Surface-supported single rare-earth atom magnets represent an ultimate limit of magnetic miniaturisation, where information storage is reduced to the scale of an individual atom. At this limit, magnetism is intrinsically quantum mechanical and governed by the interplay of strong electron correlations, crystal-field effects, and spin-orbit coupling within the localized 4f shell. In this review, we summarise and analyse recent theoretical advances in the description of rare-earth adatoms, with particular emphasis on approaches that go beyond conventional static mean-field DFT+U , which may exhibit multiple metastable solutions and treat magnetic anisotropy in a semiclassical manner. We discuss a predictive framework combining relativistic density functional theory with an Anderson impurity model treatment of the multiconfigurational 4f shell (DFT+U (HIA)), enabling a consistent description of strong correlations, multiplet structure, and quantum tunnelling effects induced by transverse crystal-field terms.As a representative case, we review the electronic structure and magnetic anisotropy of Dy adatoms on insulating MgO and spin-polarised graphene/Ni substrates. For Dy@MgO, an apparent perpendicular anisotropy is strongly reduced by quantum tunnelling driven by transverse crystal-field terms, effectively shifting the easy axis towards the surface plane. In contrast, Dy@Gr/Ni(111) realises a robust perpendicular magnetic configuration at the single-atom level. Here, the large positive magnetic anisotropy energy arises from the interplay of crystal-field splitting and strong spin-orbit coupling within the Dy 4f shell, further reinforced by the exchange field generated by the ferromagnetic Ni substrate.We argue that Dy@Gr/Ni(111) may be viewed as a limiting atomic-scale analogue of perpendicular synthetic heterostructures used in magnetic memory technologies, where exchange coupling and strong anisotropy are engineered to stabilise nanoscale bits. The insights gained from these studies establish a microscopic design principle for achieving thermally robust magnetic anisotropy at the ultimate scaling limit and highlight the broader potential of strongly correlated rare-earth adatoms for atomic-scale spintronic applications.
The rapid advance in the research and development of extracellular vesicle (EV)-based therapeutics has stimulated a paradigm shift in the field of regenerative medicine. However, translating EV-based therapies into the clinic requires robust, scalable, and Good Manufacturing Practice (GMP)-compliant bioprocesses that ensure product consistency, potency and safety. In this Perspective, we propose that metabolomics, particularly by using high-resolution nuclear magnetic resonance (NMR), can serve as a transformative analytical technology in EV manufacturing and quality control. By integrating NMR-metabolomics monitoring into upstream cell culture and downstream EV purification workflows, it becomes possible to identify metabolic fingerprints predictive of cell performance, EV yield and EV bioactivity. Drawing from the experience of the GALVANO consortium, which is developing Spain's first GMP-grade platform for EV manufacturing from clinical-grade human Wharton Jelly's mesenchymal stromal cells (WJ-MSC-EVs) with particular promise in the modulation of inflammation and tissue regeneration, we highlight how NMR-metabolomics can support Quality by Design (QbD) principles, enhance in-process analytics and accelerate regulatory harmonisation. We further discuss the need for collaborative standardisation of analytical methods and reporting frameworks to ensure reproducibility and comparability across EV batches. Together, these strategies can advance EV-based therapeutics toward reliable, large-scale clinical application.
Some of the most well-characterized interactions between biomolecules occur between antibodies and their respective antigens; these interactions are the backbone of the modern pharmaceutical and diagnostic industries. Solution equilibrium titration (SET) is the gold standard method for measuring affinities between biomolecules, where a fixed concentration of analyte is titrated with a variable concentration of titrant. However, SET measurements require innate or external signal differences to distinguish between free and bound analyte. Here, we evaluated a solution-phase reaction, solid-phase detection (SRSD) method that probes the fraction of free analyte in an equilibrium titration with titrant-coated magnetic beads to estimate the apparent binding affinity. We comprehensively compared SRSD against traditional methods using two different antibody-antigen pairs and relevant controls. We show that SRSD produces affinity measurements of the same order of magnitude as those measured by well-established label-free kinetic (SPR) and solution-phase equilibrium (SET) approaches. We anticipate that the SRSD method may be of general interest for affinity estimation, as it can be performed with unpurified analytes in complex mixtures. However, this method cannot be assumed to be generally valid or interchangeable across all systems, as the study illustrates system-specific, situational utility when appropriate validation controls are implemented.
