Tumor-associated macrophages (TAMs) represent the most abundant leukocyte population in most solid tumors and are greatly influenced by the tumor microenvironment. More importantly, these macrophages ...can promote tumor growth and metastasis through interactions with other cell populations within the tumor milieu and have been associated with poor outcomes in multiple tumors. In this review, we examine how the tumor microenvironment facilitates the polarization of TAMs. Additionally, we evaluate the mechanisms by which TAMs promote tumor angiogenesis, induce tumor invasion and metastasis, enhance chemotherapeutic resistance, and foster immune evasion. Lastly, we focus on therapeutic strategies that target TAMs in the treatments of cancer, including reducing monocyte recruitment, depleting or reprogramming TAMs, and targeting inhibitory molecules to increase TAM-mediated phagocytosis.
Despite the fact that the response of tropical hydroclimate to North Atlantic cooling events during the Heinrich Stadial 1 (HS1) has been extensively studied in African, South American and Indonesia, ...the nature of such responses remains debated. Here we investigate the tropical hydroclimate pattern over the Indo-Asian-Australian monsoon region during the HS1 by integrating hydroclimatic records, and examining a δ
O
record from Globigerinoides ruber (white) in the tropical Indian Ocean. Our findings indicate that tropical hydrological conditions were synchronously arid in both hemispheres during the early HS1 (~18.3-16.3 ka) in the Indo-Asian-Australian monsoon region, except for a narrow, wet hydrological belt in northern low latitudes, suggesting the existence of a contracted tropical precipitation belt at that time. This study reveals that the meltwater discharge and resulting changes in global temperatures and El Niño exerted a profound influence on the tropical hydroclimate in the Indo-Asian-Australian monsoon region during the early HS1.
Sedimentary phosphorites enriched in rare earth elements (i.e., REE) are an important reservoir of these critical metals and may have the potential to resolve the global REE supply risk in the ...future, which is widely distributed around world. However, the occurrence and utilizability of REE in phosphorites remain contentious. In this study, multiple-scale analysis techniques were used to investigate the mineralogical and geochemical characteristics of typical REE-enriched phosphorites from Zhijin, SW China. The mineralization was divided into two stages: early fluorapatite (Fap1) that formed during the sedimentary–diagenetic stage, and late fluorapatite (Fap2) that formed during the hydrothermal alteration stage. The in situ REE geochemical data (i.e., quantitative data and mapping analysis) and scanning electron microscopy images show that Fap1 is the main REE host phase, because it is abundant and high REE concentration. Data obtained by both laser-ablation–inductively coupled plasma–mass spectrometry and high-resolution transmission electron microscopy reveal that most REE are resident in the lattice of nano-scale fluorapatite, which could be remobilized by hydrothermal fluids during the process of dissolution of nano-scale Fap1 and reprecipitation of micro-scale Fap2. In addition, the formation of synchysite-(Y) in the altered phosphorites involved reprecipitation of the mobilized REE. We suggest that F− and SO42− in fluids play a major role in the mobilization of REE in fluorapatite and that CO32− sourced from dolomite alteration contributes to the precipitation of REE. Our results indicate that REE in fluorapatite can be remobilized and further enriched by hydrothermal alteration to REE fluorocarbonates (the current predominant economic source of REE minerals). Overall, our results reveal that REE occur mainly in the lattices of fluorapatite and synchysite-(Y) in phosphorites, and provide new insights into the mineralization mechanism and industrial availability of REE-enriched phosphorites.
•REY were mainly enriched in sedimentary–diagenetic stage.•Z-contrast image confirm most REE are resident in the lattice of fluorapatite.•REY in fluorapatite can be re-distributed to form synchysite-(Y) by hydrothermal alteration.
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•Inconsistent changing trends of SST and SSS at different parts of the northern SCS.•Declined trend of SSS near Luzon Strait is affected by the western tropical Pacific.•Increased SST ...and SSS in central northern SCS is linked to weakened Asian monsoon.
