Tumor-associated macrophages (TAMs) constitute a large population of glioblastoma and facilitate tumor growth and invasion of tumor cells, but the underlying mechanism remains undefined. In this ...study, we demonstrate that chemokine (C-C motif) ligand 8 (CCL8) is highly expressed by TAMs and contributes to pseudopodia formation by GBM cells. The presence of CCL8 in the glioma microenvironment promotes progression of tumor cells. Moreover, CCL8 induces invasion and stem-like traits of GBM cells, and CCR1 and CCR5 are the main receptors that mediate CCL8-induced biological behavior. Finally, CCL8 dramatically activates ERK1/2 phosphorylation in GBM cells, and blocking TAM-secreted CCL8 by neutralized antibody significantly decreases invasion of glioma cells. Taken together, our data reveal that CCL8 is a TAM-associated factor to mediate invasion and stemness of GBM, and targeting CCL8 may provide an insight strategy for GBM treatment.
Abstract
Deep‐red/near‐infrared (DR/NIR) organic light‐emitting diodes (OLEDs) are promising for applications such as night‐vision readable marking, bioimaging, and photodynamic therapy. To tune ...emission spectra into the DR/NIR region, red emitters generally require assistance from intermolecular interactions. But such interactions generally lead to sharp efficiency declines resulting from unwanted quenching events. To overcome this challenge, herein, an advanced method via strategically managing the intermolecular interactions of thermally activated delayed fluorescence (TADF) emitters is proposed. The proof‐of‐concept molecule called DCN‐SPTPA exhibits impressive resistance to quenching while delivering controllable aggregation behavior for redshifting the emission by installing an end‐spiro group. Consequently, two emitters demonstrate similar photophysical properties and device performance at very low doping levels; while
DCN‐SPTPA
‐based OLEDs demonstrate a 1.3–1.4‐fold enhancement of the external quantum efficiencies (EQEs) with respect to the control molecule at 5–20 wt.% doping ratios, affording DR/NIR emission at 656, 688, 696, and 716 nm with record‐breaking EQEs of 36.1%, 29.3%, 28.2%, and 24.0%, respectively. Moreover,
DCN‐SPTPA
‐based nondoped NIR device also retains a state‐of‐the‐art EQE of 2.61% peaked at 800 nm. This work first demonstrates instructive guidance for accurately manipulating the intermolecular interactions of red TADF emitters, which will spur future developments in high‐performance DR/NIR OLEDs.
Realizing efficient red/near‐infrared (NIR) electroluminescence (EL) by precisely modulating molecular aggregations of thermally activated delayed fluorescence (TADF) emitters is an attractive ...pathway, yet the molecular designs are elusive. Here, a new approach is proposed to manage molecular aggregation via a mild‐twist acceptor‐donor‐acceptor (A‐D‐A)‐type molecular design. A proof‐of‐concept TADF molecule, QCN‐PhSAC‐QCN, is developed that furnishes a fast radiative rate and obvious aggregation‐induced emission feature. Its emission bands can be facilely shifted from intrinsic yellow to the red/NIR region via fine‐tuning doping levels and molecular aggregates while maintaining elegant photoluminescence quantum yields benefiting from suppressed exciton annihilation processes. As a result, a QCN‐PhSAC‐QCN‐based organic light‐emitting diode (OLED) exhibits a record‐setting external quantum efficiency (EQE) of 39.1% at a doping ratio of 10 wt.%, peaking at 620 nm. Moreover, its nondoped NIR OLED affords a champion EQE of 14.3% at 711 nm and retains outstanding EQEs of 5.40% and 2.35% at current densities of 10 and 100 mA cm−2, respectively, which are the highest values among all NIR‐TADF OLEDs at similar density levels. This work validates the feasibility of such mild‐twist A‐D‐A‐type molecular design for precisely controlling molecular aggregation while maintaining high efficiency, thus providing a promising pathway for high‐performance red/NIR TADF OLEDs.
