Immunotherapies like the adoptive transfer of gene-engineered T cells and immune checkpoint inhibitors are novel therapeutic modalities for advanced cancers. However, some patients are refractory or ...resistant to these therapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. Immunosuppressive cells such as myeloid-derived suppressive cells, tumor-associated macrophages, tumor-associated neutrophils, regulatory T cells (Tregs), and tumor-associated dendritic cells are critical factors correlated with immune resistance. In addition, cytokines and factors secreted by tumor cells or these immunosuppressive cells also mediate the tumor progression and immune escape of cancers. Thus, targeting these immunosuppressive cells and the related signals is the promising therapy to improve the efficacy of immunotherapies and reverse the immune resistance. However, even with certain success in preclinical studies or in some specific types of cancer, large perspectives are unknown for these immunosuppressive cells, and the related therapies have undesirable outcomes for clinical patients. In this review, we comprehensively summarized the phenotype, function, and potential therapeutic targets of these immunosuppressive cells in the tumor microenvironment.
tRNA-derived small RNA (tsRNA) is a novel regulatory small non-coding RNA and participates in diverse physiological and pathological processes. However, the presence of tsRNAs in exosome and their ...diagnostic potential remain unclear. In this study, we took advantage of small RNA-seq technology to profile exosomal tsRNAs from cell culture medium and plasma, and found ubiquitous presence of tsRNAs in exosome. To explore the potential value of tsRNA for cancer diagnosis, we compared exosomal tsRNA levels between liver cancer patients and healthy donors, revealing that tsRNAs were dramatically increased in plasma exosomes of liver cancer patients. Importantly, patients with liver cancer exhibited significantly higher levels of four tsRNAs (tRNA-ValTAC-3, tRNA-GlyTCC-5, tRNA-ValAAC-5 and tRNA-GluCTC-5) in plasma exosome, demonstrating that plasma exosomal tsRNA could serve as a novel diagnostic biomarker. Taken together, our results not only expand non-coding RNA species in exosome, but also highlight the potential of tsRNAs as a promising biomarker for cancer diagnosis.
The chemokine receptor CXCR2 and its ligands are implicated in the progression of tumours and various inflammatory diseases. Activation of the CXCLs/CXCR2 axis activates multiple signalling pathways, ...including the PI3K, p38/ERK, and JAK pathways, and regulates cell survival and migration. The CXCLs/CXCR2 axis plays a vital role in the tumour microenvironment and in recruiting neutrophils to inflammatory sites. Extensive infiltration of neutrophils during chronic inflammation is one of the most important pathogenic factors in various inflammatory diseases. Chronic inflammation is considered to be closely correlated with initiation of cancer. In addition, immunosuppressive effects of myeloid-derived suppressor cells (MDSCs) against T cells attenuate the anti-tumour effects of T cells and promote tumour invasion and metastasis. Over the last several decades, many therapeutic strategies targeting CXCR2 have shown promising results and entered clinical trials. In this review, we focus on the features and functions of the CXCLs/CXCR2 axis and highlight its role in cancer and inflammatory diseases. We also discuss its potential use in targeted therapies.
Gold nanoparticles,owing to their unique physicochemical and optical properties,well-established synthetic methods and easy modifications,have been widely used in biomedical science.Therefore,for ...their safe and efficient applications,much attention has been given to the toxicological evaluations of gold nanoparticles in biological systems.A large number of studies focusing on this problem have been carried out during the past years.However,the researches on gold nanoparticles toxicity still remain fragmentary and even contradictory with each other.This may be caused by the variety in experimental conditions.In this review,we aim to provide a better understanding about the in vitro and in vivo toxicity of gold nanoparticles by reviewing and describing the up to date literatures related to this problem and we mainly focused on these properties such as the particle size and shape,the surface charge and modification.Besides,we also summarized the adverse effect of gold nanoparticles on immune systems and analyzed the origin of the toxicity.
The blood-spinal cord barrier (BSCB), a physical barrier between the blood and spinal cord parenchyma, prevents the toxins, blood cells, and pathogens from entering the spinal cord and maintains a ...tightly controlled chemical balance in the spinal environment, which is necessary for proper neural function. A BSCB disruption, however, plays an important role in primary and secondary injury processes related to spinal cord injury (SCI). After SCI, the structure of the BSCB is broken down, which leads directly to leakage of blood components. At the same time, the permeability of the BSCB is also increased. Repairing the disruption of the BSCB could alleviate the SCI pathology. We review the morphology and pathology of the BSCB and progression of therapeutic methods targeting BSCB in SCI.