The electrocardiogram (ECG) is widely used to infer infarct location and extent in anterior myocardial infarction (MI), based on either anatomical lead proximity or vectorial orientation of ST-segment deviation. However, the validity of these approaches against direct imaging of myocardial injury remains uncertain. In this prospective study, 105 patients with anterior MI underwent cardiac magnetic resonance (CMR) imaging 3-7 days after presentation. Admission ECGs were analyzed using (1) conventional ECG localization categories, and (2) simplified frontal and horizontal ST-axis orientation. CMR-defined injury distribution was assessed using late gadolinium enhancement and myocardial edema imaging. Conventional ECG localization categories demonstrated no significant association with CMR-defined infarct distribution (P = 0.24), with poor agreement (κ = 0.122) and substantial overlap across categories. Simplified ST-axis orientation showed modest and inconsistent associations with infarct location and did not meaningfully explain infarct size. In contrast, global ST-segment burden was associated with CMR-defined infarct size (ΣSTE: standardized β = 0.307, P = 0.002; lead count: standardized β = 0.267, P = 0.007). In this selected cohort of reperfused LAD-related anterior STEMI patients undergoing early CMR, conventional ECG localization categories and simplified ST-axis orientation showed poor or inconsistent correspondence with CMR-defined infarct distribution, whereas global ST-segment burden showed a modest association with infarct size. These findings suggest that, in this cohort, the ECG may be better suited to reflect the extent of myocardial injury rather than its precise anatomical location.
Peak oxygen uptake (pVO2) is a validated prognostic marker in advanced heart failure (HF), but its value in contemporary recipients of left ventricular assist devices (LVAD) is uncertain. We assessed whether pVO2 predicts long-term clinical outcomes in a cohort of exclusively HeartMate 3 recipients. We retrospectively studied 250 recipients at two European centers (2015-2025) who completed cardiopulmonary exercise testing 90-400 days postimplant. The median age was 56.7 years, 29% were female, and the median pVO2 was 13.0 (10.7-16.8) ml/kg/min. Low pVO2 (≤12 ml/kg/min on β-blocker or ≤14 off) was observed in 52%. During a median follow-up of 770 days, low pVO2 was associated with inferior 5-year overall survival (57% vs. 84%; hazard ratio [HR], 3.23; 95% confidence interval [CI], 1.49-7.14) and survival free from heart failure recurrence (44% vs. 78%; HR, 3.13; 95% CI, 1.69-5.88). Each 1 ml/kg/min increase in pVO2 reduced the hazard of death or HF recurrence by 16% (p < 0.001). Low pVO2 was also associated with a greater hospitalization burden and more ventricular arrhythmias, but no association with hemocompatibility-related adverse events. In contemporary LVAD recipients, pVO2 predicts mortality and clinically relevant nonmortality outcomes, supporting cardiopulmonary exercise testing for long-term risk stratification and management in stable LVAD patients.
The widespread contamination of micro/nano-plastics (MNPs) has become a major environmental concern, highlighting the need for efficient treatment technologies and sustainable disposal methods. Herein, a hydrophobized magnetic lignocellulosic fiber (HLF) adsorbent derived from wood waste was engineered to realize a circular "capture-and-upcycle" strategy. HLF with excellent adsorption capacity can be prepared by modifying lignocellulosic fibers from wood waste through in situ synthesis of nanoscale Fe3O4 particles and silanization. It has achieved equilibrium adsorption capacities of 2544.7 mg g-1 for micro-sized PS and 2571.1 mg g-1 for PMMA. The adsorption mechanism is a synergistic physicochemical interaction dominated by van der Waals forces and hydrophobic effects. Notably, the challenge of adsorbent disposal is addressed by directly transforming the MNPs-saturated HLF into robust functional composites via hot-pressing. The resulting HLF/MNPs composites exhibit ideal mechanical properties with a flexural strength of 151.1 MPa and a tensile strength of 37.6 MPa, far surpassing commercial wood-plastic composites. Furthermore, it exhibits self-extinguishing behavior and improves fire safety due to the action of magnetic particles, and their peak smoke release rate was reduced by 79.3% compared to non-magnetic LF/MNPs composites. This work establishes a scalable, circular approach for remediating aquatic plastic pollution while simultaneously valorizing waste into high-performance engineering materials.
