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In this study, hexylresorcinol calix[4]arene (HRCA) is introduced into the reaction system, and HRCA-capped ZnO–Ag nanocomposites are prepared via a simple one-step reflux method. HRCA is used not only as a reducing agent for deoxidizing Ag+ to Ag, but also as a protectant for wrapping around the microstructure of the formed ZnO–Ag. The prepared samples are characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy (TEM), high-resolution TEM, X-ray photoelectron spectroscopy, Fourier-transform infrared spectroscopy, and water contact angle. The Ag nanoparticles and ZnO adhere to each other and HRCA molecules encapsulate on the surface of ZnO–Ag nanocomposites. HRCA-capped ZnO–Ag nanocomposites with different Ag contents are investigated for use in photodegradation of organic pollutants (rhodamine B (RhB) and levofloxacin hydrochloride). The sample with 10.20 mol% Ag, denoted as ZA3, exhibits the highest catalytic activity for photodegradation of RhB and levofloxacin hydrochloride. Moreover, ZA3 exhibits high stability during photodegradation of organic pollutants even after multiple reuses. The possible photocatalytic mechanism is discussed. We believe that O 2 − and h+ are the chief active species responsible for the photocatalytic activity of HRCA-capped ZnO–Ag nanocomposite system. HRCA-capped ZnO–Ag nanocomposite is expected to be an effective photocatalyst with potential application to sewage treatment under sunlight. [ABSTRACT FROM AUTHOR]

Abstract: We take a new look at the multicut problem in trees, denoted multicut on trees henceforth, through the eyes of the vertex cover problem. This connection, together with other techniques that we develop, allows us to give an upper bound of on the kernel size for multicut on trees, significantly improving the upper bound given by Bousquet et al. We exploit this connection further to present a parameterized algorithm for multicut on trees that runs in time , where . This improves the previous (time) upper bound of , given by Guo and Niedermeier, for the problem. [Copyright &y& Elsevier]

Abstract: An N-acyl homoserine lactonase gene aiiA, transcribed by a strong and constitutive Escherichia coli promoter P lpp (Accession No. EU723847), was transformed into Lysobacter enzymogenes strain OH11, creating strain OH11A. The N-acyl-homoserine lactone (AHL)-degradation assay showed that transformant OH11A acquired the ability to degrade AHL molecules produced by Agrobacterium tumefaciens, Pectobacterium carotovorum, Pseudomonas syringae pv. tomato strain DC3000 and Acidovorax avenae subsp. citrulli. Pathogenicity tests showed that while the parental strain OH11 did not reduce P. carotovorum infection, the transformant OH11A caused a strong reduction of Pectobacterium virulence on Chinese cabbage and cactus, whereas strain OH11A did not seem to interfere with the normal growth of this pathogen in cabbages. In antimicrobial activity assays, strain OH11A and OH11 showed similar antimicrobial activity against Phytophthora capsici and Sclerotinia sclerotiorum. This work provided a new strategy for developing genetically engineered multi-functional L. enzymogenes strains that possessed the ability to biologically control fungal pathogens and reduce bacterial pathogenicity. [Copyright &y& Elsevier]

Abstract: CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor–ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment. [Copyright &y& Elsevier]

Sucrose phosphorylase (SPase, EC 2.4.1.7) has a wide range of application in food, cosmetics, and pharmaceutical industries because of its broad substrate specificity. However, low SPase yields produced by wild-type strains cannot meet industrial requirements due to their complex metabolic regulation mechanisms. In this study, spase gene from Thermoanaerobacterium thermosaccharolyticum was cloned and expressed in Escherichia coli BL21 (DE3), leading to 7.05 U/mL (3.71 U/mg) of T. thermosaccharolyticum SPase (Tt SPase) under optimum conditions. Co-expression of molecular chaperone teams pGro7 (GroES-GroEL), pG-KJE8 (DnaK-DnaJ-GrpE and GroES-GroEL), and pG-TF2 (GroES-GroEL-Tig) significantly enhanced the Tt SPase activities to 18.5 U/mg (59.2 U/mL), 9.52 U/mg (28.6 U/mL), and 25.7 U/mg (64.5 U/mL), respectively. Results suggested that GroES-GroEL chaperone combination could regulate protein folding processes and protect misfolded proteins from aggregation. The enzymatic characterization results showed that Tt SPase had an optimal temperature of 60 °C and optimal pH of 6.5. In particular, it had high thermostability of T 50 30 = 67 °C and half-life (t 1/2 at 70 °C) of 19 min. Furthermore, purified Tt SPase was used for hydroquinone transglycosylation and 21% of molar production yield of α-arbutin was obtained. This study provides a Tt SPase with high thermostability for potential industrial applications, and develops an effective strategy for improving soluble Tt SPase production in E. coli. • GroES-GroEL accompanied by TF greatly enhanced the soluble expression of Tt SPase. • The characterization of recombinant Tt SPase was investigated. • The recombinant Tt SPase was applied for the synthesis of α-arbutin. [ABSTRACT FROM AUTHOR]

