Computational Investigation Identified Potential Chemical Scaffolds for Heparanase as Anticancer Therapeutics

Heparanase (Hpse) is an endo-β-D-glucuronidase capable of cleaving heparan sulfate side chains. Its upregulated expression is implicated in tumor growth, metastasis and angiogenesis, thus making it an attractive target in cancer therapeutics. Currently, a few small molecule inhibitors have been reported to inhibit Hpse, with promising oral administration and pharmacokinetic (PK) properties. In the present study, a ligand-based pharmacophore model was generated from a dataset of well-known active small molecule Hpse inhibitors which were observed to display favorable PK properties. The compounds from the InterBioScreen database of natural (69,034) and synthetic (195,469) molecules were first filtered for their drug-likeness and the pharmacophore model was used to screen the drug-like database. The compounds acquired from screening were subjected to molecular docking with Heparanase, where two molecules used in pharmacophore generation were used as reference. From the docking analysis, 33 compounds displayed higher docking scores than the reference and favorable interactions with the catalytic residues. Complex interactions were further evaluated by molecular dynamics simulations to assess their stability over a period of 50 ns. Furthermore, the binding free energies of the 33 compounds revealed 2 natural and 2 synthetic compounds, with better binding affinities than reference molecules, and were, therefore, deemed as hits. The hit compounds presented from this in silico investigation could act as potent Heparanase inhibitors and further serve as lead scaffolds to develop compounds targeting Heparanase upregulation in cancer.     

Synergistic Effects of Polybenzimidazole and Aramide on Enhancing Flame-Retardancy and Solubility

Aromatic and functional polymers with processibility derived from biobased starting materials are prerequisite considering sustainable society. Poly(2,5-benzimidazole)s are rigid-rod polymers to show ultrahigh thermal stability such as flame retardance, while usually suffer from poor solubility. Here, poly(benzimidazole-co-amide)s are synthesized from two biobased monomers, 3,4-diaminobenzoic acid and a semirigid comonomer, 4-aminohydrocinnamic acid. The copolymers with an amide composition of 80 mol% and higher are soluble in widely used polar solvents to fabricate the films keeping high flame retardance, which is comparable with popular high-performance polymers such as aromatic polyimides, polyetheretherketone, polyphenylene sulfide, etc.     

Heteroalleles in Common Wheat: Multiple Differences between Allelic Variants of the Gli-B1 Locus

The Gli-B1-encoded γ-gliadins and non-coding γ-gliadin DNA sequences for 15 different alleles of common wheat have been compared using seven tests: electrophoretic mobility (EM) and molecular weight (MW) of the encoded major γ-gliadin, restriction fragment length polymorphism patterns (RFLPs) (three different markers), Gli-B1-γ-gliadin-pseudogene known SNP markers (Single nucleotide polymorphisms) and sequencing the pseudogene GAG56B. It was discovered that encoded γ-gliadins, with contrasting EM, had similar MWs. However, seven allelic variants (designated from I to VII) differed among them in the other six tests: I (alleles Gli-B1i, k, m, o), II (Gli-B1n, q, s), III (Gli-B1b), IV (Gli-B1e, f, g), V (Gli-B1h), VI (Gli-B1d) and VII (Gli-B1a). Allele Gli-B1c (variant VIII) was identical to the alleles from group IV in four of the tests. Some tests might show a fine difference between alleles belonging to the same variant. Our results attest in favor of the independent origin of at least seven variants at the Gli-B1 locus that might originate from deeply diverged genotypes of the donor(s) of the B genome in hexaploid wheat and therefore might be called “heteroallelic”. The donor’s particularities at the Gli-B1 locus might be conserved since that time and decisively contribute to the current high genetic diversity of common wheat.     

Effect of α-Lipoic Acid on the Development of Human Skin Equivalents Using a Pumpless Skin-on-a-Chip Model

Owing to the prohibition of cosmetic animal testing, various attempts have recently been made using skin-on-a-chip (SOC) technology as a replacement for animal testing. Previously, we reported the development of a pumpless SOC capable of drug testing with a simple drive using the principle that the medium flows along the channel by gravity when the chip is tilted using a microfluidic channel. In this study, using pumpless SOC, instead of drug testing at the single-cell level, we evaluated the efficacy of α-lipoic acid (ALA), which is known as an anti-aging substance in skin equivalents, for skin tissue and epidermal structure formation. The expression of proteins and changes in genotyping were compared and evaluated. Hematoxylin and eosin staining for histological analysis showed a difference in the activity of fibroblasts in the dermis layer with respect to the presence or absence of ALA. We observed that the epidermis layer became increasingly prominent as the culture period was extended by treatment with 10 μM ALA. The expression of epidermal structural proteins of filaggrin, involucrin, keratin 10, and collagen IV increased because of the effect of ALA. Changes in the epidermis layer were noticeable after the ALA treatment. As a result of aging, damage to the skin-barrier function and structural integrity is reduced, indicating that ALA has an anti-aging effect. We performed a gene analysis of filaggrin, involucrin, keratin 10, integrin, and collagen I genes in ALA-treated human skin equivalents, which indicated an increase in filaggrin gene expression after ALA treatment. These results indicate that pumpless SOC can be used as an in vitro skin model similar to human skin, protein and gene expression can be analyzed, and it can be used for functional drug tests of cosmetic materials in the future. This technology is expected to contribute to the development of skin disease models.     