This research focuses on examining heat transfer and entropy generation within a porous cavity, which contains a hybrid nanofluid known as MWCNT-Fe3O4/H2O, due to its relevance to improving thermal management systems as well as increasing energy efficiency. The study is based on an advanced Darcy-Forchheimer-Brinkmann computational model that considers inertial forces, the fluid filling the cavity, and the resultant effects of applying a magnetic field. To provide the laminar and incompressible nature of the nanofluids flux, the Darcy-Forchheimer prototype is essential. While accounting for the inertial influence of advection in the permeable coating. To solve non-dimensional equations, we employ the finite element methodology and the Darcy-Forchheimer-Brinkmann prototype. Thus, several parameters, such as ([Formula: see text]); ([Formula: see text]); ([Formula: see text]); ([Formula: see text]); ([Formula: see text]) with the use of isotherm patterns, streamlines, and other graphs, we employed on the fluid flow is evaluated. Using the Finite Element Method to solve the governing equations numerically demonstrates that by increasing the porosity of the cavity, heat transfer rates can be increased by up to 30%; however, the increase in entropy production also increases with cavity porosity while the application of a greater magnetic field helps to reduce this effect on entropy generation by approximately 20%. The results indicate that the length of the cavity and the magnitude of the applied magnetic field also impact thermal performance within the cavity. The results of this study may assist in developing efficient thermal systems based upon the use of hybrid nanofluids, thereby increasing energy efficiency overall.
Solar flares are the largest energy releasing events in the solar system, where the open magnetic field lines reconnect and form the closed flare loops. During this process, rapid magnetic reconnection, the associated shock waves, and chromospheric evaporation are expected but not yet well understood. These processes are crucial for understanding similar features in stellar flares and other astrophysical jets. Here, we report the characteristics of propagating slow-mode shocks in the flare loop system, by combining a 3D high-resolution magnetohydrodynamics modeling and spectral analysis of Extreme Ultra-Violet observations. It is found that normal slow shocks are recurrently formed after the collision between the post-reconnection downflows and evaporation flows in the flare loops, which subsequently propagate toward the chromosphere at speeds comparable to the evaporation flows. In particular, the Doppler analysis of the Fe XXI 1354 Å line normally shows a sharp change in blueshifted velocity and an asymmetrical line broadening once the line-of-sight passes through the shock front. This study highlights that propagation of slow shocks can facilitate energy release in flares and affect energy transport, suggesting an advancement in the standard flare model framework.
The thermal control of peristaltic blood flow in a curved duct under a magnetic field is a relatively unexplored phenomenon. This research fills this gap by proposing the use of a blood-based hybrid nanofluid. The blood flow is assumed to be a non-Newtonian fluid, modelled by the Casson fluid model. It is mixed with gold (20 nm) and iron oxide (25 nm) nanoparticles. The equations are expressed in a cylindrical coordinate system in order to account for the curved nature of the duct. Peristaltic waves are considered to propagate along the wall. The governing equations are obtained using the low Reynolds number approximation (Reynolds number Re) and long wavelength approximation. The finite element method (FEM) with Python programming is applied for solving the resulting strongly nonlinear partial differential equations. The obtained results are also utilized to analyze the irreversibility of the system. The main findings indicate that increasing the aspect ratio enhances the blood flow velocity at the central part. It is found that the mono nanofluid has more improvement in central velocity compared to the hybrid nanofluid. Optimal control of the magnetic parameter and duct wall elasticity can enhance the flow efficiency. It also results in a reduction of thermal losses and thermodynamic irreversibilities.
