Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating the tumor malignant biological properties within tumor microenvironment and evidences demonstrate that CAFs are a critical ...regulator of tumoral immunosuppression of the T cell response. However, the functions and regulation of CAFs in the expression of programmed death‐ligand 1 (PD‐L1) in melanoma and colorectal carcinoma (CRC) are not completely understood. Herein, by scrutinizing the expression of α‐SMA and PD‐L1 in melanoma and CRC tissues, we found that CAFs was positive correlated with PD‐L1 expression. Further analyses showed that CAFs promoted PD‐L1 expression in mice tumor cells. By detecting a majority of cytokines expression in normal mice fibroblasts and CAFs, we determined that CXCL5 was abnormal high expression in CAFs and the immunohistochemistry and in situ hybridization confirmed that were CAFs which were expressing CXCL5. In addition, CXCL5 promoted PD‐L1 expression in B16, CT26, A375 and HCT116. The silencing of CXCR2, the receptor of CXCL5, inhibited the PD‐L1 expression induced by CAFs in turn. Functionally, CXCL5 derived by CAFs promoted PD‐L1 expression in mice tumor cells through activating PI3K/AKT signaling. LY294002, the inhibitor of PI3K, confirmed that CXCL5 forested an immunosuppression microenvironment by promoting PD‐L1 expression via PI3K/AKT signaling. Meanwhile, the B16/CT26 xenograft tumor models were used and both CXCR2 and p‐AKT were found to be positively correlated with PD‐L1 in the xenograft tumor tissues. The immunosuppressive action of CAFs on tumor cells is probably reflective of them being a potential therapeutic biomarker for melanoma and CRC.
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Cancer‐associated fibroblasts (CAFs) play a key role in orchestrating tumor malignant properties within the tumor microenvironment. However, the role of CAFs in tumor PD‐L1 expression and immune evasion in melanoma and colorectal carcinoma (CRC) is not completely understood. Here, the authors observe a positive correlation between CAFs and PD‐L1 expression in patients. CAFs promote PD‐L1 expression in tumor cells by secreting CXCL5 and in turn activating the PI3K/AKT signaling pathway. The findings reveal a complex tumor‐promoting microenvironment shaped by the CXCL5‐CXCR2 axis and highlight CAFs as a promising target to curb immune evasion.
The catalytic effects of ammonium dihydrogen phosphate (ADP) on the biomass pyrolysis and its mechanism for the selective production of furfural (FF) and levoglucosenone (LGO) were investigated in ...this study. Samples were prepared with rice husk and ADP solutions with gradient-concentration and pyrolyzed via TG-FTIR and Py-GC/MS. Results showed that ADP made the decomposition of cellulose occur at a lower temperature and greatly enhanced the release of CO groups and carbohydrates below 300 °C, indicating the breakage of glycosidic bond and dehydration reaction during pyrolysis were promoted by ADP. In the pyrolysis volatiles, the production of anhydrosugars and furans was promoted significantly. Due to the rearrangement of the methoxy group, the production of methoxy phenols and CH4 was decreased simultaneously. ADP showed good selectivity for both FF and LGO. With the increased ADP dose, the yield and relative content of FF and LGO increased firstly and then kept stable. 400 °C was found the optimal temperature for the production of FF and LGO, where the sum of the relative peak area of LGO and FF could reach 52.23%. Finally, a possible formation pathway of LGO and FF under the catalysis of ADP was speculated.
•ADP enhanced the release of CO groups and carbohydrates below 300 °C.•ADP inhibited the production of methoxy phenols.•ADP showed good selectivity for both LGO and FF.•The mechanism of ADP for selective production of LGO and FF was speculated.
