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.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Spinal cord injury (SCI) favors a persistent pro-inflammatory macrophages/microglia-mediated response with only a transient appearance of anti-inflammatory phenotype of immune ...cells. However, the mechanisms controlling this special sterile inflammation after SCI are still not fully elucidated. It is known that damage-associated molecular patterns (DAMPs) released from necrotic cells after injury can trigger severe inflammation. High mobility group box 1(HMGB1), a ubiquitously expressed DNA binding protein, is an identified DAMP, and our previous study demonstrated that reactive astrocytes could undergo necroptosis and release HMGB1 after SCI in mice. The present study aimed to explore the effects and the possible mechanism of HMGB1on macrophages/microglia polarization, as well as the neuroprotective effects by HMGB1 inhibition after SCI.
Methods
In this study, the expression and the concentration of HMGB1 was determined by qRT-PCR, ELISA, and immunohistochemistry. Glycyrrhizin was applied to inhibit HMGB1, while FPS-ZM1 to suppress receptor for advanced glycation end products (RAGE). The polarization of macrophages/microglia in vitro and in vivo was detected by qRT-PCR, immunostaining, and western blot. The lesion area was detected by GFAP staining, while neuronal survival was examined by Nissl staining. Luxol fast blue (LFB) staining, DAB staining, and western blot were adopted to evaluate the myelin loss. Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay was applied to evaluate locomotor functional recovery.
Results
Our data showed that HMGB1 can be elevated and released from necroptotic astrocytes and HMGB1 could induce pro-inflammatory microglia through the RAGE-nuclear factor-kappa B (NF-κB) pathway. We further demonstrated that inhibiting HMGB1 or RAGE effectively decreased the numbers of detrimental pro-inflammatory macrophages/microglia while increased anti-inflammatory cells after SCI. Furthermore, our data showed that inhibiting HMGB1 or RAGE significantly decreased neuronal loss and demyelination, and improved functional recovery after SCI.
Conclusions
The data implicated that HMGB1-RAGE axis contributed to the dominant pro-inflammatory macrophages/microglia-mediated pro-inflammatory response, and inhibiting this pathway afforded neuroprotection for SCI. Thus, therapies designed to modulate immune microenvironment based on this cascade might be a prospective treatment for SCI.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Monofluorinated alkyl compounds are of great importance in pharmaceuticals, agrochemicals and materials. Herein, we describe a direct nickel‐catalyzed monofluoromethylation of unactivated alkyl ...halides using a low‐cost industrial raw material, bromofluoromethane, by demonstrating a general and efficient reductive cross‐coupling of two alkyl halides. Results with 1‐bromo‐1‐fluoroalkane also demonstrate the viability of monofluoroalkylation, which further established the first example of reductive C(sp3)‐C(sp3) cross‐coupling fluoroalkylation. These transformations demonstrate high efficiency, mild conditions, and excellent functional‐group compatibility, especially for a range of pharmaceuticals and biologically active compounds. Mechanistic studies support a radical pathway. Kinetic studies reveal that the reaction is first‐order dependent on catalyst and alkyl bromide whereas the generation of monofluoroalkyl radical is not involved in the rate‐determining step. This strategy provides a general and efficient method for the synthesis of aliphatic fluorides.
A direct nickel‐catalyzed monofluoroalkylation of unactivated alkyl halides has been established, by demonstrating the first example of reductive C(sp3)−C(sp3) cross‐coupling fluoroalkylation. These transformations exhibited high efficiency, mild conditions, and excellent functional‐group compatibility, especially for a range of pharmaceuticals and biologically active compounds.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Objectives
This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its ...prognostic value.
Methods
For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients.
Results
The radiomics signature comprised eight LN-status–related features and showed significant association with LN metastasis in both cohorts (
p
< 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both
p
< 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival.
Conclusions
Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making.
Key Points
• The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup.
• Prognosis of high-risk patients remains dismal after curative-intent resection.
• The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery.
Low-density compressible materials enable various applications but are often hindered by structure-derived fatigue failure, weak elasticity with slow recovery speed and large energy dissipation. Here ...we demonstrate a carbon material with microstructure-derived super-elasticity and high fatigue resistance achieved by designing a hierarchical lamellar architecture composed of thousands of microscale arches that serve as elastic units. The obtained monolithic carbon material can rebound a steel ball in spring-like fashion with fast recovery speed (∼580 mm s
), and demonstrates complete recovery and small energy dissipation (∼0.2) in each compress-release cycle, even under 90% strain. Particularly, the material can maintain structural integrity after more than 10
cycles at 20% strain and 2.5 × 10
cycles at 50% strain. This structural material, although constructed using an intrinsically brittle carbon constituent, is simultaneously super-elastic, highly compressible and fatigue resistant to a degree even greater than that of previously reported compressible foams mainly made from more robust constituents.
