Search

Two new dibenzofurans, bauhichamines A ( 1 ) and B ( 2 ), along with six known compounds ( 3 - 8 ), were isolated from the rattans of Bauhinia championii (Benth.) Benth. (Fabaceae). The structures of 1 and 2 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparison of their data with those reported in the literatures. All new compounds were evaluated for their anti-rheumatoid arthritis activities via examining their anti-proliferative effects on synoviocytes in vitro . Compounds 1 and 2 exhibited significant inhibitory effects on the proliferation of synoviocytes with the IC 50 values of 103.1 ± 1.8 and 146.4 ± 1.2 μM, respectively. [ABSTRACT FROM AUTHOR]

Carcinoembryonic antigen–related cell adhesion molecule 1 (CEACAM1) is a cell-cell adhesion receptor and is implicated in several cellular functions. It is rarely reported in ovarian tumors. The aim of this study is to determine the expression of CEACAM1 in ovarian tumors, trying to see whether CEACAM1 has different expression patterns as a function of histotype. Antigen expression was examined by immunohistochemistry with mouse anti-human antibody for CEACAM1. Immunohistochemistry was performed using avidin-biotin-diaminobenzide staining. The results were expressed as average score ± SD (0, negative; 8, highest) for each histotype. In ovarian tumors, the benign serous and mucinous cystadenoma negatively or weakly expressed CEACAM1, the malignant epithelial tumors strongly expressed CEACAM1, and there was significant difference between benign epithelial tumor and adenocarcinoma ( P < .05). The well-differentiated serous adenocarcinoma expressed CEACAM1 mainly with membrane pattern, and the intermediately and poorly differentiated serous adenocarcinomas expressed CEACAM1 mainly with cytoplasmic pattern ( P < .05). In addition, CEACAM1 expression is elevated in solid tumors of ovary but variable as a function of histotype. Compared with membranous expression, the cytoplasmic expression was observed almost in metastatic carcinoma that might decrease the adhesive interactions of the carcinoma cells with the surrounding cells, especially with tumor cells, and this could facilitate the tumor cells to metastasize to distant regions. So, we thought that cytoplasmic CEACAM1 might play an important role in tumor progression, especially in tumor metastasis. [ABSTRACT FROM AUTHOR]

Background & Aims: The pathogenesis of intrahepatic cholangiocarcinoma (ICC), the second most common hepatic cancer, is poorly understood, and the incidence of ICC is increasing worldwide. We searched for mutations in human ICC tumor samples and investigated how they affect ICC cell function. Methods: We performed whole exome sequencing of 7 pairs of ICC tumors and their surrounding nontumor tissues to detect somatic alterations. We then screened 124 pairs of ICC and nontumor samples for these mutations, including 7 exomes. We compared mutations in PTPN3 with tumor recurrence in 124 patients and PTPN3 expression levels with recurrence in 322 patients (the combination of both in 86 patients). The functional effects of PTPN3 variations were determined by RNA interference and transgenic expression in cholangiocarcinoma cell lines (RBE, HCCC-9810, and Huh28). Results: Based on exome sequencing, pathways that regulate protein phosphorylation were among the most frequently altered in ICC samples and genes encoding protein tyrosine phosphatases (PTPs) were among the most frequently mutated. We identified mutations in 9 genes encoding PTPs in 4 of 7 ICC exomes. In the prevalence screen of 124 paired samples, 51.6% of ICCs contained somatic mutations in at least 1 of 9 PTP genes; 41.1% had mutations in PTPN3. Transgenic expression of PTPN3 in cell lines increased cell proliferation, colony formation, and migration. PTPN3 L232R and PTPN3 L384H , which were frequently detected in ICC samples, were found to be gain-of-function mutations; their expression in cell lines further increased cell proliferation, colony formation, and migration. ICC-associated variants of PTPN3 altered phosphatase activity. Patients whose tumors contained activating mutations or higher levels of PTPN3 protein than nontumor tissues had higher rates of disease recurrence than patients whose tumors did not have these characteristics. Conclusions: Using whole exome sequencing of ICC samples from patients, we found that more than 40% contain somatic mutations in PTPN3. Activating mutations in and high expression levels of PTPN3 were associated with tumor recurrence. [Copyright &y& Elsevier]

