Inhibition of XPR1-dependent phosphate efflux induces mitochondrial dysfunction: A potential molecular target therapy for hepatocellular carcinoma?

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is the only known transporter associated with Pi efflux in mammals, and its impact on tumor progression is gradually being revealed. However, the role of XPR1 in hepatocellular carcinoma (HCC) is unknown. A bioinformatics screen for the phosphate exporter XPR1 was performed in HCC patients. The expression of XPR1 in clinical specimens was analyzed using quantitative real-time PCR, Western blot analysis, and immunohistochemical assays. Knockdown of the phosphate exporter XPR1 was performed by shRNA transfection to investigate the cellular phenotype and phosphate-related cytotoxicity of the Huh7 and HLF cell lines. In vivo tests were conducted to investigate the tumorigenicity of HCC cells xenografted into immunocompromised mice after silencing XPR1. Compared with that in paracancerous tissue, XPR1 expression in HCC tissues was markedly upregulated. High XPR1 expression significantly correlated with poor patient survival. Silencing of XPR1 leads to decreased proliferation, migration, invasion, and colony formation in HCC cells. Mechanistically, knockdown of XPR1 causes an increase in intracellular phosphate levels; mitochondrial dysfunction characterized by reduced mitochondrial membrane potential and adenosine triphosphate levels; increased reactive oxygen species levels; abnormal mitochondrial morphology; and downregulation of key mitochondrial fusion, fission, and inner membrane genes. This ultimately results in mitochondria-dependent apoptosis. These findings reveal the prognostic value of XPR1 in HCC progression and, more importantly, suggest that XPR1 might be a potential therapeutic target.

Tunable Non-Markovianity for Bosonic Quantum Memristors.

We studied the tunable control of the non-Markovianity of a bosonic mode due to its coupling to a set of auxiliary qubits, both embedded in a thermal reservoir. Specifically, we considered a single cavity mode coupled to auxiliary qubits described by the Tavis-Cummings model. As a figure of merit, we define the dynamical non-Markovianity as the tendency of a system to return to its initial state, instead of evolving monotonically to its steady state. We studied how this dynamical non-Markovianity can be manipulated in terms of the qubit frequency. We found that the control of the auxiliary systems affects the cavity dynamics as an effective time-dependent decay rate. Finally, we show how this tunable time-dependent decay rate can be tuned to engineer bosonic quantum memristors, involving memory effects that are fundamental for developing neuromorphic quantum technologies.

Impacts of vermicompost application on crop yield, ammonia volatilization and greenhouse gases emission on upland in Southwest China.

Ammonia (NH3) volatilization and greenhouse gas (GHG) emission are important environment pollution sources in upland agro-ecosystems. Vermicompost was used for amending purple soil and comparing NH3 and GHG emissions. A field experiment was conducted with a comparison of organic and inorganic fertilizers in a wheat-maize rotation system in the Sichuan Basin, China. The five treatments were conventional inorganic fertilizers, NPK as control; vermicompost prepared with cow dung (VCM); and pig manure (VPM); cow dung and pig manure vermicompost, respectively (VCMNPK, VPMNPK). Total nitrogen rates of all treatments were the same. Soil NH3 volatilization and GHG emissions were monitored with the static chamber method. The results showed that NH3 volatilization occurred in the first two weeks following nitrogen (N) fertilization. The cumulative fluxes of NH3 recorded in the NPK, VCM, VPM, VCMNPK, and VPMNPK treatments were 15.4, 5.7, 6.3, 10.32, and 10.29 kg N ha-1 yr-1, respectively, in the winter and 4.8, 5.5, 19.83, 12.8, and 11.9 kg N ha-1 yr-1 respectively, in the summer. The global warming potential (GWP) 773.6 and 803.9 g CO2-eq m-2 in VCM and VPM, respectively, during the wheat season 540.6 and 576.2 g CO2-eq m-2, respectively, during the maize season. The GWPs in NPK treatment were 1032.4 and 570.7 g CO2-eq m-2 during the wheat and maize seasons, respectively. The increasing effects of nutrient loops, particularly 18 % soil total nitrogen (TN) and 31 % soil organic carbon (SOC) in VCM, and crop productivity of vermicompost treatments during the wheat-maize rotation had been evaluated. This study recommends that VCM can be considered as a better organic amendment, promoting plant growth while decreasing the environmental costs of gas emissions.

Bioavailable phosphorus transport from a hillslope cropland of purple soil under natural and simulated rainfall.