Cancer-associated fibroblasts (CAFs) are the main components in the tumor microenvironment. Tumors activate fibroblasts from quiescent state into activated state by secreting cytokines, and activated CAFs may in turn promote tumor progression and metastasis. Therefore, studies targeting CAFs could enrich the therapeutic options for tumor treatment. In this study, we demonstrate that the content of lipid droplets and the expression of autophagosomes were higher in CAFs than in peri-tumor fibroblasts (PTFs), which was inhibited by 5-(tetradecyloxy)-2-furoic acid(TOFA). The expression of CD36 in CAFs was higher than that in PTFs at both mRNA and protein levels. Inhibition of CD36 activity using either the CD36 inhibitor SSO or siRNA had a significant negative impact on the proliferation and migration abilities of CAFs, which was associated with reduced levels of relevant activated genes (α-SMA, FAP, Vimentin) and cytokines (IL-6, TGF-β and VEGF-α). SSO also inhibited HCC growth and tumorigenesis in nude mice orthotopically implanted with CAFs and HCC cells. Our data further show that CD36+CAFs affected the expression of PD-1 in CTLs leading to CTL exhaustion, and that patients with high CD36 expression in CAFs were correlated with shorter overall survival (OS). Together, our data demonstrate that CAFs were active in lipid metabolism with increased lipid content and lipophagy activity. CD36 may play a key role in the regulation of the biological behaviors of CAFs, which may influence the proliferation and migration of tumor cells by reprograming the lipid metabolism in tumor cells. Thus, CD36 could be an effective therapeutic target for the treatment of HCC. [ABSTRACT FROM AUTHOR]

The combination of antiangiogenic agents and immune checkpoint inhibitors is more efficient than monotherapy in the management of hepatocellular carcinoma (HCC). Lenvatinib plus anti-PD1 antibodies have become the mainstay in HCC treatment. However, more than half the patients with HCC are non-responsive, and the mechanisms underlying drug resistance are unknown. To address this issue, we performed single-cell sequencing on samples from six HCC patients, aiming to explore cellular signals and molecular pathways related to the effect of lenvatinib plus anti-PD1 antibody treatment. GSVA analysis revealed that treatment with lenvatinib plus anti-PD1 antibody led to an increase in the TNF-NFKB pathway across all immune cell types, as compared to the non-treatment group. Mucosal-associated invariant T (MAIT) cells were found to secrete TNF, which activates TNFRSF1B on regulatory T cells, thereby promoting immunosuppression. Additionally, TNFSF9 was highly expressed in anticancer immune cells, including CD8+ effector T cells, MAIT, and γδ T cells in the treatment group. We also detected CD3+ macrophages in both HCC and pan-cancer tissues. Overall, our findings shed light on the potential mechanisms behind the effectiveness of lenvatinib plus anti-PD1 antibody treatment in HCC patients. By understanding these mechanisms better, we may be able to develop more effective treatment strategies for patients who do not respond to current therapies. [ABSTRACT FROM AUTHOR]

• Microglia release pro-inflammatory cytokines and chemokine CCL-2 following CH. • Microglia-derived CCL-2 recruits monocyte/macrophage infiltration in cerebellum. • Inhibition of microglia/CCL-2 alleviates CH-induced neuroinflammatory responses. • Inhibition of microglia/CCL-2 prevents apoptosis and dysfunction of Purkinje cells. • Suppression of microglia/CCL-2 ameliorates cerebellar injury and ataxia after CH. Ataxia, characterized by uncoordinated movement, is often found in patients with cerebellar hemorrhage (CH), leading to long-term disability without effective management. Microglia are among the first responders to CNS insult. Yet the role and mechanism of microglia in cerebellar injury and ataxia after CH are still unknown. Using Ki20227, an inhibitor for colony-stimulating factor 1 receptor which mediates the signaling responsible for the survival of microglia, we determined the impact of microglial depletion on cerebellar injury and ataxia in a murine model of CH. Microglial depletion reduced cerebellar lesion volume and alleviated gait abnormality, motor incoordination, and locomotor dysfunction after CH. Suppression of CH-initiated microglial activation with minocycline ameliorated cerebellum infiltration of monocytes/macrophages, as well as production of proinflammatory cytokines and chemokine C–C motif ligand-2 (CCL-2) that recruits monocytes/macrophages. Furthermore, both minocycline and bindarit, a CCL-2 inhibitor, prevented apoptosis and electrophysiological dysfunction of Purkinje cells, the principal neurons and sole outputs of the cerebellar cortex, and consequently improved ataxia-like motor abnormalities. Our findings suggest a detrimental role of microglia in neuroinflammation and ataxic motor symptoms after CH, and pave a new path to understand the neuroimmune mechanism underlying CH-induced cerebellar ataxia. [ABSTRACT FROM AUTHOR]