Abstract: An efficient one-pot synthesis of highly functionalized bicyclic pyrrole derivatives by a three-component domino reaction of heterocyclic ketene aminals (HKAs), arylglyoxal monohydrate, and indoles in ethanol medium catalyzed by acetic acid is described. In this procedure, three sigma bonds were formed simultaneously. The present synthesis features excellent regio-selectivity, easy purification as well as simple starting materials. [Copyright &y& Elsevier]

Abstract: Three new cycloartane triterpenoids, aphagrandinoids A–C (1–3), and a new natural product, aphagrandinoid D (4), together with a known compound, were isolated from the leaves and twigs of Aphanamixis grandifolia. Their structures were elucidated by extensive NMR and MS techniques. Aphagrandinoid A (1), a 29-nor-cycloart triterpenoid, features with a sprio ring system at the side chain, while aphagrandinoid C (3) is a pentnortriterpenoid. Antibacterial activities of these five compounds were also evaluated. Compounds 1 and 5 showed weak antibacterial activities (MIC values: 1.57–3.13μg/mL) against Staphylococcus aureus, MRSA 92#, and MRSA 98#. [ABSTRACT FROM AUTHOR]

Abstract: Chitosan oligosaccharide (COS) derivatives have attracted significant interest in drug delivery systems because of their well-known low toxicity, excellent biocompatibility, and biodegradability. Paclitaxel-loaded nanoparticles based on salicylic acid-grafted chitosan oligosaccharide (COS/SA) were synthesized and characterized. Then, in order to understand the mechanism of the actions of the paclitaxel (PTX) encapsulated by COS/SA, all-atom molecular dynamics simulations were performed to analyze the aggregation of COS/SA molecules. The van der Waals and hydrophobic interactions are the major driving forces for the drug encapsulation process. Electrostatic and hydrogen-bonding interactions also play helpful roles in the COS/SA aggregation. Analyses of the radial distribution function and solvent accessible surface area indicate that the COS/SA nanoparticles are highly hydrosoluble and that the nanoparticles can significantly enhance the aqueous solubility of a hydrophobic drug. Different drug loading systems are also investigated in this work, and the best theoretical drug loading is found to be 10% (w/w). The present work provides insights into the mechanism of the atomic structures of drug-loaded polymeric nanoparticles and presents new perspective for the design of drug delivery systems with desirable properties. [Copyright &y& Elsevier]

Abstract: Purpose: To determine the feasibility of using R2⁎ map MRI for pretreatment diagnosis and monitoring of tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Material and Methods: Twenty-eight women with breast cancer, as evidenced by pathology, underwent MR imaging prior to and after chemotherapy. All patients were examined by conventional MRI and R2⁎ map imaging. Subjects were divided into major histological response (MHR) and non-major histological response (NMHR) groups. Mean R2⁎ values of cancerous and normal glandular tissues were measured before and following NAC. Differences in R2⁎ and ΔR2⁎% values between these two groups were compared with paired or independent t tests. The relationship between ΔR2⁎% and histological response was examined using Spearman''s correlation test. Results: Before NAC, the average R2⁎ values in carcinoma were lower than in normal glandular tissue (P<.05). After two to four cycles of NAC, the R2⁎ values in carcinoma were increased (P<.05 ), but this change was not significant in normal glandular tissue. After NAC, ΔR2⁎% was significantly higher in MHR as compared to NMHR (P<.05). The ΔR2⁎% correlated with the histological response (r=0.581, P<.01). Conclusion: In women undergoing NAC for breast cancer treatment, R2⁎ and ΔR2⁎% appear to provide predictive information of tumor response which is probably associated with changes in tumor angiogenesis and tissue oxygenation. R2⁎ map imaging of breasts may therefore be useful in monitoring tumor response to NAC. [Copyright &y& Elsevier]

