Dysregulation of SOX17/NRF2 axis confers chemoradiotherapy resistance and emerges as a novel therapeutic target in esophageal squamous cell carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the sixth leading cause of cancer-associated death worldwide with a dismal overall 5-year survival rate of less than 20%. The standard first-line therapy for advanced ESCC is concomitant chemo-radiation therapy (CCRT); however, patients usually develop resistance, resulting in unfavorable outcomes. Therefore, it is urgent to identify the mechanisms underlying CCRT resistance and develop effective treatment strategies. METHODS: Patients' endoscopic biopsy tumor tissues obtained before CCRT treatment were used to perform RNA-seq and GSEA analysis. Immunohistochemical (IHC) staining, chromatin immunoprecipitation (ChIP), and promoter reporter analyses were conducted to investigate the relationship between SOX17 and NRF2. Xenograft mouse models were used to study the role of SOX17/NRF2 axis in tumor growth and the efficacy of carboxymethyl cellulose-coated zero-valent-iron (ZVI@CMC). RESULTS: In this study, a notable gene expression signature associated with NRF2 activation was observed in the poor CCRT responders. Further, IHC staining of endoscopic biopsy of 164 ESCC patients revealed an inverse correlation between NRF2 and SOX17, a tumor-suppressive transcription factor with low expression in ESCC due to promoter hypermethylation. Using ChIP and promoter reporter analyses, we demonstrated that SOX17 was a novel upstream transcriptional suppressor of NRF2. In particular, SOX17low/NRF2high nuclear level significantly correlated with poor CCRT response and poor survival, indicating that the dysregulation of SOX17/NRF2 axis played a pivotal role in CCRT resistance and tumor progression. Notably, the in-house developed nanoparticle ZVI@CMC functioned as an inhibitor of DNA methyltransferases to restore expression of SOX17 that downregulated NRF2, thereby overcoming the resistance in ESCC. Additionally, the combination of ZVI@CMC with radiation treatment significantly augmented anticancer efficacy to inhibit tumor growth in CCRT resistant cancer. CONCLUSION: This study identifies a novel SOX17low/NRF2high signature in ESCC patients with poor prognosis, recognizes SOX17 as a transcriptional repressor of NRF2, and provides a promising strategy targeting SOX17/NRF2 axis to overcome resistance.

Excretion of Ni, Pb, Cu, As, and Hg in Sweat under Two Sweating Conditions.

Physiologists have long regarded sweating as an effective and safe means of detoxification, and heavy metals are excreted through sweat to reduce the levels of such metals in the body. However, the body can sweat through many means. To elucidate the difference in the excretion of heavy metals among sweating methods, 12 healthy young university students were recruited as participants (6 men and 6 women). Sweat samples were collected from the participants while they were either running on a treadmill or sitting in a sauna cabinet. After they experienced continuous sweating for 20 min, a minimum of 7 mL of sweat was collected from each participant, and the concentrations of nickel (Ni), lead (Pb), copper (Cu), arsenic (As), and mercury (Hg) were analyzed. The results demonstrated that the sweating method affected the excretion of heavy metals in sweat, with the concentrations of Ni, Pb, Cu, and As being significantly higher during dynamic exercise than during sitting in the sauna (all p < 0.05). However, the concentrations of Hg were unaffected by the sweating method. This study suggests that the removal of heavy metals from the body through dynamic exercise may be more effective than removal through static exposure to a hot environment.

Dysregulated Kras/YY1/ZNF322A/Shh transcriptional axis enhances neo-angiogenesis to promote lung cancer progression.