To further understand the mechanism of bioavailable total P (BAP) and bioavailable dissolved P (BDP) transport by overland and subsurface flow, we exposed a runoff plot 4.5 m long × 1.5 m wide × 0.6 m deep to simulated and natural rainfall in order to study the effects of rainfall type, rainfall intensity, and vegetation cover on BAP and BDP transport. The results showed that vegetation cover could alleviate the discharge of overland flow and sediment transport and enhance subsurface flow. BAP transport significantly increased with elevated rainfall intensity. Vegetation cover reduced the BAP transport by overland flow and increased it by subsurface flow. BDP transport showed no significant relationship with vegetation cover and rainfall type. The bioavailable particulate P (BPP) transport by overland flow contributed to no less than 90% by weight of total BAP, and the BPP transport by subsurface flow contributed to no less than 60% by weight of total BAP. Short-time heavy rainfall caused more BAP transport and accelerated non-point source pollution.

Ammonia Volatilization and Greenhouse Gases Emissions during Vermicomposting with Animal Manures and Biochar to Enhance Sustainability.

There is a huge potential for nutrient recovery from organic waste materials for soil fertility restoration as well as negative environmental emission mitigation. Previous research has found vermicomposting the optimal choice for converting organic waste into beneficial organic fertilizer while reducing reactive N loss. However, a great deal of the processes of greenhouse gases (GHG) and ammonia volatilization during vermicomposting are not well-documented. A field vermicomposting experiment was conducted by deploying earthworms (Eisenia fetida) with three types of agricultural by-products-namely, cow manure (VCM), pig manure (VPM), and biochar (VBC)-and crop (maize) residues compared with traditional composting (COM) without earthworms in the Sichuan Basin, China. Results showed that vermicomposting caused a decrease in electrical conductivity (EC) and total organic carbon (TOC) while increasing total nitrogen (TN). The greatest TN increase was found with VCM. The cumulative NH3 volatilization in COM, VCM, VPM, and VBC during experimental duration was 9.00, 8.02, 15.16, and 8.91 kg N ha-1, respectively. The cumulative CO2 emissions in COM, VCM, VPM, and VBC were 2369, 2814, 3435, and 2984 (g·C·m-2), while for CH4, they were 0.36, 0.28, 4.07, and 0.19 (g·C·m-2) and, for N2O, they were 0.12, 0.06, 0.76, and 0.04 (g·N m-2), respectively. Lower emissions of N2O, CH4, and NH3 were observed in VBC. We concluded that earthworms, as ecological engineers, enhanced reactive nutrients and reduced ammonia volatilization during vermicomposting in our test system. Overall, vermicomposting is proposed as an eco-friendly, sustainable technique that helps to reduce environmental impacts and associated health risks.

[Characteristics of Deposited Sediment and Assessment of Heavy Metals in Typical Tributaries Bay Riparian Zone of the Three Gorges Reservoir].

In order to analyze the spatial variation characteristics of grain diameter, nutrient elements and heavy metal pollution with deposition sediment in tributaries bay of the Three Gorges Reservoir, we selected 9 typical tributaries bay, 54 deposited sediment samples were collected from the riparian zone for analyzing grain diameter distribution, capacity, organic matter, nutrient elements of TN, TP and K, heavy metal elements of Cr, Cu, Ni, Pb, and Zn. The results indicated that particle size distribution from Wujiang River in Fuling to the Modao stream in Yunyang presented a trend of fluctuation, deposited sediment at 160-165 m elevation was coarser than that at 165-175 m elevation,volume percent of sand and clay presented a moderate variation at both altitudes, while silt had small variation. Independent sample t test showed that characteristics difference between the upper and lower sediments in riparian zone was not significant. The geo-accumulation index of heavy metal pollutants in the sediment from riparian zone of the Three Gorges Reservoir tributaries bay indicated that, only Zn element in Zhenxi River, Longdong River and Long River, Pb element in the Modao Stream belonged to non-moderate pollution levels, whereas there were no pollution of all other elements in tributaries.

A highly sensitive and selective fluorescent probe for trivalent aluminum ion based on rhodamine derivative in living cells.

A rhodamine spirolactam derivative (1) is developed as a colormetric and fluorescent probe for trivalent aluminum ions (Al(3+)). It exhibits a highly sensitive "turn-on" fluorescent response toward Al(3+) with a 70-fold fluorescence intensity enhancement under 2 equiv. of Al(3+) added. The probe can be applied to the quantification of Al(3+) with a linear range covering from 5.0 × 10(-7) to 2.0 × 10(-5) M and a detection limit of 4.0 × 10(-8) M. Most importantly, the fluorescence changes of the probe are remarkably specific for Al(3+) in the presence of other metal ions, which meet the selective requirements for practical application. Moreover, the experiment results show that the response behavior of 1 towards Al(3+) is pH independent in neutral condition (pH 6.0-8.0) and the response of the probe is fast (response time less than 3 min). In addition, the proposed probe has been used to detect Al(3+) in water samples and image Al(3+) in living cells with satisfying results.