Rationale and Objectives: To compare diffusion-weighted (DW) with standard T2-weighted imaging for quantitative evaluation of small hepatocellular carcinoma (HCC) in cirrhosis. Materials and Methods: Fourteen patients (all men; mean age, 58.6 years; age range, 45-69 years) with 22 small HCCs (<3 cm and >1 cm in diameter) in cirrhosis were included in the study. DW imaging with breath-hold single-shot echo planar imaging (b = 0, 800 seconds/mm2) and T2-weighted imaging with respiratory triggering fat-suppressed fast spin-echo sequence were performed on a 3-T magnetic resonance unit using an eight-channel torso phased-array coil. The signal intensity (SI) of HCC and liver were measured at workstation. Contrast-to-noise ratio (CNR), contrast ratio (CR, SIlesion/SIliver), and apparent diffusion coefficient (ADC) values were calculated. CNRs and CRs obtained with DW and T2-weighted images, and ADCs of HCC and liver were compared using nonparametric tests. Results: Two lesions were excluded because of artifacts on DW images. Thus 20 lesions were analyzed. The CNRs obtained with T2-weighted images (27.12 ± 21.12) were significantly higher (P = .02) than those with DW images (17.52 ± 13.50). There were no significant difference between the CRs obtained with T2-weighted images (1.83 ± 0.56) and DW images (2.01 ± 0.67). There were no significant difference between the mean ADCs of HCC (1.22 × 10−3 mm2/second ± 0.24) and the cirrhotic liver (1.17 × 10−3 mm2/second ± 0.17), either. Conclusion: DW imaging with high b value was not superior to standard T2-weighted imaging in terms of lesion conspicuity of small HCC in cirrhosis. [Copyright &y& Elsevier]

Eucommia ulmoides (EU) Oliver seeds are rich in oil and serve as a potential edible oil, but little is known about its phytochemical substances. In this study, the sterol profiles of the supercritical CO 2 fluid extracted EU seed oil and its contents were first evaluated by GC-MS analysis, and fifteen sterols and three triterpene alcohols were determined. β -sitosterol was detected as the most abundant phytosterol in the seed oil. Additionally, seven iridoid glycosides (1 – 7), namely aucubin (1), bartsioside (2), linaride (3), geniposidic acid (4), one dimer scyphiphin D (5), two trimers ulmoidoside A (6) and ulmoidoside B (7) were identified from the defatted seed flour, and the compound 3 was reported in E. ulmoides for the first time. Natural and two acetylated compounds (1 – 9) were evaluated for their inhibitory effects on NO production in the lipopolysaccharide (LPS)-stimulated microglial cells, and 1 – 3 exerted significant inhibition of NO generation with IC 50 values of 3.60, 7.09, and 10.52 μ M, respectively. The structure-activity relationships (SARs) of these iridoids indicated that OH groups on C-10 and C-6 were more effective and the COOH group at C-4 position was highly detrimental to the activity. The results suggest that the edible EU seeds could be a potential dietary source of aucubin and β -sitosterol for reducing the risk of neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Abstract: CuO/Ce0.8Zr0.2O2 catalysts were prepared by citrate method and used for carbon monoxide oxidation. The samples were characterized by XRD, XPS, BET and ICP-AES techniques. The catalytic properties of the catalysts were studied by using a microreactor-GC system. XRD analysis showed Ce0.8Zr0.2O2 was cubic, fluorite structure for all the catalysts. The XPS indicated the valence of Ce atom was +4 and there were reduced copper species presented in the CuO/Ce0.8Zr0.2O2 catalyst. The results showed that the CuO loadings, calcination temperature and calcination time affected the catalytic activity of the catalysts for low-temperature CO oxidation. For comparison, the catalytic activities of CuO/CeO2 catalysts calcined at different temperatures were also studied. The results indicated that CuO/Ce0.8Zr0.2O2 catalyst had better thermal resistance than CuO/CeO2 catalyst and had inferior activity than the CuO/CeO2 catalyst when they were both calcined at 600°C. [Copyright &y& Elsevier]

