CCL19, CCL21, CCL24, CCL25, CXCL8, CXCL10, and XCL2 induce M1 macrophage chemotaxis, whereas CCL7 induces chemotaxis of M1 and M2 macrophages.
The homing of proinflammatory (M1) and the ...“alternatively activated” anti‐inflammatory (M2) macrophages plays a different role in the process of inflammation. Chemokines are the major mediators of macrophage chemotaxis, but how they differentially regulate M1 and M2 macrophages remains largely unclear. In the present study, we attempted to screen chemokines that differentially induce chemotaxis of M1 and M2 macrophages and to explore the underlying mechanism. Among the 41 chemokines that specifically bind to 20 chemokine receptors, CCL19, CCL21, CCL24, CCL25, CXCL8, CXCL10, and XCL2 specifically induced M1 macrophage chemotaxis, whereas CCL7 induced chemotaxis of both M1 and M2 macrophages. Whereas the differential effects of these chemokines on M1/M2 macrophage chemotaxis could be attributable to the predominant expression of their cognate receptors on the macrophage subsets, CCR7, the receptor for CCL19/CCL21, appeared to be an exception. Immunoblot analysis indicated an equivalent level of CCR7 in the whole cell lysate of M1 and M2 macrophages, but CCL19 and CCL21 only induced M1 macrophage chemotaxis. Both immunoblot and confocal microscopy analyses demonstrated that CCR7 was predominantly expressed on the cell surface of M1 but in the cytosol of M2 macrophages before ligand stimulation. As a result, CCL19 or CCL21 induced activation of both MEK1‐ERK1/2 and PI3K‐AKT cascades in M1 but not in M2 macrophages. Intriguingly, CCL19/CCL21‐mediated M1 macrophage chemotaxis was blocked by specific inhibition of PI3K rather than MEK1. Together, these findings suggest that recruitment of M1 and M2 macrophages is fine tuned by different chemokines with the involvement of specific signaling pathways.
ABSTRACTMonocytes and macrophages are important components of the immune system, specialized in either removing pathogens as part of innate immunity or contributing to adaptive immunity through ...antigen presentation. Essential to such functions is classical activation (M1) and alternative activation (M2) of macrophages. M1 polarization of macrophages is characterized by production of pro-inflammatory cytokines, antimicrobial and tumoricidal activity, whereas M2 polarization of macrophages is linked to immunosuppression, tumorigenesis, wound repair, and elimination of parasites. MiRNAs are small non-coding RNAs with the ability to regulate gene expression and network of cellular processes. A number of studies have determined miRNA expression profiles in M1 and M2 polarized human and murine macrophages using microarray and RT-qPCR arrays techniques. More specifically, miR-9, miR-127, miR-155, and miR-125b have been shown to promote M1 polarization while miR-124, miR-223, miR-34a, let-7c, miR-132, miR-146a, and miR-125a-5p induce M2 polarization in macrophages by targeting various transcription factors and adaptor proteins. Further, M1 and M2 phenotypes play distinctive roles in cell growth and progression of inflammation-related diseases such as sepsis, obesity, cancer, and multiple sclerosis. Hence, miRNAs that modulate macrophage polarization may have therapeutic potential in the treatment of inflammation-related diseases. This review highlights recent findings in miRNA expression profiles in polarized macrophages from murine and human sources, and summarizes how these miRNAs regulate macrophage polarization. Last, therapeutic potential of miRNAs in inflammation-related diseases through modulation of macrophage polarization is also discussed.
The ultimate goal of phototherapy based on nanoparticles, such as photothermal therapy (PTT) which generates heat and photodynamic therapy (PDT) which not only generates reactive oxygen species (ROS) ...but also induces a variety of anti-tumor immunity, is to kill tumors. In addition, due to strong efficacy in clinical treatment with minimal invasion and negligible side effects, it has received extensive attention and research in recent years. In this paper, the generations of nanomaterials in PTT and PDT are described separately. In clinical application, according to the different combination pathway of nanoparticles, it can be used to treat different diseases such as tumors, melanoma, rheumatoid and so on. In this paper, the mechanism of pathological treatment is described in detail in terms of inducing apoptosis of cancer cells by ROS produced by PDT, immunogenic cell death to provoke the maturation of dendritic cells, which in turn activate production of CD4+ T cells, CD8+T cells and memory T cells, as well as inhibiting heat shock protein (HSPs), STAT3 signal pathway and so on.
