Description: Aims Toll-like receptor 7 (TLR7) agonists has been applied into cancer immunotherapy, but the heterogeneity of tumor renders TLR7 behaves versatile in tumor microenvironment and the characteristic of TLR7 in oral squamous cell carcinoma (OSCC) is unclear. Methods and results 20 healthy oral tissues, 50 oral leukoplakia tissues and 166 retrospective primary OSCC samples were collected for immunohistochemical staining of TLR7 and showed up-regulated expression during carcinogenesis. Moreover, patients with high expression of TLR7 in tumor cells (TCs) had poor differentiation and prognosis. Interestingly, patients with high expression of TLR7 in stroma fibroblast-like cells (FLCs) had low tumor stage, no lymph node metastasis (LNM) and better prognosis. Furthermore, ki-67, CD3, CD4, CD8 and Foxp3 + tumor-infiltrated lymphocytes were assessed and found that TLR7 high TCs were infiltrated with fewer CD3 + CD4 + but more Foxp3 + lymphocytes. Importantly, patients with TLR7 low TCs and TLR7 high FLCs had less Foxp3 + lymphocytes infiltration and longer survival time than those who with TLR7 high TCs/TLR7 low FLCs, although TLR7 was not an independent prognostic factor for OSCC. Conclusions The low expression of TLR7 in tumor and high expression of TLR7 in stroma predict a good clinical outcome for OSCC patients and stroma FLCs might be conducive to immunotherapy by TLR7 agonist. This article is protected by copyright. All rights reserved.

Description: Soil respiration in water-limited ecosystems is affected intricately by soil water content (SWC), temperature, and soil properties. Eight sites on sand-fixed dunes revegetated in different years since1950s, with several topographical positions and various biological soil crusts (BSCs) and soil properties, were selected, as well as a moving sand dune (MSD) and a reference steppe in the Tengger Desert of China. Intact soil samples of 20 cm in depth were taken and incubated randomly at twelve levels of SWC (0 to 0.4 m 3 m −3 ) and at nine levels of temperature (5 to 45 °C) in a growth chamber; additionally, cryptogamic and microbial respiration (R M ) were measured. Total soil respiration (R T , including cryptogamic, microbial, and root respiration) was measured for two years at the MSD and five sites of sand-fixed dunes. The relationship between R M and SWC under the optimal SWC condition (0.25 m 3 m −3 ) is linear, as is the entire range of R T and SWC. The slope of linear function describes sensitivity of soil respiration to water (SRW) and reflects to soil water availability, which is related significantly to soil physical properties, BSCs, and soil chemical properties, in decreasing importance. Inversely, Q 10 for R M is related significantly to abovementioned factors in increasing importance. However, Q 10 for R T and respiration rate at 20 °C are related significantly to soil texture and depth of BSCs and subsoil only. In conclusion, through affecting SRW, soil physical properties produce significant influences on soil respiration, especially for R T . This indicates that a definition of the biophysical meaning of SRW is necessary, considering the water-limited and coarse-textured soil in most desert ecosystems.

Description: ABSTRACT We propose new implicit staggered-grid finite-difference schemes with optimal coefficients based on the sampling approximation method to improve the numerical solution accuracy for seismic modelling. We first derive the optimized implicit staggered-grid finite-difference coefficients of arbitrary even-order accuracy for the first-order spatial derivatives using the plane-wave theory and the direct sampling approximation method. Then, the implicit staggered-grid finite-difference coefficients based on sampling approximation, which can widen the range of wavenumber with great accuracy, are used to solve the first-order spatial derivatives. By comparing the numerical dispersion of the implicit staggered-grid finite-difference schemes based on sampling approximation, Taylor series expansion, and least squares, we find that the optimal implicit staggered-grid finite-difference scheme based on sampling approximation achieves greater precision than that based on Taylor series expansion over a wider range of wavenumbers, although it has similar accuracy to that based on least squares. Finally, we apply the implicit staggered-grid finite difference based on sampling approximation to numerical modelling. The modelling results demonstrate that the new optimal method can efficiently suppress numerical dispersion and lead to greater accuracy compared with the implicit staggered-grid finite difference based on Taylor series expansion. In addition, the results also indicate the computational cost of the implicit staggered-grid finite difference based on sampling approximation is almost the same as the implicit staggered-grid finite difference based on Taylor series expansion.

