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Background The proto-oncogene c-MET (mesenchymal-epithelial transition factor gene) plays a critical role in cellular proliferation, survival, migration, and invasion in cancers. The aim of this study is to explore the relationship between c-MET expression and the clinicopathological characteristics of colorectal cancer (CRC) patients. Methods A total of 337 enrolled patients were collected in present study. Here, the c-MET and EGFR expression were detected by immunohistochemistry (IHC). The mutational statuses of KRAS in exons 2, 3, and 4, NRAS in exons 2, 3, and 4, and BRAF in exon 15 from formalin-fixed sections were detected by direct DNA sequencing. Results Our results showed that high c-MET expression was significantly associated with tumor perineural invasion (P=0.007) and gender (P=0.016). High level c-MET expression (c-MET-high) in the primary tumors was observed in 68.2% of patients. In the 337 enrolled patients, 43.2% of patients had KRAS mutations, 3.3% of patients had NRAS mutations, and 4.7% of patients had BRAF mutations. However, KRAS, NRAS, and BRAF gene mutations had no association with c-MET protein levels in primary tumors. Additionally, c-MET protein expression had a strong correlation with EGFR expression (P=0.002). The survival time was not significantly longer for patients with c-MET-high primary tumors than for those with c-MET-low primary tumors. Conclusions c-MET immunohistochemistry was significantly higher in primary tumors with perineural invasion, female gender, and EGFR high expression. However, c-MET-high in the primary tumors was not significantly associated with longer survival compared with c-MET-low tumors. Further studies are required to investigate c-MET as potential molecular marker of progression and to test the possibility of its incorporation as a new therapeutic target.

Iodine is a reactive trace element in atmospheric chemistry that destroys ozone and nucleates particles. Iodine emissions have tripled since 1950 and are projected to keep increasing with rising O3 surface concentrations. Although iodic acid (HIO3) is widespread and forms particles more efficiently than sulfuric acid, its gas-phase formation mechanism remains unresolved. Here, in CLOUD atmospheric simulation chamber experiments that generate iodine radicals at atmospherically relevant rates, we show that iodooxy hypoiodite, IOIO, is efficiently converted into HIO3 via reactions (R1) IOIO + O3 → IOIO4 and (R2) IOIO4 + H2O → HIO3 + HOI + (1)O2. The laboratory-derived reaction rate coefficients are corroborated by theory and shown to explain field observations of daytime HIO3 in the remote lower free troposphere. The mechanism provides a missing link between iodine sources and particle formation. Because particulate iodate is readily reduced, recycling iodine back into the gas phase, our results suggest a catalytic role of iodine in aerosol formation.

Hypoxia problem has always been a difficult point in plateau tunneling projects. To solve this problem, a blind heading face in a plateau metal mine in western China was taken as the physical model, and the computational fluid dynamics was used to analyze the oxygen mass fraction distribution and oxygen-increasing effect in 1 m, 3 m, and 5 m roadway sections from the heading face. The optimal ventilation system was first built to obtain the optimum height and length of the airflow ducts. Then different cases with various oxygen supply duct designs were built in 2 scenarios. The results found that different oxygen supply duct design has significant influence on the oxygen distribution in the heading face. Also, each design has different optimal height of oxygen outlet. The oxygen supply effect is best when some small holes are made in the oxygen supply duct to diffuse oxygen to the working surface. The finding of this paper is helpful for effective and economical oxygen supply in roadway excavation of plateau metal mine and tunnel.

Irrigation water quality is of great concerns to the sustainable agriculture and often is neglected in most irrigation areas in Ordos Basin, a semi-arid area in China. In this paper, a hydrochemical investigation of groundwater was performed to highlight the groundwater quality and evaluate its risk/suitability for irrigation purpose in Ordos Basin. Hydrographical method, Piper diagram and PHREEQC geochemical modeling were employed to characterize the groundwater quality and the relevant geochemical processes. Electrical conductivity, sodium percentage (Na%), sodium adsorption ratio (SAR), residual sodium carbonate (RSC), permeability index, magnesium ration (MR) and Kelley’s ration (KR) were used to evaluate the suitability for irrigation purpose. In summary, 86.67% of the area is fresh water (TDS 1 g/L) on the northwest side of the study area with Cl–Ca·Mg·Na type. The distribution of nitrate contents showed that nitrate pollution is a persistent problem that affects a wide area of the aquifer. The calculated Na%, SAR, RSC, MR and KR indicate that most of the groundwater is of acceptable risk for irrigation as well as for domestic usage. The Gibbs plot showed that the hydrochemistry of groundwater samples was mainly influenced by evaporation–precipitation and water rock dominance including carbonate and silicate minerals weathering.