There is increasing evidence that acute aerobic exercise is associated with improved cognitive function. However, neural correlates of its cognitive plasticity remain largely unknown. The present ...study examined the effect of a session of acute aerobic exercise on working memory task-evoked brain activity as well as task performance. A within-subjects design with a counterbalanced order was employed. Fifteen young female participants (M = 19.56, SD = 0.81) were scanned using functional magnetic resonance imaging while performing a working memory task, the N-back task, both following an acute exercise session with 20 minutes of moderate intensity and a control rest session. Although an acute session of exercise did not improve behavioral performance, we observed that it had a significant impact on brain activity during the 2-back condition of the N-back task. Specifically, acute exercise induced increased brain activation in the right middle prefrontal gyrus, the right lingual gyrus, and the left fusiform gyrus as well as deactivations in the anterior cingulate cortexes, the left inferior frontal gyrus, and the right paracentral lobule. Despite the lack of an effect on behavioral measures, significant changes after acute exercise with activation of the prefrontal and occipital cortexes and deactivation of the anterior cingulate cortexes and left frontal hemisphere reflect the improvement of executive control processes, indicating that acute exercise could benefit working memory at a macro-neural level. In addition to its effects on reversing recent obesity and disease trends, our results provide substantial evidence highlighting the importance of promoting physical activity across the lifespan to prevent or reverse cognitive and neural decline.
Abstract
Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of ...osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre‐metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr‐1
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myeloid cells are characterized to form a pre‐metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage‐associated molecular patterns released from surgical resection contribute to the formation of pre‐metastatic niche in lung through IL‐1β secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre‐metastatic niche in lung which is with important implications for developing rational therapies during peri‐operative period.
The notion of metal‐free catalysts is used to refer to carbon materials modified with nonmetallic elements. However, some claimed metal‐free catalysts are prepared using metal‐containing precursors. ...It is highly contested that metal residues in nitrogen‐doped carbon (NC) catalysts play a crucial role in the oxygen reduction reaction (ORR). In an attempt to reconcile divergent views, a definition for truly metal‐free catalysts is proposed and the differences between NC and M‐Nx/C catalysts are discussed. Metal impurities at levels usually undetectable by techniques such as XPS, XRD, and EDX significantly promote the ORR. Poisoning tests to mask the metal ions reveal the involvement of metal residues as active sites or as modifiers of the electronic structure of the active sites in NC. The unique merits of both M‐Nx/C and NC catalysts are discussed to inspire the development of more advanced nonprecious‐metal catalysts for the ORR.
A free agent: Nitrogen‐modified carbon (NC) materials (see scheme) are of emerging importance for electrocatalysis of the oxygen reduction reaction (ORR). However, trace‐metal residues in NC catalysts can significantly influence the ORR, which has raised concerns regarding the validity of the notion of a metal‐free catalyst. A critical discussion of the role of metals in NC catalysts is given to reconcile divergent views.
Replacing the rare and precious platinum (Pt) electrocatalysts with earth‐abundant materials for promoting the oxygen reduction reaction (ORR) at the cathode of fuel cells is of great interest in ...developing high‐performance sustainable energy devices. However, the challenging issues associated with non‐Pt materials are still their low intrinsic catalytic activity, limited active sites, and the poor mass transport properties. Recent advances in material sciences and nanotechnology enable rational design of new earth‐abundant materials with optimized composition and fine nanostructure, providing new opportunities for enhancing ORR performance at the molecular level. This Review highlights recent breakthroughs in engineering nanocatalysts based on the earth‐abundant materials for boosting ORR.
Pt free: Great efforts have been devoted to designing and optimizing earth‐abundant nanomaterials for use as catalysts for the oxygen reduction reaction (ORR). These new catalysts have improved intrinsic catalytic activity, stability, and selectivity as well as performances nearing that of the classical platinum‐based catalysts. This Review highlights the recent breakthroughs in engineering non‐Pt nanomaterials with advanced structures for enhanced ORR catalysis.
Quantum key distribution (QKD) uses individual light quanta in quantum superposition states to guarantee unconditional communication security between distant parties. However, the distance over which ...QKD is achievable has been limited to a few hundred kilometres, owing to the channel loss that occurs when using optical fibres or terrestrial free space that exponentially reduces the photon transmission rate. Satellite-based QKD has the potential to help to establish a global-scale quantum network, owing to the negligible photon loss and decoherence experienced in empty space. Here we report the development and launch of a low-Earth-orbit satellite for implementing decoy-state QKD-a form of QKD that uses weak coherent pulses at high channel loss and is secure because photon-number-splitting eavesdropping can be detected. We achieve a kilohertz key rate from the satellite to the ground over a distance of up to 1,200 kilometres. This key rate is around 20 orders of magnitudes greater than that expected using an optical fibre of the same length. The establishment of a reliable and efficient space-to-ground link for quantum-state transmission paves the way to global-scale quantum networks.
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