The South China Sea (SCS) is an important moisture and heat source in the Asian monsoon system, and its environmental changes influence economic and social stability in Southeast Asia and East Asian. Previous records on sea surface temperature (SST) and salinity (SSS) were mostly from one sediment core, and/or only showed fragmentary information. It is hard to provide insights into the mechanisms of the overall paleoceanographical environmental variability in the northern SCS. In this study, paired δ18O and Mg/Ca records of planktonic foraminifer Globigerinoides ruber from Core S0204B nearby the Luzon Strait (21°13.818′N, 118°3.077′, water depth 1822 m), and Core GHE 27L (19.85°N, 115.34°E, water depth of 1533 m) in the central northern SCS, were analyzed, so as to better understand the physical process of the SST and SSS changes in the northern SCS and its relationship with the tropical Pacific. The results demonstrate that the SST is relatively stable and seawater δ18O (δ18Osw) values, a salinity proxy, shows a decrease trend since 7.0 ka BP in Core S0204B. By contrast, SST and δ18Osw in Core GHE 27L exhibit an overall increasing trend at the same time, indicating apparent regional discrepancy on the changing trend of the SST and SSS in the northern SCS. We suggest that the thermal and hydrographic conditions in Core S0204B were primarily influenced by the outer western Pacific water. However, the thermal and hydrographic conditions in Core GHE 27L may be predominantly controlled by the weakened Asian monsoon during the mid-late Holocene, which was induced by the southern migration of Intertropical Convergence Zone (ITCZ) and stronger EI Niño Southern Oscillation.
Although rare-earth elements (REEs) in authigenic phosphates and carbonates derived from marine sediments are potential proxies (e.g., REE patterns) for reconstructing paleoenvironmental conditions, ...the REE patterns appear to be inconsistent. Some marine authigenic phosphates show a “bell-shaped” pattern with an enrichment of the middle REEs (MREEs; NdHo), while others exhibit a “modern seawater-like” pattern characterized by a strong depletion in cerium and an enrichment in heavy REEs (ErLu, Y, and Sc). Although the origin of the “bell-shaped” pattern in phosphates has been extensively debated, the evidence is often ambiguous; therefore, the origin of the pattern remains unclear. In this study, we investigate the microscale and nanoscale mineralogical and geochemical characteristics of the REE-enriched Early Cambrian phosphorites. In situ elemental analyses reveal that the codeposited phosphates (“bell-shaped” REE pattern) and carbonates (“modern seawater-like” pattern) have different REE patterns. A microscale investigation shows that phosphate grains contain some dispersed goethite nanophase, and a nanoscale investigation using transmission electron microscopy coupled with electron energy-loss spectroscopy shows that Fe2+ is distributed along the rim of the goethite nanophase, indicating that the goethite were reduced. These findings suggest that the REE pattern and concentration in phosphates could have been influenced by the release of REEs during the reduction of Fe (oxyhydr)oxide in the early diagenetic process before the final deposition. Although additional evidence is required, our results are important for understanding the effects of Fe redox cycling on the REE pattern and enrichment in marine authigenic phosphates. In addition, our results suggest that compared with authigenic phosphates, authigenic carbonates would provide a more reliable reconstruction of paleoenvironmental conditions.
Vaccinia virus (VV) has been used extensively as a vaccine vehicle in the clinical application for infectious diseases and cancer. Previous studies have suggested that the unique potency of VV-based ...vaccine lies in its effective activation of the innate immune system. However, how VV activates innate immune pathways remains largely unknown. In this study, we showed that VV elicited innate immune response through both Toll-like receptor (TLR)–dependent and –independent pathways. The TLR pathway was mediated by TLR2 and MyD88, leading to the production of proinflammatory cytokines, whereas activation of the TLR-independent pathway resulted in the secretion of IFN-β. More importantly, both TLR-dependent and -independent pathways were required for activating innate and adaptive immunity to VV in vivo. These findings represent the first evidence that innate immune recognition of VV is mediated by TLR2, demonstrate that one pathogen can target both TLR and non-TLR innate immune pathways to work together in achieving efficient activation of host defense, and suggest potential new strategies for the design of effective vaccines.
