AMYGNN: A Graph Convolutional Neural Network-Based Approach for Predicting Amyloid Formation from Polypeptides.

There has been an increasing interest in the use of amyloids for constructing various functional materials. The design of amyloid-associated functional materials requires the identification of the core peptide sequences as the fundamental building block. The existing computational methods are limited in terms of delineating polypeptides, the typical non-Euclidean structural data, and they fail to capture the dynamic interactions between amino acids due to ignoring the contextual information from surrounding amino acids. Here, we first propose the use of a state-of-the-art graph convolutional neural network for predicting the trends of amyloid formation from specific peptide sequences (AMYGNN) by abstracting each polypeptide as a graph, in which the constituting amino acids are viewed as nodes and edges characterizing the connections between pairs of amino acids are established when they meet a given distance threshold (Cα-Cα ≤ 5 Å). Our model achieves high performance with accuracy (0.9208), G-mean (0.9203), MCC (0.8417), and F1 (0.9235) in determining the characteristic peptide sequences to form amyloid. 32 of 534 crucial amino acid properties that greatly contribute to the formation of amyloids are ascertained, and the ß-folding-like graph structure of a polypeptide is believed to be essential for the formation of amyloid. Our model enables the mapping of polypeptides with underlying interactions between amino acids and provides a quick and precise predictive framework for directing the construction of amyloid-associated functional materials.

circHIPK3 regulates proliferation and differentiation of myoblast through the miR-7/TCF12 pathway.

Skeletal muscle development is a complex biological process involving multiple key genes, signaling pathways and noncoding RNAs, including microRNAs and circular RNAs (circRNAs). However, the regulatory relationship among them is so complicated that it has not yet been fully elucidated. In this study, we found that miR-7 inhibited C2C12 cell proliferation and differentiation by targeting transcription factor 12 (TCF12). circHIPK3 acted as a competing endogenous RNA, and its overexpression effectively reversed the regulation of miR-7 on C2C12 cell proliferation and differentiation by increasing TCF12 expression. Taken together, our findings provide evidence that circHIPK3 regulates skeletal muscle development through the miR-7/TCF12 pathway. This study provides a scientific basis for further research on skeletal muscle development at the circRNA level.

Effects of aqueous extracts of Taraxacum Officinale on expression of tumor necrosis factor-alpha and intracellular adhesion molecule 1 in LPS-stimulated RMMVECs.

BACKGROUND: Mastitis gives rise to big financial burden to farm industry (mainly dairy production) and public health. Its incidence is currently high and therefore, highly effective treatments for therapy, especially with natural products are required. Taraxacum officinale has been reported to use for anti-inflammation. However, its effect on endothelium during mastitis has not been reported. METHODS: We firstly established inflammation experimental model of rat mammary microvascular endothelial cells (RMMVECs). We evaluated the effects of dandelion leaf aqueous extracts (DAE) on LPS-induced production of inflammatory mediators in RMMVECs by enzyme-linked immunosorbent assay and Western blot. We treated RMMVECs with 1 µg/ml LPS for 4 h and then incubated with 10, 100 and 200 µg/mL DAE for 4, 8, 12 and 24 h. The expression (mRNA and protein level) of targets (tumor necrosis factor-alpha (TNF- α) and Intracellular Adhesion Molecule 1 (ICAM1) was analyzed by employing real-time PCR and Western blots. The in vivo anti-inflammatory effect of DAE on mastitis within an Staphylococcus aureus-induced mouse model was also determined. RESULTS: The obtained results showed that dandelion extracts at the concentration of 100 and 200 µg/mL could significantly inhibit both TNF-α and ICAM-1 expression in all time points checked while 10 µg/mL of dandelion only suppress both expression at 8 and 12 h post-treatment. The in vivo tests showed that the DAE inhibited the expression of TNF-α and ICAM-1 in a time-dependent manner. CONCLUSIONS: All results suggest that the endothelium may use as as a possible target of dandelion for anti-inflammation.

