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Enhancement of malignant cell immunogenicity to relieve immunosuppression of lung cancer microenvironment is essential in lung cancer treatment. In previous study, we have demonstrated that dihydroartemisinin (DHA), a kind of phytopharmaceutical, is effective in inhibiting lung cancer cells and boosting their immunogenicity, while the initial target of DHA's intracellular action is poorly understood. The present in‐depth analysis aims to reveal the influence of DHA on the highly expressed TOM70 in the mitochondrial membrane of lung cancer. The affinity of DHA and TOM70 was analyzed by microscale thermophoresis (MST), pronase stability, and thermal stability. The functions and underlying mechanism were investigated using western blots, qRT‐PCR, flow cytometry, and rescue experiments. TOM70 inhibition resulted in mtDNA damage and translocation to the cytoplasm from mitochondria due to the disruption of mitochondrial homeostasis. Further ex and in vivo findings also showed that the cGAS/STING/NLRP3 signaling pathway was activated by mtDNA and thereby malignant cells underwent pyroptosis, leading to enhanced immunogenicity of lung cancer cells in the presence of DHA. Nevertheless, DHA‐induced mtDNA translocation and cGAS/STING/NLRP3 mobilization were synchronously attenuated when TOM70 was replenished. Finally, DHA was demonstrated to possess potent anti‐lung cancer efficacy in vitro and in vivo. Taken together, these data confirm that TOM70 is an important target for DHA to disturb mitochondria homeostasis, which further activates STING and arouses pyroptosis to strengthen immunogenicity against lung cancer thereupon. The present study provides vital clues for phytomedicine‐mediated anti‐tumor therapy. [ABSTRACT FROM AUTHOR]

Acetylation of extracellular proteins has been observed in many independent studies where particular attention has been given to the dynamic change of the microenvironmental protein post‐translational modifications. While extracellular proteins can be acetylated within the cells prior to their micro‐environmental distribution, their deacetylation in a tumor microenvironment remains elusive. Here it is described that multiple acetyl‐vWA domain‐carrying proteins including integrin β3 (ITGB3) and collagen 6A (COL6A) are deacetylated by Sirtuin family member SIRT2 in extracellular space. SIRT2 is secreted by macrophages following toll‐like receptor (TLR) family member TLR4 or TLR2 activation. TLR‐activated SIRT2 undergoes autophagosome translocation. TNF receptor associated factor 6 (TRAF6)‐mediated autophagy flux in response to TLR2/4 activation can then pump SIRT2 into the microenvironment to function as extracellular SIRT2 (eSIRT2). In the extracellular space, eSIRT2 deacetylates ITGB3 on aK416 involved in cell attachment and migration, leading to a promotion of cancer cell metastasis. In lung cancer patients, significantly increased serum eSIRT2 level correlates with dramatically decreased ITGB3‐K416 acetylation in cancer cells. Thus, the extracellular space is a subcellular organelle‐like arena where eSIRT2 promotes cancer cell metastasis via catalyzing extracellular protein deacetylation. [ABSTRACT FROM AUTHOR]

Retinoblastoma (RB) is one of the most common primary intraocular malignancies in children. Emerging researches have shown that circular RNAs (circRNAs) play critical roles in a variety of cancers. As a novel circRNA, the function of circ_0000527 in RB remains unknown. In this work, expression level of circ_0000527 and miR‐646 in RB tissues and cell lines were detected by quantitative real‐time polymerase chain reaction (qRT‐PCR). RB cell lines (SO‐Rb50 and WERI‐Rb‐1) were used as cell models in functional experiments. CCK‐8 assay, TUNEL assay and transwell assay were employed to detect the biological influence of circ_0000527 and miR‐646 on cancer cells in vitro. qRT‐PCR, luciferase reporter assay, RIP assay and western blot were used for exploring the interactions among circ_0000527, miR‐646 and BCL‐2. It was demonstrated that expression level of circ_0000527 in RB samples was significantly up‐regulated compared to normal tissues, while miR‐646 was markedly down‐regulated. Overexpression of circ_0000527 promoted the viability, migration and invasion of RB cells, while miR‐646 transfection had the opposite effects. Circ_0000527 sponged miR‐646 to regulate the expression of BCL‐2. In conclusion, circ_0000527 could promote the development of RB by indirectly modulating BCL‐2 via absorbing miR‐646. Significance of the study: Expression level of circ_0000527 in RB samples was significantly up‐regulated compared to normal tissues, while miR‐646 was markedly down‐regulated. Overexpression of circ_0000527 promoted the viability, migration and invasion of RB cells, while miR‐646 transfection had the opposite effects. Circ_0000527 sponged miR‐646 to regulate the expression of BCL‐2. [ABSTRACT FROM AUTHOR]

