Selective Binding of Cyclodextrins with Leflunomide and Its Pharmacologically Active Metabolite Teriflunomide

The selectivity of encapsulation of leflunomide and teriflunomide by native α-, β- and γ-cyclodextrins was investigated through ¹H NMR and molecular modeling. Thermodynamic analysis revealed the main driving forces involved in the binding. For α-cyclodextrin, the partial encapsulation was obtained while deep penetration was characterized for the other two cyclodextrins, where the remaining polar fragment of the molecule is located outside the macrocyclic cavity. The interactions via hydrogen bonding are responsible for high negative enthalpy and entropy changes accompanying the complexation of cyclodextrins with teriflunomide. These results were in agreement with the molecular modeling calculations, which provide a clearer picture of the involved interactions at the atomic level.     

Impact of A134 and E218 Amino Acid Residues of Tropomyosin on Its Flexibility and Function

Tropomyosin (Tpm) is one of the major actin-binding proteins that play a crucial role in the regulation of muscle contraction. The flexibility of the Tpm molecule is believed to be vital for its functioning, although its role and significance are under discussion. We choose two sites of the Tpm molecule that presumably have high flexibility and stabilized them with the A134L or E218L substitutions. Applying differential scanning calorimetry (DSC), molecular dynamics (MD), co-sedimentation, trypsin digestion, and in vitro motility assay, we characterized the properties of Tpm molecules with these substitutions. The A134L mutation prevented proteolysis of Tpm molecule by trypsin, and both substitutions increased the thermal stability of Tpm and its bending stiffness estimated from MD simulation. None of these mutations affected the primary binding of Tpm to F-actin; still, both of them increased the thermal stability of the actin-Tpm complex and maximal sliding velocity of regulated thin filaments in vitro at a saturating Ca²⁺ concentration. However, the mutations differently affected the Ca²⁺ sensitivity of the sliding velocity and pulling force produced by myosin heads. The data suggest that both regions of instability are essential for correct regulation and fine-tuning of Ca²⁺-dependent interaction of myosin heads with F-actin.     

Tissue-Specific Ferritin- and GFP-Based Genetic Vectors Visualize Neurons by MRI in the Intact and Post-Ischemic Rat Brain

(1) Background: Neurogenesis is considered to be a potential brain repair mechanism and is enhanced in stroke. It is difficult to reconstruct the neurogenesis process only from the histological sections taken from different animals at different stages of brain damage and restoration. Study of neurogenesis would greatly benefit from development of tissue-specific visualization probes. (2) Purpose: The study aimed to explore if overexpression of ferritin, a nontoxic iron-binding protein, under a doublecortin promoter can be used for non-invasive visualization of neurogenesis using magnetic resonance imaging (MRI). (3) Methods: Ferritin heavy chain (FerrH) was expressed in the adeno-associated viral backbone (AAV) under the doublecortin promoter (pDCX), specific for young neurons, in the viral construct AAV-pDCX-FerrH. Expression of the enhanced green fluorescent protein (eGFP) was used as an expression control (AAV-pDCX-eGFP). The viral vectors or phosphate-buffered saline (PBS) were injected intracerebrally into 18 adult male Sprague–Dawley rats. Three days before injection, rats underwent transient middle-cerebral-artery occlusion or sham operation. Animals were subjected to In vivo MRI study before surgery and on days 7, 14, 21, and 28 days after injection using a Bruker BioSpec 11.7 T scanner. Brain sections obtained on day 28 after injection were immunostained for ferritin, young (DCX) and mature (NeuN) neurons, and activated microglia/macrophages (CD68). Additionally, RT-PCR was performed to confirm ferritin expression. (4) Results: T2* images in post-ischemic brains of animals injected with AAV-pDCX-FerrH showed two distinct zones of MRI signal hypointensity in the ipsilesioned hemisphere starting from 14 days after viral injection—in the ischemic lesion and near the lateral ventricle and subventricular zone (SVZ). In sham-operated animals, only one zone of hypointensity near the lateral ventricle and SVZ was revealed. Immunochemistry showed that ferritin-expressing cells in ischemic lesions were macrophages (88.1%), while ferritin-expressing cells near the lateral ventricle in animals both after ischemia and sham operation were mostly mature (55.7% and 61.8%, respectively) and young (30.6% and 7.1%, respectively) neurons. RT-PCR confirmed upregulated expression of ferritin in the caudoputamen and corpus callosum. Surprisingly, in animals injected with AAV-pDCX-eGFP we similarly observed two zones of hypointensity on T2* images. Cellular studies also showed the presence of mature (81.5%) and young neurons (6.1%) near the lateral ventricle in both postischemic and sham-operated animals, while macrophages in ischemic lesions were ferritin-positive (98.2%). (5) Conclusion: Ferritin overexpression induced by injection of AAV-pDCX-FerrH was detected by MRI using T2*-weighted images, which was confirmed by immunochemistry showing ferritin in young and mature neurons. Expression of eGFP also caused a comparable reduced MR signal intensity in T2*-weighted images. Additional studies are needed to investigate the potential and tissue-specific features of the use of eGFP and ferritin expression in MRI studies.     