A two dimensional classical ferromagnetic XY model with its bound vortex-antivortex dominated quasi long range ordered phase at low temperatures is a long standing as well as well studied problem of interest in the field of condensed matter. We conduct a detailed Monte Carlo study of such model in a square lattice with rather unexplored extensions where additional anisotropic exchange coupling and Dzyaloshinskii-Moriya interactions (DMI) together affect the Kosterlitz-Thouless (KT) transition in presence/ absence of symmetry breaking fields. Without DMI, the exchange term promotes collinear (ferromagnetic) order, whereas the DMI term induces spin cantings. By tuning anisotropy upto Ising limit, we document energy, specific-heat, magnetizations as well as helicity modulus and vortex densities for different temperatures and DMI strength. We also compute the 2nd moment of correlation lengths in order to probe the spatial correlation of the spins. Furthermore, the effect of U(1) symmetry breaking 4-fold and 8-fold symmetric h4 and h8 fields are explored which shows how the double-peaked specific heat profiles changes in presence of DMI. Overall, our findings append many important updates in the low temperature phases of a topological XY ferromagnet when additional DMI and isotropy-breaking exchange and/or field terms are considered thereby providing a few practical blueprints for suitably engineering topological spin systems.
High-quality single crystals of the formula K2[M(H2O)6][Zr2F12] (M = Fe, Co), Rb2[M(H2O)6][Zr2F12] (M = Fe, Co, Ni, Cu, Zn), Cs2[M(H2O)6][Zr2F12] (M = Fe, Co, Ni), and Cs2Zr3Mn3F20 were obtained through a mild hydrothermal synthesis. The new materials crystallize in the monoclinic space group P21/n. The crystal structures and chemical compositions were determined using single crystal and powder X-ray diffraction. The thermal and optical properties of these materials are reported. UV-vis diffuse reflectance data identifies d-d electronic transitions of the Co-, Ni-, and Cu-containing compounds. Each hydrated compound (except the Fe containing compounds) exhibits similar thermal decomposition, fully dehydrating by 200 °C based on thermogravimetric analysis measurements. Magnetic measurements indicate that the new compositions are paramagnetic down to 2 K.
We develop a quantum theory of negative magnetoresistance in multi-Weyl semimetals in the E ∥ B configuration, where the chiral anomaly is activated. The magnetotransport response is governed by Landau quantization and the emergence of multiple chiral Landau levels associated with higher-order Weyl nodes. These anomaly-active modes have unidirectional dispersion fixed by the node's monopole charge and dominate charge transport. As the magnetic field increases, individual chiral branches successively cross the Fermi energy, producing discrete slope changes in the longitudinal conductivity and a step-like negative magnetoresistance. This quantized evolution provides a direct experimental signature of multi-Weyl topology. Bulk Landau levels contribute only at very low fields due to strong disorder scattering and do not affect the anomaly-driven regime. Our results establish a unified, fully quantum-mechanical framework in which negative magnetoresistance arises from the discrete Landau-quantized spectrum and microscopic impurity scattering, beyond semiclassical anomaly descriptions.
