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In this study, differently shaped silver nanoparticles used for the synthesis of gold nanoclusters with small capping ligands were demonstrated. Silver nanoparticles provide a reaction platform that plays dual roles in the formation of Au NCs. One is to reduce gold ions and the other is to attract capping ligands to the surface of nanoparticles. The binding of capping ligands to the AgNP surface creates a restricted space on the surface while gold ions are being reduced by the particles. Four different shapes of AgNPs were prepared and used to examine whether or not this approach is dependent on the morphology of AgNPs. Quasi-spherical AgNPs and silver nanoplates showed excellent results when they were used to synthesize Au NCs. Spherical AgNPs and triangular nanoplates exhibited limited synthesis of Au NCs. TEM images demonstrated that Au NCs were transiently assembled on the surface of silver nanoparticles in the method. The formation of Au NCs was observed on the whole surface of the QS-AgNPs if the synthesis of Au NCs was mediated by QS-AgNPs. In contrast, formation of Au NCs was only observed on the edges and corners of AgNPts if the synthesis of Au NCs was mediated by AgNPts. All of the synthesized Au NCs emitted bright red fluorescence under UV-box irradiation. The synthesized Au NCs displayed similar fluorescent properties, including quantum yields and excitation and emission wavelengths. [ABSTRACT FROM AUTHOR]

Simple Summary: The Derlin-1 protein, encoded by DERL1, is located in the endoplasmic reticulum membrane and is responsible for the unfolded protein response. Derlin-1 has recently drawn lots of attention with regard to cancer pathogenesis. The purpose of this study is to examine its role and molecular mechanism in upper tract urothelial carcinoma (UTUC). The protein levels of Derlin-1 in human UTUC specimens are observed by immunohistochemistry. Derlin-1 overexpression is evidently associated with cancer stage, distant metastasis, recurrence, and poor prognosis in patients with UTUC. In an in vitro study, the knockdown of Derlin-1 represses, while over-expression of Derlin-1 increases migration and invasion of UTUC cells significantly. We identify the microRNA-375-3p (miR-375-3p) as one of the potential candidate microRNAs and then examine the relationship between Derlin-1 and miR-375-3p. The dual-luciferase reporter assay confirms that miR-375-3p directly targets Derlin-1. Furthermore, we reveal that miR-375-3p modulate Derlin-1 and epithelial–mesenchymal transition (EMT) marker protein levels. However, the above effects are reversed by the restoration of Derlin-1. Our study clarifies that miR-375-3p represses invasion and migration by directly targeting Derlin-1 and regulating the expression of EMT-associated proteins in UTUC cells, suggesting Derlin-1 may act as a useful predictor of prognosis and that both Derlin-1 and miR-375-3p could be potential therapeutic targets in UTUC. Little is known regarding the molecular characterization of upper tract urothelial carcinoma (UTUC). Novel therapeutic targets and prognostic predictors are imminent. In the present study, we aim to examine the oncogenic function and molecular mechanism of Derlin-1 in UTUC. Derlin-1 overexpression is significantly associated with poor prognosis in patients with UTUC. In vitro, knockdown or over-expression of Derlin-1 markedly regulated UTUC cell invasion and migration. We further discovered miR-375-3p suppresses cell invasion and migration by inversely regulating Derlin-1 and blocking EMT in UTUC cells. Taking this together, miR-375-3p functions as a tumor suppressive microRNA by directly targeting Derlin-1 and blocking epithelial–mesenchymal transition (EMT) in UTUC. [ABSTRACT FROM AUTHOR]

A new strategy using silver nanoparticles (Ag NPs) to synthesize thiolated Au NCs is demonstrated. The quasi-spherical Ag NPs serve as a platform, functioning as a reducing agent for Au (III) and attracting capping ligands to the surface of the Ag NPs. Glutathione disulfide (GSSG) and dithiothreitol (DTT) were used as capping ligands to synthesize thiolated Au NCs (glutathione-Au NCs and DTT-Au NCs). The glutathione-Au NCs and DTT-Au NCs showed red color luminance with similar emission wavelengths (630 nm) at an excitation wavelength of 354 nm. The quantum yields of the glutathione-Au NCs and DTT-Au NCs were measured to be 7.3% and 7.0%, respectively. An electrophoretic mobility assay showed that the glutathione-Au NCs moved toward the anode, while the DTT-Au NCs were not mobile under the electric field, suggesting that the total net charge of the thiolated Au NCs is determined by the charges on the capping ligands. The detection of the KSV values, 26 M−1 and 0 M−1, respectively, revealed that glutathione-Au NCs are much more accessible to an aqueous environment than DTT-Au NCs. [ABSTRACT FROM AUTHOR]

