An Injectable Integration of Autologous Bioactive Concentrated Growth Factor and Gelatin Methacrylate Hydrogel with Efficient Growth Factor Release and 3D Spatial Structure for Accelerated Wound Healing

Growth factors are essential for wound healing owing to their multiple reparative effects. Concentrated growth factor (CGF) is a third-generation platelet extract containing various endogenous growth factors. Herein, a CGF extract solution is combined with gelatin methacrylate (GM) by physical blending to produce GM@CGF hydrogels for wound repair. The GM@CGF hydrogels show no immune rejection during autologous transplantation. Compared to CGF, GM@CGF hydrogels not only exhibit excellent plasticity and adhesivity but also prevent rapid release and degradation of growth factors. The GM@CGF hydrogels display good injectability, self-healing, swelling, and degradability along with outstanding cytocompatibility, angiogenic functions, chemotactic functions, and cell migration-promoting capabilities in vitro. The GM@CGF hydrogel can release various effective molecules to rapidly initiate wound repair, stimulate the expressions of type I collagen, transform growth factor β1, epidermal growth factor, and vascular endothelial growth factor, promote the production of granulation tissues, vascular regeneration and reconstruction, collagen deposition, and epidermal cell migration, as well as prevent excessive scar formation. In conclusion, the injectable GM@CGF hydrogel can release various growth factors and provide a 3D spatial structure to accelerate wound repair, thereby providing a foundation for the clinical application and translation of CGF.     

One‐Pot Synthesis of Aliphatic Nitro Compounds by Michael/retro‐Claisen Fragmentation Domino Reaction

A novel and concise method for the construction of γ‐nitro ketones and 1,3‐dinitro compounds with chemoselective acyl transfer has been presented under basic conditions via one‐pot reactions. These reactions feature high atom‐ and step‐economic possess, mild condition and simple operation for one‐pot synthesis of aliphatic nitro compounds. This protocol provides the products in good yields. The possible reaction mechanism has also been proposed.     

Nannocystin A: an Elongation Factor 1 Inhibitor from Myxobacteria with Differential Anti‐Cancer Properties

Cultivation of myxobacteria of the Nannocystis genus led to the isolation and structure elucidation of a class of novel cyclic lactone inhibitors of elongation factor 1. Whole genome sequence analysis and annotation enabled identification of the putative biosynthetic cluster and synthesis process. In biological assays the compounds displayed anti‐fungal and cytotoxic activity. Combined genetic and proteomic approaches identified the eukaryotic translation elongation factor 1α (EF‐1α) as the primary target for this compound class. Nannocystin A ( 1 ) displayed differential activity across various cancer cell lines and EEF1A1 expression levels appear to be the main differentiating factor. Biochemical and genetic evidence support an overlapping binding site of 1 with the anti‐cancer compound didemnin B on EF‐1α. This myxobacterial chemotype thus offers an interesting starting point for further investigations of the potential of therapeutics targeting elongation factor 1.     

Interactions of DNA with graphene and sensing applications of graphene field-effect transistor devices: A review

Graphene field-effect transistors (GFET) have emerged as powerful detection platforms enabled by the advent of chemical vapor deposition (CVD) production of the unique atomically thin 2D material on a large scale. DNA aptamers, short target-specific oligonucleotides, are excellent sensor moieties for GFETs due to their strong affinity to graphene, relatively short chain-length, selectivity, and a high degree of analyte variability. However, the interaction between DNA and graphene is not fully understood, leading to questions about the structure of surface-bound DNA, including the morphology of DNA nanostructures and the nature of the electronic response seen from analyte binding. This review critically evaluates recent insights into the nature of the DNA graphene interaction and its affect on sensor viability for DNA, small molecules, and proteins with respect to previously established sensing methods. We first discuss the sorption of DNA to graphene to introduce the interactions and forces acting in DNA based GFET devices and how these forces can potentially affect the performance of increasingly popular DNA aptamers and even future DNA nanostructures as sensor substrates. Next, we discuss the novel use of GFETs to detect DNA and the underlying electronic phenomena that are typically used as benchmarks for characterizing the analyte response of these devices. Finally, we address the use of DNA aptamers to increase the selectivity of GFET sensors for small molecules and proteins and compare them with other, state of the art, detection methods.     

“Parallel factor analysis of multi-excitation ultraviolet resonance Raman spectra for protein secondary structure determination”

Protein secondary structural analysis is important for understanding the relationship between protein structure and function, or more importantly how changes in structure relate to loss of function. The structurally sensitive protein vibrational modes (amide I, II, III and S) in deep-ultraviolet resonance Raman (DUVRR) spectra resulting from the backbone C–O and N–H vibrations make DUVRR a potentially powerful tool for studying secondary structure changes. Experimental studies reveal that the position and intensity of the four amide modes in DUVRR spectra of proteins are largely correlated with the varying fractions of α-helix, β-sheet and disordered structural content of proteins. Employing multivariate calibration methods and DUVRR spectra of globular proteins with varying structural compositions, the secondary structure of a protein with unknown structure can be predicted. A disadvantage of multivariate calibration methods is the requirement of known concentration or spectral profiles. Second-order curve resolution methods, such as parallel factor analysis (PARAFAC), do not have such a requirement due to the “second-order advantage.” An exceptional feature of DUVRR spectroscopy is that DUVRR spectra are linearly dependent on both excitation wavelength and secondary structure composition. Thus, higher order data can be created by combining protein DUVRR spectra of several proteins collected at multiple excitation wavelengths to give multi-excitation ultraviolet resonance Raman data (ME-UVRR). PARAFAC has been used to analyze ME-UVRR data of nine proteins to resolve the pure spectral, excitation and compositional profiles. A three factor model with non-negativity constraints produced three unique factors that were correlated with the relative abundance of helical, β-sheet and poly-proline II dihedral angles. This is the first empirical evidence that the typically resolved “disordered” spectrum represents the better defined poly-proline II type structure.     