The check-in before imaging is an often underestimated but clinically critical step in the radiological patient journey. In computed tomography (CT) and magnetic resonance imaging (MRI), the quality of pre-examination information substantially determines whether risks are identified, examinations are adequately planned, and workflows are efficiently managed. To describe the clinical and organizational relevance of digital check-in processes in radiology and to assess their potential benefits, limitations, and prerequisites. Narrative review focusing on radiology-specific literature on appointment management, digital patient history and informed consent, protocol selection, patient portals, and implementation barriers. Digital check-in processes can improve the completeness of relevant pre-examination information, facilitate earlier identification of radiological risk constellations, reduce no-shows, focus informed consent discussions, and support protocol planning. However, their benefit depends largely on integration into established systems, as well as on patient-centered design. The greatest added value arises not from isolated tools, but from a clinically designed, interoperable pre-examination process. Digital solutions should support physicians and improve the patient journey. HINTERGRUND: Der Check-in vor der Untersuchung ist ein oft unterschätzter, aber klinisch entscheidender Abschnitt der radiologischen Patientenreise. Für Computertomographie (CT) und Magnetresonanztomographie (MRT) bestimmt die Qualität der Vorabinformationen wesentlich, ob Risiken erkannt, Untersuchungen adäquat geplant und Abläufe effizient gesteuert werden können. Darstellung der klinischen und organisatorischen Bedeutung digitaler Check-in-Prozesse in der Radiologie sowie Bewertung ihrer Potenziale, Grenzen und Voraussetzungen. Narrative Übersicht mit Fokus auf radiologiespezifische Literatur zu Terminmanagement, digitaler Anamnese und Aufklärung, Protokollauswahl, Patientenportalen und Implementierungsbarrieren. Digitale Check-in-Prozesse können die Vollständigkeit relevanter Vorinformationen verbessern, radiologische Risikokonstellationen früher sichtbar machen, No-shows reduzieren, Aufklärungsgespräche fokussieren und die Protokollplanung unterstützen. Ihr Nutzen hängt jedoch maßgeblich von der Integration in bestehende Systeme und einer patientenzentrierten Ausgestaltung ab. Der größte Mehrwert entsteht nicht durch isolierte Tools, sondern durch einen klinisch gedachten, interoperablen Vorprozess. Digitale Lösungen sollten Ärzte unterstützen und die Patientenreise verbessern.
Gamma oscillations are critical for cognitive functions. While phase-synchronized electric and magnetic stimulation can boost oscillatory brain activities in theta, alpha, and delta bands, the effects on gamma frequencies have not been investigated yet, especially with respect to functional connectivity and cognitive effects. This study explores how novel non-invasive techniques, phase-locked 40Hz intermittent theta-burst stimulation (iTBS) and transcranial alternating current stimulation (tACS), affect working memory performance and respective functional connectivity parameters in the brain. Thirty healthy young participants underwent (1) 40Hz tACS + sham iTBS, (2) 40Hz iTBS + sham tACS, (3-4) two combined interventions (iTBS pulses phase-locked to the tACS peak sine (X-tACS peak) wave or tACS trough sine wave (X-tACS trough), and (5) sham iTBS + sham tACS condition five times during working memory task performance and five times during resting-EEG recording in random order (10 sessions in total). The target regions were the left and right dorsolateral prefrontal cortices and were stimulated by simultaneous tACS and iTBS for 20 minutes. Working memory performance and functional brain connectivity metrics for local synchronization and global network efficiency were monitored before and after each intervention. Only the 40Hz tACS + sham iTBS and iTBS + sham tACS protocols enhanced high-load working memory performance speed. The same protocols, along with the X-tACS peak protocol, more pronouncedly improved functional connectivity metrics during the 30 minutes post-intervention compared to sham, corresponding to the behavioral testing period in separate sessions. These results suggest a temporal relation between alterations of functional brain connectivity and working memory task performance.