Polyglutamine (polyQ)-mediated spinocerebellar ataxia (SCA), including SCA1, 2, 3, 6, 7, and 17, are caused by mutant genes with expanded CAG repeats, leading to the intracellular accumulation of aggregated proteins, the production of reactive oxygen species, and cell death. Among SCA, SCA3 is caused by a mutation in the ATXN3 (ataxin-3) gene. In a circumstance of polyQ aggregation, the autophagic pathway is induced to degrade the aggregated proteins, thereby suppressing downstream deleterious effects and promoting neuronal survival. In this study, we tested the effects of synthetic indole (NC009-1, -2, -3, -6) and coumarin (LM-022, -031) derivatives as chemical chaperones to assist mutant ATXN3-Q75 folding, as well as autophagy inducers to clear aggregated protein. Among the tested compounds, NC009-1, -2, and -6 and LM-031 interfered with Escherichia coli-derived ATXN3-Q75 aggregation in thioflavin T binding and filter trap assays. In SH-SY5Y cells expressing GFP-fused ATXN3-Q75, these compounds displayed aggregation-inhibitory and neurite growth-promoting potentials compared to untreated cells. Furthermore, these compounds activated autophagy by increasing the phosphatidylethanolamine-conjugated LC3 (microtubule associated protein 1 light chain 3)-II:cytosolic LC3-I ratio in these cells. A biochemical co-immunoprecipitation assay by using a mixture of HEK 293T cell lysates containing recombinant ATXN3-Q75-Venus-C-terminus (VC) or Venus-N-terminus (VN)-LC3 protein indicated that NC009-1 and -2 and LM-031 served as an autophagosome-tethering compound (ATTEC) to interact with ATXN3-Q75 and LC3, and the interaction was further confirmed by bimolecular fluorescence complementation analysis in cells co-expressing both ATXN3-Q75-VC and VN-LC3 proteins. The study results suggest the potential of NC009-1 and -2 and LM-031 as an ATTEC in treating SCA3 and, probably, other polyQ diseases. [ABSTRACT FROM AUTHOR]

Off-site reservoirs use water from other watersheds to supplement their water quantity. Water quality is usually better in off-site reservoirs than in onsite reservoirs, because in comparison to onsite reservoirs, watershed areas are smaller and fewer pollutants are collected; moreover, cleaner water is introduced. However, in Taiwan, the water quality of some off-site reservoirs can gradually worsen, and this factor needs to be addressed. In this study, the Liyutan reservoir in central Taiwan was used as an example to demonstrate the process of evaluating pollution in an off-site reservoir. Pollution loads from point sources (PSs) and nonpoint sources (NPSs) were carefully estimated. Domestic sewage and tourist wastewater were considered the major PS loads in this study. The NPS load evaluation was dependent on the results of a verified watershed model, the stormwater management model (SWMM). The observed data in 2015 and 2016 and supplementary total phosphorous (TP) samplings in upstream rivers in 2018 were used to validate the model results. Model calibration and verification were implemented during dry weather and wet weather to ensure the accuracy of the PS and NPS simulations. The results of this study showed that the average total phosphorous (TP) load generated from within the watershed was 9013 kg/y, and that the TP load from outside the watershed was 4545 kg/y. The percentages of TP loads from NPSs and PSs in the watershed were 83% and 17%, respectively. Finally, we used a verified Vollenweider model to convert the TP loads to the TP concentration in the reservoir. The pollution reduction measures and the associated predicted water quality values were assessed using the verified models. [ABSTRACT FROM AUTHOR]

Gemcitabine-based chemotherapy is the current standard treatment for biliary tract cancers (BTCs) and resistance to gemcitabine remains the clinical challenge. TP53 mutation has been shown to be associated with poor clinicopathologic characteristics and survival in patients with BTCs, indicating that p53 plays an important role in the treatment of these cancers. Herein, we comprehensively reviewed previous BTC preclinical research and early clinical trials in terms of p53, as well as novel p53-targeted treatment, alone or in combination with either chemotherapy or other targeted therapies in BTCs. Preclinical studies have demonstrated that p53 mutations in BTCs are associated with enhanced gemcitabine resistance, therefore targeting p53 may be a novel therapeutic strategy for treatment of BTCs. Directly targeting mutant p53 by p53 activators, or indirectly by targeting cell cycle checkpoint proteins (Chk1, ataxia telangiectasia related (ATR), and Wee1) leading to synthetic lethality, may be potential future strategies for gemcitabine-resistant p53 mutated BTCs. In contrast, for wild-type p53 BTCs, activation of p53 by inhibition of its negative regulators (MDM2 and wild-type p53-induced phosphatase 1 (WIP1)) may be alternative options. Combination therapies consisting of standard cytotoxic drugs and novel small molecules targeting p53 and related signaling pathways may be the future key standard approach to beat cancer. [ABSTRACT FROM AUTHOR]

This study investigated the effects of a single dose of arginine (Arg) administration at the beginning of sepsis on CD4+ T-cell regulation and liver inflammation in C57BL/6J mice. Mice were divided into normal control (NC), sham (SH), sepsis saline (SS), and sepsis Arg (SA) groups. An inducible nitric oxide (NO) synthase (iNOS) inhibitor was administered to additional sepsis groups to evaluate the role of NO during sepsis. Sepsis was induced using cecal ligation and puncture (CLP). The SS and SA groups received saline or Arg (300 mg/kg body weight) via tail vein 1 h after CLP. Mice were euthanized at 12 and 24 h post-CLP. Blood, para-aortic lymph nodes, and liver tissues were collected for further measurement. The findings showed that sepsis resulted in decreases in blood and para-aortic lymph node CD4+ T-cell percentages, whereas percentages of interleukin (IL)-4- and IL-17-expressing CD4+ T cells were upregulated. Compared to the SS group, Arg administration resulted in maintained circulating and para-aortic lymph node CD4+ T cells, an increased Th1/Th2 ratio, and a reduced Th17/Treg ratio post-CLP. In addition, levels of plasma liver injury markers and expression of inflammatory genes in liver decreased. These results suggest that a single dose of Arg administered after CLP increased Arg availability, sustained CD4+ T-cell populations, elicited more-balanced Th1/Th2/Th17/Treg polarization in the circulation and the para-aortic lymph nodes, and attenuated liver inflammation in sepsis. The favorable effects of Arg were abrogated when an iNOS inhibitor was administered, which indicated that NO may be participated in regulating the homeostasis of Th/Treg cells and subsequent liver inflammation during sepsis. [ABSTRACT FROM AUTHOR]