Abstract
Background
As an important task in bioinformatics, clustering analysis plays a critical role in understanding the functional mechanisms of many complex biological systems, which can be ...modeled as biological networks. The purpose of clustering analysis in biological networks is to identify functional modules of interest, but there is a lack of online clustering tools that visualize biological networks and provide in-depth biological analysis for discovered clusters.
Results
Here we present BioCAIV, a novel webserver dedicated to maximize its accessibility and applicability on the clustering analysis of biological networks. This, together with its user-friendly interface, assists biological researchers to perform an accurate clustering analysis for biological networks and identify functionally significant modules for further assessment.
Conclusions
BioCAIV is an efficient clustering analysis webserver designed for a variety of biological networks. BioCAIV is freely available without registration requirements at
http://bioinformatics.tianshanzw.cn:8888/BioCAIV/
.
Epidithiodioxopiperazine (ETP) alkaloids, featuring a 2,5‐diketopiperazine core and transannular disulfide bridge, exhibit a broad spectrum of biological activities. However, the structural ...complexity has prevented efficient chemical synthesis and further clinical research. In the past few decades, many achievements have been made in the biosynthesis of ETPs. Here, we discuss the biosynthetic progress and summarize them as two comprehensible metabolic principles for better understanding the complex pathways of α, α′‐ and α, β′‐disulfide bridged ETPs. Specifically, we systematically outline the catalytic machineries to install α, α′‐ and α, β′‐disulfide by flavin‐containing oxygenases. This concept would contribute to the medical and industrial applications of ETPs.
Epidithiodioxopiperazines (ETPs) alkaloids possess complex structures and exhibit a broad spectrum of biological activities. In this concept, we summarize the biosynthesis of α, α′‐ and α, β′‐disulfide bridged ETPs and outline the catalytic machineries for the transannular disulfide construction. This will facilitate the medical and industrial applications of ETPs.
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Recently, Nrf2/HO-1 has received extensive attention as the main regulatory pathway of intracellular defense against oxidative stress and is considered an ideal target for alleviating ...endothelial cell (EC) injury.
This paper aimed to summarized the natural monomers/extracts that potentially exert protective effects against oxidative stress in ECs.
A literature search was carried out regarding our topic with the keywords of “atherosclerosis” or “Nrf2/HO-1” or “vascular endothelial cells” or “oxidative stress” or “Herbal medicine” or “natural products” or “natural extracts” or “natural compounds” or “traditional Chinese medicines” based on classic books of herbal medicine and scientific databases including Pubmed, SciFinder, Scopus, the Web of Science, GoogleScholar, BaiduScholar, and others. Then, we analyzed the possible molecular mechanisms for different types of natural compounds in the treatment of atherosclerosis via the protection of vascular endothelial cells from oxidative stress. In addition, perspectives for possible future studies are discussed.
These agents with protective effects against oxidative stress in ECs mainly include phenylpropanoids, flavonoids, terpenoids, and alkaloids. Most of these agents alleviate cell apoptosis in ECs due to oxidative stress, and the mechanisms are related to Nrf2/HO-1 signaling activation. However, despite continued progress in research on various aspects of natural agents exerting protective effects against EC injury by activating Nrf2/HO-1 signaling, the development of new drugs for the treatment of atherosclerosis (AS) and other CVDs based on these agents will require more detailed preclinical and clinical studies.
Our present paper provides updated information of natural agents with protective activities on ECs against oxidative stress by activating Nrf2/HO-1. We hope this review will provide some directions for the further development of novel candidate drugs from natural agents for the treatment of AS and other CVDs.
