RESUMEN
Organic-inorganic lead halide quasi-two-dimensional (2D) perovskites are promising gain media for lasing applications because of their low cost, tunable colour, excellent stability and solution processability1-3. Optically pumped continuous-wave (CW) lasing is highly desired for practical applications in high-density integrated optoelectronics devices and constitutes a key step towards electrically pumped lasers4-6. However, CW lasing has not yet been realized at room temperature because of the 'lasing death' phenomenon (the abrupt termination of lasing under CW optical pumping), the cause of which remains unknown. Here we study lead halide-based quasi-2D perovskite films with different organic cations and observe that long-lived triplet excitons considerably impede population inversion during amplified spontaneous emission and optically pumped pulsed and CW lasing. Our results indicate that singlet-triplet exciton annihilation is a possible intrinsic mechanism causing lasing death. By using a distributed-feedback cavity with a high quality factor and applying triplet management strategies, we achieve stable green quasi-2D perovskite lasers under CW optical pumping in air at room temperature. We expect that our findings will pave the way to the realization of future current-injection perovskite lasers.
RESUMEN
Low-grade wind with airspeed Vwind < 5 m/s, while distributed far more abundantly, is still challenging to extract because current turbine-based technologies require particular geography (e.g., wide-open land or off-shore regions) with year-round Vwind > 5 m/s to effectively rotate the blades. Here, we report that low-speed airflow can sensitively enable directional flow within nanowire-anchored ionic liquid (IL) drops. Specifically, wind-induced air/liquid friction continuously raises directional leeward fluid transport in the upper portion, whereas three-phase contact line (TCL) pinning blocks further movement of IL. To remove excessive accumulation of IL near TCL, fluid dives, and headwind flow forms in the lower portion, as confirmed by microscope observation. Such stratified circulating flow within single drop can generate voltage output up to ~0.84 V, which we further scale up to ~60 V using drop "wind farms". Our results demonstrate a technology to tap the widespread low-grade wind as a reliable energy resource.
RESUMEN
Postictal generalized electroencephalographic suppression is a possible electroencephalographic marker for sudden unexpected death in epilepsy. We aimed to investigate the cortical surface area abnormalities in epilepsy patients with postictal generalized electroencephalographic suppression. We retrospectively included 30 epilepsy patients with postictal generalized electroencephalographic suppression (PGES+), 21 epilepsy patients without postictal generalized electroencephalographic suppression (PGES-), and 30 healthy controls. Surface-based analysis on high-resolution T1-weighted images was conducted and cortical surface areas were compared among the three groups, alongside correlation analyses with seizure-related clinical variables. Compared with PGES- group, we identified reduced surface area in the bilateral insula with more extensive distribution in the right hemisphere in PGES+ group. The reduced right insular surface area was associated with younger seizure-onset age. When compared with healthy controls, PGES- group presented reduced surface area in the left caudal middle frontal gyrus; PGES+ group presented more widespread surface area reductions in the right posterior cingulate gyrus, left postcentral gyrus, middle frontal gyrus, and middle temporal gyrus. Our results suggested cortical microstructural impairment in patients with postictal generalized electroencephalographic suppression. The significant surface area reductions in the insular cortex supported the autonomic network involvement in the pathology of postictal generalized electroencephalographic suppression, and its right-sided predominance suggested the potential shared abnormal brain network for postictal generalized electroencephalographic suppression and sudden unexpected death in epilepsy.
Asunto(s)
Epilepsia , Muerte Súbita e Inesperada en la Epilepsia , Humanos , Estudios Retrospectivos , Epilepsia/diagnóstico por imagen , Electroencefalografía/métodos , Convulsiones , Muerte SúbitaRESUMEN
Electrohydrodynamic printing holds both ultrahigh-resolution fabrication capability and unmatched ink-viscosity compatibility yet fails on highly insulating thick/irregular substrates. Herein, we proposed a single-potential driven electrohydrodynamic printing process with submicrometer resolution on arbitrary nonconductive targets, regardless of their geometric shape or sizes, via precoating with an ultrathin dielectric nanoparticle layer. Benefiting from the favorable Maxwell-Wagner polarization, the reversely polarized spot brought about a significant drop (â¼57% for ceramics) in the operation voltage as its induced electric field and a negligible residual charge accumulation. Thus, ordered micro/nanostructures with line widths down to 300 nm were directly written at a stage speed as low as 5 mm/s, and silver features with width of â¼2 µm or interval of â¼4 µm were achieved on insulating substrates separately. Flexible sensors and curved heaters were then high-precision printed and demonstrated successfully, presenting this technique with huge potential for fabricating flexible/conformal electronics on arbitrary 3D structures.