Accelerating musculoskeletal magnetic resonance imaging (MRI) while preserving diagnostic detail remains challenging because acquiring fully‑isotropic ground‑truth volumes is clinically costly. In routine practice, anisotropic scans with reduced through-plane resolution degrade multiplanar visualization and slice-by-slice review in reformatted planes, obscure subtle abnormalities spanning only a few slices, and limit automated three-dimensional (3D) analyses that assume comparable spatial resolution across axes. We present a two‑stage, fully self‑supervised pipeline that learns directly from anisotropic scans-obviating any paired high‑resolution data-and converts highly anisotropic (8:1) turbo‑spin‑echo volumes into isotropic images and 3D abnormality maps. Unlike prior self-supervised super-resolution methods, Stage 1 uses a single forward multi-view generative adversarial network (GAN) with patch-based contrastive and adversarial objectives rather than a backward/cycle-consistency approach. Stage 2 leverages an anatomy-conditioned denoising-diffusion model for healthy counterfactual generation, yielding voxel-wise lesion maps without external annotations. On 2225 Osteoarthritis Initiative knee scans from five different imaging centres, the framework reduced Fréchet inception distance from 407.4 → 254.4 (coronal) and 429.9 → 266.9 (axial), achieved the best Kernel Inception Distance (KID) / Learned Perceptual Image Patch Similarity (LPIPS) scores among competing unsupervised methods, and was preferred in 65-67% of blinded orthopedist comparisons. Crucially, isotropic enhancement propagated to downstream tasks: femur-tibia segmentation F1 scores increased and previously confluent bone‑marrow lesions were separated into discrete entities, enabling precise volumetric quantification. Robustness experiments demonstrated consistent gains across five imaging centers, synthetic noise/contrast perturbations, and transfer of the resolution-enhancement module to two additional MRI protocols, supporting robustness across sites and acquisition protocols. By eliminating the need for ground‑truth isotropic images while surpassing state‑of‑the‑art unsupervised super‑resolution in both perceptual quality and clinical utility, our method may facilitate retrospective cohort studies and prospective scan-time reduction in heterogeneous knee MRI settings, with preliminary transferability to additional protocols.
Hereditary spastic paraplegias are genetic disorders characterized by spasticity in the lower limbs, weakness, and sensory disturbances. Global prevalence ranges from 1.27 to 9.6 per 100 000 individuals. Mutations in the PLP1 gene cause various X-linked hereditary spastic paraplegias phenotypes, including Pelizaeus-Merzbacher disease and spastic paraplegia type 2. A 53-year-old male presented with chronic lower limb weakness since childhood, requiring a wheelchair at age 47 and exhibiting zero strength in the lower limbs. Magnetic resonance imaging revealed periventricular leukodystrophy; similar symptoms were found in maternal uncles and a nephew. The 32-year-old nephew had gait difficulties. A genetic sequencing panel identified a hemizygous variant of uncertain significance in the PLP1 gene [c.197A>T (p.His66Leu)] in both, not reported in population genetic databases. X-linked spastic paraplegia 2 is a disease primarily affecting gait and causing lower limb weakness. Reports indicate that it may also include cognitive impairment, nystagmus, and ataxia, although in the studied family, weakness predominated without cerebellar symptoms. Thirty-six families with this condition have been documented worldwide, with cases of asymptomatic carrier females. The c.197A>T (p.His66Leu) variant in the PLP1 gene, identified in this case, is novel and, despite being classified as "of uncertain significance", could be pathogenic according to bioinformatic predictors, explaining the spastic paraplegia 2 presentation in this family.
