Search

In recent years, aggregation-induced emission (AIE)-active materials have been emerging as a promising means for bioimaging and phototherapy. However, the majority of AIE luminogens (AIEgens) need to be encapsulated into versatile nanocomposites to improve their biocompatibility and tumor targeting. Herein, we prepared a tumor- and mitochondria-targeted protein nanocage by the fusion of human H-chain ferritin (HFtn) with a tumor homing and penetrating peptide LinTT1 using genetic engineering technology. The LinTT1-HFtn could serve as a nanocarrier to encapsulate AIEgens via a simple pH-driven disassembly/reassembly process, thereby fabricating the dual-targeting AIEgen-protein nanoparticles (NPs). The as designed NPs exhibited an improved hepatoblastoma-homing property and tumor penetrating ability, which is favorable for tumor-targeted fluorescence imaging. The NPs also presented a mitochondria-targeting ability, and efficiently generated reactive oxygen species (ROS) upon visible light irradiation, making them valuable for inducing efficient mitochondrial dysfunction and intrinsic apoptosis in cancer cells. In vivo experiments demonstrated that the NPs could provide the accurate tumor imaging and dramatic tumor growth inhibition with minimal side effects. Taken together, this study presents a facile and green approach for fabrication of tumor- and mitochondria-targeted AIEgen-protein NPs, which can serve as a promising strategy for imaging-guided photodynamic cancer therapy. AIE luminogens (AIEgens) show strong fluorescence and enhanced ROS generation in the aggregate state, which would facilitate the image-guided photodynamic therapy [12–14]. However, the major obstacles that hinder biological applications are their lack of hydrophilicity and selective targeting [15]. To address this issue, this study presents a facile and green approach for the fabrication of tumor‑ and mitochondria‑targeted AIEgen-protein nanoparticles via a simple disassembly/reassembly of the LinTT1 peptide-functionalized ferritin nanocage without any harmful chemicals or chemical modification. The targeting peptide-functionalized nanocage not only restricts the intramolecular motion of AIEgens leading to enhanced fluorescence and ROS production, but also confers good targeting to AIEgens. [Display omitted] [ABSTRACT FROM AUTHOR]

As we known, reproducing kernel method (RKM) has been presented for solving differential equations for initial and boundary value problems. However, the direct application of the RKM presented in the previous works cannot produce good numerical results for Burgers’ equation. To solve this problem, this paper give a modified reproducing kernel method by piecewise technique. The exact solution is given by reproducing kernel functions in a series expansion form, the approximation solution is expressed by n-term summation of reproducing kernel functions. The three numerical experiments results show that the piecewise method is more easily implemented and effective. Some numerical results are also compared with the results obtained by other methods. [ABSTRACT FROM AUTHOR]

This paper research downhole temperature distribution in oil production and water injection using reproducing kernel Hilbert space method (RKHSM) for the first time. The aim of this paper is that using the highly accurate RKHSM can solve downhole temperature problems effectively. According to 2-D mathematical models of downhole temperature distribution, the analytical solution was given in a series expansion form and the approximate solution was expressed by n -term summation of reproducing kernel functions which initial and boundary conditions were selected properly. Numerical results of downhole temperature distribution with multiple pay zones, in which different radial distance and different injection–production conditions (such as injection rate, injection temperature, injection time, oil layer thickness), were carried out by mathematical 7.0, and numerical results correspond to general knowledge and show that use RKHSM to research downhole temperature distribution is feasible and effective. [ABSTRACT FROM AUTHOR]

Recently, the reproducing kernel Hilbert space methods(RKHSM) (see Wang et al (2011) [2]; Lin and Lin (2010) [3]; Wu and Li (2011) [4]; Zhou et al. (2009) [6]; Jiang and Chen (2014) [7]; Wang et al. (2010) [8]; Du and Cui (2008) [9]; Akram et al. (2013) [10]; Lü and Cui (2010) [11]; Wang et al. (2008) [12]; Yao and Lin (2009) [13]; Geng et al. (2014) [14] ; Arqub et al. (2013) [15]) emerged one after the other. But, a lot of difficult work should be done to deal with multi-point boundary value problems(BVPs). Our work is aimed at giving a new reproducing kernel method for multi-point BVPs. We do not put the homogenization conditions into the reproducing kernel space which can avoid to compute the reproducing kernel satisfying boundary conditions and the orthogonal system. Three numerical examples are studied to demonstrate the accuracy of the present method. Results obtained by our method indicate that new algorithm has the following advantages: small computational work, fast convergence speed and high precision. [ABSTRACT FROM AUTHOR]

