Re-examination of phase relations between solid solutions in R4Al2O9-R4Si2N2O7-R4Si2O10 (R=Y,Gd, Yb) systems

Samples in Si–Al-R-O-N (R = Y, Gd, Yb) systems were prepared by solid-state reactions using R₂O₃, Al₂O₃, SiO₂ and Si₃N₄ powders as starting materials. X-ray diffraction was done to investigate RAM-J(R) solid solutions [RAM = R₄Al₂O₉, J(R) = R₄Si₂N₂O₇] formation and their equilibrium with RSO (R₄Si₂O₁₀). Phase relations between RAM, J(R) and RSO at 1700 °C were summarized in a phase diagram. It was determined that a limited solid solution of RAM and RSO could be formed along RAM-RSO tie-line, while RAM and J(R) form a continuous solid solution along RAM-J(R) tie-line. In RAM-J(R)-RSO ternary systems, the RAM-J(R) tie-lines were extended towards the RSO corner to form a continuous solid solution area of JRAMss (R = Y, Gd, Yb). The established phase relations in the Si–Al-R-O-N (R = Y, Gd, Yb) systems may facilitate compositional selections for developing JRAMss as monolithic ceramics or for SiC/Si₃N₄ based composites using the solid-solutions as a second refractory phase.     

Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

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.     

In Vivo Albumin-Binding of a C-Functionalized Cyclam Platform for 64Cu-PET/CT Imaging in Breast Cancer Model

An improved glucose-chelator-albumin bioconjugate (GluCAB) derivative, GluCAB-2^Mal, has been synthesized and studied for in vivo ⁶⁴Cu-PET/CT imaging in breast cancer mice models together with its first-generation analogue GluCAB-1^Mal. The radioligand works on the principle of tumor targeting through the enhanced permeability and retention (EPR) effect with a supportive role played by glucose metabolism. [⁶⁴Cu]Cu-GluCAB-2^Mal (99 % RCP) exhibited high serum stability with immediate binding to serum proteins. In vivo experiments for comparison between tumor targeting of [⁶⁴Cu]Cu-GluCAB-2^Mal and previous-generation [⁶⁴Cu]Cu-GluCAB-1^Mal encompassed microPET/CT imaging and biodistribution analysis in an allograft E0771 breast cancer mouse model. Tumor uptake of [⁶⁴Cu]Cu-GluCAB-2^Mal was clearly evident with twice as much accumulation as compared to its predecessor and a tumor/muscle ratio of up to 5 after 24 h. Further comparison indicated a decrease in liver accumulation for [⁶⁴Cu]Cu-Glu-CAB-2^Mal.     

Synthesis of magnetically recyclable porous CoFe2O4/Rh composites with large BET surface area for enhanced photocatalytic degradation of organic pollutant

The organic pollutants in water have been a great environment challenges to human beings, and photocatalytic degradation is an effective method to solve this problem. In this paper, the Rh-loaded cobalt ferrite CoFe₂O₄ (CFO) nanoparticles have been successfully synthesized by in situ photodeposition of Rh nanoparticles onto the porous CFO particles as the photocatalysts. After incorporating Rh nanoparticles, the CFO/Rh composite has a higher specific surface area and is more efficient in charge separation than the bare CFO. The photocatalytic efficiency of decomposing Malachite Green (MG) is improved from 70% over the bare CFO to 97% over the optimized CFO/Rh in 60 min. The CFO/Rh sample also demonstrates its durability for the degradation of MG in 5 photocatalytic reaction cycles. Additionally, hydroxyl radicals (?OH) and superoxide radicals (?O₂^?) are proved to be the crucial reactive species during the photocatalytic degradation of MG with CFO/Rh, evidenced by the active species capture experiments. This work provides a useful approach to enhance the photocatalytic activity of semiconductors for degrading organic dyes.     

Microstructure induced ultra-high energy storage density coupled with rapid discharge properties in lead-free Ba0.9Ca0.1Ti0.9Zr0.1O3–SrNb2O6 ceramics

Novel lead-free (1-x)Ba_0·9Ca_0·1Ti_0·9Zr_0·1O₃-xSrNb₂O₆ ceramics were synthesized via a two-step high energy ball milling process. The evolution of microstructural properties, phase transformation, and energy storage characteristics was comprehensively investigated to assess the applicability of material in multi-layered ceramic capacitors. The substitution of SrNb₂O₆ (SNO) in Ba_0·9Ca_0·1Ti_0·9Zr_0·1O₃ (BTCZ) has resulted in substantial improvement in materials density along with a small increase in the grain size of the synthesized ceramic. A thorough microstructural investigation indicates an excellent dispersibility and compatibility between BTCZ and SNO phases. With an increase in SNO substitution, a transition from typical ferroelectric to relaxor ferroelectric has been observed, which has led to a significantly slimmer ferroelectric loop along with frequency dispersive dielectric properties. The optimized composition (i.e., x = 0.10) exhibits an ultra-high recoverable energy density of 2.68 J/cm³ along with a moderately high energy efficiency of 83.4%. Further, SNO substituted samples have also shown an enhancement in breakdown strength. The improvement in energy storage performance and breakdown strength of SNO substituted BTCZ composites are mainly attributed to relatively homogeneous grain morphology, optimum grain size, microstructural density, and improved grain boundary interface.     

Effect of laser power density on the electrochromic properties of WO3 films obtained by pulsed laser deposition

Pulsed laser deposition (PLD) was used to prepare tungsten trioxide (WO₃) films on ITO substrates with a varying laser power density of 4.0–5.5 W/cm². XPS indicated that when the laser power density decreased, the peak positions of the W 4f and O 1s orbits shifted slightly to low energy due to the difference in oxygen vacancies. As the laser power density decreased, W⁶⁺ gradually replaced the lattice position of O^2?, increasing oxygen vacancies in the lattice. The transmittance modulated values (ΔT) were over 44% at 830 nm, indicating strong absorption by the WO₃ thin films in the near-infrared ray. The switching time of the WO₃ thin films between bleached states and coloured states decreased as the laser power density increased due to the amorphous structure, morphology, and lower oxygen deficiency at a high power density. The high ΔT and very fast switching time of t_b (1.09 s) and t_c (6.01 s) demonstrated the excellent electrochromic (EC) properties of the WO₃ films prepared by PLD.     

对“垃圾衍生燃料”RDF之探析

当前,我国水泥工业在可燃废弃物应用技术方面都还处于一家一户、自制自用、效率极低的初级阶段。发达国家的替代燃料:“垃圾衍生燃料”RDF、“固体回收燃料”SRF、“次煤”Subcoal和“纸塑垃圾衍生燃料”RPF制成的原材料都是可燃废弃物,只是处理工艺技术不同或者由垃圾中分拣出的可燃废弃物不同,制成颗粒状衍生燃料的品质不同,这些都可以替代部分甚或替代全部化石燃料在水泥窑炉中应用。我国大力发展“替代燃料”产业,有助于水泥工业消纳更多的“可燃废弃物”,为改善环境尤其是城镇环境和面貌,为我国的节能减排和绿色高质量发展发挥更大的作用。     

Structure-Activity Relationship Explorations and Discovery of a Potent Antagonist for the Free Fatty Acid Receptor 2

Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties.