A Renal Cell Carcinoma with Biallelic Somatic TSC2 Mutation: Clinical Study and Literature Review.

OBJECTIVES: To elucidate the effect of the biallelic somatic TSC2 mutations, identified in one adolescent patient, in renal cell carcinoma (RCC). METHODS: Mutation analyses, immunohistochemistry and real-time polymerase chain reaction (PCR) were conducted. RESULTS: Two novel somatic mutations of TSC2 in unilateral and solitary RCC samples from a 14-year-old female were identified. The pathological features suggest the tumor as a clear-cell renal cell carcinoma. In addition, immunohistochemistry revealed elevated levels of phosphorylated S6K1. Results from in vitro cellular experiments suggest that the mutant TSC2 proteins were quickly degraded and they failed to repress the phosphorylation of S6K1 and STAT3, which leads to constitutive activation of mTORC1 pathway and ultimately cause the development of RCC. CONCLUSIONS: Detecting TSC2 mutation in patients with early RCC onset would be beneficial and mTOR inhibitor could be a therapeutic option for TSC2 mutation-induced RCC

Histone demethylase PHF8 drives neuroendocrine prostate cancer progression by epigenetically upregulating FOXA2.

Neuroendocrine prostate cancer (NEPC) is a more aggressive subtype of castration-resistant prostate cancer (CRPC). Although it is well established that PHF8 can enhance prostate cancer cell proliferation, whether PHF8 is involved in prostate cancer initiation and progression is relatively unclear. By comparing the transgenic adenocarcinoma of the mouse prostate (TRAMP) mice with or without Phf8 knockout, we systemically examined the role of PHF8 in prostate cancer development. We found that PHF8 plays a minimum role in initiation and progression of adenocarcinoma. However, PHF8 is essential for NEPC because not only is PHF8 highly expressed in NEPC but also animals without Phf8 failed to develop NEPC. Mechanistically, PHF8 transcriptionally upregulates FOXA2 by demethylating and removing the repressive histone markers on the promoter region of the FOXA2 gene, and the upregulated FOXA2 subsequently regulates the expression of genes involved in NEPC development. Since both PHF8 and FOXA2 are highly expressed in NEPC tissues from patients or patient-derived xenografts, the levels of PHF8 and FOXA2 can either individually or in combination serve as NEPC biomarkers and targeting either PHF8 or FOXA2 could be potential therapeutic strategies for NEPC treatment. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland

Mold and Stain Resistance of Bamboo Treated with Pyraclostrobin Fungicide

Bamboo is rich in starch and sugars and can be infected by mold and stain fungi, degrading its performance, shortening its service life, and reducing its utilization value. It is crucial to investigate how to protect bamboo against mold and stain fungi. The zone of inhibition test was used to evaluate the antifungal activity of azoxystrobin, kresoxim-methyl, pyraclostrobin and 3-iodo-2-propynyl-butylcarbamate (IPBC) against stain fungi (Botryodiplodia theobromae, Fusarium moniliforme, and Alternaria alternate) and mold fungi (Aspergillus niger, Penicillium citrinum, and Trichoderma viride) to develop new chemicals to protect bamboo against stain fungi and molds. The inhibitory activity of the composite pyraclostrobin and IPBC with different ratios was evaluated. Water-based formulations of the fungi were used to treat the bamboo, and the mold and stain resistance of the bamboo was investigated at different chemical retention rates. The results showed that the antifungal activity of pyraclostrobin was significantly higher than that of azoxystrobin and kresoxim-methyl. Different degrees of inhibitory activities against the stain and mold fungi were observed, and the inhibitory activity was higher against stain fungi than against molds. The three stain fungi were completely inhibited at a 7:3 ratio of pyraclostrobin to IPBC and 0.1% concentration. As the ratio increased, the inhibitory effect against mixed mold strains improved. The control efficacy of the pyraclostrobin formulations Str-1 and Str-2 at 0.1% concentration was 100% against Alternaria alternate and 70.8% against Fusarium moniliforme. The control efficacy of the composite formulations SI-1 and SI-2 at 0.1% concentration was 100% against all three stain fungi and greater than 91.8% against the mixed mold strains. This study provides new insights into the utilization of pyraclostrobin and its composite formulations as new bamboo antifungal agents

Modulus of Elasticity Loss as a Rapid Indicator of Rot-fungal Attack on Untreated and Preservative-treated Wood in Laboratory Tests

