Macrophages play an important role in a wide variety of physiologic and pathologic processes. Plasticity and functional polarization are hallmarks of macrophages. Macrophages commonly exist in two ...distinct subsets: classically activated macrophages (M1) and alternatively activated macrophages (M2). M2b, a subtype of M2 macrophages, has attracted increasing attention over the past decade due to its strong immune‐regulated and anti‐inflammatory effects. A wide variety of stimuli and multiple factors modulate M2b macrophage polarization in vitro and in vivo. M2b macrophages possess both protective and pathogenic roles in various diseases. Understanding the mechanisms of M2b macrophage activation and the modulation of their polarization might provide a great perspective for the design of novel therapeutic strategies. The purpose of this review is to discuss current knowledge of M2b macrophage polarization, the roles of M2b macrophages in a variety of diseases and the stimuli to modulate M2b macrophage polarization.
Review outlines the current knowledge of the stimuli of M2b macrophage polarization and the roles of these cells in diseases.
Abstract
Sophisticated analysis and simplified visualization are crucial for understanding complicated structures of biomacromolecules. DSSR (Dissecting the Spatial Structure of RNA) is an integrated ...computational tool that has streamlined the analysis and annotation of 3D nucleic acid structures. The program creates schematic block representations in diverse styles that can be seamlessly integrated into PyMOL and complement its other popular visualization options. In addition to portraying individual base blocks, DSSR can draw Watson-Crick pairs as long blocks and highlight the minor-groove edges. Notably, DSSR can dramatically simplify the depiction of G-quadruplexes by automatically detecting G-tetrads and treating them as large square blocks. The DSSR-enabled innovative schematics with PyMOL are aesthetically pleasing and highly informative: the base identity, pairing geometry, stacking interactions, double-helical stems, and G-quadruplexes are immediately obvious. These features can be accessed via four interfaces: the command-line interface, the DSSR plugin for PyMOL, the web application, and the web application programming interface. The supplemental PDF serves as a practical guide, with complete and reproducible examples. Thus, even beginners or occasional users can get started quickly, especially via the web application at http://skmatic.x3dna.org.
Web 3DNA (w3DNA) 2.0 is a significantly enhanced version of the widely used w3DNA server for the analysis, visualization, and modeling of 3D nucleic-acid-containing structures. Since its initial ...release in 2009, the w3DNA server has continuously served the community by making commonly-used features of the 3DNA suite of command-line programs readily accessible. However, due to the lack of updates, w3DNA has clearly shown its age in terms of modern web technologies and it has long lagged behind further developments of 3DNA per se. The w3DNA 2.0 server presented here overcomes all known shortcomings of w3DNA while maintaining its battle-tested characteristics. Technically, w3DNA 2.0 implements a simple and intuitive interface (with sensible defaults) for increased usability, and it complies with HTML5 web standards for broad accessibility. Featurewise, w3DNA 2.0 employs the most recent version of 3DNA, enhanced with many new functionalities, including: the automatic handling of modified nucleotides; a set of 'simple' base-pair and step parameters for qualitative characterization of non-Watson-Crick double-helical structures; new structural parameters that integrate the rigid base plane and the backbone phosphate group, the two nucleic acid components most reliably determined with X-ray crystallography; in silico base mutations that preserve the backbone geometry; and a notably improved module for building models of single-stranded RNA, double-helical DNA, Pauling triplex, G-quadruplex, or DNA structures 'decorated' with proteins. The w3DNA 2.0 server is freely available, without registration, at http://web.x3dna.org.
Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) is a negative immune checkpoint pathway that inhibit immune responses, and upregulation of this pathway has implications in ...many malignancies. The search for effective PD-1/PD-L1 inhibitors has been at the forefront of academic and industrial medicinal chemistry, leading to 16 clinical candidates and the launch of six monoclonal antibodies (mAbs) drugs. Despite the unprecedented success achieved, the limitations of mAbs, including poor tissue and tumor penetration, long half-life time, poor oral bioavailability, and expensive production costs, impelled researchers to turn their attention to the development of peptide-based and non-peptide small-molecule inhibitors as potential alternatives or supplements to mAbs. However, no small-molecule inhibitors have been approved so far, indicating a challenging process of developing marketable small-molecule PD-1/PD-L1 targeted therapeutics. This review will summarize and provide insight into recent advances in the PD-1/PD-L1 pathway, including its structural basis and biology, along with the crystal structures with mAbs, peptides and small molecules. We place great emphasis on design strategies underlying reported small-molecule inhibitors and attempt to provide an outlook at the future of small-molecule PD-1/PD-L1inhibitors.
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•Applications of PD-1/PD-L1 inhibitors in immunotherapy drug discovery.•Summary of peptide-based and non-peptide small-molecule PD-1/PD-L1 inhibitors.•Insight into recent advances in the crystal structure studies of PD-1/PD-L1 inhibitors.•Outlook at the future of small-molecule PD-1/PD-L1inhibitors.
The existing literature on the self-identity of multiethnic people focuses on Western countries where mixed identities have been normalised in census-taking. It remains unknown how multiethnic people ...identify themselves in countries where ethnic classification is exclusive and rigid and ethnicity is a mainly ascriptive legal category. Based on in-depth interviews with twenty Hui-Han biethnic college students in China, this article shows how official ethnic classification and affirmative action shape these people's self-identification. Most respondents identify themselves as Hui regardless of their cultural practices, as their parents registered their official ethnicity as Hui and they have internalised this identity. The multiethnic background is more frustrating for students at China's special 'universities for ethnicities' because ethnicity is a salient topic on campus and they experience more expectations to behave like Hui. Many respondents have an essentialist understanding of ethnicity and express unsupportive attitudes towards institutionalising mixed identities.
Potassium ion batteries (KIBs) have emerged as a promising energy storage system, but the stability and high rate capability of their electrode materials, particularly carbon as the most investigated ...anode ones, become a primary challenge. Here, it is identified that pitch‐derived soft carbon, a nongraphitic carbonaceous species which is paid less attention in the battery field, holds special advantage in KIB anodes. The structural flexibility of soft carbon makes it convenient to tune its crystallization degree, thereby modulating the storage behavior of large‐sized K+ in the turbostratic carbon lattices to satisfy the need in structural resilience, low‐voltage feature, and high transportation kinetics. It is confirmed that a simple thermal control can produce structurally optimized soft carbon that has much better battery performance than its widely reported carbon counterparts such as graphite and hard carbon. The findings highlight the potential of soft carbon as an interesting category suitable for high‐performance KIB electrode and provide insights for understanding the complicated K+ storage mechanisms in KIBs.
The cycling stability of anode materials in potassium‐ion batteries (KIBs) is challenged by the large size of K+ itself. The findings not only demonstrate the promising potential of soft carbon as a category suitable for high‐performance KIB electrodes, but also provide insights into the complicated K+ storage mechanisms in carbon anodes of KIBs.
Myocardial infarction (MI) is a severe disease with increased mortality and disability rates, posing heavy economic burden for society. Exosomes were uncovered to mediate intercellular communication ...after MI. This study aims to explore the effect and mechanism of lncRNA KLF3-AS1 in exosomes secreted by human mesenchymal stem cells (hMSCs) on pyroptosis of cardiomyocytes and MI.
Exosomes from hMSCs were isolated and identified. Exosomes from hMSCs with transfection of KLF3-AS1 for overexpression were injected into MI rat model or incubated with hypoxia cardiomyocytes. Effect of KLF3-AS1 on MI area, cell viability, apoptosis, and pyroptosis was determined. The relationship among miR-138-5p, KLF3-AS1, and Sirt1 was verified by dual-luciferase reporter assay. Normal cardiomyocytes were transfected with miR-138-5p inhibitor or sh-Sirt1 to clarify whether alteration of miR-138-5p or sh-Sirt1 can regulate the effect of KLF3-AS1 on cardiomyocytes.