高稳高效海上风电安装平台关键制造技术研究

海上风电作为可再生清洁能源之一,受到世界各国的高度重视与大力发展。我国将海上风电提升至解决能源危机、减缓气候变化、调整能源结构的国家战略高度,到2030年我国单位国内生产总值二氧化碳排放将比2005年下降65%以上,非化石能源占一次能源消费比重将达到25%左右。安装平台不足将是我国海上风电场无法如期建成投产的主要障碍。对自升自航式海上风电安装平台系列高端装备及其设计制造的三大技术难题——腿站立作业易“失稳”、大平台大跨距大倾覆力矩自升易“失控”、高空吊装巨型叶片逾百螺栓精准定位易“失准”,以及焊缝缺陷修复和局部裂纹损伤的激光锻造修复再制造进行了介绍,研制的具有不同规格的系列装备在中国、英国、丹麦、德国等国家的著名海上风电场建设应用情况良好。     

高分子材料导热性能影响因素研究进展

介绍了高分子材料导热性能影响因素研究进展，重点阐释了聚合物基体的结构特性（链结构、分子间相互作用、取向、结晶度等）、导热填料（种类、含量、形态、尺寸等）以及制备方法等对高分子材料导热性能的影响。     

Spectroscopic properties and thermally stable orange-red luminescence of Sm:Zr:LiNbO3 and Sm:Hf:LiNbO3 for white LED applications

LiNbO₃ crystals activated by Sm³⁺ and co-doped with Zr⁴⁺ (Sm:Zr:LN) or Hf⁴⁺ (Sm:Hf:LN) were prepared by the Czochralski method. Detailed investigation on spectroscopic properties was conducted on the frame of Judd-Ofelt (J-O) theory. The J-O intensity parameters Ω_i (i = 2, 4, 6), fluorescence branching ratios and radiative lifetime of excited level ⁴G_5/2 were determined. Furthermore, the thermal stability of the strong orange-red emissions obtained under near-UV excitation in both crystals was evaluated. As high as 100% and 97% of integrated intensities at room temperature in Sm:Zr:LN and Sm:Hf:LN respectively were retained at 423 K, demonstrating the suppressed thermal attenuation. The temperature sensing performance based on fluorescence intensity ratio strategy was degraded at higher temperatures with relatively low sensitivities, while the shift of CIE chromaticity coordinates of Sm:Zr:LN and Sm:Hf:LN in the orange-red region was insignificant, demonstrating the color constancy with increasing temperature. With the efficient and thermally stable orange-red luminescence, Sm:Zr:LN and Sm:Hf:LN could serve as promising candidate materials for near-UV excited white light-emitting diodes.     

Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.     

Metabolic Profiling of VOCs Emitted by Bacteria Isolated from Pressure Ulcers and Treated with Different Concentrations of Bio-AgNPs

Considering the advent of antibiotic resistance, the study of bacterial metabolic behavior stimulated by novel antimicrobial agents becomes a relevant tool to elucidate involved adaptive pathways. Profiling of volatile metabolites was performed to monitor alterations of bacterial metabolism induced by biosynthesized silver nanoparticles (bio-AgNPs). Escherichia coli, Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis were isolated from pressure ulcers, and their cultures were prepared in the presence/absence of bio-AgNPs at 12.5, 25 and 50 µg mL⁻¹. Headspace solid phase microextraction associated to gas chromatography–mass spectrometry was the employed analytical platform. At the lower concentration level, the agent promoted positive modulation of products of fermentation routes and bioactive volatiles, indicating an attempt of bacteria to adapt to an ongoing suppression of cellular respiration. Augmented response of aldehydes and other possible products of lipid oxidative cleavage was noticed for increasing levels of bio-AgNPs. The greatest concentration of agent caused a reduction of 44 to 80% in the variety of compounds found in the control samples. Pathway analysis indicated overall inhibition of amino acids and fatty acids routes. The present assessment may provide a deeper understanding of molecular mechanisms of bio-AgNPs and how the metabolic response of bacteria is untangled.