DNT cells mediate resistance to CAR-T cells therapy in a pediatric patient with relapsed and refractory B-ALL.

Chimeric antigen receptor T (CAR-T) cells therapy is a milestone achievement in the immunotherapy of relapsed and refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). However, some patients treated with CAR-T cells do not achieve complete remission, the mechanisms of which have not been elucidated. In the present study, we report a 9-year-old pediatric patient with refractory B-ALL received a triple infusion of autologous CD19 CAR-T cells therapy after the second relapse. CAR-T cells expanded in the peripheral blood and bone marrow. However, the patient did not achieve complete remission, indicating a lack of response to CAR-T cells therapy. Analysis of etiological factors revealed that the number of CD4 and CD8 double-negative T (DNT) cells was significantly upregulated in the peripheral blood, bone marrow, and autologous CAR-T cells products. In conclusiont, these findings indicate that DNT cells mediated resistance to CAR-T cells therapy in this pediatric patient with R/R B-ALL.

Design and Analysis of the Dual-Band Far-Field Super-Resolution Metalens with Large Aperture.

The resolving power of metalens telescopes rely on their aperture size. Flat telescopes are advancing with the research on super-resolution confocal metalenses with large aperture. However, the aperture sizes of metalenses are usually bound within hundreds of micrometers due to computational and fabrication challenges, limiting their usage on practical optical devices like telescopes. In this work, we demonstrated a two-step designing method for the design of dual-band far-field super-resolution metalens with aperture sizes from the micro-scale to macro-scale. By utilizing two types of inserted unit cells, the phase profile of a dual-wavelength metalens with a small aperture of 100 µm was constructed. Through numerical simulation, the measured FWHM values of the focal spots of 5.81 µm and 6.81 µm at working wavelengths of 632.8 nm and 1265.6 nm were found to all be slightly smaller than the values of 0.61 λ/NA, demonstrating the super-resolution imaging of the designed metalens. By measuring the optical power ratio of the focal plane and the incident plane, the focusing efficiencies were 76% at 632.8 nm and 64% at 1265.6 nm. Based on the design method for small-aperture metalens, far-field imaging properties through the macro metalens with an aperture of 40 mm were simulated by using the Huygens-Fresnel principle. The simulation results demonstrate confocal far-field imaging behavior at the target wavelengths of 632.8 nm and 1265.6 nm, with a focal length of 200 mm. The design method for dual-band far-field super-resolution metalens with a large aperture opens a door towards the practical applications in the dual-band space telescope system.

Automated detection of focal cortical dysplasia based on magnetic resonance imaging and positron emission tomography.

PURPOSE: Focal cortical dysplasia (FCD) is a common etiology of drug-resistant focal epilepsy. Visual identification of FCD is usually time-consuming and depends on personal experience. Herein, we propose an automated type II FCD detection approach utilizing multi-modal data and 3D convolutional neural network (CNN). METHODS: MRI and positron emission tomography (PET) data of 82 patients with FCD were collected, including 55 (67.1%) histopathologically, and 27 (32.9%) radiologically diagnosed patients. Three types of morphometric feature maps and three types of tissue maps were extracted from the T1-weighted images. These maps, T1, and PET images formed the inputs for CNN. Five-fold cross-validations were carried out on the training set containing 62 patients, and the model behaving best was chosen to detect FCD on the test set of 20 patients. Furthermore, ablation experiments were performed to estimate the value of PET data and CNN. RESULTS: On the validation set, FCD was detected in 90.3% of the cases, with an average of 1.7 possible lesions per patient. The sensitivity on the test set was 90.0%, with 1.85 possible lesions per patient. Without the PET data, the sensitivity decreased to 80.0%, and the average lesion number increased to 2.05 on the test set. If an artificial neural network replaced the CNN, the sensitivity decreased to 85.0%, and the average lesion number increased to 4.65. SIGNIFICANCE: Automated detection of FCD with high sensitivity and few false-positive findings is feasible based on multi-modal data. PET data and CNN could improve the performance of automated detection.

Widespread slow oscillations support interictal epileptiform discharge networks in focal epilepsy.

