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The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients’ outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol–miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts in vivo, thus alleviating the establishment of a pro-metastatic environment for circulating lung tumor cells.

HA composite coatings added reinforcement phases could improve the mechanical properties and bonding strength of the coatings. Cold spraying is a feasible surface technology for preparing HA composite coatings. In order to investigate the influence of cold spraying parameters on the deposition behavior of a single HA/Ti composite particle, numerical and experimental investigation of gas-particle two-phase flow in cold spraying nanostructured HA/Ti composite particle were investigated in this study. The results show that the influence of different temperatures and pressures on static pressure was not significant. The effects of gas pressure on the static temperature were tiny under the same inlet temperature and different pressure conditions; however, the static temperature in the entire spray gun cavity increased as the inlet temperature increased under the same pressure and different inlet temperature conditions. There is little effect of gas pressure on the axial velocity of gas flow in the spray gun cavity; however, the axial velocity of gas flow increased with the increase in gas temperature. Meanwhile, the axial velocity of gas flow gradually increases throughout the spraying process. At a gas temperature of 573 K and 973 K, the maximum axial velocities of a gas flow at gas pressure of 2.2 MPa were 778 m/s and 942 m/s, respectively. There is little effect of gas pressure on the axial velocity of HA/30 wt.% Ti particles under the same gas temperature. The axial velocity of HA/30 wt.% Ti particles increased with the increase in gas temperature under the same gas pressure condition. The axial velocity of composite particles decreased with the increase in the particle size under the same gas pressure and gas temperature. At a gas temperature of 573 K and 973 K, the minimum axial velocity of HA/30 wt.% Ti particles with a particle size of 30 μm at a gas pressure of 2.2 MPa was 435 m/s and 467 m/s, respectively. A certain deformation of splats occurred after impacting the substrate, and the splats adhered to the surface of the Ti6Al4Vsubstrate, clearly presenting a flat shape with a central hump surrounded by a ringy band. At a gas temperature of 973 K, particles generated more severe deformation with more cracks and ejecta phenomenon. The splats attached to the substrate were increased as the gas temperature increased.

To investigate the clinical value of Tie2-expressing monocytes (TEMs) in the early diagnosis of lung cancer and assess its correlation with angiogenesis, a total of 184 patients with non-small cell lung cancer (NSCLC), 101 patients with benign pulmonary disease (BPD), and 77 healthy controls were enrolled in our study. The distribution of TEMs in lung tissue was determined by immunofluorescence staining. Lung microvascular density was assessed by immunohistochemical staining. Receiver-operating characteristic (ROC) curve analysis was performed to assess the diagnostic value of TEM frequency. Patients with NSCLC were followed up for 26 months. We found that the TEM frequency in peripheral blood monocytes of patients with NSCLC was significantly greater than that in patients with BPD and healthy controls. TEM frequency showed a correlation with NSCLC recurrence. The majority of TEMs in tumor tissues were localized around blood vessels; tumoral TEM frequency showed a positive correlation with microvascular density. High percentage of TEMs in the peripheral blood was associated with poor overall survival. ROC curve analysis revealed the potential diagnostic value of circulating TEM frequency in NSCLC. Thus, we believe that TEM frequency is related to angiogenesis in tumor tissues and may serve as a diagnostic marker for NSCLC.

Tumor-induced lymphangiogenesis promotes the formation of new lymphatic vessels, contributing to lymph nodes (LNs) metastasis of tumor cells in both mice and humans. Vessel sprouting appears to be a critical step in this process. However, how lymphatic vessels sprout during tumor lymphangiogenesis is not well-established. Here, we report that S100A4 expressed in lymphatic endothelial cells (LECs) promotes lymphatic vessel sprouting in a growing tumor by regulating glycolysis. In mice, the loss of S100A4 in a whole body (S100A4

Tumour-stroma cell interactions impact cancer progression and therapy responses. Intercellular communication between fibroblasts and cancer cells using various soluble mediators has often been reported. In this study, we find that a zinc-transporter (ZIP1) positive tumour-associated fibroblast subset is enriched after chemotherapy and directly interconnects lung cancer cells with gap junctions. Using single-cell RNA sequencing, we identify several fibroblast subpopulations, among which Zip1