Curcumin, a yellow polyphenol extracted from the rhizome of turmeric root ( Curcuma longa ) has potent anti-cancer properties in many types of tumors with ability to reverse multidrug resistance of cancer cells. However, widespread clinical application of this agent in cancer and other diseases has been limited due to its poor aqueous solubility. The recent findings of polymeric nanoparticle formulation of curcumin (NFC) have shown the potential for circumventing the problem of poor solubility, however evidences for NFC's anti-cancer and reverse multidrug resistance properties are lacking. Here we provide models of human hepatocellular carcinoma (HCC), the most common form of primary liver cancer, in vitro and in vivo to evaluate the efficacy of NFC alone and in combination with sorafenib, a kinase inhibitor approved for treatment of HCC. Results showed that NFC not only inhibited the proliferation and invasion of HCC cell lines in vitro , but also drastically suppressed primary tumor growth and lung metastases in vivo . Moreover, in combination with sorafenib, NFC induced HCC cell apoptosis and cell cycle arrest. Mechanistically, NFC and sorafenib synergistically down-regulated the expression of MMP9 via NF-κB/p65 signaling pathway. Furthermore, the combination therapy significantly decreased the population of CD133-positive HCC cells, which have been reported as cancer initiating cells in HCC. Taken together, NanoCurcumin provides an opportunity to expand the clinical repertoire of this agent. Additional studies utilizing a combination of NanoCurcumin and sorafenib in HCC are needed for further clinical development. [ABSTRACT FROM AUTHOR]

Highlights: [•] miR-612 suppresses tumorsphere and clone formation of HCC cells. [•] miR-612 reduces drug resistance of HCC cells. [•] miR-612 suppresses tumorigenesis of HCC in NOD/SCID mice. [•] miR-612 inhibits an invasive frontier of HCC xenografts. [•] miR-612 suppresses Wnt/β-catenin signaling. [Copyright &y& Elsevier]

Abstract: Cr(VI) compounds are known human carcinogens that primarily target the lungs. Cr(VI) produces reactive oxygen species (ROS), but the exact effects of ROS on the signaling molecules involved in Cr(VI)-induced carcinogenesis have not been extensively studied. Chronic exposure of human bronchial epithelial cells to Cr(VI) at nanomolar concentrations (10–100nM) for 3months not only induced cell transformation, but also increased the potential of these cells to invade and migrate. Injection of Cr(VI)-stimulated cells into nude mice resulted in the formation of tumors. Chronic exposure to Cr(VI) increased levels of intracellular ROS and antiapoptotic proteins. Transfection with catalase or superoxide dismutase (SOD) prevented Cr(VI)-mediated increases in colony formation, cell invasion, migration, and xenograft tumors. While chronic Cr(VI) exposure led to activation of signaling cascades involving PI3K/AKT/GSK-3β/β-catenin and PI3K/AKT/mTOR, transfection with catalase or SOD markedly inhibited Cr(VI)-mediated activation of these signaling proteins. Inhibitors specific for AKT or β-catenin almost completely suppressed the Cr(VI)-mediated increase in total and active β-catenin proteins and colony formation. In particular, Cr(VI) suppressed autophagy of epithelial cells under nutrition deprivation. Furthermore, there was a marked induction of AKT, GSK-3β, β-catenin, mTOR, and carcinogenic markers in tumor tissues formed in mice after injection with Cr(VI)-stimulated cells. Collectively, our findings suggest that ROS is a key mediator of Cr(VI)-induced carcinogenesis through the activation of PI3K/AKT-dependent GSK-3β/β-catenin signaling and the promotion of cell survival mechanisms via the inhibition of apoptosis and autophagy. [Copyright &y& Elsevier]

Abstract: Autophagy is a lysosomal degradation pathway that can degrade bulk cytoplasm and superfluous or damaged organelles, such as mitochondria, to maintain cellular homeostasis. It is now known that dysregulation of autophagy can cause pathogenesis of numerous human diseases. Here, we discuss the critical roles that autophagy plays in the pathogenesis of liver diseases such as non-alcoholic and alcoholic fatty liver, drug-induced liver injury, protein aggregate-related liver diseases, viral hepatitis, fibrosis, aging and liver cancer. In particular, we discuss the emerging therapeutic potential by pharmacological modulation of autophagy for these liver diseases. [Copyright &y& Elsevier]

