Dual effect synergistically triggered Ce:(Y,Tb)3(Al,Mn)5O12 transparent ceramics enabling a high color-rendering index and excellent thermal stability for white LEDs

Ce:Y₃Al₅O₁₂ transparent ceramics (TCs) with appropriate emission light proportion and high thermal stability are significant to construct white light emitting diode devices with excellent chromaticity parameters. In this work, strategies of controlling crystal-field splitting around Ce³⁺ ion and doping orange-red emitting ion, were adopted to fabricate Ce:(Y,Tb)₃(Al,Mn)₅O₁₂ TCs via vacuum sintering technique. Notably, 85.4 % of the room-temperature luminescence intensity of the TC was retained at 150 °C, and the color rendering index was as high as 79.8. Furthermore, a 12 nm red shift and a 16.2 % increase of full width at half maximum were achieved owing to the synergistic effects of Tb³⁺ and Mn²⁺ ions. By combining TCs with a 460 nm blue chip, a warm white light with a low correlated color temperature of 4155 K was acquired. Meanwhile, the action mechanism of Tb³⁺ ion and the energy transfer between Ce³⁺ and Mn²⁺ ions were verified in prepared TCs.     

深共融溶剂催化制备二酯类化合物

二酯类化合物广泛应用于有机中间体、药物、增塑剂、香料等领域,开发其绿色、高效的合成新方法具有重要意义.报道了以二元羧酸(或二羧酸酐)和脂肪醇为原料,以深共融溶剂(DESs)为催化剂催化合成二酯类化合物.以n(氯化胆碱):n(对甲苯磺酸)=1:2为催化剂,产率最高可达95％,并且DESs使用8次后产率仍保持在88％以上.运用1HNMR和13CNMR对产物进行了结构表征.该方法具有操作简单、产率高、易分离和催化剂可循环使用等优点.     

Biodegradable Polymeric Nanoparticles Containing an Immune Checkpoint Inhibitor (aPDL1) to Locally Induce Immune Responses in the Central Nervous System

Immunotherapy is an efficient approach to clinical oncology. However, the immune privilege of the central nervous system (CNS) limits the application of immunotherapeutic strategies for brain cancers, especially glioblastoma (GBM). Tumor resistance to immune checkpoint inhibitors is a further challenge in immunotherapies. To overcome the immunological tolerance of brain tumors, a novel multifunctional nanoparticle (NP) for highly efficient synergetic immunotherapy is reported. The NP contains an anti-PDL1 antibody (aPDL1), upconverting NPs, and the photosensitizer 5-ALA; the surface of the NP is conjugated with the B1R kinin ligand to facilitate transport across the blood-tumor-barrier. Upon irradiation with a 980 nm laser, 5-ALA is transformed into protoporphyrin IX, generating reactive oxygen species. Photodynamic therapy (PDT) further promotes intratumoral infiltration of cytotoxic T lymphocytes and sensitizes tumors to PDL1 blockade therapy. It is demonstrated that combining PDT and aPDL1 can effectively suppress GBM growth in mouse models. The proposed NPs provide a novel and effective strategy for boosting anti-GBM photoimmunotherapy.     

Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL

Background: Recently, it was reported that leucine-rich repeat-containing G-protein-coupled receptor 4 (LGR4, also called GPR48) is another receptor for RANKL and was shown to compete with RANK to bind RANKL and suppress canonical RANK signaling during osteoclast differentiation. The critical role of the protein triad RANK–RANKL in osteoclastogenesis has made their binding an important target for the development of drugs against osteoporosis. In this study, point-mutations were introduced in the RANKL protein based on the crystal structure of the RANKL complex and its counterpart receptor RANK, and we investigated whether LGR4 signaling in the absence of the RANK signal could lead to the inhibition of osteoclastogenesis.; Methods: The effects of point-mutated RANKL (mRANKL-MT) on osteoclastogenesis were assessed by tartrate-resistant acid phosphatase (TRAP), resorption pit formation, quantitative real-time polymerase chain reaction (qPCR), western blot, NFATc1 nuclear translocation, micro-CT and histomorphological assay in wild type RANKL (mRANKL-WT)-induced in vitro and in vivo experimental mice model. Results: As a proof of concept, treatment with the mutant RANKL led to the stimulation of GSK-3β phosphorylation, as well as the inhibition of NFATc1 translocation, mRNA expression of TRAP and OSCAR, TRAP activity, and bone resorption, in RANKL-induced mouse models; and Conclusions: The results of our study demonstrate that the mutant RANKL can be used as a therapeutic agent for osteoporosis by inhibiting RANKL-induced osteoclastogenesis via comparative inhibition of RANKL. Moreover, the mutant RANKL was found to lack the toxic side effects of most osteoporosis treatments.     

Diphenyl-Methane Based Thyromimetic Inhibitors for Transthyretin Amyloidosis

Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases.     