Interplay of volatility distribution and particle viscosity governs the gas-to-particle partitioning dynamics of atmospheric secondary organic aerosol (SOA) constituents. Temperature-induced shifts in both particle volatility distribution and viscosity can influence the evaporation behavior of atmospheric SOA particles. However, knowledge of the particle evaporation at low temperatures is still limited. Here, we combined the isothermal evaporation measurements and processes modelling to explore the evaporation of α-pinene ozonolysis (αpinO3) and photooxidation (αpinOH) SOA particles under a series of relative humidity (RH) at two different temperatures. Experimental results revealed that the particle evaporation was hindered at low temperature, in agreement with the temperature dependence of the effective saturation vapor concentration and the possible temperature impact on the particle viscosity. Both αpinO3 and αpinOH SOA particles showed similar evaporation rates at 80% RH when particles were in a liqu...

Anammox is a distinctive bacterium that is extremely sensitive to and inhibited by organic matter. This weakness becomes a limiting factor for the application of anammox to treat wastewater especially that the underlying mechanisms in the inhibition of phenol remain unclear. In this study, phenol was chosen to determine the possible factors leading to the inhibition of anammox through community variation and molecular simulations. Results of the short-time batch experiment showed that 400 mg L−1 or 1000 mg L−1 of phenol immediately inhibited the anammox activity. Profiles from 16S rRNA sequences showed that the community structures remained unchanged during the first four hours. Molecular simulation between phenol and the key enzyme hydrazine synthase (HZS) showed that phenol combined with HZS and even had the ability to competitively bind with HZSα-haem αI and HZSγ-haem γI sites.

Interactions between metal-organic frameworks (MOFs) and nucleic acids are of great importance in molecular assembly. However, current MOF-nucleic acid interactions lack diversity and are normally realized in an uncontrollable manner. Herein, the interaction of zirconium-based MOFs (Zr-MOFs) with nucleic acids is enabled by the formation of Zr-O-P bonds and further manipulated by a phosphate-induced site-occupying effect. Covering Zr ions in clusters of MOFs with phosphates impedes the formation of Zr-O-P bonds with nucleic acids, rendering the MOF-nucleic acid interaction tunable and stimulus-responsive. Notably, the experimental results demonstrate that various phosphates, Zr-MOFs, and nucleic acids can all be adopted in the tunable interaction. On the basis of these findings, fluorescent DNA and typical Zr-MOFs are proposed as functional probe-quencher pairs to establish molecular sensing and logic systems. Accordingly, alkaline phosphatase and inorganic pyrophosphatase can be quantified simultaneously, and the overall relation of different phosphates and phosphatases is facilely displayed. The work provides a general strategy for modulating MOF-nucleic acid interactions, which is conducive to the development of molecular intelligent systems.

Complex characteristics of the plateau environment such as low oxygen content seriously restrict the exploitation of abundant mineral resources in plateau areas. To regulate the hypoxia environment and improve the comfort of workers engaged in intense physical labor like tunnel excavation operations in plateau mines, an individual oxygen-supply device for tunnel of plateau mine was proposed to create local oxygen enrichment in the area around the human nose. The Computational Fluid Dynamics (CFD) method was used to judge the application&rsquo, s effect of the individual oxygen-supply device in plateau mine, revealing the oxygen diffusion law under the influence of different oxygen enrichment factors. The orthogonal design and range analysis were used to measure the degree of influence of major factors such as oxygen-supply velocity, oxygen-supply concentration, and tunnel airflow velocity. The results demonstrate that the oxygen mass fraction of the air inhaled by the human had a positive correlation exponential function, a positive correlation linear function, and a negative correlation exponential function, respectively, concerning oxygen-supply velocity, oxygen-supply concentration, and tunnel airflow velocity. The range analysis revealed that the major influencing factors of oxygen enrichment in the tunnel of the plateau mine were, in a descending sequence, as follows: oxygen-supply concentration, tunnel airflow velocity, and oxygen-supply velocity, and the corresponding ranges were 2.86, 2.63, and 1.83, respectively. The individual oxygen-supply device achieved the best oxygen enrichment effect when the oxygen-supply velocity was 5 m/s, the oxygen-supply concentration was 60%, and the tunnel airflow velocity was 0.2 m/s, which increased the oxygen mass fraction of air inhaled by the human to 30.42%. This study has a positive guiding significance for the improvement of the respiration environment in the tunnel of plateau mine.

