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Abstract: In this paper, an efficient l 1-regularized reconstruction method named the primal-dual interior-point (PDIP) method is presented for three-dimensional bioluminescence tomography (BLT) based on the adaptive finite element framework. Taking into account the sparse characteristic of the bioluminescent source, the BLT inverse problem is considered to be a linear programming problem and is represented by its primal and dual form. The source localization and quantification are obtained by solving the primal-dual Newton equation system. The comparisons between PDIP and the classical conjugate gradient least square (CGLS) algorithm are implemented to validate our method. Results from numerical simulation and an in vivo mouse experiment demonstrate the credibility and the potential of the proposed method in practical BLT reconstruction. [Copyright &y& Elsevier]

Abstract: PD-L1 (CD274) is a critical membrane-bound costimulatory molecule that inhibits immune responses through its receptor, PD-1. Previous data have showed that this molecule is associated with autoimmune diseases, chronic viral infections and tumor immune escape. However, the existence and role of soluble form of human PD-L1 (sPD-L1) remain unknown. We show here that a novel enzyme-linked immunosorbent assay (ELISA) was developed to detect the sPD-L1 protein. Many culture supernatants of the PD-L1+ cell lines contain high levels of this factor. Interestingly, the sPD-L1 is detectable in human serum and the concentration increases in an age-dependent manner. Human sPD-L1 has a unique protein form in the serum and the matrix metalloproteinase inhibitor (MMPI) could suppress sPD-L1 production. Moreover, the sPD-L1 could specially bind to PD-1. Together, these data demonstrate that the existence of circulating sPD-L1 in human serum might play an important role in immunoregulation. [Copyright &y& Elsevier]

Abstract: CD40 is expressed in many tumor cells, however, its role in tumor biology is yet to be demonstrated. In the present study, we investigated the role of CD40 in gliomas. In vivo, we evaluated CD40 expression in 95 glioma tissues and 10 non-tumorous brain tissues and investigated the relationship between histopathological parameters, vascular density, and vascular endothelial growth factor (VEGF) expressions. In vitro, we aimed to understand the biological relevance of CD40 and VEGF in glioma cell lines. The results clearly demonstrated that CD40 expression, including membranous and cytoplasmic staining, was significantly higher in poorly differentiated and well differentiated gliomas than in the non-tumorous brain tissues (P =0.045 and P =0.043, respectively). In gliomas, the expression of CD40 was significantly correlated with tumor size, VEGF expressions and microvessel density (MVD) (P =0.022, P =0.023 and P =0.0316, respectively). In the in vitro study, stimulation of human glioma cells by CD40 ligation induced the expression and secretion of VEGF and was blocked by anti-CD40 monoclonal antibody. These observations provide evidence that CD40 ligation supports the expression and secretion of VEGF and may be involved in neovascularization of gliomas, they also suggest that CD40 and VEGF may be useful biomarkers for evaluating the risk of developing gliomas, and may also be used as a target for therapy. [Copyright &y& Elsevier]

Dysbiosis of the gut microbiota has important roles in various diseases and pathological states of the host. However, the changes of the gut microbiota during partial hepatectomy (PH)-induced acute liver injury have so far remained elusive. The present study investigated the gut microbiome and its related pathways following PH-induced acute liver injury. A total of 50 male C57/BL6 mice were divided into a normal control (NC), sham-operation and liver resection (LR) group (50% PH). Samples were collected at 3 and 14 days post-operation to obtain specimens for the Sham3, Sham14, LR3 and LR14 groups (10 mice/group). Specimens of NC group (n=10) were obtained at the same time as those of Sham3 group. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were determined using an automatic chemical analyzer and the gut microbiota was assessed by 16S ribosomal RNA gene sequencing of small intestinal contents. The serum levels of ALT and AST in the LR3 group were significantly increased, while those in the LR14 group were decreased again to near-normal levels. In the LR3 group, the operational taxonomic units, species richness (Chao1) and species diversity (Shannon and Simpson indices) were decreased, although without any significant difference. Furthermore, in the LR3 group, significant Cyanobacteria enrichment and Fusobacteria depletion compared with the NC and Sham3 groups was observed, while in the LR14 group, a significant depletion of the abundance of Verrucomicrobia, Chloroflexi and Deferribacteres compared to the LR3 group was obtained. The abundance of Firmicutes was increased in the LR3 group and decreased again in the LR14 group. However, the abundance of Bacteroidetes and Actinobacteria decreased in the LR3 group and increased again in the LR14 group. The alterations of the gut microbiota at the genus level were also revealed, as significant increases in Chloroplast, Curvibacter, Pelomonas, Ruminococcaceae UCG-005 and Blautia and a sharp decrease in Akkermansia and Eubacterium coprostanoligenes were caused by acute liver injury. Furthermore, functional metagenome prediction was performed by Phylogenetic Investigation of Communities by Reconstruction of Unobserved States based on the Greengenes database, revealing alterations in signal transduction, transcription and cell motility, as well as metabolism of amino acids, lipids, glucose, cofactors and terpenoids, and xenobiotics pathways. An improved understanding of the structural and functional changes of the gut microbiota following 50% PH-induced acute liver injury and repair may provide novel strategies for the recovery of hosts undergoing hepatectomy. [ABSTRACT FROM AUTHOR]