Angiogenesis enhances cancer metastasis and progression, however, the roles of transcription regulation in angiogenesis are not fully defined. ZNF322A is an oncogenic zinc-finger transcription factor. Here, we demonstrate a new mechanism of Kras mutation-driven ZNF322A transcriptional activation and elucidate the interplay between ZNF322A and its upstream transcriptional regulators and downstream transcriptional targets in promoting neo-angiogenesis. Methods: Luciferase activity, RT-qPCR and ChIP-qPCR assays were used to examine transcription regulation in cell models. In vitro and in vivo angiogenesis assays were conducted. Immunohistochemistry, Kaplan-Meier method and multivariate Cox regression assays were performed to examine the clinical correlation in tumor specimens from lung cancer patients. Results: We validated that Yin Yang 1 (YY1) upregulated ZNF322A expression through targeting its promoter in the context of Kras mutation. Reconstitution experiments by knocking down YY1 under KrasG13V activation decreased KrasG13V-promoted cancer cell migration, proliferation and ZNF322A promoter activity. Knockdown of YY1 or ZNF322A attenuated angiogenesis in vitro and in vivo. Notably, we validated that ZNF322A upregulated the expression of sonic hedgehog (Shh) gene which encodes a secreted factor that activates pro-angiogenic responses in endothelial cells. Clinically, ZNF322A protein expression positively correlated with Shh and CD31, an endothelial cell marker, in 133 lung cancer patient samples determined using immunohistochemistry analysis. Notably, patients with concordantly high expression of ZNF322A, Shh and CD31 correlated with poor prognosis. Conclusions: These findings highlight the mechanism by which dysregulation of Kras/YY1/ZNF322/Shh transcriptional axis enhances neo-angiogenesis and cancer progression in lung cancer. Therapeutic strategies that target Kras/YY1/ZNF322A/Shh signaling axis may provide new insight on targeted therapy for lung cancer patients.

Effects of Surfactants on the Degradation of Diclofenac by Manganese Oxide.

Amine-containing pharmaceuticals are the most often detected pharmaceuticals in wastewater and ambient aquatic environments. They can usually be degraded by manganese oxide (MnO2), which is a common natural oxidant in soils. Surfactants often coexist with pharmaceuticals in wastewater. Some amine-containing pharmaceuticals, such as diclofenac (DIC), are acidic and are thus ionic compounds in neutral conditions. These compounds, therefore, have similar properties to surfactants. Surfactants, thus, may influence the adsorption and degradation processes of DIC by MnO2. The effect of the type of surfactant on the degradation of DIC by MnO2 was investigated in this study with the addition of two common biodegradable surfactants (cetyltrimethyl-ammonium bromide (CTAB) and sodium dodecylsulfate (SDS)). The results indicated that the cationic surfactant (CTAB) significantly increased the degradation rate in neutral and alkaline conditions. On the other hand, the anionic surfactant (SDS) slightly increased the DIC removal rate in an acidic condition but significantly decreased the removal in neutral and alkaline conditions. Coexisting cationic surfactants not only influenced the kinetics but also altered the transformation mechanism of DIC by MnO2. Decarboxylation is the main transformation mechanism of DIC in the presence of CTAB, while both decarboxylation and hydroxylation are the main transformation mechanisms in the absence of CTAB.

Comparative Study of the Composition of Sweat from Eccrine and Apocrine Sweat Glands during Exercise and in Heat.

This preliminarily study was made to examine the differences in sweat excretions from human eccrine and apocrine sweat glands in dynamic exercise and heat conditions. Sweat samples were collected from six young males while they were either running on a treadmill or sitting in a sauna cabinet. Sweat samples of at least 5 mL from the eccrine (upper-back) and apocrine (armpit) sweat glands were collected during a 20-min running (or inactive overheating) period. The samples were then analyzed for urea, uric acid, and electrolyte (Na+, Cl-, and K+) excretions. The results from a two-way repeated-measures analysis of variance (ANOVA) revealed that the secretions of urea and K+ were significantly higher during running than during inactive overheating for both glands, as were Na+ secretions for the apocrine glands (all P < 0.05). Under the same sweating conditions, urea and K+ excretions from the apocrine glands were also higher than those from the eccrine glands (all P < 0.05). Significant differences were observed between the Na+ secretions of the apocrine and eccrine glands under the running condition. The effects of various sweating methods and sweat glands on Cl- secretions were nonsignificant, and little uric acid was excreted. A higher urea excretion level during running rather than in hot conditions could be attributed to an elevated metabolic rate.

Factors Controlling Changes in Epilithic Algal Biomass in the Mountain Streams of Subtropical Taiwan.