The automated design of imaging systems involving no or minimal human effort has always been the expectation of scientists, researchers and optical engineers. In addition, it is challenging to choose ...an appropriate starting point for an optical system design. In this paper, we present a novel design framework based on a point-by-point design process that can automatically obtain high-performance freeform systems. This framework only requires a combination of planes as the input based on the configuration requirements or the prior knowledge of designers. This point-by-point design framework is different from the decades-long tradition of optimizing surface coefficients. Compared with the traditional design method, whereby the selection of the starting point and the optimization process are independent of each other and require extensive amount of human effort, there are no obvious differences between these two processes in our design framework, and the entire design process is mostly automated. This automated design process significantly reduces the amount of human effort required and does not rely on advanced design skills and experience. To demonstrate the feasibility of the proposed design framework, we successfully designed two high-performance systems as examples. This point-by-point design framework opens up new possibilities for automated optical design and can be used to develop automated optical design in the areas of remote sensing, telescopy, microscopy, spectroscopy, virtual reality and augmented reality.
Sepsis is the major cause of death in the intensive care unit (ICU). Numerous biomarkers have been studied to identify the cause and severity of sepsis but these factors cannot differentiate between ...infectious and non-infectious inflammatory response. MicroRNAs (miRNAs) are non-coding RNA transcripts that regulate the expression of genes by repressing translation or degrading mRNA. Importantly, miRNAs can be released outside cells and easily detectable in bodily fluids such as blood, sweat, urine and breast milk. Numerous studies have explored the idea of utilizing extracellular miRNAs as biomarkers for sepsis by profiling the dysregulation of miRNAs in blood samples of sepsis patients. So far, miR-223, miR-146a and miR-150 have been identified to have promising prognostic and diagnostic value to sepsis. In addition, various intracellular miRNAs have been implicated to play critical roles in regulating the TLR-NF-κB pathway, which is a well-known inflammatory signaling pathway involved in the process of sepsis. Here, we summarize the recent progress on the role of extracellular and intracellular miRNAs in sepsis. Specifically, we discuss the possible role of circulating miRNA biomarkers for the diagnosis of sepsis and how intracellular miRNAs regulate the inflammatory responses in sepsis.
•MicroRNAs silence genes by inhibiting translation or degrading mRNA.•Extracellular microRNAs are dysregulated in blood samples of sepsis patients.•Intracellular microRNAs regulate the TLR-NF-κB-mediated inflammatory response.
Despite incorporation of organic groups into silica‐based aerogels to enhance their mechanical flexibility, the wide temperature reliability of the modified silicone aerogel is inevitably degraded. ...Therefore, facile synthesis of soft silicone aerogels with wide‐temperature stability remains challenging. Herein, novel silicone aerogels containing a high content of Si are reported by using polydimethylvinylsiloxane (PDMVS), a hydrosilylation adduct with water‐repellent groups, as a “flexible chain segment” embedded within the aerogel network. The poly(2‐dimethoxymethylsilyl)ethylmethylvinylsiloxane (PDEMSEMVS) aerogel is fabricated through a cost‐effective ambient temperature/pressure drying process. The optimized aerogel exhibits exceptional performance, such as ultra‐low density (50 mg cm−3), wide‐temperature mechanical flexibility, and super‐hydrophobicity, in comparison to the previous polysiloxane aerogels. A significant reduction in the density of these aerogels is achieved while maintaining a high crosslinking density by synthesizing gel networks with well‐defined macromolecules through hydrolytic polycondensation crosslinking of PDEMSEMVS. Notably, the pore/nanoparticle size of aerogels can be fine‐tuned by optimizing the gel solvent type. The as‐prepared silicone aerogels demonstrate selective absorption, efficient oil–water separation, and excellent thermal insulation properties, showing promising applications in oil/water separation and thermal protection.
A soft polysiloxane aerogel is designed and successfully fabricated through the condensation process of polydimethylvinylsiloxane macromolecules. In addition to its ultra‐lightweight nature, this material possesses several advantageous properties, including exceptional mechanical stability when exposed to liquid nitrogen, effective thermal insulation, super‐hydrophobicity, and notable advancements in porous material development.