Objective: To investigate the molecular mechanism of toll-like receptor adaptor protein SARM1 in glaucomatous optic neuropathy. Methods: The experimental study was conducted from February 2024 to October 2025. A chronic ocular hypertension glaucoma model was established by injecting micro-magnetic beads into the anterior chamber of 8- to 10-week-old male Wistar rats. At 3 days, 1 week, and 2 weeks post-modeling, retinal and optic nerve tissues from 6 eyes of 6 rats were collected as the chronic ocular hypertension glaucoma model group, and 6 eyes from 6 wild-type rats that received an equal volume of saline via anterior chamber injection served as the control group. Intraocular pressure was measured using a TonoLab tonometer. Retinal whole-mounts were prepared and POU domain class 4 transcription factor 1 (POU4F1 or Brn3A) immunofluorescence staining was used to detect retinal ganglion cell loss. Western blotting was performed to detect the expression levels of SARM1 and SNPH in the rat retina and optic nerve. Immunofluorescence staining was used to examine their distribution in these tissues. Furthermore, CRISPR/Cas9 technology was used to knock down the expression of SARM1 and SNPH in mouse 661W retinal ganglion cells, respectively. Cells were collected 48 hours after transfection, and Western blotting was performed to detect the expression levels of SARM1 and SNPH. Normally distributed continuous data are presented as mean±SEM. Comparisons between two groups were performed using the Student's t-test, while comparisons among multiple groups were assessed by the one-way analysis of variance followed by the Tukey's multiple comparisons test. Results: Western blot analysis revealed that in the glaucoma model group, the relative expression level of SARM1 protein in the optic nerve at one week post-modeling (1.22±0.06) was significantly higher than that in the control group (1.03±0.01; P=0.027, q=4.38). In contrast, the expression level of SARM1 in the retina at three days post-modeling (0.79±0.02) was significantly lower than that in the control group (1.04±0.03; P<0.001, q=6.86). Concurrently, the expression level of SNPH at three days post-modeling (0.74±0.01) was lower than that in the control group (1.03±0.04; P=0.040, q=0.58), and its expression at one week post-modeling (1.19±0.10; P=0.002, q=4.36) was significantly higher than that at three days (0.74±0.01). Consistent with the Western blot results, immunofluorescence staining results showed that in the optic nerve of the glaucoma model group, the expression of SARM1 was significantly higher than that in the control group at one week post-modeling, while the expression of SNPH was lower than that in the control group at three days post-modeling. Both proteins partially co-localized with the neuronal marker β3-tubulin. Immunofluorescence staining also revealed co-localization of these two proteins within axons. Additionally, SARM1 co-localized with the mitochondrial marker protein TOM20. Western blot results from 661W cells showed that the knockdown of SARM1 expression (0.54±0.04) significantly reduced SNPH expression (0.54±0.05; P=0.003, q=7.98), whereas the knockdown of SNPH expression (0.39±0.06) did not markedly affect SARM1 levels (0.75±0.05; P=0.010, q=6.39). Conclusion: The elevated expression of SARM1 protein in the axons of the rat glaucoma model can promote retinal ganglion cell axonal pathology by localizing to axonal mitochondria and regulating SNPH expression. 目的： 探讨Toll样受体适配蛋白含无菌α基序及Toll/白介素受体基序蛋白1（SARM1）调控轴突线粒体锚定蛋白（SNPH）表达参与青光眼视神经病变的机制。 方法： 实验研究，于2024年2月至2025年10月开展。用简单随机法将8~10周Wistar雄性大鼠分为对照组和青光眼模型组，每组6只动物，均取右眼纳入实验。模型组进行前房微粒磁珠注射，构建慢性高眼压青光眼模型，在造模后3 d、1周和2周取视网膜和视神经进行实验；对照组大鼠前房注射等体积生理盐水。使用TonoLab眼压计测量大鼠眼压。采用视网膜铺片Brn3A免疫荧光染色检测视网膜神经节细胞（RGC）丢失情况。采用Western印迹检测大鼠视网膜和视神经中SARM1和SNPH的表达情况。采用免疫荧光染色法检测大鼠SARM1和SNPH在视网膜和轴突中的表达分布情况。并利用成簇规律间隔短回文重复序列（CRISPR）/核酸内切酶9（Cas9）技术分别降低小鼠视网膜神经节细胞系661W中SARM1和SNPH的表达，转染48 h后收集细胞。采用Western印迹检测细胞中SARM1和SNPH的表达情况。采用独立样本t检验、单因素方差分析、Tukey多重比较进行统计学分析。 结果： Western印迹结果显示，模型组造模后1周，视神经中的SARM1蛋白的相对表达量（1.22±0.06）高于对照组（1.03±0.01，P=0.027，q=4.38）。而视网膜中SARM1蛋白表达量在造模后3 d（0.79±0.02）低于对照组（1.04±0.03，P<0.001，q=6.86）。SNPH的表达量在造模后3 d（0.74±0.01）低于对照组（1.03±0.04，P=0.040，q=0.58），并在造模后1周（1.19±0.10，P=0.002，q=4.36）表达量高于造模后3 d（0.74±0.01）。免疫荧光染色结果显示，模型组RGC轴突中SARM1的表达在造模后1周高于对照组，SNPH的表达在造模后3 d低于对照组与Western印迹结果一致。并且都与神经元标志物微管蛋白部分共定位。并且免疫荧光染色结果还显示这两种蛋白在视神经中共定位。SARM1与线粒体标志物蛋白TOM20共定位。661W细胞中Western印迹结果显示，SARM1表达降低（0.54±0.04）可降低SNPH（0.54±0.05，P=0.003，q=7.98）的表达，但SNPH表达降低（0.39±0.06）对SARM1表达影响较小（0.75±0.05，P=0.010，q=6.39）。 结论： SARM1蛋白在大鼠青光眼模型组中的视神经中表达升高，通过定位于线粒体调控SNPH表达参与RGCs视神经病变。.
