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.
Hybrid formation is a fundamental process in normal development and tissue homeostasis, while the presence and the biological role of hybrids between tumor-associated macrophages (TAMs) and ...glioblastoma (GBM) cells remain elusive. In this study, we observed that TAM-GBM cell hybrids existed in human GBM specimens as demonstrated by co-expression of glioma biomarkers (GFAP, IDH1R132H and PDGFRA) and macrophage biomarkers (CD68 and CD14). Furthermore, TAM-GBM cell hybrids could also be found in C57BL/6 mice orthotopically inoculated with mouse GBM cells labeled with RFP and after co-culture of bone marrow-derived macrophages from GFP-expressed mice with RFP-labeled GBM cells. The hybrids underwent nuclear reprogramming with unique gene expression profile as compared to parental cells. Moreover, glioma invasion-associated genes were enriched in the hybrids that possessed higher invasiveness, and more hybrids in the invasive margin of GBM were observed as compared to GBM core area. Our data demonstrate the presence of TAM-GBM cell hybrids that enhance GBM invasion. With a better understanding of TAM-GBM cell hybrids, new therapeutic strategies targeting GBM will be developed to treat GBM patients.
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•Hybrids formed by TAMs and tumor cells exist in GBM.•TAM-GBM cell hybrids bear nuclear reprogramming with unique gene expression profile.•TAM-GBM cell hybrids contribute to GBM invasion.
Gene targeting (GT) allows precise manipulation of genome sequences, such as knock-ins and sequence substitutions, but GT in seed plants remains a challenging task. Engineered sequence-specific ...nucleases (SSNs) are known to facilitate GT via homology-directed repair (HDR) in organisms. Here, we demonstrate that Cas12a and a temperature-tolerant Cas12a variant (ttCas12a) can efficiently establish precise and heritable GT at two loci in Arabidopsis thaliana (Arabidopsis) through a sequential transformation strategy. As a result, ttCas12a showed higher GT efficiency than unmodified Cas12a. In addition, the efficiency of transcriptional and translational enhancers for GT via sequential transformation strategy was also investigated. These enhancers and their combinations were expected to show an increase in GT efficiency in the sequential transformation strategy, similar to previous reports of all-in-one strategies, but only a maximum twofold increase was observed. These results indicate that the frequency of double strand breaks (DSBs) at the target site is one of the most important factors determining the efficiency of genetic GT in plants. On the other hand, a higher frequency of DSBs does not always lead to higher efficiency of GT, suggesting that some additional factors are required for GT via HDR. Therefore, the increase in DSB can no longer be expected to improve GT efficiency, and a new strategy needs to be established in the future. This research opens up a wide range of applications for precise and heritable GT technology in plants.
Abstract
Developing novel lanthanide metal-organic frameworks (Ln-MOFs) to rapidly and reliably differentiate both metal ions in solution and volatile organic compounds (VOCs) in vapor is highly ...challenging. Here, we describe versatile Eu
3+
/Tb
3+
-MOFs based on a flexible ligand. It is noteworthy that the film fabricated using bimetallic Eu
0.47
Tb
0.63
-MOF and polyvinyl alcohol could serve as an easy and convenient luminescent platform for distinguishing different metal ions and VOCs. The luminescent film exhibits notable fingerprint correlation between the metal ions/VOCs and the emission intensity ratio of Eu
3+
/Tb
3+
ions in Ln-MOFs. As a result, the bimetallic Ln-MOFs show fast recognition of Fe
3+
ion with a response time of <10 s, and can effectively probe styrene vapor within 4 min. Since the developed Ln-MOF film is stable and reliable, this work presents a promising strategy to explore luminescent platforms capable of effectively sensing different metal ions and VOCs.
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.
Conspectus Sustainable and environmentally benign catalytic processes are vital for the future to supply the world population with clean energy and industrial products. The replacement of ...conventional metal or metal oxide catalysts with earth abundant and renewable nonmetallic materials has attracted considerable research interests in the field of catalysis and material science. The stable and efficient catalytic performance of nanocarbon materials was discovered at the end of last century, and these materials are considered as potential alternatives for conventional metal-based catalysts. With its rapid development in the past 20 years, the research field of carbon catalysis has been experiencing a smooth transition from the discovery of novel nanocarbon materials or related new reaction systems to the atomistic-level mechanistic understanding on the catalytic process and the subsequent rational design of the practical catalytic reaction systems. In this Account, we summarize the recent progress in the kinetic and mechanistic studies on nanocarbon catalyzed alkane oxidative dehydrogenation (ODH) reactions. The paper attempts to extract general concepts and basic regularities for carbon catalytic process directing us on the way for rational design of novel efficient metal-free catalysts. The nature of the active sites for ODH reactions has been revealed through microcalorimetric analysis, ambient pressure X-ray photoelectron spectroscopy (XPS) measurement, and in situ chemical titration strategies. The detailed kinetic analysis and in situ catalyst structure characterization suggests that carbon catalyzed ODH reactions involve the redox cycles of the ketonic carbonyl–hydroxyl pairs, and the key physicochemical parameters (activation energy, reaction order, and rate/equilibrium constants, etc.) of the carbon catalytic systems are proposed and compared with conventional transition metal oxide catalysts. The proposal of the intrinsic catalytic activity (TOF) provides the possibility for the fair comparisons of different nanocarbon catalysts and the consequent structure–function relation regularity. Surface modification and heteroatom doping are proved as the most effective strategies to adjust the catalytic property (activity and product selectivity etc.) of the nanocarbon catalysts. Nanocarbon is actually a proper candidate platform helping us to understand the classical catalytic reaction mechanism better, since there is no lattice oxygen and all the catalytic process happens on nanocarbon surface. This Account also exhibits the importance of the in situ structural characterizations for heterogeneous nanocarbon catalysis. The research strategy and methods proposed for carbon catalysts may also shed light on other complicated catalytic systems or fields concerning the applications of nonmetallic materials, such as energy storage and environment protection etc.