The modulus of elasticity (MOE) of wood is a sensitive indicator of rot-fungal attack. To develop an alternative method of rapid assessment of fungal decay in the laboratory, changes in static MOE of untreated and preservative-treated wood were measured during exposure to the brown-rot fungus, Gloeophyllum trabeum, and the white-rot fungus, Trametes versicolor, in a standard soil bottle assay. Static MOE loss was compared with mass loss. The results showed that the MOE of wood was a sensitive and reliable indicator of rot-fungal attack, regardless of fungus or wood species. The MOE analysis of untreated wood reduced the 12- to 16-week exposure time necessary for the standard mass loss measurement to four weeks. Also, the exposure time for preservative-treated wood was reduced to eight weeks. Untreated wood was determined to be susceptible to decay if the MOE loss was 40% or more after a four-week exposure, while treated wood was considered susceptible to decay if the MOE loss was 40% or more after an eight-week exposure

Vapor growth of V-doped MoS2 monolayers with enhanced B-exciton emission and broad spectral response

Abstract Dynamically engineering the optical and electrical properties in two-dimensional (2D) materials is of great significance for designing the related functions and applications. The introduction of foreign-atoms has previously been proven to be a feasible way to tune the band structure and related properties of 3D materials; however, this approach still remains to be explored in 2D materials. Here, we systematically demonstrate the growth of vanadium-doped molybdenum disulfide (V-doped MoS2) monolayers via an alkali metal-assisted chemical vapor deposition method. Scanning transmission electron microscopy demonstrated that V atoms substituted the Mo atoms and became uniformly distributed in the MoS2 monolayers. This was also confirmed by Raman and X-ray photoelectron spectroscopy. Power-dependent photoluminescence spectra clearly revealed the enhanced B-exciton emission characteristics in the V-doped MoS2 monolayers (with low doping concentration). Most importantly, through temperature-dependent study, we observed efficient valley scattering of the B-exciton, greatly enhancing its emission intensity. Carrier transport experiments indicated that typical p-type conduction gradually arisen and was enhanced with increasing V composition in the V-doped MoS2, where a clear n-type behavior transited first to ambipolar and then to lightly p-type charge carrier transport. In addition, visible to infrared wide-band photodetectors based on V-doped MoS2 monolayers (with low doping concentration) were demonstrated. The V-doped MoS2 monolayers with distinct B-exciton emission, enhanced p-type conduction and broad spectral response can provide new platforms for probing new physics and offer novel materials for optoelectronic applications. Graphical abstrac

Leachability and Anti-Mold Efficiency of Nanosilver on Poplar Wood Surface

Water-based antimicrobial agents, used in environmentally friendly applications, are widely used in wood protection industries. Furthermore, nanomaterials as antimicrobial agents, because of their biocidal component, huge specific surface area, and unique nanoscale effect, have attracted attention in the field of biodurability. We employed aqueous dispersed nano-silver with a diameter of 10 nm~20 nm to treat poplar wood and evaluated its leaching resistance and anti-mold effect on the wood surface. The results revealed that the higher the retention of the nano-silver, the stronger the protection efficiency of the wood surface against three molds (Aspergillus niger V. Tiegh, Penicillium citrinum Thom, and Trichoderma viride Pers. ex Fr); and the leachability of the nano-silver presented a slowly growing trend with the increase in the retention. When the wood surface attained a silver retention of 0.324 g·m−2, its anti-mold efficiency against Aspergillus niger V. Tiegh, Penicillium citrinum Thom, and Trichoderma viride Pers. ex Fr reached 80, 75, and 80%, respectively, which achieved or even exceeded the required standard value of effective mold inhibition (75%). Notably, the nano-silver leaching rate at this retention attained merely 4.75 %. The nanoparticle, well distributed on a wood surface, may promote sufficient contact with fungi as well as strong interaction with wood cell wall components, which probably contributed to the effective anti-mold efficiency and the leaching resistance. This study provided positive evidence for the anti-mold effect of nano-silver on wood surface

The Effects of the Recombinant CCR5 T4 Lysozyme Fusion Protein on HIV-1 Infection.

Insertion of T4 lysozyme (T4L) into the GPCR successfully enhanced GPCR protein stability and solubilization. However, the biological functions of the recombinant GPCR protein have not been analyzed.We engineered the CCR5-T4L mutant and expressed and purified the soluble recombinant protein using an E.coli expression system. The antiviral effects of this recombinant protein in THP-1 cell lines, primary human macrophages, and PBMCs from different donors were investigated. We also explored the possible mechanisms underlying the observed antiviral effects.Our data showed the biphasic inhibitory and promotion effects of different concentrations of soluble recombinant CCR5-T4L protein on R5 tropic human immunodeficiency virus-1 (HIV-1) infection in THP-1 cell lines, human macrophages, and PBMCs from clinical isolates. We demonstrated that soluble recombinant CCR5-T4L acts as a HIV-1 co-receptor, interacts with wild type CCR5, down-regulates the surface CCR5 expression in human macrophages, and interacts with CCL5 to inhibit macrophage migration. Using binding assays, we further determined that recombinant CCR5-T4L and [125I]-CCL5 compete for the same binding site on wild type CCR5.Our results suggest that recombinant CCR5-T4L protein marginally promotes HIV-1 infection at low concentrations and markedly inhibits infection at higher concentrations. This recombinant protein may be helpful in the future development of anti-HIV-1 therapeutic agents

Recombinant CCR5-T4L down-regulates surface CCR5 expression in MDMs, and inhibits MDM migration and binding properties.