Chemotherapeutic drugs have been successfully used to treat several cancers, including melanoma. However, metastasis occasionally occurs after chemotherapy. Here, we reported that paclitaxel (PTX) treatment for B16F10 tumour in mice led to an enhanced lymphatic metastasis of the melanoma cells, although a significant inhibition of tumour growth at the injection site was observed. Further study demonstrated that PTX upregulated the expression of C-C chemokine receptor type 7 (CCR7) in B16F10 cells, enhancing their migration through the activation of JNK and p38 signalling pathways. Loss of CCR7 or blockade of C-C motif chemokine ligand 21 (CCL21)/CCR7 axis abolished the pro-migration effect of PTX on B16F10 melanoma cells. Importantly, combination of PTX and CCR7 mAb could simultaneously delay the tumour growth and reduce the lymphatic metastasis in B16F10 melanoma. The blockade of CCL21/CCR7 axis may collectively serve as a strategy for lymphatic metastasis in some melanoma after chemotherapy.

Expressed in macrophages and endothelial cells, the receptor for angiopoietin, tyrosine kinase with immunoglobulin and epidermal growth factor homology-2 (Tie2), is required for the reconstruction of blood vessels in tumor recurrence after chemotherapy. Thus, small therapeutic peptides that target and block Tie2 activity are promising as a therapeutic for the prevention of tumor relapse after chemotherapy. However, such small peptides often have low bioavailability, undergo rapid enzymatic degradation, and exhibit a short circulation half-life, making them ineffective in cancer therapy. Herein, we designed a dual-responsive amphiphilic peptide (mPEG1000-K(DEAP)-AAN-NLLMAAS) to modify the small peptide T4 (NLLMAAS) as a Tie2 inhibitor, endowing it with the ability to endure in circulation and specifically target tumor tissue. The ultimate nanoformulation (P-T4) releases T4 in response to the combination of the acidic tumor microenvironment and the presence of legumain, which is commonly overexpressed in tu...

WC-Co cermet materials serving as protective coatings are widely used in many fields. Conventional WC-17Co coatings were formed in high-velocity oxygen-fuel (HVOF), warm spraying (WS), and cold spraying (CS), respectively. Deposition behavior of a single WC-17Co particle, as well as the microstructure, microhardness, fracture toughness, and abrasive wear of WC-17Co coatings formed in various spraying ways were investigated. The results show that the deposition behavior of a single WC-17Co particle was different after it was deposited onto a Q235 steel substrate in various spraying ways. The WC-17Co splat deposited by HVOF showed a center hump and some molten areas, as well as some radial splashes presented at the edge of the splat. The WC-17Co splat deposited by WS presented a flattened morphology with no molten areas. However, the WC-17Co splat deposited by CS remained nearly spherical in shape and embedded into the substrate to a certain depth. All the WC-17Co coatings had the same phase compositions with that of feedstock. The microstructure of all the WC-17Co coatings was dense with no cracks or abscission phenomena between the coatings and substrate. Moreover, fine WC particles were formed in the coatings due to the fracture of coarse WC particles, and the content of fine WC particles in the cold-sprayed coating was significantly more than the other coatings. A stripe structure was formed by the slippage of fine WC particles with a plastic flow of Co binder in the warm-sprayed and cold-sprayed coatings. More fine WC particles, as well as the stripe structure, in the coatings were conducive to improve the microhardness and fracture toughness of the coating. The microhardness and fracture toughness of the cold-sprayed WC-17Co coating were the highest among the coatings. The main wear mechanism of all coatings was the groove and some peel-offs. The cold-sprayed WC-17Co coating with the lowest wear loss presented the highest wear resistance among the coatings.