Description: Shear stress provided by a hydrocyclone was employed to remove the oil from oil-contaminated catalysts. Understanding the deoiling mechanism and providing quantitative analysis of the interaction between shear stress fields and deoiling are necessary to improve deoiling efficiency. In this study, a numerical simulation was conducted for the velocity field and shear stress field of a hydrocyclone, both of which are difficult to measure using other methods. Results showed that the shear stress field in the wall layer, where oil-contaminated catalysts are usually located, was robust. Increasing inlet flow rates resulted in a higher shear rate distribution along the wall layer. Numerical results were also compared with the experimental data. In the deoiling process, higher shear stress rates promoted faster transport of oil from catalysts into the fluid, thereby increasing the deoiling efficiency. Deoiling by the shear stress of a hydrocyclone is an efficient method for cleaning oil-contaminated catalysts within a short period of time.

Description: Four new iridoids, incarvoids D–F ( 1 – 3 , resp.) and incarvoid B 9- O - β - D -glucopyranoside ( 4 ), and one new monoterpenoid, argutoid B ( 5 ), along with 14 known compounds, were isolated from Rhododendron microphyton. Their structures were established by comprehensive 1D- and 2D-NMR spectroscopic analysis.

Description: The deep sea is one of the most extensive ecosystems on earth. Organisms living there survive in an extremely harsh environment, and their mitochondrial energy metabolism might be a result of evolution. As one of the most important organelles, mitochondria generate energy through energy metabolism and play an important role in almost all biological activities. In this study, the mitogenome of a deep-sea sea anemone ( Bolocera sp.) was sequenced and characterized. Like other metazoans, it contained 13 energy pathway protein-coding genes and two ribosomal RNAs. However, it also exhibited some unique features: just two transfer RNA genes, two group I introns, two transposon-like noncanonical open reading frames (ORFs), and a control region-like (CR-like) element. All of the mitochondrial genes were coded by the same strand (the H-strand). The genetic order and orientation were identical to those of most sequenced actiniarians. Phylogenetic analyses showed that this species was closely related to Bolocera tuediae . Positive selection analysis showed that three residues (31 L and 42 N in ATP6 , 570 S in ND5 ) of Bolocera sp. were positively selected sites. By comparing these features with those of shallow sea anemone species, we deduced that these novel gene features may influence the activity of mitochondrial genes. This study may provide some clues regarding the adaptation of Bolocera sp. to the deep-sea environment. The deep sea is regarded as the most extensive ecosystem on earth, and the organisms living there survive in an extremely harsh environment. The mitochondrial energy metabolism of some organisms may be different from that of shallow sea species. We uncovered a number of mitochondrial genome features that may provide some clues for Bolocera sp. on the adaptation of the seamount Bolocera sp. to the deep-sea environment.

Description: Tumors depend on their microenvironment for sustained growth, invasion, and metastasis. In this environment, endothelial cells (ECs) are an important stromal cell type interacting with malignant cells to facilitate tumor angiogenesis and cancer cell extravasation. Of note, lysosomal acid lipase (LAL) deficiency facilitates melanoma growth and metastasis. ECs from LAL-deficient (lal−/−) mice possess enhanced proliferation, migration, and permeability of inflammatory cells by activating the mammalian target of rapamycin (mTOR) pathway. Here we report that lal−/− ECs facilitated in vivo tumor angiogenesis, growth, and metastasis, largely by stimulating tumor cell proliferation, migration, adhesion, and transendothelial migration via increased expression of IL-6 and monocyte chemoattractant protein 1 (MCP-1). This prompted us to look for lysosomal proteins that are involved in lal−/− EC dysfunctions. We found that lal−/− ECs displayed increased expression of Rab7, a late endosome/lysosome-associated small GTPase. Moreover, Rab7 and mTOR were co-increased and co-localized to lysosomes and physically interacted in lal−/− ECs. Rab7 inhibition reversed lal−/− EC dysfunctions, including decreasing their enhanced migration and permeability of tumor-stimulatory myeloid cells, and suppressed EC-mediated stimulation of in vitro tumor cell transmigration, proliferation, and migration and in vivo tumor growth and metastasis. Finally, Rab7 inhibition reduced overproduction of reactive oxygen species and increased IL-6 and MCP-1 secretion in lal−/− ECs. Our results indicate that metabolic reprogramming resulting from LAL deficiency enhances the ability of ECs to stimulate tumor cell proliferation and metastasis through stimulation of lysosome-anchored Rab7 activity.