Interictal epileptiform discharges (IEDs) often co-occur across spatially-separated cortical regions, forming IED networks. However, the factors prompting IED propagation remain unelucidated. We hypothesized that slow oscillations (SOs) might facilitate IED propagation. Here, the amplitude and phase synchronization of SOs preceding propagating and non-propagating IEDs were compared in 22 patients with focal epilepsy undergoing intracranial electroencephalography (EEG) evaluation. Intracranial channels were categorized into the irritative zone (IZ) and normal zone (NOZ) regarding the presence of IEDs. During wakefulness, we found that pre-IED SOs within the IZ exhibited higher amplitudes for propagating IEDs than non-propagating IEDs (delta band: p = 0.001, theta band: p < 0.001). This increase in SOs was also concurrently observed in the NOZ (delta band: p = 0.04). Similarly, the inter-channel phase synchronization of SOs prior to propagating IEDs was higher than those preceding non-propagating IEDs in the IZ (delta band: p = 0.04). Through sliding window analysis, we observed that SOs preceding propagating IEDs progressively increased in amplitude and phase synchronization, while those preceding non-propagating IEDs remained relatively stable. Significant differences in amplitude occurred approximately 1150 ms before IEDs. During non-rapid eye movement (NREM) sleep, SOs on scalp recordings also showed higher amplitudes before intracranial propagating IEDs than before non-propagating IEDs (delta band: p = 0.006). Furthermore, the analysis of IED density around sleep SOs revealed that only high-amplitude sleep SOs demonstrated correlation with IED propagation. Overall, our study highlights that transient but widely distributed SOs are associated with IED propagation as well as generation in focal epilepsy during sleep and wakefulness, providing new insight into the EEG substrate supporting IED networks.

Rational design of bifunctional hydroxide/sulfide heterostructured catalyst for efficient electrochemical seawater splitting.

Heterostructure engineering is one of the most promising strategies for efficient water splitting by electrocatalysts. However, it remains challenging to design heterostructured catalysts to achieve the desired goals in both hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in seawater splitting. Here, particulate heterostructures of FeCoNi hydroxide/sulfide supported on nickel foams were prepared by hydrothermal methods to achieve a high-performance bifunctional catalyst. The synthesized FeCoNi hydroxide/sulfide exhibited excellent electrocatalytic performance, requiring an overpotential of 195 mV for OER and 76 mV for HER to achieve a current density of 10 mA cm-2 while showing excellent stability. The catalyst maintains its excellent performance even in artificial or natural seawater with high salinity, which is a harsh environment. When applied directly to a water splitting system, the catalyst achieves a current density of 10 mA cm-2 at only 1.5 V (1.57 V in alkaline seawater). The FeCoNi hydroxide/sulfide heterostructure is an excellent electrocatalytic bifunctional catalyst due to compositional modulation, systematic charge transfer optimization, improved intermediates adsorption, and increased electrocatalytic active sites and the synergistic effect of the heterostructure.

Transcutaneous amorphous preparation co-delivering curcumin and modified aptamer as a synergistic approach for the amelioration of psoriasis-like skin inflammation.

The aim is to achieve the targeting function of Aptamer 21-2 (Apt) by modifying glycyrrhizic acid (GA) to obtain Apt-GA and by delivering it through mesoporous silica in µm-size (µmS). Moreover, it is planned to induce synergistic effects of the novel amorphous preparation of Apt-GA with curcumin (Cur) in the treatment of psoriasis. UV/vis spectrophotometric analysis and Fourier transform infrared spectroscopy were performed to demonstrate the linkage of Apt and GA. The replacement of GA with Apt-GA in GA-Cur-µmS did not make a difference in the amorphous state, but showed superior fluorescence of Cur in the inflamed dermis similar to psoriatic induced by imiquimod. Consequently, compared to GA-Cur-µmS and Apt, Apt-GA-Cur-µmS exhibited less pronounced psoriatic characteristics in vivo, including Psoriasis Area and Severity Index, histological image, immunohistochemistry and immuno-fluorescence labeling neutrophils. The enzyme-linked immunosorbent assay showed a similar phenomenon that less IL-17A was observed after treatment with Apt-GA-Cur-µmS than with GA-Cur-µmS or Apt. Our finding suggests that this novel Apt delivery system achieved the Apt targeting function in the dermis by taking advantage of GA and µmS, and exhibited synergistic anti-psoriatic effect by co-delivering curcumin.