The lung is one of the most common sites for cancer metastasis. Collagens in the lung provide a permissive microenvironment that supports the colonization and outgrowth of disseminated tumor cells. Therefore, down-regulating the production of collagens may contribute to the inhibition of lung metastasis. It has been suggested that miR-29 exhibits effective anti-fibrotic activity by negatively regulating the expression of collagens. Indeed, our clinical lung tumor data shows that miR-29a-3p expression negatively correlates with collagen I expression in lung tumors and positively correlates with patients' outcomes. However, suitable carriers need to be selected to deliver this therapeutic miRNA to the lungs. In this study, we found that the chemotherapy drug cisplatin facilitated miR-29a-3p accumulation in the exosomes of lung tumor cells, and this type of exosomes exhibited a specific lung-targeting effect and promising collagen down-regulation. To scale up the preparation and simplify the delivery system, we designed a lung-targeting liposomal nanovesicle (by adjusting the molar ratio of DOTAP/cholesterol-miRNAs to 4:1) to carry miR-29a-3p and mimic the exosomes. This liposomal nanovesicle delivery system significantly down-regulated collagen I secretion by lung fibroblasts

Aims Cancer associated fibroblasts (CAFs) play a crucial role in lung tumor development, but the underlying mechanism is still not fully understood. Main methods SCRIB expression in the CAFs of human lung cancer tissues was examined by immunohistochemistry (IHC). A coculture of mouse Lewis lung cancer cells (LLC) and fibroblasts was used to investigate SCRIB expression in cocultured fibroblasts. Proliferation, scratch wound, and transwell assays were used to examine the proliferation, migration and invasion ability of SCRIB knockdown fibroblasts and their effects on LLC. A 3D-coculture system and co-injection xenograft model were used to examine LLC invasion. RNA sequencing and transwell experiments were used to explore the molecules that may participate in LLC invasion. Key findings Herein, we found that the low expression of SCRIB in CAFs is correlated with advanced tumor stages and poor survival for human lung squamous cell carcinoma. SCRIB expression in fibroblasts is drastically downregulated by LLC cells. SCRIB knockdown fibroblasts not only enhance invasion but also facilitate LLC invasion in a 3D-coculture system and in an in vivo subcutaneous transplantation model. The upregulation of asporin in SCRIB knockdown fibroblasts is involved in LLC invasion in vitro. Significance Collectively, the results indicate that fibroblasts with low SCRIB expression promote lung cancer cell invasion, which suggests that the downregulated expression of SCRIB may represent one of the important characteristics of tumor-promoting CAFs in lung squamous cell cancer.

Tumour‐derived exosomes have been shown to induce pre‐metastatic niche formation, favoring metastatic colonization of tumour cells, but the underlying molecular mechanism is still not fully understood. In this study, we showed that exosomes derived from the LLC cells could indeed significantly enhance their intrapulmonary colonization. Circulating LLC‐derived exosomes were mainly engulfed by lung fibroblasts and led to the NF‐κB signalling activation. Further studies indicated that the exosomal miR‐3473b was responsible for that by hindering the NFKB inhibitor delta's (NFKBID) function. Blocking miR‐3473b could reverse the exosome‐mediated NF‐κB activation of fibroblasts and decrease intrapulmonary colonization of lung tumour cells. Together, this study demonstrated that the miR‐3473b in exosomes could mediate the interaction of lung tumour cells and local fibroblasts in metastatic sites and, therefore, enhance the metastasis of lung tumour cells.

Summary Inflammaging is associated with an increased risk of chronic disease. Monocytes are the principal immune cells for the production of inflammatory cytokines and contribute to inflammaging in the elderly. However, the underlying mechanisms remain largely unknown. Here, we found that monocytes from aged individuals contained high levels of lipid droplets (LDs), and this increase was correlated with impaired fatty acid oxidation. Downregulated peroxisome proliferator-activated receptor (PPAR)-α may be responsible for the pro-inflammatory phenotype of monocytes in aged individuals, as it was positively correlated with LD accumulation and increasing TNF-α concentration. Interestingly, interventions that result in PPAR-α upregulation, such as fenofibrate treatment, TNF-α neutralization, or calorie restriction, reversed the effect of aging on monocytes. Thus the downregulation of PPAR-α and LD levels in monocytes represents a novel biomarker for inflammaging. Furthermore, PPAR-α activation in the elderly may also alleviate long-term inflammaging, preventing the development of life-limiting chronic diseases., Graphical abstract, Highlights • Monocytes from aged individuals contained high levels of lipid droplets (LDs) • Downregulated PPAR-α is responsible for the aged monocytes profiles • TNF-α might accelerate monocyte aging by downregulating PPAR-α expression • PPAR-α activation in the elderly may also alleviate long-term inflammaging, Human metabolism; Immunology; Cell biology