Monofluoroalkanes are important in many pharmaceuticals, agrochemicals and functional materials. However, the lack of easily available and transformable monofluoroalkylating reagents that facilitate ...a broad array of transformations has hampered the application of monofluoroalkylation. Herein, we report a general and efficient method of preparing diverse aliphatic monofluorides with monofluoroalkyl triflate as the synthetic scaffold. Using both nickel‐catalyzed hydromonofluoroalkylation of unactivated alkenes and copper‐catalyzed C−C bond formation, the general diversification of the monofluoroalkylating scaffold has been exhibited. The broad utility of this monofluoroalkylating reagent is shown by concise conversion into various conventional fluoroalkylating reagents and construction of monofluoro‐alkoxy, ‐alkylamino motifs with commercially available heteroatom‐based coupling partners.
A general method allows preparation of diverse monofluorides based on the monofluoroalkyl triflate scaffold. Both nickel‐catalyzed hydromonofluoroalkylation of unactivated alkenes and copper‐catalyzed monofluoroalkylation of Grignard reagents were studied. Further utilities including conversion into conventional fluoroalkylating reagents and construction of monofluoro‐alkoxy, ‐alkylamino motifs.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Inflammation is implicated in epileptogenesis. Activated microglia and macrophages (MG/MΦ) are found in the brains of patients with epilepsy-related diseases and animal models of epilepsy. It is not ...yet known how the MG/MΦ activation phenotype affects pathological changes in the brain after a single seizure. In this study, we had 2 main purposes: first, to characterize post-status epilepticus (SE) inflammation by tracking MG/MΦ polarization, and, second, to explore the role of an innate immune receptor adaptor protein, namely, myeloid differentiation primary response gene 88 (MyD88), in the induction of SE in a mouse model. A lithium–pilocarpine model of seizure conditions was generated in C57BL/6 mice. The intensity and distribution of MG/MΦ polarization were tracked by fluorescent immunohistochemistry and Western blotting for the polarization markers inducible nitrogen oxygenized synthase, arginase-1, CD163, and mannose receptor. We observed steadily increasing M1 MG/MΦ along with MyD88 signal upregulation after SE in the hippocampi of mice, whereas the M2 marker arginase-1 was localized mainly in astrocytes rather than in MG/MΦ. Inhibition or gene knockout of MyD88 reduced M1 MG/MΦ and gliosis although increasing M2 MG/MΦ in the hippocampi of SE mice. MyD88 inhibition also augmented glutamate transporter 1 expression and reduced N-methyl-D-aspartate receptor NR1 subunit expression in the hippocampus to protect pyramidal neurons from apoptosis. These data suggest that MG/MΦ polarization after SE impacts the pathological outcome of the hippocampus via MyD88 signaling and point to MyD88 as a potential neuroprotective target for epilepsy therapy.
A nickel‐catalyzed direct trifluoroethylation of aryl iodides with an industrial raw material CF3CH2I has been developed, demonstrating high efficiency, excellent functional‐group compatibility, ...especially with large sterically hindered groups. The key to success is the combination of nickel with readily available nitrogen and phosphine ligands. The powerful potential of this strategy is further demonstrated by the late‐stage modification of several derived bioactive molecules.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
A novel method by a one-step introduction of axial chirality and sterically hindered group has been developed for facile synthesis of axially chiral styrene-type carboxylic acids. With the ...palladium-catalyzed C–H arylation and olefination of readily available cinnamic acid established, this transformation demonstrated excellent yield, excellent stereocontrol (up to 99% yield and 99% ee), and broad substrate scope under mild conditions. The axially chiral styrene-type carboxylic acids produced have been successfully applied to Cp*Co III -catalyzed asymmetric C–H activation reactions, indicating their potential as chiral ligands or catalysts in asymmetric synthesis.
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IJS, KILJ, NUK, UL, UM, UPUK
In this paper, the tracking performance of networked control systems (NCSs) under energy constraints with time-delay and encoding-decoding is studied. Through spectral factorization and partial ...decomposition techniques, we can obtain the explicit representation of the optimal performance. It is shown that the optimal performance is affected by non minimum phase (NMP) zeros, unstable poles and other multiple communication constraints such as time-delay, encoding-decoding and additive white Gaussian noise (AWGN). At the same time, the obtained result shows that a two-parameter compensator is superior to a one-parameter compensator. In addition, it is found that time-delay, encoding-decoding and AWGN affected the tracking capability of NCSs. Finally, an example is given for verifying the correctness of the conclusions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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