Supramolecular Architectures of Nucleic Acid/Peptide Hybrids

Supramolecular architectures that are built artificially from biomolecules, such as nucleic acids or peptides, with structural hierarchical orders ranging from the molecular to nano-scales have attracted increased attention in molecular science research fields. The engineering of nanostructures with such biomolecule-based supramolecular architectures could offer an opportunity for the development of biocompatible supramolecular (nano)materials. In this review, we highlighted a variety of supramolecular architectures that were assembled from both nucleic acids and peptides through the non-covalent interactions between them or the covalently conjugated molecular hybrids between them.     

Hydroxyl Group Separation Distances in Anti-Freeze Compounds and Their Effects on Ice Nucleation

Since the discovery of biological antifreeze glycoproteins (AFGPs), which can inhibit ice nucleation, there has been considerable interest in understanding their mechanisms and mimicking them in synthetic polymers. In this study, we used molecular dynamics simulations of modified polyvinyl alcohol (PVA) compounds to show that the hydroxyl (OH) group distance is a key factor in whether certain compounds promote or inhibit ice nucleation. A hydroxyl distance smaller than ~2.8 Å but greater than ~7.1 Å in modified PVA (MPVA) compounds was associated with the promotion of ice nucleation, while a hydroxyl group separation distance of approximately ~5.0 Å was correlated with a delay in ice nucleation, owing to changes in the energy of the system. Thus, these results may help explain some of the mechanisms of current known anti-freeze compounds and may have implications for designing new anti-freeze compounds in the future.     

碱性添加剂在钛硅分子筛/H2O2催化丙烯环氧化反应中的作用

考察了反应溶液中碱性添加剂{氨水（NH₄OH）、氢氧化钠（NaOH）、碳酸钠（Na₂CO₃）、碳酸铵[(NH₄)₂CO₃]和四甲基氢氧化铵（TMAOH）}及其浓度对钛硅分子筛（TS-1）催化丙烯环氧化反应性能的影响，并采用紫外拉曼光谱（UV-Raman）与气相色谱（GC）联用原位分析（Raman-GC）碱性添加剂的作用机理。结果表明：反应体系中添加碱性添加剂可有效改善TS-1催化丙烯环氧化反应的选择性。不同碱性添加剂对TS-1催化丙烯环氧化活性和稳定性影响不同，NaOH、Na₂CO₃和TMAOH的添加造成催化活性和稳定性降低。NH₄OH或(NH₄)₂CO₃作为添加剂改善环氧化反应选择性的同时提高了反应稳定性，其中以(NH₄)₂CO₃效果最佳。添加(NH₄)₂CO₃浓度为8.0×10^-4mol/L时，TS-1催化丙烯环氧化在固定床反应器上连续运行336h时，X(H₂O₂)仍保持在90%以上。原位Raman-GC分析发现，反应体系中NH₄OH和(NH₄)₂CO₃添加可加快反应活性中间体Ti-OOH(η²)基团的生成，促进反应产物从活性中心快速扩散，从而提高丙烯环氧化反应选择性和稳定性。     