RESUMEN
Ribosome profiling and mass spectrometry have revealed thousands of previously unannotated small and alternative open reading frames (sm/alt-ORFs) that are translated into micro/alt-proteins in mammalian cells. However, their prevalence across human tissues and biological roles remains largely undefined. The placenta is an ideal model for identifying unannotated microproteins and alt-proteins due to its considerable protein diversity that is required to sustain fetal development during pregnancy. Here, we profiled unannotated microproteins and alt-proteins in human placental tissues from preeclampsia patients or healthy individuals by proteomics, identified 52 unannotated microproteins or alt-proteins, and demonstrated that five microproteins can be translated from overexpression constructs in a heterologous cell line, although several are unstable. We further demonstrated that one microprotein, XRCC6P1, associates with translation initiation factor eIF3 and negatively regulates translation when exogenously overexpressed. Thus, we revealed a hidden sm/alt-ORF-encoded proteome in the human placenta, which may advance the mechanism studies for placenta development as well as placental disorders such as preeclampsia.
RESUMEN
Tumor heterogeneity remains a significant obstacle in cancer therapy due to diverse cells with varying treatment responses. Cancer stem-like cells (CSCs) contribute significantly to intratumor heterogeneity, characterized by high tumorigenicity and chemoresistance. CSCs reside in the depth of the tumor, possessing low reactive oxygen species (ROS) levels and robust antioxidant defense systems to maintain self-renewal and stemness. A nanotherapeutic strategy is developed using tumor-penetrating peptide iRGD-modified high-density lipoprotein (HDL)-mimetic nanodiscs (IPCND) that ingeniously loaded with pyropheophorbide-a (Ppa), bis (2-hydroxyethyl) disulfide (S-S), and camptothecin (CPT) by synthesizing two amphiphilic drug-conjugated sphingomyelin derivatives. Photoactivatable Ppa can generate massive ROS which as intracellular signaling molecules effectively shut down self-renewal and trigger differentiation of the CSCs, while S-S is utilized to deplete GSH and sustainably imbalance redox homeostasis by reducing ROS clearance. Simultaneously, the depletion of GSH is accompanied by the release of CPT, which leads to subsequent cell death. This dual strategy successfully disturbed the redox equilibrium of CSCs, prompting their differentiation and boosting the ability of CPT to kill CSCs upon laser irradiation. Additionally, it demonstrated a synergistic anti-cancer effect by concurrently eliminating therapeutically resistant CSCs and bulk tumor cells, effectively suppressing tumor growth in CSC-enriched heterogeneous colon tumor mouse models.
Asunto(s)
Resistencia a Antineoplásicos , Homeostasis , Células Madre Neoplásicas , Oxidación-Reducción , Especies Reactivas de Oxígeno , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/patología , Humanos , Homeostasis/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Línea Celular Tumoral , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Camptotecina/farmacología , Camptotecina/química , Clorofila/análogos & derivados , Clorofila/química , Clorofila/farmacología , Nanoestructuras/química , Ratones , Biomimética/métodos , Glutatión/metabolismo , Lipoproteínas HDL/química , Lipoproteínas HDL/metabolismo , Oligopéptidos/química , Oligopéptidos/farmacologíaRESUMEN
PURPOSE: To present a Swin Transformer-based deep learning (DL) model (SwinIR) for denoising single-delay and multi-delay 3D arterial spin labeling (ASL) and compare its performance with convolutional neural network (CNN) and other Transformer-based methods. METHODS: SwinIR and CNN-based spatial denoising models were developed for single-delay ASL. The models were trained on 66 subjects (119 scans) and tested on 39 subjects (44 scans) from three different vendors. Spatiotemporal denoising models were developed using another dataset (6 subjects, 10 scans) of multi-delay ASL. A range of input conditions was tested for denoising single and multi-delay ASL, respectively. The performance was evaluated using similarity metrics, spatial SNR and quantification accuracy of cerebral blood flow (CBF), and arterial transit time (ATT). RESULTS: SwinIR outperformed CNN and other Transformer-based networks, whereas pseudo-3D models performed better than 2D models for denoising single-delay ASL. The similarity metrics and image quality (SNR) improved with more slices in pseudo-3D models and further improved when using M0 as input, but introduced greater biases for CBF quantification. Pseudo-3D models with three slices achieved optimal balance between SNR and accuracy, which can be generalized to different vendors. For multi-delay ASL, spatiotemporal denoising models had better performance than spatial-only models with reduced biases in fitted CBF and ATT maps. CONCLUSIONS: SwinIR provided better performance than CNN and other Transformer-based methods for denoising both single and multi-delay 3D ASL data. The proposed model offers flexibility to improve image quality and/or reduce scan time for 3D ASL to facilitate its clinical use.
