by cells expressing rodent and human transporters showed no statistically significant differences across metals. In vivo studies in mice similarly showed no statistically significant differences in hepatic uptake across metals, with the exception of reduced uptake observed for Sc-EOB-DTPA in wild-type animals. No evidence of free metal accumulation in soft tissue was detected. Chelate clearance via renal and hepatobiliary pathways was similar across metals. Within the class of trivalent metals examined and for EOB-DTPA and BOPTA chelates, transporter-mediated uptake, biodistribution, and clearance were largely independent of metal identity under the conditions tested. These findings support the use of common chelate scaffolds across multiple metals, while highlighting the importance of ligand structure and transporter interactions in governing pharmacology.
Cyclodextrins (CDs) are cyclic oligosaccharides composed of α-(1,4)-linked glucopyranose units that have emerged as multifunctional and versatile pharmaceutical excipients. One of the major challenges in modern drug development is that nearly half of newly discovered drug molecules exhibit poor aqueous solubility, which adversely affects formulation development, bioavailability, and therapeutic efficacy. CDs address this limitation by forming non-covalent inclusion and non-inclusion complexes, thereby enhancing drug solubility, stability, dissolution rate, and overall biopharmaceutical performance. This review provides a comprehensive overview of CDs, including their historical background, structural characteristics, and production through starch conversion by the enzyme cyclodextrin glucanotransferase (CGTase). Special emphasis is placed on the transglycosylation reactions catalyzed by CGTase, including cyclization, coupling, and disproportionation, which play a critical role in CD synthesis. Recent advances in structural elucidation techniques, such as X-ray crystallography, nuclear magnetic resonance spectroscopy, molecular dynamics simulations, and ion mobility mass spectrometry, are also discussed. The pharmaceutical applications of CDs are critically evaluated, with particular emphasis on their roles as solubility enhancers, taste-masking agents, and stabilizers in nanocarrier-based and targeted drug delivery systems. Their applications in cosmetics and dermopharmaceuticals are also explored, particularly in improving formulation stability and enabling controlled drug delivery. Furthermore, the pharmacokinetics, toxicological safety, and regulatory acceptability of various CDs are discussed. Overall, this review highlights the growing importance of CDs as pharmaceutical excipients that bridge supramolecular chemistry and advanced drug delivery systems.
Gastroesophageal reflux in young children is most commonly evaluated with gastroesophageal scintigraphy (milk scan); however, reflux may be incidentally identified on other nuclear medicine examinations. We report a case of gastroesophageal reflux extending to the upper esophagus incidentally detected on hepatobiliary scintigraphy performed for evaluation of suspected biliary dyskinesia in a 17-month-old boy.
While papillary thyroid carcinoma (PTC) with gene rearrangements is associated with specific pathological features, further validation is needed to determine whether screening based on these specific pathological findings is useful. RNA sequencing was performed on 103 patients with PTC having wild-type BRAF. Group 1 (n = 57) included cases selected by an endocrine pathologist based on distinct pathological features such as multinodular invasive growth, prominent intratumoral stromal fibrosis, mixed growth patterns with varying degrees of nuclear atypia, pale eosinophilic to clear cytoplasm, and/or multiple lymph node (LN) metastases. These cases underwent pan-TRK, ALK and RET IHC and RNA sequencing. Group 2 (n = 46) consisted of randomly selected cases that underwent RNA sequencing. Gene rearrangements were identified in 66 patients (64.1%), with a significantly higher proportion in Group 1 (78.9%) than in Group 2 (45.7%). NTRK was the most frequent gene rearrangement (30.1%), followed by RET (19.4%), ALK (9.7%), and BRAF (2.9%). Patients with gene rearrangements were significantly younger and had smaller primary tumors, although they demonstrated greater extrathyroidal extension and LN metastasis than those without rearrangements. Pan-TRK IHC showed a sensitivity of 52% and a specificity of 94%, whereas RET and ALK IHC demonstrated higher sensitivities (78% and 88%) and specificities (81% and 100%), respectively. This study suggests that pathologic prescreening can enrich for targetable gene rearrangements in BRAF wild-type PTC and serve as a resource-sparing strategy before RNA sequencing. In prescreened cases, ALK IHC performed well, while pan-TRK and RET IHC had limitations.