A ratiometric fluorescent probe with unexpected high selectivity for ATP and its application in cell imaging.

Naphthalimide-rhodamine compound (NR) is developed as a ratiometric fluorescent probe for ATP detection based on the FRET mechanism. It shows an unexpected high selectivity for ATP over other anions, especially organic phosphate anions, due to simultaneous interactions of two recognition sites, which benefits fluorescence imaging in living cells.

Ratiometric near-infrared chemosensor for trivalent chromium ion based on tricarboyanine in living cells.

A tricarboyanine derivative (IRPP) is applied as a ratiometric near-infrared chemosensor for detecting trivalent chromium ions (Cr(3+)) in living cells. Upon the addition of Cr(3+) to a solution of IRPP, large-scale shifts in the emission spectrum (from 755 nm to 561 nm) are observed. In the newly developed sensing system, these well-resolved emission peaks yield a sensing system that covers a linear range from 1.0×10(-7) to 1.0×10(-5) M with a detection limit of 2.5×10(-8) M. The experimental results show the response behavior of IRPP towards Cr(3+) is pH independent under neutral conditions (6.0-7.5). Most importantly, the fast response time (less than 3 min) and selectivity for Cr(3+) over other common metal ions provide a strong argument for the use of this sensor in real world applications. As a proof of concept, the proposed chemosensor has been used to detect and quantify Cr(3+) in river water samples and to image Cr(3+) in living cells with encouraging results.

[The mutation patterns of HBV P gene and genotyping in patients with lanivudine-resistant chronic hepatitis B].

OBJECTIVE: To analyze the mutation patters of HBV P gene and genotyping of heptitis B virus in patients with chronic hepatitis B (CHB) after the emergence of drug-resistance during lamivudine (LAM) therapy. METHODS: LAM-resistant mutations and genotype of HBV were dectected in patients with LAM-resistant CHB in our hospital from Sep. 2008 to June. 2010. RESULT: 107 patients had 8 mutation patterns. YMDD mutations happened in 100%, only YMDD mutation were 43 patients, while others were YMDD combined with rtL180M mutations; the HBV genotype among 107chronic hepatitis was mainly B (25.2%) and C (73.8%) and only 1 patient was happend B and C mixed infection. Genetype C was mainly YMDD combined with rtL180M mutations pattern, the rate is 60.7% (48/79); while genetype B was mainly rtM204 mutation pattern, the rate is 66.7% (18/27); there were significant difference between the genetype B and C in mutation pattern (chi2 = 8.4, 7.2, respectively, P < 0. 01). CONCLUSION: YMDD mutation is the major mutation pattern of HBV P gene after emergence of LAM-resistance. Genotypes of hepatitis B virus can determine the related mulation patterns of HBV P gene.

[Clinical value of CD64 expression in adults with measles complicating bacterial pneumonia].

OBJECTIVE: To study the clinical value of expression of peripheral blood neutrophil CD64 in adults with measles complicating pneumonia. METHODS: 106 patients were divided into two groups by clinical manifestation and bacteria study: measles complicating bacterial pneumonia group and measles complicating viral pneumonia, using flow cytometry determination of CD64, C-reactive protein (CRP) and white blood cell (WBC) count. RESULTS: The expression of CD64 in the bacterial pneumonia group with eruptive stage was (32.15 +/- 11.07) MFI, which was significantly higher than that in the group of with recovery stage (10.6 +/- 3.23) MFI (P < 0.01) and viral pneumonia (9.55 +/- 3.48) MFI (P < 0.01). These markers were considered positive if CD64 > or = 8.5 MFI, CRP > or = 10 mg/L and WBC > or = 9.05 x 10(9)/L. Their sensitivity was 78.12%, 80.48% and 59.37%. Their specificity was 76.19% ,67.67% and 64.28%. Their accuracy rate was 77.35%, 74.52%, 61.32%; CD64 has a positive relationship with CRP. CONCLUSION: Compared to CRP, expression of peripheral blood neutrophil CD64 can be a better marker in the early diagnosis of patients with measles complicating bacterial pneumonia and as one of the indicators of disease conditions.