Intolerance of uncertainty (IU) is a transdiagnostic risk factor of psychopathology, but its neural underpinnings remain poorly established. Here, we combined connectome-based predictive modeling (CPM) and edge timeseries in a functional magnetic resonance imaging task design to model the network dynamics of IU (N = 85). First, CPM during passive viewing of surprised faces identified an IU-predictive network, characterized by positive Visual-Salience and negative Subcortical-Motor couplings. Prospective IU was related to both the positive and negative networks, but inhibitory IU was only related to the negative network. IU was better predicted when the uncertainty signal embedded within the facial features of surprise was maximized. Using edge timeseries, we found that individuals with higher IU showed sustained IU-related network engagement during post-task resting-state. Finally, we tested the generalizability of the IU-related network dynamics in an independent large-scale dataset with a sample size greater by tenfold (N = 878). The same network dynamics were associated with internalizing symptoms during a gambling task, but not during pre-task resting-state. Together, these findings suggest that an IU-related network, sensitive to the uncertainty evoked, exhibits sustained temporal dynamics generalizable to clinical symptoms in an independent dataset.
To characterize the clinical features, treatment response, and mortality of patients with systemic sclerosis (SSc) associated fibrosing myopathy. In this retrospective study, we identified patients enrolled in the Johns Hopkins Scleroderma Center Research Registry with histopathological evidence of fibrosing myopathy. Data were collected regarding SSc features, treatment exposures, and outcomes. Muscle involvement was characterized using muscle enzyme levels, muscle magnetic resonance imaging (MRI) findings, electromyography (EMG) data, and histopathologic features. 16 patients were included in the analysis. 14/16 patients (87.5%) received treatment specifically for muscle disease. Response based on muscle strength testing was evaluated at 6-12 months after treatment initiation. 9/16 patients (56.3%) had significant improvement, 4/16 (25%) showed no significant improvement, and 3/16 (18.8%) had inadequate follow-up. The most commonly used treatments were intravenous immunoglobulin, mycophenolate, and rituximab. After a mean follow-up time of 5.5 ± 4.7 years, 8/16 patients (50%) were deceased, with a cardiopulmonary cause of death in 4/8 (50%) of these patients. The baseline median CK value was 97 U/L (interquartile range 46-300 U/L). Myopathic changes were identified in 14/15 patients (93.3%) who had an EMG performed, while muscle edema was identified in 11/12 patients (91.7%) who underwent an MRI. A notable histopathological finding was myofiber atrophy in the perifascicular region in 9/16 patients (56.3%). SSc-associated fibrosing myopathy is a distinct entity associated with a high mortality rate in our cohort of patients. Early recognition and initiation of treatment is important due to the potential for improvement in muscle strength.
Pediatric airway endoscopy, including nasopharyngolaryngoscopy (NPL), microlaryngobronchoscopy (MLB), and flexible bronchoscopy, plays an essential role diagnosing and managing airway disorders in children. Each technique offers unique distinct advantages, and when paired with imaging modalities such as X-rays, fluoroscopy, computed tomography (CT), and magnetic resonance imaging (MRI), clinicians gain a more comprehensive and accurate assessment of the airway. This review explores the complementary role of endoscopy and imaging in pediatric airway evaluation, emphasizing how their combined use improves diagnostic accuracy, guides treatment planning, and facilitates multidisciplinary care. While endoscopy remains the gold standard for visualizing airway pathology, integrating imaging enhances understanding of both structural and functional abnormalities, ultimately improving clinical outcomes in this vulnerable patient population.