Summary: Glypican-3 (GPC3), a member of heparan sulfate proteoglycans, plays a role in cell growth, differentiation, and migration. The objectives of this study were to assess the diagnostic value of GPC3 immunostaining in hepatocellular carcinomas (HCCs) and to analyze its expression profile in preneoplastic lesions. Tissue microarrays were built by sampling 54 HCCs and adjacent liver tissues (21 developing from cirrhosis and 33 from normal liver) and 94 cirrhotic macronodules. Fourteen typical liver cell adenomas and 5 with malignant foci were also included. Sections were assessed for GPC3 expression by immunohistochemistry. GPC3 staining was observed in 19 (90%) of 21 HCC cases with cirrhosis and in 18 (64%) of 28 HCC cases with normal liver (P < .01). When staining was positive, it was both membranous and cytoplasmic. Positive staining was observed in 1 case of nonneoplastic adjacent liver. In cases of adenomas, only malignant foci were positive. Among the 94 macronodules, GPC3 immunostaining was noted in 48% (14/29) of high-grade dysplastic or early HCC and in 3% (2/65, P < .001) of benign or low-grade dysplastic macronodules. This study shows that GPC3 is an efficient diagnostic marker of HCC, potentially useful in the differential diagnosis of liver cell adenomas and well-differentiated HCC. Our results also suggest that GPC3 may be considered as an early marker of liver carcinogenesis because it is able to identify some cirrhotic macronodules with malignant potential. [Copyright &y& Elsevier]

Summary: Dental caries is a slowly progressive infectious disease with high risks. In response to dental caries stimuli, the tertiary dentin might be formed, protecting the dental pulp. Tertiary dentinogenesis contributes greatly to the treatment of carious lesions as well as the preservation and restoration of entire tooth function. A number of studies have found that application of exogenous growth factors such as transforming growth factors and bone morphogenetic proteins on unexposed pulps are able to signal tertiary dentinogenesis. Since precise mechanism of tertiary dentinogenesis is still not clear, more potential signaling factors might contribute to this process. Dentinogenesis shares many similarities with osteogenesis. The factors involved in osteogenesis and bone repair such as bone morphogenetic proteins 2, 7 and core binding factor α1 play important roles in dentinogenesis. LIM mineralization protein 1 is a critical positive regulator of osteoblast differentiation, bone formation and repair. It is logical to postulate that LIM mineralization protein 1 might be involved in odontoblast differentiation and dentin formation both in normal and in pathological conditions. Application of LIM mineralization protein 1 might be a promising approach for inducing tertiary dentinogenesis in dental caries treatment. [Copyright &y& Elsevier]

Background & Aims No targeted therapies have been found to be effective against hepatocellular carcinoma (HCC), possibly due to the large degree of intratumor heterogeneity. We performed genetic analyses of different regions of HCCs to evaluate levels of intratumor heterogeneity and associate alterations with responses to different pharmacologic agents. Methods We obtained samples of HCCs (associated with hepatitis B virus infection) from 10 patients undergoing curative resection, before adjuvant therapy, at hospitals in China. We collected 4–9 spatially distinct samples from each tumor (55 regions total), performed histologic analyses, isolated cancer cells, and carried them low-passage culture. We performed whole-exome sequencing, copy-number analysis, and high-throughput screening of the cultured primary cancer cells. We tested responses of an additional 105 liver cancer cell lines to a fibroblast growth factor receptor (FGFR) 4 inhibitor. Results We identified a total of 3670 non-silent mutations (3192 missense, 94 splice-site variants, and 222 insertions or deletions) in the tumor samples. We observed considerable intratumor heterogeneity and branched evolution in all 10 tumors; the mean percentage of heterogeneous mutations in each tumor was 39.7% (range, 12.9%–68.5%). We found significant mutation shifts toward C>T and C>G substitutions in branches of phylogenetic trees among samples from each tumor ( P < .0001). Of note, 14 of the 26 oncogenic alterations (53.8%) varied among subclones that mapped to different branches. Genetic alterations that can be targeted by existing pharmacologic agents (such as those in FGF19, DDR2, PDGFRA , and TOP1 ) were identified in intratumor subregions from 4 HCCs and were associated with sensitivity to these agents. However, cells from the remaining subregions, which did not have these alterations, were not sensitive to these drugs. High-throughput screening identified pharmacologic agents to which these cells were sensitive, however. Overexpression of FGF19 correlated with sensitivity of cells to an inhibitor of FGFR 4; this observation was validated in 105 liver cancer cell lines ( P = .0024). Conclusions By analyzing genetic alterations in different tumor regions of 10 HCCs, we observed extensive intratumor heterogeneity. Our patient-derived cell line-based model, integrating genetic and pharmacologic data from multiregional cancer samples, provides a platform to elucidate how intratumor heterogeneity affects sensitivity to different therapeutic agents. [ABSTRACT FROM AUTHOR]