The full-field electroretinogram (ERG) is a mass electrophysiological response to diffuse flashes of light and is used widely to assess generalized retinal function. This document, from the ...International Society for Clinical Electrophysiology of Vision (ISCEV), presents an updated and revised ISCEV Standard for clinical ERG testing. Minimum protocols for basic ERG stimuli, recording methods and reporting are specified, to promote consistency of methods for diagnosis, monitoring and inter-laboratory comparisons, while also responding to evolving clinical practices and technology. The main changes in this updated ISCEV Standard for clinical ERGs include specifying that ERGs may meet the Standard without mydriasis, providing stimuli adequately compensate for non-dilated pupils. There is more detail about analysis of dark-adapted oscillatory potentials (OPs) and the document format has been updated and supplementary content reduced. There is a more detailed review of the origins of the major ERG components. Several tests previously tabulated as additional ERG protocols are now cited as published ISCEV extended protocols. A non-standard abbreviated ERG protocol is described, for use when patient age, compliance or other circumstances preclude ISCEV Standard ERG testing.
Human brain organoids provide unique platforms for modeling development and diseases by recapitulating the architecture of the embryonic brain. However, current organoid methods are limited by ...interior hypoxia and cell death due to insufficient surface diffusion, preventing generation of architecture resembling late developmental stages. Here, we report the sliced neocortical organoid (SNO) system, which bypasses the diffusion limit to prevent cell death over long-term cultures. This method leads to sustained neurogenesis and formation of an expanded cortical plate that establishes distinct upper and deep cortical layers for neurons and astrocytes, resembling the third trimester embryonic human neocortex. Using the SNO system, we further identify a critical role of WNT/β-catenin signaling in regulating human cortical neuron subtype fate specification, which is disrupted by a psychiatric-disorder-associated genetic mutation in patient induced pluripotent stem cell (iPSC)-derived SNOs. These results demonstrate the utility of SNOs for investigating previously inaccessible human-specific, late-stage cortical development and disease-relevant mechanisms.
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•SNOs maintain growth and laminar expansion over long-term culture•SNOs exhibit separated upper and deep cortical layers•Layer-specific WNT/β-catenin signaling regulates neuronal fate specification•DISC1 mutation causes deficits in cortical neuron fate specification
Cortical organoids can be used to model human brain development and disorders. Ming and colleagues overcome the diffusion limit using a slicing method to prevent interior cell death and sustain organoid growth over long-term culture. The resulting organoids recapitulate late-stage human cortical developmental features, including formation of distinct cortical layers.
Transforming growth factor-β (TGF-β) belongs to a group of pleiotropic cytokines that are involved in a variety of biological processes, such as inflammation and immune reactions, cellular phenotype ...transition, extracellular matrix (ECM) deposition, and epithelial–mesenchymal transition. TGF-β is widely distributed throughout the body, including the nervous system. Following injury to the nervous system, TGF-β regulates the behavior of neurons and glial cells and thus mediates the regenerative process. In the current article, we reviewed the production, activation, as well as the signaling pathway of TGF-β. We also described altered expression patterns of TGF-β in the nervous system after nerve injury and the regulatory effects of TGF-β on nerve repair and regeneration in many aspects, including inflammation and immune response, phenotypic modulation of neural cells, neurite outgrowth, scar formation, and modulation of neurotrophic factors. The diverse biological actions of TGF-β suggest that it may become a potential therapeutic target for the treatment of nerve injury and regeneration.
Recently, State of energy (SOE) has become one of the most fundamental parameters for battery management systems in electric vehicles. However, current information is critical in SOE estimation and ...current sensor is usually utilized to obtain the latest current information. However, if the current sensor fails, the SOE estimation may be confronted with large error. Therefore, this paper attempts to make the following contributions: Current sensor fault detection and SOE estimation method is realized simultaneously. Through using the proportional integral observer (PIO) based method, the current sensor fault could be accurately estimated. By taking advantage of the accurate estimated current sensor fault, the influence caused by the current sensor fault can be eliminated and compensated. As a result, the results of the SOE estimation will be influenced little by the fault. In addition, the simulation and experimental workbench is established to verify the proposed method. The results indicate that the current sensor fault can be estimated accurately. Simultaneously, the SOE can also be estimated accurately and the estimation error is influenced little by the fault. The maximum SOE estimation error is less than 2%, even though the large current error caused by the current sensor fault still exists.