In upstream reaches, epilithic algae are one of the major primary producers and their biomass may alter the energy flow of food webs in stream ecosystems. However, the overgrowth of epilithic algae may deteriorate water quality. In this study, the effects of environmental variables on epilithic algal biomass were examined at 5 monitoring sites in mountain streams of the Wuling basin of subtropical Taiwan over a 5-year period (2006-2011) by using a generalized additive model (GAM). Epilithic algal biomass and some variables observed at pristine sites obviously differed from those at the channelized stream with intensive agricultural activity. The results of the optimal GAM showed that water temperature, turbidity, current velocity, dissolved oxygen (DO), pH, and ammonium-N (NH4-N) were the main factors explaining seasonal variations of epilithic algal biomass in the streams. The change points of smoothing curves for velocity, DO, NH4-N, pH, turbidity, and water temperature were approximately 0.40 m s-1, 8.0 mg L-1, 0.01 mg L-1, 8.5, 0.60 NTU, and 15°C, respectively. When aforementioned variables were greater than relevant change points, epilithic algal biomass was increased with pH and water temperature, and decreased with water velocity, DO, turbidity, and NH4-N. These change points may serve as a framework for managing the growth of epilithic algae. Understanding the relationship between environmental variables and epilithic algal biomass can provide a useful approach for maintaining the functioning in stream ecosystems.

MS title: Catalytic oxidation and removal of arsenite in the presence of Fe ions and zero-valent Al metals.

Arsenic immobilization in acid mine drainage (AMD) is required prior to its discharge to safeguard aquatic organisms. Zero-valent aluminum (ZVAl) such as aluminum beverage cans (AlBC) was used to induce the oxidation of As(III) to As(V) and enhance the subsequent As removal from an artificially prepared AMD. While indiscernible As(III) oxidation was found in aerated ZVAl systems, the addition of 0.10-0.55mM Fe(II) or Fe(III) into the AMD significantly promoted the As(V) production. Reactions between Fe(II) and H2O2, which was produced through an oxidative reaction of ZVAl with dissolved oxygen, generated OH radicals. Such OH radicals subsequently induced the As(III) oxidation. Over the course of the Fenton like reaction, ZVAl not only directly generated the H2O2, but indirectly enhanced the OH radical production by replenishing Fe(II). Arsenite oxidation in the aerated ZVAl/Fe and AlBC/Fe systems followed zero- and first-order kinetics. Differences in the kinetic reactions of ZVAl and AlBC with respect to As(III) oxidation were attributed to higher productive efficiency of the oxidant in the AlBC systems. After the completion of As(III) oxidation, As(V) could be removed simultaneously with Al(III) and Fe(III) by increasing solution's pH to 6 to produce Al/Fe hydroxides as As(V) scavengers or to form Al/Fe/As co-precipitates.

Molecular Structures of Al/Si and Fe/Si Coprecipitates and the Implication for Selenite Removal.

Aluminum and iron oxides have been often used in the coagulation processes during water purification due to their unique surface properties toward anions. In the presence of silica, the coprecipitation of Al/Si or Fe/Si might decrease the efficiency of wastewater purification and reuse. In this study, surface properties and molecular structures of Al/Si and Fe/Si coprecipitates were characterized using spectroscopic techniques. Also, the selenite removal efficiency of Al/Si and Fe/Si coprecipitates in relation to their surface and structural properties was investigated. While dissolved silicate increased with increasing pH from Fe/Si coprecipitates, less than 7% of silicate was discernible from Al/Si samples over the range from acidic to alkaline conditions. Our spectroscopic results showed that the associations between Al and Si were relatively stronger than that between Fe and Si in coprecipitates. In Al/Si coprecipitates, core-shell structures were developed with AlO6/AlO4 domains as the shells and Si frameworks polymerized from the SiO2 as the cores. However, Si framework remained relatively unchanged upon coprecipitation with Fe hydroxides in Fe/Si samples. The Si core with Al shell structure of Al/Si coprecipitates shielded the negative charges from SiO2 and thereby resulted in a higher adsorption capacity of selenite than Fe/Si coprecipitates.

BOTTLE MATERIAL AND CLEANSING PROCEDURES OF INFANT FEEDING BOTTLES.