A new type of waterborne polyurethane acrylate was synthesized for use as a UV curing coating. The N,N-dihydroxy methyl ethyl-3-Methyl aminopropanoate monomer was first prepared via adding reactions of methyl acrylate and diethanol amine with methyl alcohol as the solvent. Then, the hyperbranched prepolymer was obtained by addition of trimethylolpropane with toluenesulfonic acid as catalyst and N,N-dimethyl formamide as solvent. The resulting hyperbranched and organosilicone modified waterborne polyurethane acrylates was synthesized through the mixed reaction of prepolymer and Hydroxy silicone oil, polyethylene glycol-1000, toluene diisocynate, dimethylolpropionic acid, 1,2-propylene glycol, hydroxyethyl acrylate, and triethylamine with dibutyltin dilaurate as the catalyst. The molecular structures were characterized by FT-IR and 1H NMR spectroscopy and GPC analysis and the thermal stability was studied by using TGA. Moreover, the influence of contemodnt of hydroxyl silicone oil, dimethylolpropionic acid, polyethylene glycol-1000, and prepolymer to various of properties such as glossiness, hardness, adhesive force, abrasion resistance, water absorption, elongation at break and tensile strength of films were analyzed. The temperature and catalyst dosage impact on percent conversion of isocyanate group (–NCO) were also studied. It was proven that the best dosage of hydroxyl silicone oil and dimethylolpropionic acid were 4.6%, the dosage of polyethylene glycol-1000 was 50%, and the amount of hyperbranched prepolymer was 0.5%, which could make the film achieve the optimum properties. The percent conversion of isocyanate group (–NCO) was maximum when reacting two hours at 80 °C with 0.2% catalyst. [ABSTRACT FROM AUTHOR]

Radical resection is the most effective method for malignant tumor treatments. However, conventional imaging cannot fully satisfy the clinical needs of surgical navigation. This study presents a novel triple‐modality positron emission tomography (PET)–Cerenkov radiation energy transfer (CRET)–confocal laser endomicroscopy (CLE) imaging strategy for intraoperative tumor imaging and surgical navigation. Using clinical radiopharmaceuticals and fluorescein sodium (FS), this strategy can accurately detect the tumor and guide the tumor surgery. The FS emission property under Cerenkov radiation excitation is investigated using 2‐deoxy‐2‐18F‐fluoroglucose and 11C‐choline. Performances of the PET–CRET–CLE imaging and the CRET–CLE image‐guided surgery are evaluated on mouse models. The CRET signal at 8 mm depth is stronger than the Cerenkov luminescence at 1 mm depth in phantoms. In vivo experiments indicate that 0.5 mL kg−1 of 10% FS generates the strongest CRET signal, which can be observed immediately after FS injection. A surgical navigation study shows that the tumors are precisely detected and resected using intraoperative CRET–CLE. In summary, a PET–CRET–CLE triple‐modality imaging strategy is developed. This strategy can detect the tumors and precisely guide the tumor resection using clinical pharmaceuticals. This triple‐modality imaging shows high potential in surgical navigation research and clinical translation. [ABSTRACT FROM AUTHOR]