A caisson breakwater may experience various modes of motions under wave action. The elementary motion modes are classified into two categories, i.e. the horizontal and rotational vibration coupled motion and the horizontal slide and rotational vibration coupled motion. The motion modes of caisson will transform from one to another depending on the wave forces and the motion behaviours of a caisson. The numerical models of the two motion modes of caisson are developed, the numerical simulation procedure for joint motion process of the two modes of caisson breakwater under wave excitation is presented and tested by a physical model experiment. It is concluded that the simulation procedure is reliable and can be applied to the dynamic stability analysis of caisson breakwaters. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Soil fungi play an important role in soil nutrient cycling and carbon storage in natural ecosystems. Dominant tree species showed altitude distribution in Huoditang forest in Qinling Mountains, whereas the corresponding changes of soil characteristics and microbial communities are still unclear. In this study, the variations of soil characteristics were investigated at five altitudes (1500, 1700, 1900, 2100 and 2300 m). The collected soil samples were sequenced by Illumina MiSeq sequencing platform, and the pattern of fungal community was studied. The results showed that soil available phosphorus concentration (AP) and soil pH increased significantly whereas soil moisture showed a downward trend with increasing altitude. The Shannon diversity index of soil fungi decreased and ACE richness index showed an opposite trend with increasing altitude. Basidiomycota (68.2%), Ascomycota (19.9%), and Mortierellomycota (1.7%) were dominant fungal phyla, which showed a 'U' shape or 'peak' pattern according to altitude. Agaricomycetes (64.2%), Sordariomycetes (5.8%), and Leotiomycetes (4.1%) were the dominant fungal classes. Results of redundancy analysis (RDA) showed that 89.1% of the total variations of soil fungal community were explained by soil characteristics, while AP, pH and altitude were the main driving factors for altitude variations of soil fungal communities. Soil characteristics had certain differences with altitude changes in Huoditang forest region in Qinling Mountains, which affected soil fungal community composition.

Rapid urbanization destroys the ecological network connectivity among habitat patches. The research on the construction of regional ecological network at the patch level is obviously insufficient. The morphological spatial pattern analysis (MSPA) and minimum cumulative resistance (MCR) were used to identify ecological sources and to extract potential ecological corridors in Qinling Mountains, respectively. The ecological network was effectively constructed. We analyzed the structural characteristics and landscape compositions of the network. Based on the gravity model, the importance of patches in the ecological network was graded and the structural characteristics and landscape composition of the network were analyzed. The results showed that there were 10 ecological sources, 45 potential ecological corridors and 38 stepping stones in the ecological network of Qinling Mountains in Shaanxi Province, with a total area of 29686.15 km 2 . There were good connectivity in potential ecological corridors and ecological network nodes as indicated by network closure (0.11), line point rate (1.18), network connectivity (0.42) and cost ratio (0.99). The connectivity between ecological source was low, but the cost of network reconstruction was high. The important ecological corridors were mainly composed of forest, grassland, and cultivated land. Fore-sts accounted for 89.2% of the total corridor area (571.00 km 2 ), indicating the good landscape structure in Qinling Mountains. The protection of ecological source areas must be strengthened, and priority should be given to the establishment and protection of important ecological corridors and ecological nodes. Our results would provide the scientific reference and basis for the ecological environment protection and high-quality development in Qinling Mountains.

An immerging role of TNF-α in collagen synthesis and cardiac fibrosis implies the significance of TNF-α production in the development of myocardial remodeling. Our previous study showed a reduction of TNF-α and attenuated cardiac remodeling in CXCR6 knockout (KO) mice after ischemia/reperfusion injury. However, the potential mechanism of TNF-α-mediated cardiac fibrosis with pressure overload has not been well elucidated. In the present study, we aim to investigate the role of CXCR6 in TNF-α release and myocardial remodeling in response to pressure overload. Pressure overload was performed by constriction of transverse aorta (TAC) surgery on CXCR6 KO mice and C57 wild-type (WT) counterparts. At 6 weeks after TAC, cardiac remodeling was assessed by echocardiography, cardiac TNF-α release and its type I receptor (TNFRI), were detected by ELISA and western blot, collagen genes Col1a1 (type I) and Col3a1 (type III) were examined by real-time PCR. Compared with CXCR6 WT mice, CXCR6 KO mice exhibited less cardiac dysfunction, reduced expression of TNFRI, Col1a1 and Col3a. In vitro, we confirmed that CXCR6 deficiency led to reduced homing and infiltration of CD11b(+) monocytes, which contributed to attenuated TNF-α release in myocardium. Furthermore, TNFRI antagonist pretreatment blocked AT1 receptor signaling and NOX4 expression, reduced collagen synthesis, and blunted the activity of MMP9 in CXCR6 WT mice after TAC, but these were not observed in CXCR6 KO mice. In the present work, we propose a mechanism that CXCR6 is essential for pressure overload-mediated myocardial recruitment of monocytes, which contributes to cardiac fibrosis through TNF-α-dependent MMP9 activation and collagen synthesis.

Objective: To study the regulatory effects of psoralen (PSO) plus ultraviolet A (UVA), which is PUVA, on cell apoptosis of human leukemia cell line NB4 and signal pathway of cell apoptosis., Methods: Human leukemia cell line NB4 was cultured in vitro. The NB4 cells were treated with PSO extracted from Chinese medicine psoralea fruits at different concentrations (0, 5, 10, 20 and 40 microL) plus UVA of wave length 360 nm at different irradiation time points (0 and 5 min). The apoptosis ratio was detected by flow cytometry (FCM). The ultrastructure changes were observed using transmission electron microscope (TEM). The expressions of Caspase-8 and Caspase-8 protein were detected by immunocytochemical method (ICC)., Results: After treatment of PSO at different concentrations with a 0 and 5-min exposure of UVA, the apoptosis rate of NB4 cells increased dose-and time-dependently, and was up to peak after treatment of PSO at 40 microg/mL with 5-min exposure of UVA. An interaction was shown between the two factors (P <0. 01). There were obvious morphological apoptosis of NB4 cells under TEM after treated with PUVA. The expressions of Caspase-3 and Caspase-8 protein were up-regulated by PSO, UVA, and PUVA, but the effects of PUVA on Caspase-3 protein were stronger than PSO and UVA at 12 h time-dependently (P <0.01).An interaction was shown between the concentration of PSO and time of UVA (P <0.01)., Conclusions: The optimal combination of PUVA was PSO in 40 microg/mL and 5-min exposure of UVA. PUVA could induce the apoptosis of NB4 cells and in vitro activate Caspase-3 and Caspase-8 genes.