The inner structure of realistic materials make them exhibit momentum relaxation. In this paper we study the Joule-Thomson effect on AdS black holes in which translational invariance is broken by two ...methods: First by considering planar black holes in general relativity supported by scalar fields with a linear dependence on the horizon coordinates and secondly by considering black holes in massive gravity models in which momentum relaxation is obtained by breaking the bulk diffeomorphism invariance of the theory. In contrast with black holes studied so far, for both theories it is possible to obtain inversion curves with two branches reproducing the behavior of Van der Waals fluids. Moreover in the specific case of the massive gravity model we show that black holes can heat up when crossing the inversion curve.
Down‐regulation of microRNA‐26a (miR‐26a) is associated with poor prognosis of hepatocellular carcinoma (HCC), but its functional mechanism in HCC remains unclear. In this study, we investigated the ...roles of miR‐26a in tumor growth and metastasis of HCC and found that miR‐26a was frequently down‐regulated in HCC tissues. Down‐regulation of miR‐26a correlated with HCC recurrence and metastasis. Through gain‐ and loss‐of‐function studies, miR‐26a was demonstrated to significantly inhibit in vitro cell proliferation, migration, and invasion. In addition, miR‐26a induced G1 arrest and promoted apoptosis of HCC cells. Importantly, miR‐26a suppressed in vivo tumor growth and metastasis in nude mice models bearing human HCC. Interleukin‐6 (IL‐6) was identified as a target of miR‐26a. Knockdown of IL‐6 induced effects on HCC cells similar to those induced by miR‐26a. In contrast, IL‐6 treatment abrogated the effects induced by miR‐26a up‐regulation. Moreover, miR‐26a dramatically suppressed expression of signal transducer and activator of transcription 3 (Stat3) target genes, including Bcl‐2, Mcl‐1, cyclin D1, and MMP2. IL‐6 treatment antagonized this effect, while knockdown of IL‐6 by IL‐6 short hairpin RNA (shIL‐6) induced inhibitory effects on the expression of p‐Stat3 and its main target genes, similar to miR‐26a. The messenger RNA and protein levels of IL‐6 inversely correlated with miR‐26a in HCCs. Patients with high miR‐26a or low IL‐6 in HCC tissues had a better prognosis with longer overall survival (OS) and time to recurrence (TTR). In multivariate analysis, miR‐26a, IL‐6, and their combination were demonstrated to be independent prognostic indicators for OS and TTR of HCC patients. Conclusion: miR‐26a could suppress tumor growth and metastasis of HCC through IL‐6‐Stat3 signaling and is a novel prognostic marker and therapeutic target for HCC. (HEPATOLOGY 2013)
In the tumour microenvironment, critical drivers of immune escape include the oncogenic activity of the tumour cell-intrinsic osteopontin (OPN), the expression of programmed death ligand 1 (PD-L1) ...and the expansion of tumour-associated macrophages (TAMs). We investigated the feasibility of targeting these pathways as a therapeutic option in hepatocellular carcinoma (HCC) mouse models.
We analysed the number of tumour-infiltrating immune cells and the inflammatory immune profiles in chemically induced liver tumour isolated from wild-type and
knockout (KO) mice. In vitro cell cocultures were further conducted to investigate the crosstalk between TAMs and HCC cells mediated by OPN, colony stimulating factor-1 (CSF1) and CSF1 receptor (CSF1R). The in vivo efficacy of anti-PD-L1 and CSF1/CSF1R inhibition was evaluated in OPN overexpressing subcutaneous or orthotopic mouse model of HCC.
The numbers of TAMs, as well as the expression levels of M2 macrophage markers and PD-L1 were significantly decreased, but the levels of cytokines produced by T-helper 1 (Th1) cells were upregulated in tumour tissues from OPN KO mice compared with that from the controls. In addition, we observed a positive association between the OPN and PD-L1 expression, and OPN expression and TAM infiltration in tumour tissues from patients with HCC. We further demonstrated that OPN facilitates chemotactic migration, and alternative activation of macrophages, and promotes the PD-L1 expression in HCC via activation of the CSF1-CSF1R pathway in macrophages. Combining anti-PD-L1 and CSF1R inhibition elicited potent antitumour activity and prolonged survival of OPN
tumour-bearing mice. Histological, flow cytometric and ELISA revealed increased CD8
T cell infiltration, reduced TAMs and enhanced Th1/Th2 cytokine balance in multiple mouse models of HCC.
OPN/CSF1/CSF1R axis plays a critical role in the immunosuppressive nature of the HCC microenvironment. Blocking CSF1/CSF1R prevents TAM trafficking and thereby enhances the efficacy of immune checkpoint inhibitors for the treatment of HCC.
