Self-assembled nanoparticles based on DNA origami and a nitrated T helper cell epitope as a platform for the development of personalized cancer vaccines.

Neoantigen vaccines constitute an emerging and promising cancer immunotherapy. However, not all neoantigens have anti-tumor activity, as poor CD4+ epitope recognition can lead to the lack of greatly limit the persistence of the CD8+ T cell response. Therefore, we designed a self-assembled nanoplatform hereinafter referred to as DNA-coupled nitrated T helper cell epitope nanoparticle (DCNP) based on DNA origami containing a nitrated CD4 + T cell epitope, which can facilitate the effective activation of neoantigen-specific CD8+ T cells. Moreover, we embedded the cytidine-phosphate-guanosine oligonucleotide (CpG ODN) motif sequence in the DNA skeleton to function as a built-in adjuvant to activate Toll-like receptor 9. DCNP can markedly improve adjuvant and neoantigen co-delivery to lymphoid organs and promote neoantigen presentation on dendritic cells. Moreover, DCNP induced robust, and long-lived neoantigen-specific CD8+ T cell responses that significantly delayed tumor growth. Further, these effects were largely dependent on the nitrated T cell epitope. Collectively, our findings indicate that DCNP is a promising platform that could improve the development of personalized therapeutic neoantigen vaccines for cancer immunotherapy.

Multi-Depth Computer-Generated Hologram Based on Stochastic Gradient Descent Algorithm with Weighted Complex Loss Function and Masked Diffraction.

In this paper, we propose a method to generate multi-depth phase-only holograms using stochastic gradient descent (SGD) algorithm with weighted complex loss function and masked multi-layer diffraction. The 3D scene can be represented by a combination of layers in different depths. In the wave propagation procedure of multiple layers in different depths, the complex amplitude of layers in different depths will gradually diffuse and produce occlusion at another layer. To solve this occlusion problem, a mask is used in the process of layers diffracting. Whether it is forward wave propagation or backward wave propagation of layers, the mask can reduce the occlusion problem between different layers. Otherwise, weighted complex loss function is implemented in the gradient descent optimization process, which analyzes the real part, the imaginary part, and the amplitude part of the focus region between the reconstructed images of the hologram and the target images. The weight parameter is used to adjust the ratio of the amplitude loss of the focus region in the whole loss function. The weight amplitude loss part in weighted complex loss function can decrease the interference of the focus region from the defocus region. The simulations and experiments have validated the effectiveness of the proposed method.

Anisotropic Growth of Centimeter-Size CsCu2 I3 Single Crystals with Ultra-Low Trap Density for Aspect-Ratio-Dependent Photodetectors.

Low-dimensional ternary copper iodide metal halide with strong quantum confinement effects has made great progress in optoelectronic fields. However, efficient regulation of anisotropic growth of metal halides single crystal still remains a great challenge. Herein, 2 cm size CsCu2 I3 single crystals with tunable aspect ratio and the trap states (ntrap ) as low as 5.38 × 109  cm-3 are fabricated by optimized anti-solvent vapor-assisted method, in which the growth cycle is shortened by half. Evidenced by real-time observation and the LaMer growth model, the rapid and anisotropic growth mechanism is ascribed to preferential 1D growth, promoted by high concentration and fast vapor rate. Furthermore, the aspect-ratio-dependent optoelectronic performance is observed, the on-off ratio for 2 cm CsCu2 I3 single crystal are enhanced 350 times compared with those of short and thick single crystal, which shows ultrahigh on-off ratio of 1570, D* of 1.34 × 1012  Jones, Rλ of 276.94 mA W-1 , t rise /t decay of 0.37 and 1.08 ms, and EQE of 95.53%, which are clearly at very high level among lead-free perovskite-based photodetectors. This study not only provides a new strategy for overcoming anisotropic growth limitations of low-dimensional metal halides, but also paves a way for high-performance optoelectronic applications.

Study on the Magnetic Noise Characteristics of Amorphous and Nanocrystalline Inner Magnetic Shield Layers of SERF Co-Magnetometer.

With the widespread use of magneto-sensitive elements, magnetic shields are an important part of electronic equipment, ultra-sensitive atomic sensors, and in basic physics experiments. Particularly in Spin-exchange relaxation-free (SERF) co-magnetometers, the magnetic shield is an important component for maintaining the SERF state. However, the inherent noise of magnetic shield materials is an important factor limiting the measurement sensitivity and accuracy of SERF co-magnetometers. In this paper, both amorphous and nanocrystalline materials were designed and applied as the innermost magnetic shield of an SERF co-magnetometer. Magnetic noise characteristics of different amorphous and nanocrystalline materials used as the internal magnetic shielding layer of the magnetic shielding system were analyzed. In addition, the effects on magnetic noise due to adding aluminum to amorphous and nanocrystalline materials were studied. The experimental results show that compared with an amorphous material, a nanocrystalline material as the inner magnetic shield layer can effectively reduce the magnetic noise and improve the sensitivity and precision of the rotation measurement. Nanocrystalline material is very promising for inner shield composition in SERF co-magnetometers. Furthermore, its ultra-thin structure and low cost have significant application value in the miniaturization of SERF co-magnetometers.

Transvenous endovascular treatment for vein of Galen aneurysmal malformation with idiopathic bilateral sigmoid sinus occlusion.