Experimental study on the fiber pull-out of composites using digital gradient sensing technique

A method to measure the stress field at the fiber tip in the fiber pull out test was proposed by using a digital gradient sensing technique. First, the principle of digital gradient sensing is introduced, and the non-contact optical system of digital gradient sensing developed. Then, a fiber reinforced composite model specimen, where a nail was inserted in epoxy resin to act as a fiber, was performed, and a pull out test was conducted on the specimen using the digital gradient sensing technique. Finally, the angular deflections contour at the fiber tip was obtained, and the stress intensity factor was extracted from the angular deflections. The results show that the stress intensity factor at the fiber tip extracted from the angular deflections agreed with the results calculated by the finite element method.     

Screening anti‐tumor compounds from Ligusticum wallichii using cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry

Tyrosine 367 Cysteine‐fibroblast growth factor receptor 4 cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry was developed. Tyrosine 367 Cysteine‐HEK293 cells were used as the cell membrane stationary phase. The specificity and reproducibility of the cell membrane chromatography was evaluated using 1‐tert‐butyl‐3‐{2‐[4‐(diethylamino)butylamino]‐6‐(3,5‐dimethoxyphenyl)pyrido[2,3‐d]pyrimidin‐7‐yl}urea, nimodipine and dexamethasone acetate. Then, anti‐tumor components acting on Tyrosine 367 Cysteine‐fibroblast growth factor receptor 4 were screened and identified from extracts of Ligusticum wallichii. Components from the extract were retained on the cell membrane chromatographic column. The retained fraction was directly eluted into high‐performance liquid chromatography with mass spectrometry system for separation and identification. Finally, Levistolide A was identified as an active component from Ligusticum wallichii extracts. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐tetrazolium bromide‐formazan colorimetric assay revealed that Levistolide A inhibits proliferation of overexpressing the mutated receptor cells with dose‐dependent manner. Phosphorylation of fibroblast growth factor receptor 4 was also decrease under Levistolide A treatment. Flex dock simulation verified that Levistolide A could bind with the tyrosine kinase domain of fibroblast growth factor receptor 4. Therefore, Levistolide A screened by the cell membrane chromatography combined with high‐performance liquid chromatography and mass spectrometry can arrest cell growth. In conclusion, the two‐dimensional high‐performance liquid chromatography method can screen and identify potential anti‐tumor ingredients that specifically act on the tyrosine kinase domain of the mutated fibroblast growth factor receptor 4.     

高中学业水平考试试题难度模型建构*

利用主成分分析方法厘清试题难度影响因素之间的关系,进而从问题表征、问题解决和结果输出等3个维度上建立了影响高中学业水平考试试题难度的主要因素。通过编写高中学业水平考试测试题进行实证研究,建立影响因素常见呈现类型的难易赋值规则。选用机器学习的线性回归方法建构试题难度分析模型,并使用高考化学江苏卷部分试题的实测难度数据进行校验,模型难度预测值和高考难度实测值具有较好的拟合度,表明模型具有较好的应用价值和推广意义。     

Enhanced stability designs of cell membrane chromatography for screening drug leads

Cell membrane chromatography is an effective method for screening bioactive components acting on specific receptors in complex systems, which maintains the biological activity of the membrane receptors and improves screening efficiency. However, traditional cell membrane chromatography suffers from poor stability, resulting in a limited life span and low reproducibility, greatly limiting the application of this method. To address this problem, cyanuric chloride-decorated silica gel was used for the covalent immobilization of the cell membranes. Cyanuric chloride reacts with amino groups on the cell membranes and membrane receptors to form covalent bonds. In this way, the cell membranes are not easy to fall off. The column life of the cyanuric chloride-decorated epidermal growth factor receptor/cell membrane chromatography column was extended to more than 8 days, whereas the column life of the normal cell membrane chromatography column dropped sharply in the first 3 days. A cyanuric chloride-decorated epidermal growth factor receptor/cell membrane chromatography online HPLC-IT-TOF-MSn system was applied for screening drug leads from Trifolium pratense L. One potential drug lead, formononetin, which acts on the epidermal growth factor receptor, was screened. Our strategy of covalently immobilizing cell membrane receptors also improved the stability of cell membrane chromatography.     

治疗非小细胞肺癌脑转新药:Zorifertinib

新药Zorifertinib是阿斯利康公司针对非小细胞肺癌(NSCLC)脑转研发的一种表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI),对EGFR 19外显子缺失和EGFR 21外显子L858R突变有高选择性和高抑制性,相较于其他EGFR-TKIs的突出优势是具有优秀的血脑屏障渗透性。临床研究表明Zorifertinib可以在脑内达到等同血浆的药物浓度,有效抑制脑内肿瘤生长,减少脑内肿瘤面积,并且预防脑内肿瘤形成。本文将对该新药的作用机制、研发历程、药代动力学、临床研究和安全性进行综述,为广大研究者以及今后的临床应用提供参考。