Background & Aims: Overexpression of CD151 is associated with poor prognosis for hepatocellular carcinoma (HCC), yet its role in pathogenesis is not known. Methods: We analyzed the expression of the integrin subunit α6 by quantitative, real-time polymerase chain reaction and immunoblot analyses of 120 HCC tissue samples; its clinical significance was investigated using tissue microarray (TMAs) analysis of samples from 335 patients with HCC. Immunoprecipitation was used to assess the relationship between α6 and CD151. The molecular effects of high expression levels of α6 and CD151 in HCC cells were determined using RNA interference and pharmacologic approaches. Results: Overexpression of α6 correlated with poor prognosis of patients with HCC; α6 formed a complex with endogenous CD151 in HCC cells. In cells that expressed high levels of α6 and CD151, laminin-5 promoted cell spreading by inducing the epithelial–mesenchymal transition (EMT); this effect was not observed in cells that expressed high levels of only α6 or CD151. Cells that expressed high levels of α6 and CD151 underwent the EMT in response to laminin-5, through hyperactivation of phosphatidylinositol-3-kinase (PI3K), primarily induced via the PI3K–protein kinase B (Akt)–Snail–phosphatase and tensin homolog feedback pathway. The EMT was reversed by PI3K inhibitors and antibodies against CD151 or α6 in vitro, and was delayed by specific interference with CD151 and α6 in vivo. Conclusions: High expression levels of CD151 and α6 promote invasiveness of HCC cells. Either of these proteins, or PI3K signaling, might be targets for therapeutics for subgroups of patients with HCC. [Copyright &y& Elsevier]

Abstract: Four new compounds, including three new steroids (1–3) and one new sesquiterpene (6), and two new natural products (4–5), as well as three known steroids (7–9) were isolated from the twigs of Turraea pubescens. Compounds 3–5 are C22 steroids isolated from the Meliaceae family for the first time. Their structures were elucidated by extensive NMR and MS analyses. Compound 1 exhibited inhibitory activity against lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 cells with an IC50 value of 11.5μM. [Copyright &y& Elsevier]

The prognostic value and clinical relevance of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA) remain unclear. Thus, we aimed to investigate the prognostic value and functional involvement of TLSs in iCCA. We retrospectively included 962 patients from 3 cancer centers across China. The TLSs at different anatomic subregions were quantified and correlated with overall survival (OS) by Cox regression and Kaplan-Meier analyses. Multiplex immunohistochemistry (mIHC) was applied to characterize the composition of TLSs in 39 iCCA samples. A quaternary TLS scoring system was established for the intra-tumor region (T score) and peri-tumor region (P score) respectively. T scores positively correlated with favorable prognosis (p < 0.001), whereas a high P score signified worse survival (p < 0.001). mIHC demonstrated that both T follicular helper and regulatory T cells were significantly increased in intra-tumoral TLSs compared to peri-tumoral counterparts (p < 0.05), and regulatory T cell frequencies within intra-tumoral TLSs were positively associated with P score (p < 0.05) rather than T score. Collectively, the combination of T and P scores stratified iCCAs into 4 immune classes with distinct prognoses (p < 0.001) that differed in the abundance and distribution pattern of TLSs. Patients displaying an immune-active pattern had the lowest risk, with 5-year OS rates of 68.8%, whereas only 3.4% of patients with an immune-excluded pattern survived at 5 years (p < 0.001). The C-index of the immune class was statistically higher than the TNM staging system (0.73 vs. 0.63, p < 0.001). These results were validated in an internal and 2 external cohorts. The spatial distribution and abundance of TLSs significantly correlated with prognosis and provided a useful immune classification for iCCA. T follicular helper and regulatory T cells may play a critical role in determining the functional orientation of spatially different TLSs. Tertiary lymphoid structures (TLSs) are associated with favorable prognosis in a number of cancers. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains unclear. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed the opposite prognostic impacts of TLSs located within or outside the tumor. This difference could be mediated by the different immune cell subsets present within the spatially distinct TLSs. Based on our analysis, we were able to stratify iCCAs into 4 immune subclasses associated with varying prognoses. [Display omitted] • Tertiary lymphoid structures (TLSs) within and outside the tumor have opposite prognostic impacts on patients with iCCA. • The heterogeneous distribution of Tfh and Treg cells within distinct TLSs might be a determinant of their functional state. • The geographic integration of TLSs stratified iCCAs into 4 immune subclasses with distinct clinical outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Nanostructure Ce0.8Zr0.2O2 powders used as the support were synthesized by a hydrothermal route and the Au/Ce0.8Zr0.2O2 catalysts were prepared via deposition-precipitation method. The samples were characterized by X-ray diffraction pattern (XRD), Fourier transform Raman spectra (FT-Raman), high-resolution transmission electron microscope (HRTEM), X-ray photoelectron spectra (XPS) and temperature-programmed reduction (TPR) techniques. The influence of the pH values, Au loadings, calcination temperature and calcination time on the catalytic activity of the Au/Ce0.8Zr0.2O2 catalysts was investigated. The suitable pH value to prepare the catalysts was 7.0 and the suitable calcination conditions were 300°C and 3h. The Au(2wt.%)/Ce0.8Zr0.2O2 catalyst showed the best catalytic performance among all the prepared samples. TPR analysis indicated that the addition of gold can improve the reducibility of the catalyst obviously. XPS analysis revealed that both Ce4+ and Ce3+ were present on the surface of the catalyst. According to TPR and XPS analyses, the gold particles (Au0 and Au3+) existed in the catalyst, which played an important role in the catalytic activity. XRD and XPS results showed that the high dispersion degree of gold particles on the support was responsible for the superior catalytic property. [Copyright &y& Elsevier]