Ions enhance the formation rate of atmospheric aerosol particles, which play an important role in Earth’s radiative balance. Ion-induced nucleation involves the stepwise accretion of neutral monomers onto a molecular cluster containing an ion, which helps to stabilize the cluster against evaporation. Although theoretical frameworks exist to calculate the collision rate coefficients between neutral molecules and ions, they need to be experimentally confirmed, ideally under atmospherically relevant conditions of around 1000 ion pairs cm−3. Here, in experiments performed under atmospheric conditions in the CERN CLOUD chamber, we have measured the collision rate coefficients between neutral iodic acid (HIO3) monomers and charged iodic acid molecular clusters containing up to 11 iodine atoms. Three methods were analytically derived to calculate ion-polar molecule collision rate coefficients. After evaluation with a kinetic model, the 50% appearance time method is found to be the most robust. The measured collision rate coefficient, averaged over all iodine clusters, is (2.4 ± 0.8)×10−9 cm3 s−1, which is close to the expectation from the surface charge capture theory.

Removal of excessive nutrients (N and P) is one of the most concerned issues for wastewater treatment. This study presents a paired electrolytic system consisting of Al cathode and RuO2/Ti anode for the simultaneous removal of phosphate and ammonia in wastewaters. The comparative study on the dissolving behaviors of Al cathode and Al anode showed that Al cathode could achieve a continuous and stable dissolution of aluminum, thereby forming flocs and small amounts of water soluble aluminum species for decontamination. The electrogenerated OH– in the vicinity of cathode raised the local alkalinity and caused the chemical dissolution of aluminum. According to the experiment of non-electrolytic dissolution of aluminum in alkaline solution, the local pH resulting in the cathodic dissolution of Al was estimated. The paired electrolytic system showed the capability to simultaneously remove ammonia and phosphate in simulated wastewater, and the pH neutralizing effect in association with the formation of Al species could promote the electrochemical oxidation of ammonia. When the paired electrolytic system was applied to the treatment of landfill leachate, 96.9% of ammonia nitrogen, 87.4% of total phosphorous and 89.9% of COD could be eliminated after three hours of electrolysis at 80 mA/cm2. The results shown in study reveal that the dissolution process of Al cathode enables a convenient control on the dissolving-out amounts of aluminum via regulating the applied current density, and the paired electrolytic system can be developed as an energy-efficient electrochemical wastewater treating method.

Investigations on interaction between small molecules and DNA are the basis of designing advanced bioanalytical systems. We herein propose a novel interaction between heterocyclic aromatic compounds (HACs) and single-stranded DNA (ssDNA). Taking methylene blue (MB) as a typical HAC, it is found that MB can interact with cytosine (C)-rich ssDNA in an enthalpy-driven process. The interaction between MB and C-rich ssDNA is sequence and structure dual-dependent: at least three consecutive C and single-stranded structure are necessary, affecting the fluorescence response of metal nanoparticles. With the exception of the single-stranded structure, double-stranded, i-motif, and C-Ag-C mismatch structures will remarkably impede the interaction with MB. UV-vis absorption, fluorescent, and electrochemical curves demonstrate that the conjugated system, electron transition, and electron transfer of MB are remarkably affected by MB-C-rich ssDNA interaction. In particular, the absorption peak of MB at 664 nm decreases, and a new peak at 538 nm emerges. Therefore, the interaction can be characterized by a colorimetric and ratiometric signal. Relying on the inhibition of C-Ag-C mismatch and the enhanced analytical performances of the ratiometic signal, the MB-C-rich ssDNA interaction is further employed to quantify silver ions (Ag