S-1 monotherapy is widely used following gemcitabine failure in pancreatic cancer, especially in East Asia. We performed a meta-analysis to determine whether S-1-based combination therapy had better efficacy and safety compared with S-1 monotherapy. We searched Pubmed, Web of Science, ClinicalTrials.gov, and Cochrane CENTRAL and subsequently included five trials with a total of 690 patients. The combined hazard ratio (HR) or risk ratio; the corresponding 95% confidence intervals of progression-free survival, overall survival, and overall response rate; and grade 3-4 adverse events were examined. Five randomized controlled trials were included. Meta-analysis demonstrated S-1-based combination therapy significantly increased progression-free survival (HR = 0.78, 95% confidence interval [CI]: 0.67-0.90, p = 0.0009) and overall response rate (HR = 1.74, 95% CI: 1.20-2.52, p = 0.003). Evidence was insufficient to confirm that S-1-based combined regimens improved overall survival (HR = 0.87, 95% CI: 0.75-1.00, p = 0.05). There was no significant difference in adverse events between the two treatment arms. In conclusion, S-1-based combination therapy improved progression-free survival and overall response rate compared to S-1 monotherapy with acceptable toxicity. [ABSTRACT FROM AUTHOR]

Background:Ischemia-reperfusion (I/R) injury is associated with intestinal microbial dysbiosis. The “gut-liver axis” closely links gut function and liver function in health and disease. Ischemic preconditioning (IPC) has been proven to reduce I/R injury in the surgery. This study aims to explore the effect of IPC on intestinal microbiota and to analyze characteristics of microbial structure shift following liver transplantation (LT). Methods:The LT animal models of liver and gut IPC were established. Hepatic graft function was assessed by histology and serum ALT/AST. Intestinal barrier function was evaluated by mucosal ultrastructure, serum endotoxin, bacterial translocation, fecal sIgA content and serum TNF-α. Intestinal bacterial populations were determined by quantitative PCR. Microbial composition was characterized by DGGE and specific bacterial species were determined by sequence analysis. Principal Findings:Liver IPC improved hepatic graft function expressed as ameliorated graft structure and reduced ALT/AST levels. After administration of liver IPC, intestinal mucosal ultrastructure improved, serum endotoxin and bacterial translocation mildly decreased, fecal sIgA content increased, and serum TNF-α decreased. Moreover, liver IPC promoted microbial restorations mainly through restoring Bifidobacterium spp., Clostridium clusters XI and Clostridium cluster XIVab on bacterial genus level. DGGE profiles indicated that liver IPC increased microbial diversity and species richness, and cluster analysis demonstrated that microbial structures were similar and clustered together between the NC group and Liver-IPC group. Furthermore, the phylogenetic tree of band sequences showed key bacteria corresponding to 10 key band classes of microbial structure shift induced by liver IPC, most of which were assigned to Bacteroidetes phylum. Conclusion:Liver IPC cannot only improve hepatic graft function and intestinal barrier function, but also promote restorations of intestinal microbiota following LT, which may further benefit hepatic graft by positive feedback of the “gut-liver axis”. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of death worldwide and total number of cases globally is increasing. Novel treatment strategies are therefore desperately required for radical treatment of cancers and long survival of patients. A new technology using high pulsed electric field has emerged from military application into biology and medicine by applying nsPEF as a means to inhibit cancer. However, molecular mechanisms of nsPEF on tumors or cancers are still unclear. In this paper, we found that nsPEF had extensive biological effects in cancers, and clarified its possible molecular mechanisms in vitro and in vivo. It could not only induce cell apoptosis via dependent-mitochondria intrinsic apoptosis pathway that was triggered by imbalance of anti- or pro-apoptosis Bcl-2 family proteins, but also inhibit cell proliferation through repressing NF-κB signaling pathway to reduce expressions of cyclin proteins. Moreover, nsPEF could also inactivate metastasis and invasion in cancer cells by suppressing Wnt/β-Catenin signaling pathway to down-regulating expressions of VEGF and MMPs family proteins. More importantly, nsPEF could function safely and effectively as an anti-cancer therapy through inducing tumor cell apoptosis, destroying tumor microenvironment, and depressing angiogenesis in tumor tissue in vivo. These findings may provide a creative and effective therapeutic strategy for cancers. [ABSTRACT FROM AUTHOR]