We have revealed that molecular oxygen breaks into carbon nanotubes forming active sites to abstract hydrogen from propane. Various carbonaceous species (carbon defects and debris) on carbon ...nanotubes were identified and their effects on the oxo-functionalization as well as the catalytic performance in the oxidative dehydrogenation of propane were thoroughly investigated. The results indicate that certain amount of accessible skeleton defects is beneficial to the selective introduction of ether and ketonic carbonyl groups. However, amorphous carbons are poorly selective during oxo-functionalization and the related functionalities decompose easily during the long-term catalytic test. The proportion of ether and ketonic carbonyl groups obtained from oxygen functionalization reaches to 93%, which is twice more than that obtained from acidic solution treatment. Turnover frequency of 1.5 h−1 in the oxidative dehydrogenation of propane is successfully correlated with ketonic carbonyl groups (CO), while there is no obvious correlation between the activity and the amount of ether groups (C–O–C).
Exposure to greenness has been shown to be beneficial to health, but few studies have examined the association between residential greenness and prostate cancer (PCa) risk. Our main objectives were ...to identify the determinants of residential greenness, and to investigate if residential greenness was associated with PCa risk in Singapore.
The hospital-based case-control study was conducted between April 2007 and May 2009. The Singapore Prostate Cancer Study (SPCS) comprised 240 prostate cancer cases and 268 controls, whose demographics and residential address were collected using questionnaires. Residential greenness was measured by normalized difference vegetation index (NDVI) around the participants’ homes using a buffer size of 1 km. Determinants of NDVI were identified using a multivariable linear regression model. Logistic regression models were used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of associations between NDVI and PCa risk, adjusting for potential confounders.
Having a BMI within the second quartile, as compared to the lowest quartile, was associated with higher levels of NDVI (β-coefficient = 0.263; 95% CI = 0.040–0.485) after adjusting for covariates. Additionally, being widowed or separated, as compared to being married, was associated with lower levels of NDVI (β-coefficient = −0.393; 95% CI = −0.723, −0.063). An interquartile range (IQR) increase in NDVI was positively associated with prostate cancer risk OR = 1.45; 95% CI = 1.02–2.07). Stratified analysis by tumour grade and stage showed that higher NDVI was associated with higher risk of low grade PCa.
Our findings suggested that residential greenness was associated with higher risk of PCa in Singapore. Future studies on the quality and type of green spaces, as well as other factors of residential greenness, in association with PCa risk should be conducted to better understand this relationship.
•Residential greenness around the participants' homes was measured by normalized difference vegetation index (NDVI).•BMI and marital status were associated with NDVI.•NDVI with a buffer size of 1 km was associated with higher prostate cancer risk, particularly low grade prostate cancer.
A series of sulfonated carbon materials (sulfonated glucose-derived carbon, carbon nanotubes, activated carbon and ordered mesoporous carbon, denoted as Sglu, SCNT, SAC and SCMK, respectively) were ...synthesized and applied as acid catalysts in phenylacetylene (PA) hydration reactions. The sulfonic acid groups (-SO
H) were identified to be the only kind of active sites and were quantified with XPS and a cation exchange process. Mechanistic studies revealed that the catalytic PA hydration reaction follows pseudo first order reaction kinetics. Sglu exhibits a higher reaction rate constant (
) and lower apparent activation energy (
) in the hydration reactions than SCNT catalysts. NH
-temperature programmed desorption measurement results revealed that the relatively high catalytic activity of Sglu was attributed to both the stronger acidity and larger number of -SO
H active sites. This work exhibited the performance of carbon materials without any extra acidic additives in PA hydration reaction and investigated the intrinsic catalytic activity by kinetics. The present work provides the possibility for acid catalytic applications of carbon materials, which sheds light on the environmentally friendly and sustainable production strategy for aldehyde ketone compounds
the catalytic alkyne hydration reactions.
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