State‐of‐the‐art red/near‐infrared organic light‐emitting diodes are realized by modulating molecular aggregation based on an intrinsic yellow acceptor‐donor‐acceptor‐type molecule with mild twists. Its doped red device delivers a record‐setting external quantum efficiency (EQE) of 39.1% at 620 nm. Furthermore, its nondoped near‐infrared device also offers a topmost EQE of 14.3% at 711 nm and retains decent EQEs at high current densities.
Eriophyoid mites (Acari: Eriophyoidea) are among the smallest of terrestrial arthropods and the most species‐rich group of herbivorous mites with a high host specificity. However, knowledge of their ...species diversity has been impeded by the difficulty of their morphological differentiation. This study assembles a DNA barcode reference library that includes 1850 mitochondrial COI sequences which provides coverage for 45% of the 930 species of eriophyoid mites known from China, and for 37 North American species. Sequence analysis showed a clear barcode gap in nearly all species, reflecting the fact that intraspecific divergences averaged 0.97% versus a mean of 18.51% for interspecific divergences (minimum nearest‐neighbour distances) in taxa belonging to three families. Based on these results, we used DNA barcoding to explore the species diversity of eriophyoid mites as well as their host interactions. The 1850 sequences were assigned to 531 barcode index numbers (BINs). Analyses examining the correspondence between these BINs and species identifications based on morphology revealed that members of 45 species were assigned to two or more BINs, resulting in 1.16 times more BINs than morphospecies. Richness projections suggest that over 2345 BINs occurred at the sampled locations. Host plant analysis showed that 89% of these mites (BINs) attack only one or two congeneric host species, but the others have several hosts. Furthermore, host‐mite network analyses demonstrate that eriophyoid mites are high host‐specific, and modularity is high in plant‐mite networks. By creating a highly effective identification system for eriophyoid mites in the Barcode of Life Data Systems database (BOLD), DNA barcoding will advance our understanding of the diversity of eriophyoid mites and their host interactions.
Intense infiltration of tumour-associated macrophages (TAMs) facilitates malignant growth of glioblastoma (GBM), but the underlying mechanisms remain undefined. Herein, we report that TAMs secrete ...abundant pleiotrophin (PTN) to stimulate glioma stem cells (GSCs) through its receptor PTPRZ1 thus promoting GBM malignant growth through PTN-PTPRZ1 paracrine signalling. PTN expression correlates with infiltration of CD11b
/CD163
TAMs and poor prognosis of GBM patients. Co-implantation of M2-like macrophages (MLCs) promoted GSC-driven tumour growth, but silencing PTN expression in MLCs mitigated their pro-tumorigenic activity. The PTN receptor PTPRZ1 is preferentially expressed in GSCs and also predicts GBM poor prognosis. Disrupting PTPRZ1 abrogated GSC maintenance and tumorigenic potential. Moreover, blocking the PTN-PTPRZ1 signalling by shRNA or anti-PTPRZ1 antibody potently suppressed GBM tumour growth and prolonged animal survival. Our study uncovered a critical molecular crosstalk between TAMs and GSCs through the PTN-PTPRZ1 paracrine signalling to support GBM malignant growth, indicating that targeting this signalling axis may have therapeutic potential.
Chemotherapeutic resistance in triple-negative breast cancer (TNBC) has brought great challenges to the improvement of patient survival. The mechanisms of taxane chemoresistance in TNBC have not been ...well investigated. Our results illustrated C-C motif chemokine ligand 20 (CCL20) was significantly elevated during taxane-containing chemotherapy in breast cancer patients with nonpathologic complete response. Furthermore, CCL20 promoted the self-renewal and maintenance of breast cancer stem cells (BCSCs) or breast cancer stem-like cells through protein kinase Cζ (PKCζ) or p38 mitogen-activated protein kinase (MAPK)-mediated activation of p65 nuclear factor kappa B (NF-κB) pathway, significantly increasing the frequency and taxane resistance of BCSCs. Moreover, CCL20-promoted NF-κB activation increased ATP-binding cassette subfamily B member 1 (ABCB1)/multidrug resistance 1 (MDR1) expression, leading to the extracellular efflux of taxane. These results suggested that chemotherapy-induced CCL20 mediated chemoresistance via up-regulating ABCB1. In addition, NF-κB activation increased CCL20 expression, forming a positive feedback loop between NF-κB and CCL20 pathways, which provides sustained impetus for chemoresistance in breast cancer cells. Our results suggest that CCL20 can be a novel predictive marker for taxane response, and the blockade of CCL20 or its downstream pathway might reverse the taxane resistance in breast cancer patients.