The Gray-Scott model is the representative bistable system in many reaction–diffusion models. Numerical simulation of this model is very difficult especially for space fractional case. In this paper, a novel numerical approach is introduced. We introduce the Runge–Kutta method for time discretization and Fourier transform for spatial discretization. The error has been reduced effectively by using Richardson Extrapolation. We perform stability and convergence analysis for the present method. Numerical experiments show that present method has low computational complexity and higher precision. Long time diffusion behavior of pattern can be observed. [ABSTRACT FROM AUTHOR]

Background: Recently, there is evidence that the number of mast cells in various solid cancers increases with tumor progression. The role of mast cells in promoting tumor progression, however, has not been well studied in pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate the prognostic value of mast cell counts in different zones of the neoplasm in patients with PDAC after curative resection. Methods: Numbers of mast cells and microvessels were assessed by immunohistochemistry in tissues from 103 patients with PDAC and 10 patients with normal pancreas. All patients with PDAC underwent partial pancreatic resection. The investigators paid particular attention to the distribution of mast cells in each specimen. Results: High mast cell counts in the intratumoral border zone correlated with the presence of lymphatic and microvascular invasion, lymph node metastasis, and TNM stage, and were an independent prognostic factor for overall survival (P < .001). In contrast, neither in the intratumoral center zone nor in the peritumoral zones was mast cell count associated with OS. Mast cell counts in the intratumoral border zone, but not in the peritumoral or in the intratumoral center zone, were correlated with microvessel counts. Conclusion: The present study shows a zone-specific distribution of mast cells in PDAC and highlights the importance of invasive front in the prognosis of patients with PDAC after curative resection. Zone-specific evaluation of mast cell and microvessel counts may be helpful for prognostic assessment and therapeutic decision making in PDAC. [ABSTRACT FROM AUTHOR]

A process of intermittently cyclic activated sludge-membrane bioreactor (ICAS-MBR) was developed to enhance the performance of biological phosphorus removal (EBPR), which was constructed under sequencing anoxic/anaerobic/aerobic condition. The performance between ICAS-MBR and conventional anoxic/aerobic-membrane bioreactor (A/O-MBR) in terms of phosphorus removal, nitrification performance and microbial aspects were investigated in this study. The experimental results indicated that the phosphorus removal efficiency in ICAS-MBR process increased from 65% to 83% when compared with A/O-MBR. It was also found that the COD removal efficiencies of the two processes were over 94%, and –N and TN average removal efficiencies were 96% and 69% in ICAS-MBR and 96% and 78% in A/O-MBR, respectively. Furthermore, micrographs observation obtained confirmed the succession and diversification of microorganisms in the two systems followed a similar regularity. [Copyright &y& Elsevier]

Abstract Heme oxygenase (HO-1), which may be induced by Cobaltic protoporphyrin IX chloride (CoPPIX) or Rosiglitazone (Ros), is a neuroprotective agent that effectively reduces ischemic stroke. Previous studies have shown that the neuroprotective mechanisms of HO-1 are related to JNK signaling. The expression of HO-1 protects cells from death through the JNK signaling pathway. This study aimed to ascertain whether the neuroprotective effect of HO-1 depends on the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and further influences the JNK signal transmission through HO-1. Prior to the ischemia-reperfusion experiment, CoPPIX was injected through the lateral ventricle for 5 consecutive days or Ros was administered via intraperitoneal administration in the week prior to transient ischemia. Our results demonstrated that HO-1 could inhibit the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and could ultimately diminish the phosphorylation of JNK3. Furthermore, the inhibition of JNK3 phosphorylation downregulated the level of p-c-Jun and elevated neuronal cell death in the CA1 of the hippocampus. Taken together, these findings suggested that HO-1 could ameliorate brain injury by regulating the MLK3-MKK7-JNK3 signaling module, which was scaffolded by JIP1 and JNK signaling during cerebral ischemia/reperfusion. [ABSTRACT FROM AUTHOR]

Highlights: [•] Mandatory national surveillance of IPD in Taiwan began on October 2007. [•] 3659 IPD cases were in 2008–2012, with an incidence of 3.2/100,000 population. [•] Case fatality ratio was 9.2% for all, and 19.0% for adults ≥75 years. [•] PCV7 preventable IPD declined from 59.8% in 2008 to 37.2% in 2012 for all ages. [•] S. pneumoniae serotype 19A became the most prevalent serotype in 2010. [Copyright &y& Elsevier]