Secondary organic aerosol (SOA) is an important constituent of the atmosphere where SOA particles are formed chiefly by the condensation or reactive uptake of oxidation products of volatile organic compounds (VOC). The mass yield in SOA particle formation, as well as the chemical composition and volatility of the particles are determined by the identity of the VOC precursor(s) and the oxidation conditions they experience. In this study, we used an oxidation flow reactor to generate biogenic SOA from the oxidation of Scots pine emissions. Mass yields, chemical composition, and volatility of the SOA particles were characterized and compared with SOA particles formed from oxidation of α-pinene and of a mixture of acyclic/monocyclic sesquiterpenes (farnesenes and bisabolenes), which are significant components of the Scots pine emissions. SOA mass yields for Scots pine emissions dominated by farnesenes were lower than for α-pinene, but higher than for the artificial mixture of farnesenes and bisabolenes. The reduction in the SOA yield in the farnesenes and bisabolenes dominated mixtures is due to C=C bond scission in these acyclic/monocyclic sesquiterpenes during ozonolysis leading to smaller and generally more volatile products. SOA particles from the oxidation of Scots pine emission had similar or lower volatility than SOA particles formed from either of single precursor. Applying physical stress to the Scots pine plants increased monoterpene emissions, which further decreased SOA particle volatility and increased SOA mass yield. Our results highlight the need to account for the chemical complexity and structure of real-world biogenic VOC emissions and stress-induced changes to plant emissions when modelling SOA production and properties in the atmosphere. These results emphasize that simple increase or decrease of relative monoterpene and sesquiterpene emissions should not be used as indicator of SOA particle volatility.

The contamination of ground water with arsenic is a great public health concern. This paper discusses the possible formation mechanism of high As groundwater; identify the main influences of natural and anthropogenic factors on As occurrence in groundwater; and finally estimates As-induced potential health hazards in an intensive agricultural region, Datong Basin (Northern China). Our findings indicate that the predominant controlling factors of As in groundwater can be divided into natural factors and anthropogenic activities. Natural factors can be classified as natural potential source of As, environmental geological characteristics and hydrochemical conditions; anthropogenic activities are manifested in industrial coal mining, domestic coal burning, agricultural irrigation return flow and excessive application of fertilizers, and groundwater exploitation. Microbial and/or chemical reduction desorption of arsenate from Fe-oxide/hydroxide and/or clay minerals, As-bearing Fe-oxide/hydroxide reduction coupled with sulfate reduction, and competition with phosphorus are postulated to be the major process dominating As enrichment in the alkaline and anoxic groundwater. In addition, age-dependent human health risk assessment (HHRS) was performed, and high risk values reveal a high toxic and carcinogenic risk of As contaminate for population who is subject to the continuous and chronic exposure to elevated As.

In recent years, the spontaneous combustion of coal has led to numerous gas explosions in mines that have resulted in hundreds of fatalities and very substantial damage to facilities. The present work developed a fully coupled model capable of simulating spontaneous coal combustion and carbon monoxide (CO) release together with methane (CH4) desorption rates, concentration distributions and migration. The aim was to evaluate the combined hazard posed by spontaneous coal combustion and CH4 build-up in mine as a result of the heat release generated by coal oxidation. The results show that the zone representing the highest degree of compound hazard is in the shape of an inclined strip located between 75 and 115 m from the working face on the inlet airway side but closer to the working face on the return airway side. Increases in the CH4 concentration in the return corner decrease as the ventilation flux increases, while the potential danger zone moves deeper into the gob. A greater initial CH4 release rate from the coal increases the size of the danger zone and moves this zone closer to the working face. The danger zone also moves away from the working face with decreases in the residual coal thickness and in the coal oxidation rate. Multivariate functions were developed to predict the positions of the gas explosive zone and the oxidation zone in the gob, and a model for assessing the risk of the compound hazard was established based on evaluating the index gas concentrations in the return corner.

In this study, 95 accessions of proso millet (Panicum miliaceum L.) were characterized for starch physicochemical properties, including apparent amylose content (AAC), gel textural properties, Rapid Visco Analyzer (RVA) pasting viscosity properties, thermal and retrogradation properties. Based on genotypic data, the genetic diversity and inter-relationship of these starch traits were analyzed. Diverse starch quality was found, for example, AAC ranged from 0 to 32.3%, gelatinization temperature (GT) varied from 71.5 to 79.0 ℃, and RVA profile showed distinct patterns among proso millet of different AAC types. Interestingly, high AAC proso millet usually had GT lower than that of low AAC proso millet, which is different from the findings in rice starch. Many starch traits were significantly correlated and most of the 18 tested traits could be classified as either AAC-related traits or GT-related traits. In summary, the information presented here will be useful for further development of proso millet products.