The presence of multifocal tumors, developed either from intrahepatic metastasis (IM) or multicentric occurrence (MO), is a distinct feature of hepatocellular carcinoma (HCC). Immunogenomic characterization of multifocal HCC is important for understanding immune escape in different lesions and developing immunotherapy. We combined whole-exome/transcriptome sequencing, multiplex immunostaining, immunopeptidomes, T cell receptor (TCR) sequencing and bioinformatic analyses of 47 tumors from 15 patients with HCC and multifocal lesions. IM and MO demonstrated distinct clonal architecture, mutational spectrum and genetic susceptibility. The immune microenvironment also displayed spatiotemporal heterogeneity, such as less T cell and more M2 macrophage infiltration in IM and higher expression of inhibitory immune checkpoints in MO. Similar to mutational profiles, shared neoantigens and TCR repertoires among tumors from the same patients were abundant in IM but scarce in MO. Combining neoantigen prediction and immunopeptidomes identified T cell-specific neoepitopes and achieved a high verification rate in vitro. Immunoediting mainly occurred in MO but not IM, due to the relatively low immune infiltration. Loss of heterozygosity of human leukocyte antigen (HLA) alleles, identified in 17% of multifocal HCC, hampered the ability of major histocompatibility complex to present neoantigens, especially in IM. An integrated analysis of Immunoscore, immunoediting, TCR clonality and HLA loss of heterozygosity in each tumor could stratify patients into 2 groups based on whether they have a high or low risk of recurrence (p = 0.038). Our study comprehensively characterized the genetic structure, neoepitope landscape, T cell profile and immunoediting status that collectively shape tumor evolution and could be used to optimize personalized immunotherapies for multifocal HCC. Immunogenomic features of multifocal hepatocellular carcinoma (HCC) are important for understanding immune-escape mechanisms and developing more effective immunotherapy. Herein, comprehensive immunogenomic characterization showed that diverse genomic structures within multifocal HCC would leave footprints on the immune landscape. Only a few tumors were under the control of immunosurveillance, while others evaded the immune system through multiple mechanisms that led to poor prognosis. Our study revealed heterogeneous immunogenomic landscapes and immune-constrained tumor evolution, the understanding of which could be used to optimize personalized immunotherapies for multifocal HCC. • Immunogenomic discrepancies among multifocal HCC vary within patients and shape tumor evolutionary trajectories. • Immune escape involves HLA alterations, M2 macrophage infiltration, inhibitory ligands and immunoediting. • Immune context imprinted by genetics can exert selective pressures. • Immune evasion correlates with tumor regression and can predict postoperative recurrence. • Personalized immunotherapy strategies should be adopted for multifocal HCC to maximize efficacy. [ABSTRACT FROM AUTHOR]