Developing efficient adsorbents for the removal of water pollutants is of great significance for environmental protection. In this study, conjugated triaryl triazines (CTT), containing intramolecular ...hydrogen-bonding patterns, were recognized to be intriguing building blocks for the construction of porous organic polymer (POP) adsorbents. These planar monomers with multiple phenolic hydroxyl groups facilitated the formation of aza-linked polymers with hierarchical porous structures, sheet-like morphology, good surface wettability, and high degree of functionality. Such structural characteristics of the CTT-POP adsorbents provided superfast adsorption of various cationic dyes from water. For the adsorption of methylene blue dye, the pseudo-second-order rate constant of CTT-POP-1 is 12.9 g mg–1 min–1, superior to those reported in the existing literature. In addition, CTT-POP-1 can be regenerated at least seven times with no loss in performance, indicating its potential application in water treatment.
Extensive research has reported that the tumor microenvironment components play crucial roles in tumor progression. Thus, blocking the supports of tumor microenvironment is a promising approach to ...prevent cancer progression. We aimed to determine whether blocking extracellular ATP-P2RY2 axis could be a potential therapeutic approach for PDAC treatment.
Expression of P2RY2 was determined in 264 human PDAC samples and correlated to patient survival. P2RY2 was inhibited in human PDAC cell lines by antagonist and shRNA, respectively, and cell viability, clonogenicity, and glycolysis were determined. RNA sequencing of PDAC cell line was applied to reveal underlying molecular mechanisms. Multiple PDAC mouse models were used to assess the effects of the P2RY2 inhibition on PDAC progression.
P2RY2 was upregulated and associated with poor prognosis in PDAC. Activated P2RY2 by increased extracellular ATP in tumor microenvironment promoted PDAC growth and glycolysis. Further studies showed that the agonist-activated P2RY2 triggered PI3K/AKT-mTOR signaling by crosstalk with PDGFR mediated by Yes1, resulting in elevated expression of c-Myc and HIF1α, which subsequently enhanced cancer cell glycolysis. Genetic and pharmacologic inhibition of P2RY2 impaired tumor cell growth in subcutaneous and orthotopic xenograft model, as well as delayed tumor progression in inflammation-driven PDAC model. In addition, synergy was observed when AR-C118925XX, the selective antagonist of P2RY2 receptor, and gemcitabine were combined, resulting in prolonged survival of xenografted PDAC mice.
These findings reveal the roles of the P2RY2 in PDAC metabolic reprogramming, suggesting that P2RY2 might be a potential metabolic therapeutic target for PDAC.
Ionic liquid (IL)-assisted pretreatment of lignocellulosic biomass has been extensively studied. Cellulose and hemicelluloses are rich resources of sugars for biofuels. Lignin is a valuable feedstock ...for aromatic-based platform chemicals. In this study, a series of ionic liquids (ILs) were prepared with one-step synthesis and were investigated for their activity to pretreat lignocelluloses. High yields of lignin (61.0% and 60.4%) were achieved through HpyCl and HmimCl pretreatment of poplar. Lignin yields of 51.7% and 50.3% were obtained with a HpyCl and HnmpCl pretreatment of bamboo. Improving enzymatic hydrolysis was observed from the regenerated poplar with HpyCl pretreatment and the regenerated bamboo with HmimCl pretreatment. The isolated fractions were characterized by FTIR (Fourier transform infrared) spectroscopy. SEM (Scanning electron microscopy) and XRD (X-ray diffractometry) were employed to examine the cellulose-rich materials. A 2D
1
H-
13
C heteronuclear single quantum coherence (HSQC) nuclear magnetic resonance (NMR) spectroscopy was employed to analyze lignin fraction. These ionic liquids were particularly effective to extract lignin from lignocelluloses to obtain cellulose-rich materials for biofuels.
Ionic liquid (IL)-assisted pretreatment of lignocellulosic biomass has been extensively studied.
High-performance liquid chromatography (HPLC) and linear-ion trap (LTQ)/Orbitrap high-resolution mass spectrometry were used to identify porcine gelatins extracted at different temperatures. ...Moreover, shear stress rheological detection techniques and a texture analyzer were applied to evaluate the gelling properties of various porcine gelatins. The results showed that, with an increased in the extraction temperature, the gel strength, gelation point and melting point of the porcine gelatin gradually decreased, indicating that the temperature significantly affected the gelling properties of gelatin. HPLC- LTQ/Orbitrap high-resolution mass spectrometry indicated that porcine gelatins prepared at different extraction temperatures also showed internal uniqueness, namely, diverse marker peptides for gelatin identification. Compared with the established theoretical sequence fragment database of porcine gelatin and bovine gelatin, 64, 74 and 71 tryptic porcine peptides in gelatins were extracted at 55 °C, 65 °C and 75 °C, respectively. Notably, regardless of the extraction temperature, 47 common peptides were detected in the tryptic hydrolysates of porcine gelatins. Using these common tryptic peptides can effectively improve the accuracy of the porcine gelatin identification.
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•Extraction temperature would affect the identification of porcine gelatin.•64, 74 and 71 peptides were extracted at 55 °C, 65 °C and 75 °C, respectively.•47 common peptides were detected regardless of the extraction temperature.•Gel strength and gelling-melting points decreased as the temperature rising.
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