Asunto(s)
Aprendizaje Profundo , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Encéfalo/diagnóstico por imagen , Encéfalo/irrigación sanguínea , Marcadores de Spin , Arterias , Circulación Cerebrovascular/fisiología , Procesamiento de Imagen Asistido por Computador/métodosRESUMEN
Dietary fiber metabolism by gut microorganisms plays important roles in host physiology and health. Alginate, the major dietary fiber of daily diet seaweeds, is drawing more attention because of multiple biological activities. To advance the understanding of alginate assimilation mechanism in the gut, we show the presence of unsaturated alginate oligosaccharides (uAOS)-specific alginate utilization loci (AUL) in human gut microbiome. As a representative example, a working model of the AUL from the gut microorganism Bacteroides clarus was reconstructed from biochemistry and transcriptome data. The fermentation of resulting monosaccharides through Entner-Doudoroff pathway tunes the metabolism of short-chain fatty acids and amino acids. Furthermore, we show that uAOS feeding protects the mice against dextran sulfate sodium-induced acute colitis probably by remodeling gut microbiota and metabolome. IMPORTANCE: Alginate has been included in traditional Chinese medicine and daily diet for centuries. Recently discovered biological activities suggested that alginate-derived alginate oligosaccharides (AOS) might be an active ingredient in traditional Chinese medicine, but how these AOS are metabolized in the gut and how it affects health need more information. The study on the working mechanism of alginate utilization loci (AUL) by the gut microorganism uncovers the role of unsaturated alginate oligosaccharides (uAOS) assimilation in tuning short-chain fatty acids and amino acids metabolism and demonstrates that uAOS metabolism by gut microorganisms results in a variation of cell metabolites, which potentially contributes to the physiology and health of gut.
Asunto(s)
Alginatos , Microbioma Gastrointestinal , Oligosacáridos , Alginatos/metabolismo , Oligosacáridos/metabolismo , Ratones , Animales , Humanos , Colitis/microbiología , Colitis/inducido químicamente , Ratones Endogámicos C57BL , Ácidos Grasos Volátiles/metabolismo , Inflamación/metabolismo , Sulfato de Dextran , Fibras de la Dieta/metabolismoRESUMEN
OBJECTIVES: We aimed to investigate the value of deep learning (DL) models based on multimodal ultrasonographic (US) images to quantify RA activity. METHODS: Static greyscale (SGS), dynamic greyscale (DGS), static power Doppler (SPD) and dynamic power Doppler (DPD) US images were collected and evaluated by two expert radiologists according to the EULAR-OMERACT Synovitis Scoring system. Four DL models were developed based on the ResNet-type structure, evaluated on two separate test cohorts, and finally compared with the performance of 12 radiologists with different levels of experience. RESULTS: In total, 1244 images were used for the model training, and 152 and 354 for testing (cohort 1 and 2, respectively). The best-performing models for the scores of 0/1/2/3 were the DPD, SGS, DGS and SPD models, respectively (Area Under the receiver operating characteristic Curve [AUC] = 0.87/0.95/0.74/0.95; no significant differences). All the DL models provided results comparable to the experienced radiologists on a per-image basis (intraclass correlation coefficient: 0.239-0.756, P < 0.05). The SPD model performed better than the SGS one on test cohort 1 (score of 0/2/3: AUC = 0.82/0.67/0.95 vs 0.66/0.66/0.75, respectively) and test cohort 2 (score of 0: AUC = 0.89 vs 0.81). The dynamic DL models performed better than the static ones in most of the scoring processes and were more accurate than the most of senior radiologists, especially the DPD model. CONCLUSION: DL models based on multimodal US images allow a quantitative and objective assessment of RA activity. Dynamic DL models in particular have potential value in assisting radiologists to improve the accuracy of RA US-based grading.
Asunto(s)
Artritis Reumatoide , Aprendizaje Profundo , Humanos , Ultrasonografía , Artritis Reumatoide/diagnóstico por imagen , Curva ROC , RadiólogosRESUMEN
We demonstrate the post-induction of high-quality microcavities on a silicon photonic crystal (PC) waveguide by integrating a few-layer GaSe crystal, which promises efficient on-chip optical frequency conversions. The integration of GaSe shifts the dispersion bands of the PC waveguide mode into the bandgap, resulting in localized modes confined by the bare PC waveguides. Thanks to the small contrast of refractive index at the boundaries of the microcavity, it is reliable to obtain quality factors exceeding 104. With the enhanced light-GaSe interaction by the microcavity modes and GaSe's high second-order nonlinearity, remarkable second-harmonic generation (SHG) and sum-frequency generation (SFG) are achieved with continuous-wave (CW) lasers.
RESUMEN
TNF stimulation generates pro-survival signals through activation of NF-κB that restrict the build-in death signaling triggered by TNF. The competition between TNF-induced survival and death signals ultimately determines the fate of a cell. Here, we report the identification of Bclaf1 as a novel component of the anti-apoptotic program of TNF. Bclaf1 depletion in multiple cells sensitizes cells to TNF-induced apoptosis but not to necroptosis. Bclaf1 exerts its anti-apoptotic function by promoting the transcription of CFLAR, a caspase 8 antagonist, downstream of NF-κB activation. Bclaf1 binds to the p50 subunit of NF-κB, which is required for Bclaf1 to stimulate CFLAR transcription. Finally, in Bclaf1 siRNA administered mice, TNF-induced small intestine injury is much more severe than in control mice with aggravated signs of apoptosis and pyroptosis. These results suggest Bclaf1 is a key regulator in TNF-induced apoptosis, both in vitro and in vivo.
Asunto(s)
Apoptosis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD , FN-kappa B , Proteínas Represoras , Factor de Necrosis Tumoral alfa , Animales , Apoptosis/genética , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/biosíntesis , Proteína Reguladora de Apoptosis Similar a CASP8 y FADD/genética , Intestino Delgado/lesiones , Intestino Delgado/metabolismo , Intestino Delgado/fisiopatología , Ratones , FN-kappa B/genética , FN-kappa B/metabolismo , Proteínas Represoras/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
Traditional information encryption materials that rely on fluorescent/phosphorescent molecules are facing an increasing risk of counterfeiting or tampering due to their static reading mode and advances in counterfeiting technology. In this study, a series of Mg2-xZnxSnO4 (x = 0.55, 0.6, 0.65, 0.7 0.75, 0.8) that realizes the writing, reading, and erasing of dynamic information is developed. When heated to 90 °C, the materials exhibit a variety of dynamic emission changes with the concentration of Zn2+ ions. As the doping concentration increased, the ratio of the shallow trap to deep trap changed from 7.77 to 20.86. When x = 0.55, the proportion of deep traps is relatively large, resulting in a higher temperature and longer time required to read the information. When x = 0.80, the proportion of shallow traps is larger and the encrypted information is easier to read. Based on the above features, encryption binary codes device was designed, displaying dynamic writing, reading, and erasing of information under daylight and heating conditions. Accordingly, this work provides reliable guidance on advanced dynamic information encryption.
RESUMEN
Punishment is a common tactic to sustain cooperation and has been extensively studied for a long time. While most of previous game-theoretic work adopt the imitation learning framework where players imitate the strategies of those who are better off, the learning logic in the real world is often much more complex. In this work, we turn to the reinforcement learning paradigm, where individuals make their decisions based upon their experience and long-term returns. Specifically, we investigate the prisoners' dilemma game with a Q-learning algorithm, and cooperators probabilistically pose punishment on defectors in their neighborhood. Unexpectedly, we find that punishment could lead to either continuous or discontinuous cooperation phase transitions, and the nucleation process of cooperation clusters is reminiscent of the liquid-gas transition. The analysis of a Q-table reveals the evolution of the underlying "psychologic" changes, which explains the nucleation process and different levels of cooperation. The uncovered first-order phase transition indicates that great care needs to be taken when implementing the punishment compared to the continuous scenario.