Natural killer (NK) cells play an essential role in innate immune control of poxviral infections in vivo. However, the mechanism(s) underlying NK cell activation and function in response to ...poxviruses remains poorly understood. In a mouse model of infection with vaccinia virus (VV), the most studied member of the poxvirus family, we identified that the Toll-like receptor (TLR) 2-myeloid differentiating factor 88 (MyD88) pathway was critical for the activation of NK cells and the control of VV infection in vivo. We further showed that TLR2 signaling on NK cells, but not on accessory cells such as dendritic cells (DCs), was necessary for NK cell activation and that this intrinsic TLR2-MyD88 signaling pathway was required for NK cell activation and played a critical role in the control of VV infection in vivo. In addition, we showed that the activating receptor NKG2D was also important for efficient NK activation and function, as well as recognition of VV-infected targets. We further demonstrated that VV could directly activate NK cells via TLR2 in the presence of cytokines in vitro and TLR2-MyD88-dependent activation of NK cells by VV was mediated through the phosphatidylinositol 3-kinase (PI3K)-extracellular signal-regulated kinase (ERK) pathway. Taken together, these results represent the first evidence that intrinsic TLR signaling is critical for NK cell activation and function in the control of a viral infection in vivo, indicate that multiple pathways are required for efficient NK cell activation and function in response to VV infection, and may provide important insights into the design of effective strategies to combat poxviral infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Natural killer (NK) cells, as part of the innate immune system, play a key role in host defense against viral infections. Recent advances have indicated that NK cell activation and function are ...regulated by the interplay between inhibitory and activating signals. Thus, a better understanding of mechanisms responsible for NK cell activation and function in the control of viral infections will help develop NK cell-based therapies. In this review, we will first discuss how NK cells are activated in response to viral infections. We will then focus on the recruitment of activated NK cells to the site of infection as well as on NK cell effector mechanisms against virally infected cells.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Hexokinase 3 (HK3) is one of the key enzymes involved in glucose phosphorylation (the first step in most glucose metabolic pathways). Many studies have demonstrated the vital role of dysregulation of ...HK3 in several tumors. However, there is a need for in-depth characterization of the role of HK3 in glioblastoma multiforme (GBM).
All data were sourced from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Kaplan-Meier analysis and univariate regression were applied for survival analysis. Gene set enrichment analysis (GSEA) was used for enrichment analysis. Tumor Immune Single Cell Hub (TISCH) database was applied for single-cell analysis. Tumor Immune Dysfunction and Exclusion (TIDE) analysis was applied to evaluate the immune response.
HK3 expression was upregulated in GBM and correlated with poor prognosis. The high HK3 expression group was primarily enriched in adaptive immune response, chemokine signaling pathway, and cytokine-cytokine receptor interaction. The high HK3 expression group showed significantly greater enrichment of the majority of immune cells and immune-related pathways. HK3 showed significant correlation with most immune cells, especially macrophages (
< .001, R = .81). TISCH analysis showed that HK3 was predominantly expressed in macrophages in most cancers. HK3 showed significant correlation with most immune-related genes, such as PD-1 (
< .001, R = .41), PDL-1 (
< .001, R = .27), and CTLA-4 (
< .001, R = .29). TIDE analysis revealed that the low HK3 expression group has a lower TIDE score and may benefit from immunotherapy. Drug sensitivity analysis showed that patients with high HK3 expression frequently showed drug resistance.
HK3 was associated with poor prognosis and may serve as a biomarker of macrophages in GBM. HK3 was also associated with immune response and drug resistance. Our findings may provide novel insights for GBM immunotherapy.
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