Astragalus membranaceus (A. membranaceus) is a type of traditional Chinese medicine with a long history of clinical application. It is used in the improvement and treatment of various diseases as medicine and food to invigorate the spleen and replenish qi. The main components of A. membranaceus are Astragalus polysaccharide (APS), flavonoids compounds, saponins compounds, alkaloids, etc. APS is the most important natural active component in A. membranaceus, and possesses multiple pharmacological properties. At present, APS possess the huge potential to develop a drug improving or treating different diseases. In this review, we reveal the potential approaches of pretreating and preparation on APS as much as possible and the study on content of APS and its chemical composition including different monosaccharides. More importantly, this paper summarize pharmacological actions on immune regulation, such as enhancing the immune organ index, promoting the proliferation of immune cells, stimulating the release of cytokines, and affecting the secretion of immunoglobulin and conduction of immune signals; anti-aging; anti-tumor by enhancing immunity, inducing apoptosis of tumor cells and inhibiting the proliferation and transfer of tumor cells; antiviral effects; regulation of blood glucose such as type I diabetes mellitus, type II diabetes mellitus and diabetic complications; lipid-lowering; anti-fibrosis; antimicrobial activities and anti-radiation. It provided theoretical basis for the further research such as its structure and mechanism of action, and clinical application of APS.

Direct lineage conversion is a promising approach to generate therapeutically important cell types for disease modeling and tissue repair. However, the survival and function of lineage-reprogrammed cells in vivo over the long term has not been examined. Here, using an improved method for in vivo conversion of adult mouse pancreatic acinar cells toward beta cells, we show that induced beta cells persist for up to 13 months (the length of the experiment), form pancreatic islet-like structures and support normoglycemia in diabetic mice. Detailed molecular analyses of induced beta cells over 7 months reveal that global DNA methylation changes occur within 10 d, whereas the transcriptional network evolves over 2 months to resemble that of endogenous beta cells and remains stable thereafter. Progressive gain of beta-cell function occurs over 7 months, as measured by glucose-regulated insulin release and suppression of hyperglycemia. These studies demonstrate that lineage-reprogrammed cells persist for >1 year and undergo epigenetic, transcriptional, anatomical and functional development toward a beta-cell phenotype.

Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum MMP inhibitors have limited clinical utility, which has spurred the development of inhibitors selective for individual MMPs. Attaining selectivity has been technically challenging because of sequence and structural conservation across the various MMPs. Here, through a biochemical and structural screening paradigm, we have identified JNJ0966, a highly selective compound that inhibited activation of MMP-9 zymogen and subsequent generation of catalytically active enzyme. JNJ0966 had no effect on MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14 catalytic activity and did not inhibit activation of the highly related MMP-2 zymogen. The molecular basis for this activity was characterized as an interaction of JNJ0966 with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106, which is distinct from the catalytic domain. JNJ0966 was efficacious in reducing disease severity in a mouse experimental autoimmune encephalomyelitis model, demonstrating the viability of this therapeutic approach. This discovery reveals an unprecedented pharmacological approach to MMP inhibition, providing an opportunity to improve selectivity of future clinical drug candidates. Targeting zymogen activation in this manner may also allow for pharmaceutical exploration of other enzymes previously viewed as intractable drug targets. MMPs2 are a family of structurally related zinc-binding proteolytic enzymes that digest extracellular matrix proteins and participate in tissue remodeling and signaling events (1). Currently, ϳ23 MMPs have been identified, comprising secreted and membrane-bound forms, and different family members share some common structural and functional domains and have varying degrees of substrate specificity. Abnormal expression and activation of MMPs has been implicated in the pathogenesis and pathological progression of several different human diseases that are centered in many different tissues in the periphery and central nervous system (2, 3). Initial clinical exploration of synthetic MMP inhibitors was focused on oncology indications, as preventing the breakdown of tissue matrices and barriers was viewed as a potential mechanism to limit tumor metastasis.Despite intensive efforts over many years to develop synthetic MMP inhibitors, only a single MMP inhibitor, Periostat, a tetracycline derivative used in periodontal disease, has progressed into regular clinical use (4). Of the ϳ50 other clinical trials conducted with active site MMP inhibitors, all have failed due to the onset of significant dose-limiting musculoskeletal toxicity ...

To search for a novel sensor to detect the presence of formaldehyde (HCOH), we investigate reactivities of the intrinsic and boron-doped (B-doped) single-walled (8, 0) carbon nanotube (SWCNT) with HCOH using density functional theory calculations. Compared with the intrinsic SWCNT, the B-doped SWCNT presents high sensitivity to HCOH. This is attributed to the strongly chemical interaction between the electron-rich oxygen atom of HCOH and the electron-scarce boron atom of the doped SWCNT. B-doped SWCNTs are expected to be a potential candidate for detecting the presence of HCOH.

Supporting Information and the ORCID identification number(s) for the author(s) of this article can be found under: https://doi.

Boron-doped (B-doped) single-walled (8, 0) carbon nanotubes (SWCNTs) are investigated using density functional theory (DFT) calculations as sensor models to detect the presence of cyanides, such as hydrogen cyanide (HCN) and cyanogen chloride (CNCl). Comparing the results of the intrinsic SWCNTs with HCN and CNCl, we discover that B-doped SWCNTs present a high sensitivity to the gaseous cyanide molecules, which is indicated by optimized geometry and electronic properties of these systems. On the basis of calculated results, we call attention to the fact that B-doped SWCNTs would be potential candidates for the detection of gaseous cyanide molecules. The present results provide guidance to experimental scientists in developing CNT-based chemical sensors.

Background: Glutamate, a major excitatory amino acid neurotransmitter, causes apoptotic neuronal cell death at high concentrations. Our previous studies have shown that depending on the neuronal cell type, glutamate-induced apoptotic cell death was associated with regulation of genes such as Bcl-2, Bax, and/or caspase-3 and mitochondrial cytochrome c. To further delineate the intracellular mechanisms, we have investigated the role of calpain, an important calcium-dependent protease thought to be involved in apoptosis along with mitochondrial apoptosis inducing factor (AIF) and caspase-3 in primary cortical cells and a mouse hippocampal cell line HT22.

The ordered magnetic states of MnWO 4 at low temperatures were examined by evaluating the spin exchange interactions between the Mn 2+ ions of MnWO 4 on the basis of first principles density functional calculations and by performing classical spin analysis with the resulting spin exchange parameters. Our work shows that the spin exchange interactions are frustrated within each zigzag chain of Mn 2+ ions along the cdirection and between such chains of Mn 2+ ions along the a-direction. This explains the occurrence of a spiral-spin order along the c-and a-directions in the incommensurate magnetic state AF2, and that of a ↑↑↓↓ spin order along the c-and a-directions in the commensurate magnetic state AF1. The ferroelectric polarization of MnWO 4 in the spiral-spin state AF2 was examined by performing Berry phase calculations for a model superstructure to find that the ferroelectric polarization occurs along the b-direction, in agreement with experiment. N )( J 2 J 2 J 2 J 2 J 2 J 2 J 2 J 2 J 2