Fabricating Composite Cell Sheets for Wound Healing: Cell Sheets Based on the Communication Between BMSCs and HFSCs Facilitate Full-Thickness Cutaneous Wound Healing.

BACKGROUND: Insufficient angiogenesis and the lack of skin appendages are critical challenges in cutaneous wound healing. Stem cell-fabricated cell sheets have become a promising strategy, but cell sheets constructed by a single cell type are inadequate to provide a comprehensive proregenerative microenvironment for wound tissue. METHODS: Based on the communication between cells, in this study, bone marrow mesenchymal stem cells (BMSCs) and hair follicle stem cells (HFSCs) were cocultured to fabricate a composite cell sheet (H/M-CS) for the treatment of full-thickness skin wounds in mice. RESULTS: Experiments confirmed that there is cell-cell communication between BMSCs and HFSCs, which enhances the cell proliferation and migration abilities of both cell types. Cell-cell talk also upregulates the gene expression of pro-angiogenic-related cytokines in BMSCs and pro-hair follicle-related cytokines in HFSCs, as well as causing changes in the properties of secreted extracellular matrix components. CONCLUSIONS: Therefore, the composite cell sheet is more conducive for cutaneous wound healing and promoting the regeneration of blood vessels and hair follicles.

Cysteine-Derived Chiral Carbon Quantum Dots: A Fibrinolytic Activity Regulator for Plasmin to Target the Human Islet Amyloid Polypeptide for Type 2 Diabetes Mellitus.

The fibrillization and deposition of the human islet amyloid polypeptide (hIAPP) are the pathological hallmark of type 2 diabetes mellitus (T2DM), and these insoluble fibrotic depositions of hIAPP are considered to strongly affect insulin secretion by inducing toxicity toward pancreatic islet ß-cells. The current strategy of preventing amyloid aggregation by nanoparticle-assisted inhibitors can only disassemble fibrotic amyloids into more toxic oligomers and/or protofibrils. Herein, for the first time, we propose a type of cysteine-derived chiral carbon quantum dot (CQD) that targets plasmin, a core natural fibrinolytic protease in humans. These CQDs can serve as fibrinolytic activity regulators for plasmin to cleave hIAPP into nontoxic polypeptides or into even smaller amino acid fragments, thus alleviating hIAPP's fibrotic amyloid-induced cytotoxicity. Our experiments indicate that chiral CQDs have opposing effects on plasmin activity. The l-CQDs promote the cleavage of hIAPP by enhancing plasmin activity at a promotion ratio of 23.2%, thus protecting ß-cells from amyloid-induced toxicity. In contrast, the resultant d-CQDs significantly inhibit proteolysis, decreasing plasmin activity by 31.5% under the same reaction conditions. Second harmonic generation (SHG) microscopic imaging is initially used to dynamically characterize hIAPP before and after proteolysis. The l-CQD promotion of plasmin activity thus provides a promising avenue for the hIAPP-targeted treatment of T2DM to treat low fibrinolytic activity, while the d-CQDs, as inhibitors of plasmin activity, may improve patient survival for hyperfibrinolytic conditions, such as those existing during surgeries and traumas.

IFN-γ induces IFN-α and IFN-ß expressions in cultured rat intestinal mucosa microvascular endothelial cells.