Description: Activation of hepatic stellate cells (HSCs) is a critical step in the development of liver fibrosis. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerols (TAGs), cholesteryl esters, and retinyl esters (REs). We previously provided evidence for the presence of two distinct LD pools, a preexisting and a dynamic LD pool. Here we investigate the mechanisms of neutral lipid metabolism in the preexisting LD pool. To investigate the involvement of lysosomal degradation of neutral lipids, we studied the effect of lalistat, a specific lysosomal acid lipase (LAL/Lipa) inhibitor on LD degradation in HSCs during activation in vitro. The LAL inhibitor increased the levels of TAG, cholesteryl ester, and RE in both rat and mouse HSCs. Lalistat was less potent in inhibiting the degradation of newly synthesized TAG species as compared with a more general lipase inhibitor orlistat. Lalistat also induced the presence of RE-containing LDs in an acidic compartment. However, targeted deletion of the Lipa gene in mice decreased the liver levels of RE, most likely as the result of a gradual disappearance of HSCs in livers of Lipa−/− mice. Lalistat partially inhibited the induction of activation marker α-smooth muscle actin (α-SMA) in rat and mouse HSCs. Our data suggest that LAL/Lipa is involved in the degradation of a specific preexisting pool of LDs and that inhibition of this pathway attenuates HSC activation.

Description: Solid tumors often suffer from suboptimal oxygen and nutrient supplies. This stress underlies the requirement for metabolic adaptation. Aberrantly activated de novo lipogenesis is critical for development and progression of human hepatocellular carcinoma (HCC). However, whether de novo lipogenesis influences biologic behaviors of HCCs under conditions of metabolic stress are still poorly understood. Here we show that HCCs display distinct levels of glucose-derived de novo lipogenesis, which are positively correlated with their survival responses to glucose limitation. The enhanced lipogenesis in HCCs is characterized by an increased expression of rate-limiting enzyme acetyl-CoA carboxylase (ACCα). ACCα-mediated fatty acid synthesis determines the intracellular lipid content that is required to maintain energy hemostasis and inhibit cell death by means of fatty acid oxidation (FAO) during metabolic stress. In accordance, overexpression of ACCα facilitates tumor growth. ACCα forms a complex with carnitine palmitoyltransferase 1 (CPT1A) and prevents its mitochondria distribution under nutrient-sufficient condition. During metabolic stress, phosphorylation of ACCα leads to dissociation of the complex and mitochondria localization of CPT1A, thus promoting FAO-mediated cell survival. Therefore, ACCα could provide both the substrate and enzyme storage for FAO during glucose deficiency. Upregulation of ACCα is also significantly correlated with poorer overall survival and disease recurrence after surgery. The multivariate Cox regression analysis identified ACCα as an effective predictor of poor prognosis. Conclusion : These results present novel mechanistic insight into a pivotal role of ACCα in maintaining HCCs survival under metabolic stress. It could be exploited as novel diagnostic marker and therapeutic target. This article is protected by copyright. All rights reserved.

Description: To understand the differences of the bacteria associated with different mosses, a phylogenetic study of bacterial communities in three mosses was carried out based on 16S rDNA and 16S rRNA sequencing. The mosses used were Hygroamblystegium noterophilum , Entodon compressus and Grimmia montana , representing hygrophyte, shady plant and xerophyte, respectively. In total, the operational taxonomic units (OTUs), richness and diversity were different regardless of the moss species and the library level. All the examined 1183 clones were assigned to 248 OTUs, 56 genera were assigned in rDNA libraries and 23 genera were determined at the rRNA level. Proteobacteria and Bacteroidetes were considered as the most dominant phyla in all the libraries, whereas abundant Actinobacteria and Acidobacteria were detected in the rDNA library of Entodon compressus and approximately 24.7% clones were assigned to Candidate division TM7 in Grimmia montana at rRNA level. The heatmap showed the bacterial profiles derived from rRNA and rDNA were partly overlapping. However, the principle component analysis of all the profiles derived from rDNA showed sharper differences between the different mosses than that of rRNA-based profiles. This suggests that the metabolically active bacterial compositions in different mosses were more phylogenetically similar and the differences of the bacteria associated with different mosses were mainly detected at the rDNA level. Obtained results clearly demonstrate that combination of 16S rDNA and 16S rRNA sequencing is preferred approach to have a good understanding on the constitution of the microbial communities in mosses.