Collagen stabilization through irreversible cross‐linking is thought to promote hepatic fibrosis progression and limit its reversibility. However, the mechanism of this process remains poorly ...defined. We studied the functional contribution of lysyl oxidase (LOX) to collagen stabilization and hepatic fibrosis progression/reversal in vivo using chronic administration of irreversible LOX inhibitor β‐aminopropionitrile (BAPN, or vehicle as control) in C57Bl/6J mice with carbon tetrachloride (CCl4)‐induced fibrosis. Fibrotic matrix stability was directly assessed using a stepwise collagen extraction assay and fibrotic septae morphometry. Liver cells and fibrosis were studied by histologic, biochemical methods and quantitative real‐time reverse‐transcription PCR. During fibrosis progression, BAPN administration suppressed accumulation of cross‐linked collagens, and fibrotic septae showed widening and collagen fibrils splitting, reminiscent of remodeling signs observed during fibrosis reversal. LOX inhibition attenuated hepatic stellate cell activation markers and promoted F4/80‐positive scar‐associated macrophage infiltration without an increase in liver injury. In reversal experiments, BAPN‐treated fibrotic mice demonstrated accelerated fibrosis reversal after CCl4 withdrawal. Our findings demonstrate for the first time that LOX contributes significantly to collagen stabilization in liver fibrosis, promotes fibrogenic activation of attenuated hepatic stellate cells, and limits fibrosis reversal. Our data support the concept of pharmacologic targeting of LOX pathway to inhibit liver fibrosis and promote its resolution.—Liu, S. B., Ikenaga, N., Peng, Z.‐W., Sverdlov, D. Y., Greenstein, A., Smith, V., Schuppan, D., Popov, Y. Lysyl oxidase activity contributes to collagen stabilization during liver fibrosis progression and limits spontaneous fibrosis reversal in mice. FASEB J. 30, 1599–1609 (2016). www.fasebj.org
This study extends prior studies by analyzing how business strategies affect corporate social responsibility (CSR) engagement. Studies in the business strategy and compensation literature further ...investigate whether firms have superior CSR if they tend to align their compensation with their company's overall strategy. This tendency would tend to encourage firms to make their investment decisions on the basis of a long‐term sustainability development perspective. The data consist of a broad cross‐section of companies and industries in the United States for the 2003–2012 period. To avoid a potential endogenous effect, a two‐stage instrumental variables regression is also adopted in this study. It is found that the prospector business strategy has a strong positive association with CSR. In addition, CEOs with short‐term compensation have less incentive to invest in CSR if their firms adopt a defender strategy. The opposite is true for the prospector group, suggesting that sometimes, misfits may also produce good CSR outcomes.
An iron‐catalyzed hydrofluorination of unactivated alkenes has been developed. The use of a multidentate ligand and the fluorination reagent N‐fluorobenzenesulfonimide (NFSI) proved to be critical ...for this reaction, which afforded various fluorinated compounds in up to 94 % yield.
H(igh)–F(ive): The combination of a multidentate ligand, (EtO)3SiH, and N‐fluorobenzenesulfonimide (NFSI) proved critical in facilitating an iron‐catalyzed hydrofluorination of unactivated alkenes to provide a variety of substituted fluorinated compounds. The reaction was shown to proceed by a radical mechanism and to be suitable for the fluorination of various biologically active substrates.
Background
Immunotherapy targeting PD-1 provides a limited survival benefit in patients with unresectable advanced or recurrent gastric cancer (GC). Beside PD-L1, the expression of inhibitory ligands ...such as CEACAM-1 and LSECtin on GC cells account for this limitation. Here we assessed their expression and immune suppressive effect in GC patients.
Methods
Using multiplexed immunohistochemistry staining, we evaluated the distribution of different inhibitory ligands, including PD-L1, CEACAM-1, LSECtin, and MHC class II, in 365 GC patients. We analyzed their correlations and overall survival (OS) based on the expression of each inhibitory ligand and the independent prognostic factors that affect OS. Subsequently, we evaluated the additive effect of anti-PD-1 mAb or anti-PD-L1 mAb with/without anti-Lag-3 mAb with/without anti-Tim-3 mAb in cytotoxic assay using tumor-antigen specific CTL clones against GC cell lines.
Results
Co-expression of the inhibitory ligands for PD-1, Tim-3, and Lag-3 was observed in the largest proportion (34.7%). CEACAM-1, LSECtin, and MHC class II expression showed significant correlation with PD-L1 expression and OS. Multivariable analysis demonstrated that CEACAM-1 low is an independent prognostic factor. Furthermore, combining dual and triple ICIs yielded additive effect on cytotoxicity of CTL clones against each immune inhibitory ligand positive GC cell lines.
Conclusions
Our findings suggested that the expression of inhibitory ligands for Tim-3 and Lag-3 on GC cells serve as potential biomarkers to predict the response to anti-PD-1 therapy and the combinatorial immunotherapy with ICIs targeting for PD-1, Tim-3, and Lag-3 has a therapeutic potential for GC patients.
Smart ultra-stable foams stabilized by cellulose nanocrystal (CNC)-based gels were fabricated. The stabilization is ascribed to the dense films and three-dimensional networks at the interface and in ...the bulk induced by the charge shielding effect and electrostatic attraction between protonated bis(2-hydroxyethyl)oleylamine (BOA-H
) micelles and negatively charged CNC colloids. The as-prepared foam could maintain its morphology without breaking or drainage for two months, showing high stability. Outstanding CO
/N
reversibility endows the system with on-demand control of foaming/defoaming, which is necessary in many aspects. The functionalized foam is expected to open up an opportunity for the design of intelligent oilfield chemicals and extinguishant systems.
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