In this study, starch was isolated from 13 genotypes of 12 Lycoris species, and the morphology, granule size distribution and physicochemical properties, including apparent amylose content (AAC), Rapid Visco Analyzer (RVA) pasting properties, textural properties, thermal and retrogradation properties were characterized. The majority of starch granules of the 13 Lycoris genotypes were oval in shape, and granule size followed a normal distribution with a mean diameter of 20–30 μm. Contrary to previously published findings, the XRD results revealed that lycoris starches had either C-type or CA-type crystallinity. All lycoris starches showed high AAC varying from 25.6% to 32.7%, and low gelatinization temperature (GT) ranging from 58.8 to 69.7 ℃. Inter-relationships among 18 starch quality traits were analyzed based on correlation analysis. The present study provides information on lycoris starch characteristics which should serve as a useful guide for later studies on lycoris starch utilization in food and non-food industries.

Esophageal carcinoma, with a increasing incidence, is one of the most aggressive carcinomas in gastrointestinal tract. Epidemiologic studies demonstrate an association of oral pathogens with multiple diseases, including rheumatoid arthritis, cardiovascular diseases, diabetes, and gastrointestinal malignancies. Nevertheless, a causal relationship between oral pathogens and esophageal squamous cell carcinoma (ESCC) has not been elucidated. Here, we found that Porphyromonas was significantly enriched in the saliva of patients with ESCC, compared with that in normal human. In vitro studies showed that Porphyromonas gingivalis (P. gingivalis) promoted the proliferation and motility of ESCC cells, as evidenced by up regulated expression of key molecules implicated in NF-κB signaling pathway. These findings, for the first time, demonstrated a role of oral pathogens in inducing ESCC tumorigenesis and metastasis, which might involve regulation of NF-κB signaling pathway.

Feasibility and superiority of the bioelectrochemical system integrated with biocontact oxidation (BES-BCO) for degradation and/or mineralization of azo dyes have been confirmed. In this study, the effects of hydraulic retention time (HRT), applied voltage, and dissolved oxygen (DO) concentration at the bioanode on the performance of BES-BCO and traditional BES were investigated. Using the response surface methodology, the optimum values of HRT, applied voltage, and DO concentration at the bioanode of BES-BCO were investigated to obtain the maximum decolouration and COD removal efficiency and minimum specific energy consumption (SEC). The microbial community structure in BES-BCO was studied for analyzing the change following the introduction of oxygen. The optimised solution was an applied voltage of 0.59V, HRT of 12h, and DO concentration of 0.96mg/L at the bioanode. Under such conditions, the DE, COD removal efficiency, and SEC values were 94.62±0.63%, 89.12±0. 32%, and 687.57±3.86J/g, respectively. In addition, after changing from BES to BES-BCO, the bacterial community structure of the bioanode underwent significant changes. Several aerobic aniline-degrading bacteria and anode-respiration bacteria (ARB) were found to dominate the community of the anode biofilm. The results showed that the removal of azo dye degradation by-products was closely correlated with the o-bioanode and the BCO bacterial community structure.

The formation of secondary organic aerosol (SOA) has been widely studied in the presence of dry seed particles at low relative humidity (RH). At higher RH, seed particles can exist as dry or wet particles. Here, we investigated the formation of SOA from the photooxidation of toluene using an oxidation flow reactor under a range of OH exposures on initially wet or dry ammonium sulfate (AS) seed particles at an RH of 68 %. At an OH exposure of 4.66 × 1010 molecules cm -3 s, the ratio of the SOA yield on wet AS seeds to that on dry AS seeds was 1.31 ± 0.02. However, this ratio decreased to 1.01 ± 0.01 at an OH exposure of 5.28 × 1011 molecules cm -3 s. The decrease in the ratios of SOA yields as the increase of OH exposure may be due to the early deliquescence of initially dry AS seeds after coated by highly oxidized toluene-derived SOA. SOA formation lowered the deliquescence RH of AS and resulted in the uptake of water by both AS and SOA. Hence the initially dry AS seeds contained aerosol liquid water (ALW) soon after a large fraction of SOA formed and the SOA yield and ALW approached those of the initially wet AS seeds as OH exposure and ALW increased. However, a higher oxidation state of the SOA on initially wet AS seeds than that on dry AS seeds was observed at all levels of OH exposure. The difference in mass fractions of m/z 29, 43 and 44 of SOA mass spectra indicated that SOA formed on initially wet seeds may be enriched in earlier-generation products containing carbonyl functional groups at low OH exposures and later-generation products containing acidic functional groups at high exposures. Our results suggest that AS dry seeds soon turn to at least partially deliquesced particles during SOA formation and more studies on the interplay of SOA formation and ALW are warranted.