Abstract: Epidermal growth factor receptor variant III (EGFRvIII), the most common EGFR mutation, is associated with cell migration of glioblastoma multiforme (GBM) cases; however, the mechanism has not been elucidated. In this study, we found that the EGFRvIII-promoted glioma cell migration was closely linked to high levels of tyrosine phosphorylation in focal adhesion kinase (FAK) Y397. We also demonstrated that EGFRvIII formed a complex with FAK, resulting in enhanced tyrosine phosphorylation levels of FAK Y397 and EGFR Y1068. After knockdown of FAK expression via anti-FAK shRNA, the U87ΔEGFR cell migration was significantly inhibited, accompanying with the reduced phosphorylation levels of extracellular signal-regulated kinase (ERK1/2). Furthermore, the role of ERK1/2 in FAK-regulated cell migration was confirmed. Taken together, our results suggest that FAK and its downstream molecule ERK were involved in EGFRvIII-promoted glioma cell migration in U87ΔEGFR cells. [ABSTRACT FROM AUTHOR]

The Asian citrus psyllid, Diaphorina citri , is the principal vector of Huanglongbing pathogen Candidatus Liberibacter asiaticus (CLas), which causes severe economic losses to citrus industry worldwide. Use of broad-spectrum insecticides to control D. citri has resulted in considerable resistance development. Specific chemosensory proteins such as odorant binding proteins (OBPs) are potentially involved in reduced insecticide susceptibility. However, functional data on the contribution of OBPs to reduced susceptibility of D. citri are unavailable. We found that DcitOBP2 was stably expressed in different developmental stages and highly expressed in the legs, head and cuticle of D. citri. Expression of DcitOBP2 was significantly induced by 12 to 48 h of imidacloprid exposure and ranged from a 1.34- to 2.44-fold increase. RNAi of DcitOBP2 increased the susceptibility of D. citri adults to imidacloprid. The purified recombinant protein of DcitOBP2 expressed in Escherichia coli showed strong in vitro binding activity (K d = 62.39 nM) to imidacloprid using microscale thermophoresis technology (MST). DcitOBP2 also had strong binding ability to thiamethoxam and dinotefuran but it had no response to abamectin, fenpropathrin and chlorpyrifos. The results showed that DcitOBP2 can interact with several neonicotinoid insecticides. This suggests that DcitOBP2 is involved in the decreased susceptibility of D. citri to imidacloprid. Our data reveal a new function of insect OBPs as a buffering protein that helps insects survive insecticide exposure. Our investigation may also aid in the development of new methods for resistance management of D. citri. Unlabelled Image • DcitOBP2 can be significantly induced by imidacloprid exposure. • RNAi of DcitOBP2 increased the susceptibility of D. citri to imidacloprid. • Recombinant protein DcitOBP2 had a strong binding property to imidacloprid in vitro. [ABSTRACT FROM AUTHOR]

Hepatocarcinogenesis is a complicated process that is affected by a variety of microenvironmental factors, such as secretory chemokines and cell-extracellular matrix (ECM). Retinoic acid receptor-related orphan receptor (ROR)-α has been shown to attenuate tumor invasiveness by inducing suppressive cell microenvironment, and its low expression was associated with a worse prognosis in HCC patients. In the present study, we attempted to investigate the role and mechanism of the dominant transcript of ROR-α, ROR-α-1, in HCC development and progression. Among the four transcripts (ROR-α-1/-2/-3/-4), overexpression of ROR-α-1 dramatically suppressed the capacity of MHCC97H cells to proliferate, migrate and invade. We analyzed the differentially expressed genes in ROR-α-1-overexpressed and non-overexpressed MHCC97H cells, performed Gene Ontology (GO) enrichment analysis on these differentially-expressed genes, and found out that factors involved in the tumor microenvironment and ECM are related to the anti-tumor effects of ROR-α-1. Among these factors, chemokine CXCL5 was significantly downregulated by ROR-α-1 overexpression. Overexpression of ROR-α-1 remarkably inhibited the capacity of HCC cells to proliferate, migrate, invade, and downregulated the protein levels of β-catenin, c-Myc, Cyclin D1, and N-cadherin, suggesting the tumor-suppressive role of ROR-α-1 in MHCC97H cells. Moreover, overexpression of CXCL5 dramatically attenuated the suppressive effects of cell proliferation, migration and invasion induced by ROR-α-1 overexpression in MHCC97H, suggesting that ROR-α-1 exerts its anti-tumor effects via downregulating CXCL5. In conclusion, we demonstrate the tumor-suppressive role of ROR-α-1 in MHCC97H cells and that ROR-α-1 might play a tumor-suppressive role via regulation of chemokine CXCL5. [ABSTRACT FROM AUTHOR]