Although researchers have recently begun to pay more attention to the immunological characteristics of microvascular endothelial cells (MVECs), there are no reports on whether activation of MVECs by interferon-γ (IFN-γ) exerts any influence on the expressions of IFN-α/ß. In the present study, we examined the influence of IFN-γ on the expressions of IFN-α/ß in rat intestinal mucous MVECs (RIMMVECs). Different concentrations of IFN-γ were used to stimulate cultured RIMMVECs in vitro, and the cells and cell supernatants were collected at different time intervals. The influence of IFN-γ on the expressions of IFN-α/ß in the RIMMVECs was examined at the mRNA and protein levels by real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA), respectively. The results indicated that IFN-γ was able to activate RIMMVECs, thereby leading to upregulated expressions of IFN-α/ß. The real-time quantitative PCR analyses indicated that the IFN-α/ß mRNA expression levels in RIMMVECs achieved their peak values after stimulation with IFN-γ at 20 ng/mL for 6 h and were increased by 14.88- and 3.82-fold, respectively, when compared with the levels in negative control cells. The ELISA analyses revealed that the IFN-α/ß protein expression levels achieved their peak values after stimulation with IFN-γ at 40 ng/mL. The expression of IFN-α protein achieved its peak value at 12 h, while the expression of IFN-ß protein achieved its peak value after 6 h. The present results suggest that the expression and secretion of IFNs may participate in the immunologic barrier function of MVECs.

Effect of Graphene Nanosheet Addition on the Wettability and Mechanical Properties of Sn-20Bi-xGNS/Cu Solder Joints.

Graphene nanosheets (GNSs) have an extensive application in materials modification. In this study, the effects of graphene nanosheets on the wettability of Sn-20Bi lead-free solder on copper (Cu) substrate and the growth behavior of intermetallic compound (IMC) layers at Sn-20Bi-xGNS/Cu solder joints were investigated. The experimental results indicate that the wettability of Sn-20Bi solder firstly diminished and then increased by the addition of GNSs. Meanwhile, a prism-shaped and scallop-shaped Cu6Sn5 IMC layer was clearly observed at the interface of the solder/substrate system. Moreover, it was found that a small amount of GNS addition can significantly inhibit the growth of the IMC layer at the interface as well as refine the microstructure. Additionally, by nano-indentation apparatus, it can be concluded that the hardness and elastic module of IMCs show the same variation trend, which firstly decreased and then increased. Besides, to intuitively demonstrate the reliability of IMCs, the relationship between the hardness and elastic module was established, and the ratio of hardness/elastic module (H/E) was adopted to characterize the reliability of IMCs. The results show that when the addition of GNSs was 0.02 wt%, the value of H/E is the minimum and the solder joint has the highest reliability.

[Effect of electroacupuncture on expression of IFN-gamma-like immunoreactive substance in spinal cord of the rat ].

OBJECTIVE: To observe effect of electroacupuncture at "Zusanli" (ST 36) on expression of interferon-gamma (IFN-gamma)-like immunoreactive substance in spinal cord of the rat and to probe the mechanism. METHODS: The IFN-gamma-like immunoreactive positive cell number in spinal cord of the rat was investigated with immunohistochemical SP method and microscopy. RESULTS: After electroacupuncture at "Zusanli" (ST 36), IFN-gamma-like immunoreactive positive cell number in the spinal cord of the rat with electroacupuncture plus immunosuppression did not significantly change (P > 0.05). The number of positive cells in the dorsal horn in the rats with immunosuppression was significantly less than that in the normal control group (P < 0.05) with no significant change in other parts and with no significant difference between the electroacupuncture group and the control group (P > 0.05). CONCLUSION: Electroacupuncture at "Zusanli" (ST 36) can increase expression of IFN-gamma-like immunoreactive substance in spinal cord of the rat, and acupuncture activates the nerve-immunoregulative network possibly by IFN-gamma as medium.

[Determination of antioxidants butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in cosmetics by gas chromatography-mass spectrometry selected ion method].

A new method for the determination of butylated hydroxyanisole (BHA) and butylated hydroxytoluene (BHT) in cosmetics by gas chromatography-mass spectrometry selected ion storage (SIS) method was developed. The BHA and BHT in samples were extracted by methanol. The m/z 165 and m/z 205 were the monitoring ion for BHA and BHT respectively. The detection limits of BHA and BHT in samples were 2.5 micrograms/g and 0.5 microgram/g, respectively. The method is simple, rapid and accurate.