Adding proper content of Na+ and/or Li+ as well as altering the Si/Al ratio during the synthesis can be used to adjust the Al siting or the distribution of acid sites in ZSM-11 zeolite framework and ...hence regulate its catalytic performance in MTO.
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•Al siting or acid sites distribution in ZSM-11 can be adjusted by adding alkali ions.•Adding Na+ or Li+ in synthesis gel can elevate Al fraction in the intersection cavity.•Increasing Si/Al ratio in alkali free system can relatively enrich Al in the strait channel.•Catalytic performance of ZSM-11 in MTO is related to the Al siting in zeolite lattices.•Acid sites in the intersection cavity (strait channel) benefit the aromatic (alkene) cycle.
The catalytic performance of acid zeolite in the conversion of methanol to olefins (MTO) is closely related to the location of aluminum (Al) in the lattice sites; however, it is still a great challenge to finely tune the siting of framework Al and thereon purposefully regulate the performance of zeolite catalyst. In this work, adding proper alkali metal ions in the synthesis gel was used to alter the Al siting in ZSM-11 zeolite and the effect of Al siting on the catalytic performance of ZSM-11 in MTO was then investigated. The results indicate that the addition of Na+ and/or Li+ in the synthesis gel can elevate the fraction of Al sited in the intersection cavity of ZSM-11, whereas in the alkali metal ions free synthesis system, an increase in the Si/Al ratio leads to a more prominent decrease of Al sited in the intersection cavity and a relative enrichment of Al distributed in the straight channel. The variation of Al siting has a significant influence on the catalytic performance of ZSM-11 in MTO, which can be well explained by the dual-cycle hydrocarbons pool (HCP) mechanism. More Al atoms located in the straight channel can enhance the alkene-based cycle that produces more propene and butene; in contrast, an increase in the fraction of Al in the intersection cavity can then promote the aromatic-based cycle and facilitate the formation of ethene and aromatics. This work provides an efficient method to finely tune the siting of Al in ZSM-11 zeolite lattices and controllably regulate its catalytic performance in MTO; moreover, the insight shown in this work is also helpful for a better understanding on the relationship between the Al siting/acid sites distribution and the performance of a zeolite catalyst.
This study investigated the exosomal circular RNAs (CircRNAs) produced by tumor-associated macrophages and delivered into the microenvironment of cholangiocarcinoma cells in order to use them as ...molecular targets for clinical therapy. Tumor-associated M2 macrophages (TAMs) were induced from THP-1 cells and identified by flow cytometry. The TAM-secreted exosomes were isolated from conditioned medium and a CircRNA microarray assay was performed to identify CircRNAs that were uniquely expressed in the isolated exosomes. Circ_0020256 was especially identified based on having the highest differential expression level among all of the CircRNA candidates. In vitro and in vivo experiments were performed to assess the effects of TAMs, exosomes, and Circ_0020256 on the growth and migration of cholangiocarcinoma (CCA) cells. The induced TAMs promoted the proliferation, migration, and invasion of CCA cells and those effects were mediated by exosomes secreted by the TAMs. In CCA cells (RBE and HCCC-9810), Circ_0020256 significantly promoted cellular activity by interacting with its intra-cellular microRNA target, miR-432-5p. In contrast, overexpression of transcription factor E2F3 in CCA cells restored the CCA cellular activities that were inhibited by miR-432-5p. On the other hand, treatment with small interference RNA (siRNA) for Circ_0020256 inhibited CCA cell proliferation, migration, and invasion both in vitro and in vivo. In conclusion, Circ_0020256 in TAM-secreted exosomes promoted the proliferation, migration, and invasion of CCA cells, and that promotional activity was regulated via a Circ_0020256/miR-432-5p/E2F3 axis.
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