不同类型催化剂对异丁烯齐聚反应过程的影响

采用固定床反应器分别探究了三类催化剂（固体磷酸催化剂、酸性阳离子交换树脂催化剂以及分子筛催化剂）对异丁烯齐聚过程的影响。实验结果表明：固体磷酸催化剂适用于C₈烯烃的生产，酸性阳离子树脂催化剂及改性的分子筛催化剂（Hβ）适合生产C₁₂烯烃。异丁烯齐聚产物C₈～C₁₆（清洁燃料油）因无芳烃、无硫，在石化工业中具有非常广泛的应用潜力；由三种类催化剂的评价结果来看，C₈～C₁₆的选择性最高时均能接近100%，但是固体磷酸催化剂和酸性阳离子树脂催化剂的异丁烯原料转化率比Hβ分子筛催化剂低，Hβ催化作用下异丁烯转化率可以达到88%。     

低浓度挥发性有机物吸附浓缩材料的研究进展

由于挥发性有机物（VOCs）会对环境造成严重的危害，因此VOCs的处理一直备受人们的关注，但发展高效的VOCs处理技术仍然存在严峻的挑战。本文针对大风量、低浓度VOCs的处理展开了综述，重点围绕吸附、催化燃烧处理展开讨论。对于大风量的低浓度VOCs，虽然浓度较低但VOCs排放量非常巨大。通过VOCs浓缩技术，提高浓度减少风量成为降低VOCs处理成本的有效途径。其中，发展高性能VOCs吸附材料是VOCs浓缩技术的关键。阐明了活性炭、分子筛等重要吸附材料的性质及其吸附VOCs的原理，并对吸附材料性质和VOCs种类对吸附效果的影响进行了探讨。展望了活性炭浓缩-催化燃烧技术和分子筛转轮浓缩-催化燃烧技术在大风量的低浓度VOCs处理中的应用前景。     

Two-Dimensional Silicene–Stanene Heterostructures by Epitaxy

The synthesis of new Xenes and their potential applications prototypes have achieved significant milestones so far. However, to date the realization of Xene heterostructures in analogy with the well known van der Waals heterostructures remains an unresolved issue. Here, a Xene heterostructure concept based on the epitaxial combination of silicene and stanene on Ag(111) is introduced, and how one Xene layer enables another Xene layer of a different nature to grow on top is demonstrated. Single-phase (4 × 4) silicene is synthesized using stanene as a template, and stanene is grown on top of silicene on the other way around. In both heterostructures, in situ and ex situ probes confirm layer-by-layer growth without intercalations and intermixing. Modeling via density functional theory shows that the atomic layers in the heterostructures are strongly interacting, and hexagonal symmetry conservation in each individual layer is sequence selective. The results provide a substantial step toward currently missing Xene heterostructures and may inspire new paths for atomic-scale materials engineering.     

Engineering of Lipid Nanoparticles by the Multifunctionalization of the Surface with Amino Acid Derivatives for the Neutralization of a Target Toxic Peptide

Protein affinity reagents (e.g., antibodies) are often used for basic research, diagnostics, separations, and disease therapy. Although a lot of “synthetic” protein affinity reagents have been developed as a cost-effective alternative to antibodies, their low biocompatibility is a considerable problem for clinical application. Lipid nanoparticles (LNP) represent a highly biocompatible drug delivery agent. However, little has been reported that LNP itself works as a protein affinity reagent in living animals. Here, LNP is engineered for binding to and neutralizing a target toxic peptide in living animals by multifunctionalization with amino acid derivatives. Multifunctionalized LNP (MF-LNP) is prepared using amino acid derivative-conjugated lipids. Optimized MF-LNP exhibits nanomolar affinity to the target toxic peptide and inhibits toxic peptide-dependent hemolysis and cytotoxicity. In addition, MF-LNP captures and neutralizes the toxic peptide after intravenous injection in the bloodstream; in addition, MF-LNP does not release the toxic peptide in the accumulated organ. These results reveal the potential of using LNP as a highly biocompatible protein affinity reagent such as an antidote.