Abstract: Aberrant c-Met activation has been demonstrated to be implicated in tumorigenesis and anti-cancer drug resistance. Discovery of c-Met inhibitors has attracted much attention in recent years. In this study, a support vector machine (SVM) classification model that discriminates c-Met inhibitors and non-inhibitors was first developed. Evaluation through screening a test set indicates that combined SVM-based and docking-based virtual screening (SB/DB-VS) considerably increases hit rate and enrichment factor compared with the individual methods. Thus the combined SB/DB-VS approach was adopted to screen PubChem, Specs, and Enamine for c-Met inhibitors. 75 compounds were selected for in vitro assays. Eight compounds display a good inhibitory potency against c-Met. Five of them are found to have novel scaffolds, implying a good potential for further chemical modification. [Copyright &y& Elsevier]

Abstract: Co-infection with hookworm and schistosomes is a common phenomenon in sub-Saharan Africa, as well as in parts of South America and southeast Asia. As a first step towards understanding the metabolic response of a hookworm-schistosome co-infection in humans, we investigated the metabolic consequences of co-infection in an animal model, using a nuclear magnetic resonance (NMR)-based metabolic profiling technique, combined with multivariate statistical analysis. Urine and serum samples were obtained from hamsters experimentally infected with 250 Necator americanus infective L3 and 100 Schistosoma japonicum cercariae simultaneously. In the co-infection model, similar worm burdens were observed as reported for single infection models, whereas metabolic profiles of co-infection represented a combination of the altered metabolite profiles induced by single infections with these two parasites. Consistent differences in metabolic profiles between the co-infected and non-infected control hamsters were observed from 4weeks p.i. onwards. The predominant metabolic alterations in co-infected hamsters consisted of depletion of amino acids, tricarboxylic acid cycle intermediates (e.g. citrate and succinate) and glucose. Moreover, alterations of a series of gut microbial-related metabolites, such as decreased levels of hippurate, 3-hydroxyphenylpropionic acid, 4-hydroxyphenylpropionic acid and trimethylamine-N-oxide, and increased concentrations of 4-cresol glucuronide and phenylacetylglycine were associated with co-infection. Our results provide a first step towards understanding the metabolic response of an animal host to multiple parasitic infections. [Copyright &y& Elsevier]

Abstract: We reported four foodborne disease outbreaks in Taiwan caused by sucrose-nonfermenting and by β-galactosidase-deficient variants of non-O1, non-O139 Vibrio cholerae. The sucrose-nonfermenting vibrios collected from three outbreaks were biochemically identified to be V. mimicus and the β-galactosidase-deficient vibrios from an outbreak to be V. alginolyticus. However, molecular methods including DNA–DNA hybridization, fatty acid profile analysis, and sequence analysis of 16S rRNA, oriC, pyrH, recA, and rpoA indicated that these vibrios should be V. cholerae. These V. cholerae variants carried two hemolysin genes, hlyA and hlx, but contained neither cholera toxin gene, ctx, V. mimicus hemolysin gene, vmh, nor thermo-directed hemolysin, tdh. The sucrose-nonfermenting variants of V. cholerae shared a high level of genetic relatedness; they could derive from a common clone. In our record from 1995 to date, this was the first time that V. cholerae variants were discovered as etiologic agents for foodborne disease outbreaks in Taiwan. [Copyright &y& Elsevier]

Cerebral ischemia/reperfusion (I/R) injury is a leading cause of learning and memory dysfunction. Hydrogen sulfide (H 2 S) has been shown to confer neuroprotection in various neurodegenerative diseases, including cerebral I/R-induced hippocampal CA1 injury. However, the underlying mechanisms have not been completely understood. In the present study, rats were pretreated with SAM/NaHS (SAM, an H 2 S agonist, and NaHS, an H 2 S donor) only or SAM/NaHS combined with CaM (an activator of CaMKII) prior to cerebral ischemia. The Morris water maze test demonstrated that SAM/NaHS could alleviate learning and memory impairment induced by cerebral I/R injury. Cresyl violet staining was used to show the survival of hippocampal CA1 pyramidal neurons. SAM/NaHS significantly increased the number of surviving cells, whereas CaM weakened the protection induced by SAM/NaHS. The immunohistochemistry results indicated that the number of Iba1-positive microglia significantly increased after cerebral I/R. Compared with the I/R group, the number of Iba1-positive microglia in the SAM/NaHS groups significantly decreased. Co-Immunoprecipitation and immunoblotting were conducted to demonstrate that SAM/NaHS suppressed the assembly of CaMKII with the ASK1-MKK3-p38 signal module after cerebral I/R, which decreased the phosphorylation of p38. In contrast, CaM significantly inhibited the effects of SAM/NaHS. Taken together, the results suggested that SAM/NaHS could suppress cerebral I/R injury by downregulating p38 phosphorylation via decreasing the assembly of CaMKII with the ASK1-MKK3-p38 signal module. [ABSTRACT FROM AUTHOR]