Exosomes from hMSCs were successfully extracted. Transfection of KLF3-AS1 exosome in rats and incubation with KLF3-AS1 exosome in hypoxia cardiomyocytes both verified that overexpression of KLF3-AS1 in exosomes leads to reduced MI area, decreased cell apoptosis and pyroptosis, and attenuated MI progression. KLF3-AS1 can sponge miR-138-5p to regulate Sirt1 expression. miR-138-5p inhibitor transfection and KLF3-AS1 exosome incubation contribute to attenuated pyroptosis and MI both in vivo and in vitro, while transfection of sh-Sirt1 could reverse the protective effect of exosomal KLF3-AS1 on hypoxia cardiomyocytes.
LncRNA KLF3-AS1 in exosomes secreted from hMSCs by acting as a ceRNA to sponge miR-138-5p can regulate Sirt1 so as to inhibit cell pyroptosis and attenuate MI progression.
Insight into the three-dimensional architecture of RNA is essential for understanding its cellular functions. However, even the classic transfer RNA structure contains features that are overlooked by ...existing bioinformatics tools. Here we present DSSR (Dissecting the Spatial Structure of RNA), an integrated and automated tool for analyzing and annotating RNA tertiary structures. The software identifies canonical and noncanonical base pairs, including those with modified nucleotides, in any tautomeric or protonation state. DSSR detects higher-order coplanar base associations, termed multiplets. It finds arrays of stacked pairs, classifies them by base-pair identity and backbone connectivity, and distinguishes a stem of covalently connected canonical pairs from a helix of stacked pairs of arbitrary type/linkage. DSSR identifies coaxial stacking of multiple stems within a single helix and lists isolated canonical pairs that lie outside of a stem. The program characterizes 'closed' loops of various types (hairpin, bulge, internal, and junction loops) and pseudoknots of arbitrary complexity. Notably, DSSR employs isolated pairs and the ends of stems, whether pseudoknotted or not, to define junction loops. This new, inclusive definition provides a novel perspective on the spatial organization of RNA. Tests on all nucleic acid structures in the Protein Data Bank confirm the efficiency and robustness of the software, and applications to representative RNA molecules illustrate its unique features. DSSR and related materials are freely available at http://x3dna.org/.
Chinese medicine (CM) is usually prescribed as CM formula to treat disease. The lack of effective research approach makes it difficult to elucidate the molecular mechanisms of CM formula owing to its ...complicated chemical compounds. Network pharmacology is increasingly applied in CM formula research in recent years, which is identified suitable for the study of CM formula. In this review, we summarized the methodology of network pharmacology, including network construction, network analysis and network verification. The aim of constructing a network is to achieve the interaction between the bioactive compounds and targets and the interaction between various targets, and then find out and validate the key nodes via network analysis and network verification. Besides, we reviewed the application in CM formula research, mainly including targets discovery, bioactive compounds screening, toxicity evaluation, mechanism research and quality control research. Finally, we proposed prospective in the future and limitations of network pharmacology, expecting to provide new strategy and thinking on study for CM formula.
The co-doping of graphene with nitrogen and sulfur was investigated aiming at understanding their interactions with the presence of oxygen in graphene. The co-doped graphene (NS-G) was synthesized ...via a one-pot hydrothermal route using graphene oxide as starting material and L-cysteine, an amino acid containing both N and S, as the doping agent. The obtained NS-G with a three-dimensional hierarchical structure containing both macropores and mesopores exhibited excellent mechanical stabilities under both wet and dry conditions. As compared to N or S singly doped graphene, the co-doped sample contains significantly higher concentrations of N and S species especially pyrollic N groups. The co-doped sample considerably outperformed the singly doped samples when used as free-standing electrode in supercapacitors due to enhanced pseudocapacitance. The simultaneous incorporation of S and N species with the presence of oxygen significantly modified the surface chemistry of carbon leading to considerably higher doping levels, although directly bonding between N and S is neither likely nor detected. Hence, the synergetic effect between N and S occurred through carbon atoms in neighboring hexagonal rings in a graphene sheet.
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