The heart is a very complex conglomeration of organized interactions between various different cell types that all aid in facilitating myocardial function through contractility, sufficient perfusion, ...and cell-to-cell reception. In order to make sure that all features of the heart work effectively, it is imperative to have a well-controlled communication system among the different types of cells. One of the most important ways that the heart regulates itself is by the use of extracellular vesicles, more specifically, exosomes. Exosomes are types of nano-vesicles, naturally released from living cells. They are believed to play a critical role in intercellular communication through the means of certain mechanisms including direct cell-to-cell contact, long-range signals as well as electrical and extracellular chemical molecules. Exosomes contain many unique features like surface proteins/receptors, lipids, mRNAs, microRNAs, transcription factors and other proteins. Recent studies indicate that the exosomal contents are highly regulated by various stress and disease conditions, in turn reflective of the parent cell status. At present, exosomes are well appreciated to be involved in the process of tumor and infection disease. However, the research on cardiac exosomes is just emerging. In this review, we summarize recent findings on the pathologic effects of exosomes on cardiac remodeling under stress and disease conditions, including cardiac hypertrophy, peripartum cardiomyopathy, diabetic cardiomyopathy and sepsis-induced cardiovascular dysfunction. In addition, the cardio-protective effects of stress-preconditioned exosomes and stem cell-derived exosomes are also summarized. Finally, we discuss how to epigenetically reprogram exosome contents in host cells which makes them beneficial for the heart.
•Secretion of exosomes from living cells occurs in normal physiological conditions.•Secretion of exosomes is increased in response to stress or pathological conditions.•Pathological exosomes may be harmful for cardiac remodeling through the transfer of exosomal contents.•Exosomes released from stem cells are protective in the heart.•Exosomes collected from ischemic-preconditioned cells/tissues are protective in the heart.
In this paper, the historical power load data from the National Electricity Market (Australia) is used to analyze the characteristics and regulations of electricity (the average value of every eight ...hours). Then, considering the inverse of Euclidean distance as the weight, this paper proposes a novel short-term load forecasting model based on the weighted k-nearest neighbor algorithm to receive higher satisfied accuracy. In addition, the forecasting errors are compared with the back-propagation neural network model and the autoregressive moving average model. The comparison results demonstrate that the proposed forecasting model could reflect variation trend and has good fitting ability in short-term load forecasting.
Images captured under low-light environments typically have poor visibility, affecting many advanced computer vision tasks. In recent years, there have been some low-light image enhancement models ...based on deep learning, but they have not been able to effectively mine the deep multiscale features in the image, resulting in poor generalization performance and instability of the model. The disadvantages are mainly reflected in the color distortion, color unsaturation and artifacts. Current methods unable to adjust the exposure effectively, resulting in uneven exposure or partial overexposure. To address these issues, we propose an end-to-end low-light image enhancement model, which is called multiscale low-light image enhancement network with illumination constraint (MLLEN-IC), to achieve preferable generalization ability and stable performance. On the one hand, we use the squeeze-and-excitation-Res2Net block (SE-Res2block) as a base unit to enhance the model's ability by extracting deep multiscale features. On the other hand, to make the model more adaptable in low-light image enhancement tasks, we calculate the illumination constraint by the low-light itself to prevent overexposure, uneven exposure, and unsaturated colors. Extensive experiments are conducted to demonstrate MLLEN-IC not only adjusts light levels, but also has a more natural visual effect, and avoids problems such as color distortion, artifacts, and uneven exposure. In particular, MLLEN-IC has pretty generalization and stability performance. The source code and supplementary are available at https://github.com/CCECfgd/MLLEN-IC .
ABSTRACTMacrophage, as an integral component of the immune system and the first responder to local damage, is on the front line of defense against infection. Over the past century, the prevailing ...view of macrophage origin states that all macrophage populations resided in tissues are terminally differentiated and replenished by monocytes from bone-marrow (BM) progenitors. Nonetheless, this theory has been reformed by ground-breaking discoveries from the past decades. It is now believed that tissue-resident macrophages (TRMs) are originated from the embryonic precursors and seeded in tissue prenatally. They can replenish via self-renewal throughout the lifespan. Indeed, recent studies have demonstrated that tissue-resident macrophages should not be classified by the over-simplified macrophage polarization (M1/M2) dogma during inflammation. Moreover, multiple lines of evidence have indicated that tissue-resident macrophages play critical roles in maintaining tissue homeostasis and facilitating tissue repair through controlling infection and resolving inflammation. In this review, we summarize the properties of resident macrophages in the lung, spleen and heart, and further highlight the impact of TRM populations on inflammation control and tissue repair. We also discuss the potential role of local proliferation in maintaining a physiologically stable TRM pool in response to acute inflammation.
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