BACKGROUND: Vein of Galen Malformations (VGAM) and bilateral idiopathic occlusion of the sigmoid sinuses are extremely rare. We report a child with Vein of Galen Aneurysmal Malformation (VGAM) and Idiopathic bilateral sigmoid sinus occlusion simultaneously, and managed through endovascular therapy in one session. This case highlights the coexistence of the lesions, as well as the one-session technical feasibility and good clinical outcome for endovascular treatment. CLINICAL PRESENTATION: The child presented with enlarged head circumference and epilepsy. The frequency of seizure increased from one time to several times a day. CTA/CTV confirmed coexistence of Vein of Galen Malformations and idiopathic bilateral sigmoid sinus occlusion. CONCLUSION: One session trans-venous approach was performed. The VGAM was completely occluded and the dominant sigmoid sinus was recanalized. Thirteen months telephone follow-up confirmed normal head growth. The patient is seizure-free and recovered very well with normal neurological and developmental condition. This study provides evidentiary support for one-session endovascular therapy in patient with VGAM and idiopathic bilateral sigmoid sinus occlusion.

Efficaciousness of dexmedetomidine in children undergoing cleft lip and palate repair: a systematic review and meta-analysis.

OBJECTIVE: To systematically assess the efficacy and safety of dexmedetomidine as an anaesthesia adjuvant for cleft lip and palate (CLP) repair in children. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP) and Wanfang (up to October 2020). Studies in languages other than English and Chinese were excluded. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) evaluating the impact of dexmedetomidine on emergence agitation (EA), the need for postoperative rescue analgesics, postoperative nausea and vomiting (PONV), and other adverse events in paediatric patients during CLP repair. DATA EXTRACTION AND SYNTHESIS: The quality of evidence was assessed by using the Cochrane Review Methods and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were screened, extracted and assessed by two independent authors. Outcomes were reported as a risk ratio (RR) with a 95% CI. A random-effect model was used when heterogeneity was detected. RESULTS: Thirteen studies including 1040 children met the inclusion criteria. The incidence of EA was significantly decreased in the dexmedetomidine group (RR, 0.19; 95% CI 0.10 to 0.36; p<0.00001; I2=56%) as compared with the control group. Paediatric patients receiving dexmedetomidine had lower postoperative analgesic requirements (RR, 0.27; 95% CI 0.10 to 0.73; p=0.01; I2=84%) and a lower incidence of respiratory adverse events (RR, 0.49; 95% CI 0.31 to 0.78; p=0.003; I2=0%). There were no significant differences in the risk of PONV and cardiovascular adverse events. CONCLUSIONS: There was a lack of high-quality studies in this field. Perioperative administration of dexmedetomidine reduced the need for postoperative rescue analgesics and the incidence of EA in children without side effects undergoing CLP repair. However, further verification with larger samples and higher-quality RCTs is needed.

Light-Controlled Tyrosine Nitration of Proteins.

Tyrosine nitration of proteins is one of the most important oxidative post-translational modifications in vivo. A major obstacle for its biochemical and physiological studies is the lack of efficient and chemoselective protein tyrosine nitration reagents. Herein, we report a generalizable strategy for light-controlled protein tyrosine nitration by employing biocompatible dinitroimidazole reagents. Upon 390 nm irradiation, dinitroimidazoles efficiently convert tyrosine residues into 3-nitrotyrosine residues in peptides and proteins with fast kinetics and high chemoselectivity under neutral aqueous buffer conditions. The incorporation of 3-nitrotyrosine residues enhances the thermostability of lasso peptide natural products and endows murine tumor necrosis factor-α with strong immunogenicity to break self-tolerance. The light-controlled time resolution of this method allows the investigation of the impact of tyrosine nitration on the self-assembly behavior of α-synuclein.

Role of endovascular embolisation for curative treatment of intracranial non-Galenic pial arteriovenous fistula.

BACKGROUND AND PURPOSE: The safety and effectiveness of endovascular treatment for non-Galenic pial arteriovenous fistula (NGPAVF) is inadequately known. The aim of this study is to explore the role of endovascular embolisation for curative treatment of NGPAVF. MATERIALS AND METHODS: Patients with NGPAVF underwent endovascular treatment from January 2011 to November 2019 in our institution were retrospectively reviewed. Demographics, clinical information, treatment details and clinical outcomes were collected. Factors associated with clinical outcomes were statistically analysed. RESULTS: Twenty patients were included, with a total of 22 (2 patients have 2 fistulas) lesions. A total of 25 procedures were performed and 5 patients underwent 2 procedures. Follow-up ranged from 3 to 84 months (mean=34.5 months). Thirteen (59.1%) lesions in 12 (60.0%) patients acquired immediate occlusion after initial treatment (immediately occluded group) and follow-up confirmed the complete obliteration. A total of 17 (77.3%) lesions in 15 (75.0%) patients were cured at last follow-up. The maximal diameter of feeding arteries (p=0.04) and the maximal diameter of the varix (p=0.01) in immediately occluded group was smaller than non-immediately occluded group. The number of feeding artery (p=0.004) and the maximal diameter of the varix (p<0.001) were much smaller in curative group than non-curative group. Seven patients suffered procedure-related complications. No patients had an increased Modified Rankin Scale (mRS) and all patients had favourable clinical outcome (mRS ≥2) at last follow-up. CONCLUSIONS: Endovascular therapy plays an important role in curative treatment of NGPAVF. Patients with less feeding arteries and small varix may be easier to be cured by endovascular embolisation.