Progress in the study of molecular mechanisms of intervertebral disc degeneration.

Degenerative intervertebral disc disease (IVDD) is one of the main spinal surgery, conditions, which markedly increases the incidence of low back pain and deteriorates the patient's quality of life, and it imposes significant social and economic burdens. The molecular pathology of IVDD is highly complex and multilateral however still not ompletely understood. New findings indicate that IVDD is closely associated with inflammation, oxidative stress, cell injury and extracellular matrix metabolismdysregulation. Symptomatic management is the main therapeutic approach adopted for IVDD, but it fails to address the basic pathological changes and the causes of the disease. However, research is still focusing on molecular aspects in terms of gene expression, growth factors and cell signaling pathways in an attempt to identify specific molecular targets for IVDD treatment. The paper summarizes the most recent achievements in molecularunderstanding of the pathogenesis of IVDD and gives evidence-based recommendations for clinical practice.

A new strategy for intervertebral disc regeneration: The synergistic potential of mesenchymal stem cells and their extracellular vesicles with hydrogel scaffolds.

Intervertebral disc degeneration (IDD) is a disease that severely affects spinal health and is prevalent worldwide. Mesenchymal stem cells (MSCs) and their derived extracellular vesicles (EVs) have regenerative potential and have emerged as promising therapeutic tools for treating degenerative discs. However, challenges such as the harsh microenvironment of degenerated intervertebral discs and EVs' limited stability and efficacy have hindered their clinical application. In recent years, hydrogels have attracted much attention in the field of IDD therapy because they can mimic the physiologic microenvironment of the disc and provide a potential solution by providing a suitable growth environment for MSCs and EVs. This review introduced the biological properties of MSCs and their derived EVs, summarized the research on the application of MSCs and EVs in IDD, summarized the current clinical trial studies of MSCs and EVs, and also explored the mechanism of action of MSCs and EVs in intervertebral discs. In addition, plenty of research elaborated on the mechanism of action of different classified hydrogels in tissue engineering, the synergistic effect of MSCs and EVs in promoting intervertebral disc regeneration, and their wide application in treating IDD. Finally, the challenges and problems still faced by hydrogel-loaded MSCs and EVs in the treatment of IDD are summarized, and potential solutions are proposed. This paper outlines the synergistic effects of MSCs and EVs in treating IDD in combination with hydrogels and aims to provide theoretical references for future related studies.

Analyses of artificial morel soil bacterial community structure and mineral element contents in ascocarp and the cultivated soil.

This study explored the differences among various artificial morel cultivations as well as the factors that influence these differences, including soil bacterial community structure, yield, and mineral element contents of ascocarp and the cultivated soil. High-throughput sequencing results revealed that the dominant bacterial phyla in all the samples, including Proteobacteria, Acidobacteria, Chloroflexi, Bacteroides, and Gemmatimonadetes, were found not only in morel soils (experimental group) but also in wheat soil (control group); the highest richness and diversity in the soil bacteria were observed during the primordial differentiation stage. The M6 group exhibited the highest yield (271.8 g/m2) and had an unexpectedly high proportion of Pseudomonas (25.30%) during the primordial differentiation stage, which was 1.77∼194.62 times more than the proportion of Pseudomonas in other samples. Pseudomonas may influence the growth of morel. The mineral element contents of the different soil groups and the ascocarp were determined by electrothermal digestion and inductively coupled plasma mass spectrometry. The results revealed that morel had high enrichment effects on phosphorus (P, bioconcentration factor = 16.83), potassium (K, 2.18), boron (B, 1.47), zinc (Zn, 1.36), copper (Cu, 1.15), and selenium (Se, 2.27). P levels were the highest followed by Se and K, and the mineral element contents in ascocarp were positively correlated with the soil element contents.

Controlled Self-Assembled NiFe Layered Double Hydroxides/Reduced Graphene Oxide Nanohybrids Based on the Solid-Phase Exfoliation Strategy as an Excellent Electrocatalyst for the Oxygen Evolution Reaction.

Layered double hydroxides (LDHs), as an effective oxygen evolution reaction (OER) electrocatalyst, face many challenges in practical applications. The main obstacle is that bulk materials limit the exposure of active sites. At the same time, the poor conductivity of LDHs is also an important factor. Exfoliation is one of the most direct and effective strategies to increase the electrocatalytic properties of LDHs, leading to exposure of many active sites. However, developing an efficient exfoliation strategy to exfoliate LDHs into stable monolayer nanosheets is still challenging. Therefore, we report a new and efficient solid-phase exfoliation strategy to exfoliate NiFe LDH and graphene oxide (GO) into monolayer nanosheets and the exfoliating ratios of NiFe LDH and GO can reach up to 10 and 5 wt %, respectively. Based on the solid-phase exfoliation strategy, we accidentally discovered that there is a dynamic evolution process between NiFe-LDH nanosheets (NiFe-LDH-NS) and GO nanosheets (GO-NS) to assemble new NiFe-LDH/GO nanohybrids, i.e., NiFe-LDH-NS could be horizontal bespreading on GO-NS or well-organized standing on GO-NS, or both simultaneously. The electrocatalytic OER property test results show that NiFe-LDH/RGO-3 (NFRG-3) nanohybrids obtained by the reduction treatment of NiFe-LDH/GO-3 (NFGO-3) nanohybrids, in which NiFe-LDH-NS are well-organized standing on GO-NS, have excellent electrocatalytic properties for OER in an alkaline solution (with a small overpotential of 273 mV and a Tafel slope of 49 mV dec-1 at the current density of 30 mA cm-2). The excellent electrocatalytic properties for OER of NFRG-3 nanohybrids could be attributed to the unique three-dimensional arraylike structure with many active sites. At the same time, reduced graphene oxide (RGO) with excellent conductivity can improve the charge-transfer efficiency and synergistically improve OER properties of nanohybrids.