Since abnormal metabolism of histidine (His) is defined as an indicator of several diseases, detection of His in biological fluids becomes increasingly urgent to us. However, due to similar structures and properties of different amino acids, selective quantification of His is difficulty, and typically needs the participation of special reagents. In this work, we report for the first time that nickel ions (Ni2+) can induce the allostery of G-quadruplex, and is thus able to manipulate the activity of G-quadruplex DNAzyme. Experimental results indicate the interaction between Ni2+ and guanine is critical to the allostery. In comparison with Ni2+-guanine interaction, Ni2+-His interaction exhibits higher affinity. Therefore, a colorimetric His biosensor is fabricated, and His can be facilely discriminated by naked eyes. Relying on the high activity of DNAzyme, His in a range of 50 nM–400 μM is determined with this method, and low detection limit (36 nM) is obtained. More importantly, His can be directly distinguished in the absence of other toxic reagents. In addition, the amount of His in serum is also measured, suggesting the applicability of this biosensor in real sample detection. Overall, this work provides an alternative way to design G-quadruplex DNAzyme-based analytical approaches.

Cooking is an important source of volatile organic compounds (VOCs) and a potential source of secondary organic aerosol (SOA) both indoors and outdoors. In this study, VOC emissions from heating corn oil and stir-frying spices (i.e. garlic, ginger, myrcia and zanthoxylum piperitum (Sichuan pepper)) were characterized using an on-line membrane inlet vacuum ultraviolet single-photon ionization time-of-flight mass spectrometer (VUV-SPI-TOFMS). VOC emissions from heating corn oil were dominated by aldehydes, which were enhanced by factors of one order of magnitude when stir-frying spices. Stir-frying any of the spices studied generated large amounts of methylpyrrole (m/z 81). In addition, stir-frying garlic produced abundant dihydrohydroxymaltol (m/z 144) and diallyldisulfide (DADS) (m/z 146), while stir-frying ginger, myrcia and zanthoxylum piperitum produced abundant monoterpenes (m/z 136) and terpenoids (m/z 152, 154). SOA formed from emissions of stir-frying spices through reactions with excess ozone in a flow reactor as well as primary organic aerosol (POA) emissions were characterized using a scanning mobility particle sizer (SMPS) and a high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS). Stir-frying garlic and ginger generated similar POA concentrations to those from heating corn oil while stir-frying myrcia and zanthoxylum piperitum generated double the amount of emissions. No SOA was observed from stir-frying garlic and ginger. The rates of SOA production from stir-frying myrcia and zanthoxylum piperitum were 1.8μgmin-1gspice-1 and 8.7μgmin-1gspice-1, equivalent to 13.4% and 53.1% of their own POA emission rates, respectively. Therefore, the contribution of stir-frying spices to ambient organic aerosol levels is likely dominated by POA. The rates of total terpene emission from stir-frying myrcia and zanthoxylum piperitum were estimated to be 5.1μgmin-1gspice-1 and 24.9μgmin-1gspice-1, respectively. Our results suggest that stir-frying spices could be an important source of terpenes in indoor environments in Hong Kong, at least during cooking.

We reported previously the in vivo detection of ectopic and transient expression of creatine kinase gene (ck) in the liver by phosphorus-31 magnetic resonance spectroscopy ((31)P MRS). Here we demonstrate the feasibility of using ck as a reporter gene to monitor the transfer of low-density lipoprotein receptor (LDLr) gene to LDLr(/) mice, a preclinical model for familial hypercholesterolemia. A recombinant adenovirus was generated that carries the creatine kinase gene (ck) and human LDL receptor gene (hLDLr) linked by an internal ribosomal entry site sequence. Intravenous injection of the adenovirus into LDLr(/)mice (1 x 10(11) viral particles/mouse) resulted in transduction of more than 90% of hepatocytes in the liver. Simultaneous expression of ck and LDLr was confirmed by Western analysis of the transduced livers. Through precise regulation of transgene expression in hepatocytes in vitro, an excellent correlation (R(2) = 0.96) between LDLr and ck expression was demonstrated over a wide range of viral dose. In vivo 31P MRS was employed to detect the metabolic product (i.e., phosphocreatine) of the creatine kinase protein (CK) reaction. CK activity, which is a true measure of ck gene expression, was quantified in vivo by magnetization transfer. Because ck is expressed abundantly in human muscle and brain but is absent from the liver, ck is useful to monitor any liver directed gene transfer. Use of the ck reporter would facilitate the clinical translation of gene therapy by providing a nondestructive readout of the level and duration of therapeutic gene expression.