RESUMEN
OBJECTIVE: To describe the ultrasound characteristics of nodular localized cutaneous neurofibroma (NLCN). MATERIALS AND METHODS: Clinical features and ultrasound characteristics of 43 lesions of 40 patients pathologically proven as NLCNs at Peking University Shenzhen Hospital from October 2014 to May 2022 were analyzed retrospectively. The location, length-to-thickness (L/T) ratio, thickness-to-width (T/W) ratio, shape, margin, capsule, echogenicity, echotexture, posterior features, vascularity, and "rat tail sign" were evaluated. RESULTS: All ultrasound findings showed almost perfect agreement. More than a half of NLCNs (n = 24, 55.8%, p < 0.001) were located in the subcutaneous fat layer wholly with well-demarcation from dermis and deep fascia. Most of the NLCNs were fusiform shape (n = 27, 62.8%, p < 0.001) in the long axis and oval shape (n = 35, 81.4%, p < 0.001) in the short axis. The other ultrasound findings of NLCNs included well-defined (n = 42, 97.7%, p < 0.001), encapsulated (n = 39, 90.7%, p < 0.001), predominately hypoechoic (n = 34, 79.1%, p < 0.001), homogeneous (n = 39, 90.7%, p < 0.001), posterior enhancement (n = 29, 67.4%, p = 0.033), and avascularity (n = 37, 86.0%, p < 0.001). Only a quarter (n = 11, 25.6%, p = 0.002) of lesions were recognized with the "rat tail sign." CONCLUSION: NLCNs present as fusiform shape in long axis and round shape in short axis. The common ultrasound findings of NLCNs are well-defined, encapsulated, predominately hypoechoic, homogeneous lesion with posterior enhancement, and poor blood supply. The "rat tail sign" has low sensitivity in NLCNs.
Asunto(s)
Neurofibroma , Neoplasias Cutáneas , Ultrasonografía , Humanos , Femenino , Neurofibroma/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto , Ultrasonografía/métodos , Neoplasias Cutáneas/diagnóstico por imagen , Neoplasias Cutáneas/patología , Adulto Joven , Adolescente , Anciano , Piel/diagnóstico por imagen , Piel/patología , NiñoRESUMEN
INTRODUCTION: We investigated whether retinal capillary perfusion is a biomarker of cerebral small vessel disease and impaired cognition among Black Americans, an understudied group at higher risk for dementia. METHODS: We enrolled 96 Black Americans without known cognitive impairment. Four retinal perfusion measures were derived using optical coherence tomography angiography. Neurocognitive assessment and brain magnetic resonance imaging (MRI) were performed. Multiple linear regression analyses were performed. RESULTS: Lower retinal capillary perfusion was correlated with worse Oral Symbol Digit Test (P < = 0.005) and Fluid Cognition Composite scores (P < = 0.02), but not with the Crystallized Cognition Composite score (P > = 0.41). Lower retinal perfusion was also correlated with higher free water and peak width of skeletonized mean diffusivity, and lower fractional anisotropy (all P < 0.05) on MRI (N = 35). DISCUSSION: Lower retinal capillary perfusion is associated with worse information processing, fluid cognition, and MRI biomarkers of cerebral small vessel disease, but is not related to crystallized cognition.
Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales , Vasos Retinianos , Humanos , Vasos Retinianos/diagnóstico por imagen , Vasos Retinianos/patología , Negro o Afroamericano , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Cognición , Perfusión , Imagen por Resonancia Magnética , Biomarcadores , Enfermedades de los Pequeños Vasos Cerebrales/patologíaRESUMEN
Fulfilling potentials of ultrahigh field for pseudo-Continuous Arterial Spin Labeling (pCASL) has been hampered by B1/B0 inhomogeneities that affect pCASL labeling, background suppression (BS), and the readout sequence. This study aimed to present a whole-cerebrum distortion-free three-dimensional (3D) pCASL sequence at 7T by optimizing pCASL labeling parameters, BS pulses, and an accelerated Turbo-FLASH (TFL) readout. A new set of pCASL labeling parameters (Gave = 0.4 mT/m, Gratio = 14.67) was proposed to avoid interferences in bottom slices while achieving robust labeling efficiency (LE). An OPTIM BS pulse was designed based on the range of B1/B0 inhomogeneities at 7T. A 3D TFL readout with 2D-CAIPIRINHA undersampling (R = 2 × 2) and centric ordering was developed, and the number of segments (Nseg) and flip angle (FA) were varied in simulation to achieve the optimal trade-off between SNR and spatial blurring. In-vivo experiments were performed on 19 subjects. The results showed that the new set of labeling parameters effectively achieved whole-cerebrum coverage by eliminating interferences in bottom slices while maintaining a high LE. The OPTIM BS pulse achieved 33.3% higher perfusion signal in gray matter (GM) than the original BS pulse with a cost of 4.8-fold SAR. Incorporating a moderate FA (8°) and Nseg (2), whole-cerebrum 3D TFL-pCASL imaging was achieved with a 2 × 2 × 4 mm3 resolution without distortion and susceptibility artifacts compared to 3D GRASE-pCASL. In addition, 3D TFL-pCASL showed a good to excellent test-retest repeatability and potential of higher resolution (2 mm isotropic). The proposed technique also significantly improved SNR when compared to the same sequence at 3T and simultaneous multislice TFL-pCASL at 7T. By combining a new set of labeling parameters, OPTIM BS pulse, and accelerated 3D TFL readout, we achieved high resolution pCASL at 7T with whole-cerebrum coverage, detailed perfusion and anatomical information without distortion, and sufficient SNR.
Asunto(s)
Encéfalo , Imagenología Tridimensional , Humanos , Imagenología Tridimensional/métodos , Encéfalo/diagnóstico por imagen , Marcadores de Spin , Arterias , Angiografía por Resonancia Magnética/métodos , Circulación Cerebrovascular , Corteza CerebralRESUMEN
The tumour microenvironment (TME) is a complex system composed of cancer cells, stromal cells and immune cells. Regulatory T cells (Tregs) in the TME impede immune surveillance of tumours and suppress antitumor immune responses. Transcription factor forkhead box protein 3 (FOXP3) is the main marker of Tregs, which dominates the function of Tregs. FOXP3 was originally thought to be a Tregs-specific expression molecule, and recent studies have found that FOXP3 is expressed in a variety of tumours with inconsistent functional roles. This review summarizes the recent progress of infiltrating Treg-FOXP3 and tumour-FOXP3 in TME, discusses the communication mechanism between FOXP3+ cells and effector T cells in TME, the relationship between FOXP3 and clinical prognosis, and the potential of FOXP3-targeted therapy.
Asunto(s)
Factores de Transcripción Forkhead , Neoplasias , Humanos , Factores de Transcripción Forkhead/genética , Microambiente Tumoral , Linfocitos Infiltrantes de Tumor , Neoplasias/patología , Pronóstico , Linfocitos T ReguladoresRESUMEN
Biomedical micro/nanorobots as active delivery systems with the features of self-propulsion and controllable navigation have made tremendous progress in disease therapy and diagnosis, detection, and biodetoxification. However, existing micro/nanorobots are still suffering from complex drug loading, physiological drug stability, and uncontrollable drug release. To solve these problems, micro/nanorobots and nanocatalytic medicine as two independent research fields were integrated in this study to achieve self-propulsion-induced deeper tumor penetration and catalytic reaction-initiated tumor therapy in vivo. We presented self-propelled Janus nanocatalytic robots (JNCRs) guided by magnetic resonance imaging (MRI) for in vivo enhanced tumor therapy. These JNCRs exhibited active movement in H2O2 solution, and their migration in the tumor tissue could be tracked by non-invasive MRI in real time. Both increased temperature and reactive oxygen species production were induced by near-infrared light irradiation and iron-mediated Fenton reaction, showing great potential for tumor photothermal and chemodynamic therapy. In comparison with passive nanoparticles, these self-propelled JNCRs enabled deeper tumor penetration and enhanced tumor therapy after intratumoral injection. Importantly, these robots with biocompatible components and byproducts exhibited biosecurity in the mouse model. It is expected that our work could promote the combination of micro/nanorobots and nanocatalytic medicine, resulting in improved tumor therapy and potential clinical transformations.
Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Robótica , Animales , Ratones , Peróxido de Hidrógeno , Hipertermia Inducida/métodos , Línea Celular Tumoral , Neoplasias/terapia , Nanopartículas/uso terapéutico , Imagen por Resonancia Magnética/métodosRESUMEN
Vogt-Koyanagi-Harada (VKH) disease, a major blinding eye disease, is characterized by an autoimmune response against melanocytes in multiple organs throughout the body. Currently, the aetiology and pathogenesis of VKH disease are unclear, and the treatment strategy needs to be further optimized. The retinal pigment epithelium (RPE), a monolayer of pigmented cells of the fundus, is essential for maintaining normal visual function and is involved in both the acute and chronic stages of VKH disease. Therefore, the functions of the RPE may play a critical role in the aetiology and treatment of VKH disease. Herein, we established a human induced pluripotent stem cell (hiPSC) RPE model of VKH disease by reprogramming peripheral blood mononuclear cells (PBMCs) into iPSCs and then differentiating them into RPE cells. Patient-derived RPE cells exhibited barrier disruption, impaired phagocytosis, and depigmentation compared with those from normal controls, which was consistent with the features of VKH disease. Furthermore, a small molecular compound targeting EGR2 was found to rescue the barrier and phagocytic functions of the hiPSC-RPE cells through high-throughput virtual screening and functional studies, suggesting a promising strategy for the treatment of VKH disease.
Asunto(s)
Células Madre Pluripotentes Inducidas , Síndrome Uveomeningoencefálico , Humanos , Síndrome Uveomeningoencefálico/tratamiento farmacológico , Evaluación Preclínica de Medicamentos , Leucocitos Mononucleares , Epitelio Pigmentado de la RetinaRESUMEN
Background Synovial hypoxia is a hallmark of rheumatoid arthritis (RA). Photoacoustic (PA) imaging, based on the use of laser-generated US, can detect the oxygenation status of tissue in individuals with RA. However, large studies are lacking, with few investigating the correlation between oxygenation status and disease activity. Purpose To measure synovial oxygenation status in participants with RA by using a multimodal PA US imaging system and to determine the correlation between PA imaging-measured oxygen saturation (SO2) and disease activity. Materials and Methods In this prospective observational cohort study, multimodal PA US imaging examinations were performed on small joints of consecutive participants with RA, who were treated at two outpatient rheumatology clinics from 2019 to 2021, and healthy controls. The SO2 values of the synovium were measured with dual-wavelength PA imaging and classified into three categories-hyperoxia, intermediate oxygenation status, or hypoxia-based on the signal coloration and clustering analysis of the SO2 values. The correlations of oxygenation status with power Doppler US (PDUS) scoring and clinical disease activity index were evaluated with one-way analysis of variance and the Kruskal-Wallis test with Bonferroni correction. Results A total of 118 participants with RA (median age, 55 years [IQR, 41-62 years]; 92 women) and 15 healthy control participants (median age, 37 years [IQR, 33-41 years]; 11 women) were included. The wrist synovium was categorized as hyperoxic in 36 participants with RA, of intermediate oxygenation status in 48 participants, and hypoxic in 34 participants. All control participants had hyperoxic synovial tissues. For participants with RA, hyperoxic synovium had more affluent Doppler US-depicted vasculature than those with hypoxia and intermediate oxygenation status (mean PDUS grade: hyperoxia, 2.7 ± 0.6 [SD]; intermediate, 1.3 ± 0.7; hypoxia, 1.1 ± 0.8; P < .001). Participants with intermediate status synovium had a lower clinical disease activity index than those with hypoxia (intermediate, 11.0 [IQR, 5.0-21.5] vs hypoxia, 26.0 [IQR, 18.0-39.0]; P = .001). Conclusion Photoacoustic imaging-detected hypoxia in thickened synovium correlated with less vascularization and higher disease activity in participants with rheumatoid arthritis. Clinical trial registration no. NCT04297475 © RSNA, 2022 Online supplemental material is available for this article.