Fibroblast growth factor 21 (FGF21), a known risk factor for atherosclerosis, is readily regulated by exercise, and it can inhibit NOD-like receptor protein 3 (NLRP3)-mediated pyroptosis. However, it ...is not clear whether aerobic exercise inhibits atherosclerosis via these pathways. Eight-week-old apolipoprotein E-deficient (ApoE.sup.-/-) mice on a high-fat diet were randomly divided into 1-h post-exercise (EX-1h), 24-h post-exercise (EX-24h), and sedentary (SED) groups. C57BL/6J wild-type mice fed normal chow served as controls (WT group). Mice in the EX-1h and EX-24h groups were subjected to treadmill exercise training for 12 weeks. Aerobic exercise reduced body weight; blood glucose, lipid, and inflammation levels; and aortic plaque area proportion. Aerobic exercise increased the sensitivity of FGF21 by upregulating the expression of the downstream receptor adiponectin (ApN); the serum FGF21 level after exercise increased initially, and then decreased. Aerobic exercise downregulated the expression of NLRP3 inflammasome-mediated pyroptosis-related markers in the aorta, and FGF21 may participate in the above process. Meanwhile, the liver may be the tissue source of serum FGF21 during aerobic exercise. In conclusion, aerobic exercise may inhibit atherogenesis by regulating FGF21 and NLRP3 inflammasome-mediated pyroptosis. Our study provides new information on the atherosclerosis-preventing mechanism of aerobic exercise.
Aims
The aim of this study was to investigate the tumor microenvironment immune types (TMIT) based on tumor cell programmed cell death ligand 1 (PD‐L1) expression and tumor‐infiltrating lymphocytes ...(TILs) distribution and whether distinct TMIT subtypes (TMIT I, PD‐L1high/TILhigh; TMIT II, PD‐L1low/TILlow; TMIT III, PD‐L1high/TILlow; and TMIT IV, PD‐L1low/TILhigh) differentially affect clinical outcomes of patients with lung adenocarcinoma (LAC) and squamous cell carcinoma (SCC).
Methods and results
Immunohistochemistry (IHC) was applied to evaluate the expression of PD‐L1 and the spatial distribution of programmed cell death 1 (PD‐1) and CD8 TILs on the surgically resected specimens from 205 cases of LAC and 149 cases of SCC. PD‐1 and CD8 TILs were more frequently distributed in SCC than those in LAC, regardless of their infiltrating in the tumor islets or stroma. The density of TILs was a poor prognostic factor in LAC but a favorable one in SCC. PD‐L1 levels and its clinical prognostic significance differed in LAC vs SCC. LAC patients with TMIT III and SCC patients with TMIT I had the longest survival, respectively (P = .0197 and .0049). Moreover, TMIT stratification based on tumor cell PD‐L1 expression and stromal CD8+ TILs could be considered as an independent prognostic factor of SCC patients' survival as determined by both univariate and multivariate analysis.
Conclusion
Our study indicates that different type of TMIT provides its specific microenvironment with diverse impact on survival of LAC and SCC patients and highlights the importance of the integrative assessment of PD‐L1 status and TILs' spatial distribution to predict patients' prognosis.
Our study indicates that different type of TMIT provides its specific microenvironment with diverse impact on survival of lung adenocarcinoma and squamous cell carcinoma patients and highlights the importance of the integrative assessment of programmed cell death ligand 1 status and tumor‐infiltrating lymphocytes' spatial distribution to predict patients' prognosis.
Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus ...(AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHN
) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHN
neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHN
neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHN
neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.
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