Because of the rapid development in the utilization hydrogen energy, various hydrogen storage techniques have attracted much attention. Among them, the hydrolysis of ammonia borane (NH 3 BH 3 , AB) over high-efficient and low-cost catalysts is one of the most interesting pathways. In this work, the magnetic collagen powder-graphene oxide hybrids (CGP-GO-Fe 3 O 4) are synthesized by a facile self-assembly method combined with co-precipitation synthesis routes. Then, the hybrids are employed to immobilize palladium nanoparticles with an in-situ reduction strategy. The as-prepared Pd/CGP-GO-Fe 3 O 4 catalysts exhibit good catalytic activity and excellent recyclability for H 2 generation from AB. Under the present reaction conditions, the activation energy and turnover frequency for the hydrolysis of AB are 36.5 kJ mol−1 and 27.4 m o l H 2 · m o l P d − 1 · m i n − 1 , respectively. In addition, the hydrolysis reaction is found to be of 0.93 and 0.40 orders with respect to the palladium and AB concentrations, respectively. The results demonstrate that Pd/CGP-GO-Fe 3 O 4 could be efficiently applied in the utilization of hydrogen energy. Image 1 • A new magnetic organic-inorganic hybrid (CGP-GO-Fe 3 O 4) was facilely assembled. • Pd/CGP-GO-Fe 3 O 4 exhibited superior catalytic performance for AB hydrolysis. • The magnetic catalysts obtained can be easily separated from the reaction system. [ABSTRACT FROM AUTHOR]

Urinary tract infection (UTI), primarily caused by uropathogenic Escherichia coli (UPEC), is one of the most common infectious diseases worldwide. Emerging antibiotic resistance requires novel treatment strategies. Luteolin, a dietary polyphenolic flavonoid, has been confirmed as a potential antimicrobial agent. Here, we evaluated the sub-MICs of luteolin for potential properties to modulate the UPEC infection. We found that luteolin significantly decreased the attachment and invasion of UPEC J96 or CFT073 in human bladder epithelial cell lines T24. Meanwhile, obvious decreased expression of type 1 fimbriae adhesin fimH gene, lower bacterial surface hydrophobicity and swimming motility, were observed in luteolin-pretreated UPEC. Furthermore, luteolin could attenuate UPEC-induced cytotoxicity in T24 cells, which manifested as decreased activity of lactate dehydrogenase (LDH). Simultaneously, the inhibition of luteolin on UPEC-induced cytotoxicity was confirmed by ethidium bromide/acridine orange staining. Finally, the luteolin-pretreated UPEC showed a lower ability of biofilm formation. Collectively, these results indicated that luteolin decreased the attachment and invasion of UPEC in bladder epithelial cells, attenuated UPEC-induced cytotoxicity and biofilm formation via down-regulating the expression of adhesin fimH gene, reducing the bacterial surface hydrophobicity and motility. [ABSTRACT FROM AUTHOR]

Abstract: The formation and interfacial adsorption of glycinin/chitosan (CS) soluble complex were investigated at acidic pH. The stability of the mixed emulsion stabilized by the complex was also evaluated at pH 4.5. Turbidimetric analysis, isothermal titration calorimetry (ITC) and dynamic light scattering were used to characterize the dynamic formation of the complex. The results showed that soluble complexes were formed mainly at pHs between 4.0 and 6.0, depending on CS/Glycinin mixing ratio. At pH 4.5, soluble complex was formed and saturated at mixing ratio = 0.1, showing a maximum size distribution at 164.2 nm. We found that the glycinin/CS soluble complex showed improved interfacial adsorption than glycinin at pH 4.5. In detail, dynamic interfacial adsorption data showed the coefficient of diffusion (K diff), unfolding (K 1) and rearrangement (K 2) for soluble complex (K diff, K 1 and K 2: 0.58 mNm−1 s−0.5, 2.23 E−4 s−1 and 5.78 E−4 s−1) were higher than those of the glycinin (K diff, K 1 and K 2: 0.32 mNm−1 s−0.5, 1.72 E−4 s−1 and 4.63 E−4 s−1). The droplet size and confocal observation of the mixed emulsion fabricated with glycinin/CS soluble complex displayed improved stability at mixing ratios of 0.1 to/and 0.2, suggesting the synergistic effect of the two molecules. We concluded that interfacial and emulsifying properties of glycinin could be improved by formation of glycinin/CS soluble complex at acidic pH. [Copyright &y& Elsevier]