Screening of novel histone deacetylase 7 inhibitors through molecular docking followed by a combination of molecular dynamics simulations and ligand-based approach.

Histone acetylation/deacetylation is a key mechanism for transcription regulation which plays an important role in control of gene expression, tissue growth, and development. In particular, histone deacetylase 7 (HDAC7), a member of class IIa HDACs, is crucial to maintain cell homeostasis, and HDAC7 has emerged as a new target for cancer therapy. In this study, molecular docking was applied to screen candidate inhibitors and 21 compounds were found. Following the 50 ns molecular dynamics simulations and binding free energy calculation, ZINC00156160, ZINC01703144, ZINC04293665, and ZINC13900201 were identified as potential HDAC7 inhibitors, which would provide a sound starting point for further studies involving molecular modeling coupled with biochemical experiments. Meanwhile, similarity computation and substructure search were combined, and then we found that compounds sharing common backbone "CC(=O)N[C@@H](CSc1ccccc1)C(=O)O" could be efficient to inhibit the bioactivity of HDAC7. Then comparative molecular similarity indices analysis (CoMSIA) techniques were implemented to investigate the relationship between properties of the substituent group and bioactivities of small molecules. The CoMSIA model exhibited powerful predictivity, with satisfactory statistical parameters such as q2 of 0.659, R2 of 0.952, and F of 268.448. Contour maps of the CoMSIA model gave insight into the feature requirements of the common backbone for the HDAC7 inhibitory activity. Finally, details of designing novel HDAC7 inhibitors were confirmed by a combination of receptor-based docking and ligand-based structure-activity relationship. Communicated by Ramaswamy H. Sarma.

Identification of two potential glycogen synthase kinase 3ß inhibitors for the treatment of osteosarcoma.

Osteosarcoma is the most common primary malignant bone tumor among adolescents worldwide with high mortality rate. Glycogen synthase kinase 3ß (GSK3ß) is a serine/threonine kinase and is considered as a validated target in osteosarcoma therapy. Therefore, the study of GSK3ß inhibitors is one of the most popular fields in anti-osteosarcoma drug development. Here, the tools of bioinformatics were used to screen novel effective inhibitors of GSK3ß from ZINC Drug Database. The molecular docking, molecular dynamic simulations, MM/GBSA, and energy decomposition analysis were performed to identify the inhibitors. Finally, ZINC08383479 and ZINC08441251 were selected as potential GSK3ß inhibitors. These two inhibitors were evaluated by GSK3ß kinase inhibition assay in vitro. The inhibition of cell proliferation was tested in osteosarcoma cell lines U2OS and MG63 in vitro. The result showed that ZINC08383479 and ZINC08441251 had high inhibition activity against GSK3ß. We found that CHIR99021 (a known GSK3ß inhibitor), ZINC08383479, and ZINC08441251 had significant inhibition activity in U2OS cells and MG63 cells. These findings may provide new ideas for the design of more potent GSK3ß inhibitors and therapeutic targets for osteosarcoma.

CM-viewer: Visualizing interaction network of co-mutated and mutually exclusively mutated cancer genes.

Cancer genes usually play a crucial role in regulating cell growth. Normal cells transform into malignant tumors by the acquisition of accumulated genetic mutations that enable them to evade normal growth control. It is therefore important to understand the relationships between mutations during cancer development and progression. Although cancer genes with co-occurring and mutually exclusive mutations have already been studied on different scales, there is no timely updated interaction network available for co-mutated and mutually exclusively mutated cancer genes. Therefore, we firstly downloaded 567 cancer genes from COSMIC (catalogue of somatic mutations in cancer) cancer gene census. Secondly, somatic mutations of 71 cancer genomics projects were downloaded from the ICGC (International Cancer Genome Consortium) data portal. Thirdly, mutated cancer genes and affected donors were extracted from the ICGC data to form a mutation matrix where rows are genes, columns are donors, 1 denotes occurrence, and 0 denotes absence of mutation. Afterwards, co-mutated and mutually exclusively mutated cancer gene pairs were identified using DISCOVER (discrete independence statistic controlling for observations with varying event rates). Finally, CM-viewer was developed to visualize the interaction network of cancer genes with co-occurring and mutually exclusive mutations. It is an online visualization tool as well as a biological database. It promises to understand how gene mutations contribute to tumorigenesis and to identify key biomarkers and drug targets for cancer. CM-viewer is freely available at http://www.zhounan.org/comutgene.

[Analysis of Common Issues and Research Progress in Loop Mediated Isothermal Amplification].

Loop mediated isothermal amplification(LAMP)technology is a newly developed isothermal amplification technology for in vitro detection of nucleic acids. Although the LAMP assay is rapid, specific, sensitive, simple and has been widely applied for rapid detection of nucleic acids, it continues to improve and develop. In this paper, we summarize approaches to addressing amplification product contamination, primer design to avoid false positives, and the development of related techniques based on LAMP technology. This paper could serve as a reference for the application of the assay at the grassroots level.