<p>A and B) Effect of soluble recombinant CCR5-T4L or CCL5 on surface CCR5 expression in MDMs. MDMs were treated with soluble recombinant CCR5-T4L (1 μg/ml), CCL5 (1 μg/ml), or PBS for 24 h at 37°C. Surface (A) and intracellular CCR5 (B) were analyzed using flow cytometry and the PE-conjugated monoclonal antibody (2D7). Recombinant CCL5 protein was used as a control. The cellular distribution of CCR5 receptors was analyzed by fixing and permeabilizing cells using BD Cytofix/Cytoperm buffer. Data shown are from one representative experiment that was independently repeated at least three times. C) Dose-dependent effects of CCR5-T4L or CCL5 on surface CCR5 expression in MDM. D and E) Dose-dependent effects on MDM migration by CCR5-T4L (D) or CCL5 (100 nM) plus different concentrations of CCR5-T4L protein (E). F and G) Dose-dependent effects on [125I]-CCR5 binding by CCR5-T4L (F) or CCL5 (100 nM) plus different concentrations of CCR5-T4L protein (G). H and I) Dose-dependent effects on CCL5-induced [³⁵S]GTPγS binding to membranes from human macrophages cells treated with CCR5-T4L (H) or CCL5 (100 nM) plus different concentrations of CCR5-T4L protein (I). Data are the mean ± SD of triplicate cultures, which are representative of three experiments.</p

Metformin Inhibits Prostate Cancer Progression by Targeting Tumor-Associated Inflammatory Infiltration

PURPOSE: Inflammatory infiltration plays important roles in both carcinogenesis and metastasis. We are interested in understanding the inhibitory mechanism of metformin on tumor-associated inflammation in prostate cancer. EXPERIMENTAL DESIGN: By using TRAMP mouse model, in vitro macrophage migration assays, and patient samples, we examined the effect of metformin on tumor-associated inflammation during the initiation and after androgen deprivation therapy of prostate cancer. RESULTS: Treating TRAMP mice with metformin delays prostate cancer progression from LGPIN to HGPIN, WD to UD, and PIN to adenocarcinoma with concurrent inhibition of inflammatory infiltration evidenced by reduced recruitment of macrophages. Furthermore, metformin is capable of inhibiting the following processes: inflammatory infiltration after ADT induced by surgically castration in mice, bicalutamide treatment in patients and hormone deprivation in LNCaP cells. Mechanistically, metformin represses inflammatory infiltration by downregulating both COX2 and PGE2 in tumor cells. CONCLUSIONS: Metformin is capable of repressing prostate cancer progression by inhibiting infiltration of tumor-associated macrophages, especially those induced by ADT, by inhibiting COX2/PGE2 axis, suggesting that a combination of ADT with metformin could be a more efficient therapeutic strategy for prostate cancer treatment

Expression and purification of soluble recombinant CCR5-T4L protein in an <i>E</i>. <i>coli</i> system.

<p>A) Large scale purification and identification of recombinant CCR5-T4L. Recombinant CCR5-T4L was expressed in <i>E</i>. <i>coli</i>. The pET-20b expression vector was transformed into Rosetta 2 (DE3) golden BL21 pLysS cells and analyzed using Coomassie brilliant blue R-250. Lane M: protein marker; lane 1: uninduced bacterial lysate; lane 2: IPTG-induced bacteria lysate; lane 3: small amount of soluble fraction purified on a Ni-nitrilotriacetic acid (NTA) histidine-binding column; lane 4: small amount of membrane fraction purified using a Ni-nitrilotriacetic acid (NTA) histidine-binding column; lane 5: large amount of soluble fraction purified by fast protein liquid chromatography (FPLC) using an AKTA purifier; lane 6: large amount of membrane fraction purified by fast protein liquid chromatography (FPLC) using an AKTA purifier. B and C) Western blot analyses using the anti-6×His tag monoclonal or anti-human CCR5 monoclonal antibodies (3A9).</p