Contribution of Invariant Natural Killer T Cells to the Clearance of Pseudomonas aeruginosa from Skin Wounds

Chronic infections are considered one of the most severe problems in skin wounds, and bacteria are present in over 90% of chronic wounds. Pseudomonas aeruginosa is frequently isolated from chronic wounds and is thought to be a cause of delayed wound healing. Invariant natural killer T (iNKT) cells, unique lymphocytes with a potent regulatory ability in various inflammatory responses, accelerate the wound healing process. In the present study, we investigated the contribution of iNKT cells in the host defense against P. aeruginosa inoculation at the wound sites. We analyzed the re-epithelialization, bacterial load, accumulation of leukocytes, and production of cytokines and antimicrobial peptides. In iNKT cell–deficient (Jα18KO) mice, re-epithelialization was significantly decreased, and the number of live colonies was significantly increased, when compared with those in wild-type (WT) mice on day 7. IL-17A, and IL-22 production was significantly lower in Jα18KO mice than in WT mice on day 5. Furthermore, the administration of α-galactosylceramide (α-GalCer), a specific activator of iNKT cells, led to enhanced host protection, as shown by reduced bacterial load, and to increased production of IL-22, IL-23, and S100A9 compared that of with WT mice. These results suggest that iNKT cells promote P. aeruginosa clearance during skin wound healing.     

Turbulent boundary layer control with a spanwise array of DBD plasma actuators

The turbulent boundary layer control on NACA 0012 airfoil with Mach number ranging from 0.3 to 0.5 by a spanwise array of dielectric barrier discharge(DBD)plasma actuators by hot-film sensor technology is investigated.Due to temperature change mainly caused through heat produced along with plasma will lead to measurement error of shear stress measured by hot-film sensor,the correction method that takes account of the change measured by another sensor is used and works well.In order to achieve the value of shear stress change,we combine computational fluid dynamics computation with experiment to calibrate the hot-film sensor.To test the stability of the hot-film sensor,seven repeated measurements of shear stress at Ma = 0.3 are conducted and show that confidence interval of hot-film sensor measurement is from-0.18 to 0.18 Pa and the root mean square is 0.11 Pa giving a relative error 0.5％over all Mach numbers in this experiment.The research on the turbulent boundary layer control with DBD plasma actuators demonstrates that the control makes shear stress increase by about 6％over the three Mach numbers,which is thought to be reliable through comparing it with the relative error 0.5％,and the value is hardly affected by burst frequency and excitation voltage.     

Statistical Piezotronic Effect in Nanocrystal Bulk by Anisotropic Geometry Control

Utilizing inner-crystal piezoelectric polarization charges to control carrier transport across a metal-semiconductor or semiconductor–semiconductor interface, piezotronic effect has great potential applications in smart micro/nano-electromechanical system (MEMS/NEMS), human-machine interfacing, and nanorobotics. However, current research on piezotronics has mainly focused on systems with only one or rather limited interfaces. Here, the statistical piezotronic effect is reported in ZnO bulk composited of nanoplatelets, of which the strain/stress-induced piezo-potential at the crystals’ interfaces can effectively gate the electrical transport of ZnO bulk. It is a statistical phenomenon of piezotronic modification of large numbers of interfaces, and the crystal orientation of inner ZnO nanoplatelets strongly influence the transport property of ZnO bulk. With optimum preferred orientation of ZnO nanoplatelets, the bulk exhibits an increased conductivity with decreasing stress at a high pressure range of 200–400 MPa, which has not been observed previously in bulk. A maximum sensitivity of 1.149 µS m⁻¹ MPa⁻¹ and a corresponding gauge factor of 467–589 have been achieved. As a statistical phenomenon of many piezotronic interfaces modulation, the proposed statistical piezotronic effect extends the connotation of piezotronics and promotes its practical applications in intelligent sensing.     

Effect of milling ball size on the densification and optical properties of transparent Y2O3 ceramics

In this study, we report highly transparent Y₂O₃ ceramics fabricated by hot-pressing only at 1500 °C without a HIP treatment, featuring in-line transmittance levels of 77% and 84% at a wavelength of 400 and 1100 nm, respectively with the grain size suppressed to 710 nm. The effect of the ball size during the grinding of Y₂O₃ powders on the correlation between the thus-prepared Y₂O₃ powders and the optical properties of the hot-pressed samples is demonstrated for the first time. With a decrease in the diameter of the ZrO₂ balls from 5 mm to 1 mm, the milling efficiency was enhanced and admirable transparency of Y₂O₃ was attained at a short milling time. However, several micron-sized pores remained in the transparent specimens prepared with 1 mm balls, originating from the inhomogeneously packed region of the green body. Finally, the 2 mm was found to be optimum for obtaining a fine-grained and pore-free microstructure with the best in-line transmittance of Y₂O₃ ceramics.