The cleanliness of feeding bottles is vital for child health. Although machine cleansing of bottles in the food industry has been established, mechanical and manual cleansing methods are highly variable. This study was undertaken to determine the differences in the cleanliness of bottles that were cleaned using various combinations of bottle materials [glass and polypropylene (PP)], rinsing water volumes (1/3, 1/2, and 2/3 capacity of a bottle), and sustained shaking times (5 seconds and 20 seconds). Total organic carbon (TOC) and conductivity measurements were respectively used to evaluate the rinsed quantities of organic and inorganic formula residue from feeding bottles. The results indicated that glass bottles filled with rinsing water to 2/3 of their capacity showed the most efficient cleansing performance. However, the PP bottles exhibited a relatively poor cleansing result, particularly for organic cleanliness. The organic residue tends to accumulate on the PP bottle interior because of the aggregation of compounds with similar properties. The shaking time hardly influenced the cleanliness. The glass bottle was superior to the PP bottle in both organic and inorganic cleanliness, and organic constituents were more difficult to rinse from the bottle than the inorganic constituents were.

Rainfall Threshold Assessment Corresponding to the Maximum Allowable Turbidity for Source Water.

This study aims to assess the upstream rainfall thresholds corresponding to the maximum allowable turbidity of source water, using monitoring data and artificial neural network computation. The Taipei Water Source Domain was selected as the study area, and the upstream rainfall records were collected for statistical analysis. Using analysis of variance (ANOVA), the cumulative rainfall records of one-day Ping-lin, two-day Ping-lin, two-day Tong-hou, one-day Guie-shan, and one-day Tai-ping (rainfall in the previous 24 or 48 hours at the named weather stations) were found to be the five most significant parameters for downstream turbidity development. An artificial neural network model was constructed to predict the downstream turbidity in the area investigated. The observed and model-calculated turbidity data were applied to assess the rainfall thresholds in the studied area. By setting preselected turbidity criteria, the upstream rainfall thresholds for these statistically determined rain gauge stations were calculated.

Degradation of antibiotic amoxicillin using 1 x 1 molecular sieve-structured manganese oxide.

The kinetics and mechanism ofamoxicillin (AMO) degradation using a 1 x 1 molecular sieve-structured manganese oxide (MnO2) was studied. The presence of the buffer solution (i.e., NaHCO3, NaH2PO4 and KH2PO4) diminished AMO binding to MnO2, thus reducing AMO degradation in the pretest; therefore, all other experiments in this study were conducted without the addition of a buffer. Third-order rate constants, second-order on AMO and first-order on MnO2 increased with elevating pH level (2.81-7.23) from 0.54 to 9.17 M(-2) s(-1), and it decreased to 4.27 M(-2) s(-1) at pH 8.53 beyond the pk(a2) of AMO (7.3). The dissolution of the MnO2 suspension with and without AMO exhibited a similar trend; that is, Mn2+ concentration increased with decreasing pH. However, the dissolution of MnO2 with AMO was greater than that without AMO, except for the reaction occurring at pH 8.53, partially indicating that MnO2 acts as an oxidant in AMO degradation. The preliminary chromatogram data display different products with varying pH reaction s, implying that AMO elimination using this 1 x 1 molecular sieve-structured MnO2 is by adsorption as well as oxidative degradation. A complementary experiment indicates that the amount of oxidatively degraded AMO increases substantially from 65.5% at 4 h to 95% at 48 h, whereas the AMO adsorbed onto MnO2 decreases slightly from 4.5% at4 h to 2.4% at 48 h. The oxidative degradation accounted for more AMO removal than adsorption over the whole reaction course, indicating that the oxidative reaction of AMO on MnO2 dominated the AMO removal.

Catalytic pyrolysis of sugarcane bagasse by using microwave heating.

The aim of this study was to research the catalytic effects on the microwave pyrolysis of sugarcane bagasse and thus to discuss the reaction performance, product distribution, and kinetic analysis. With the addition of metal-oxides served as catalysts, reaction results such as mass reduction ratio and reaction rate increased, even the maximum temperature decreased. Adding either NiO or CaO slightly increased the production of H2, while adding either CuO or MgO slightly decreased it. The addition of either CaO or MgO enhanced the gaseous production, and either NiO or CuO addition enhanced the liquid production. There could be several secondary reactions such as self-gasification and interactions among the gases originally produced during the pyrolysis stage to alter the composition of gaseous product and the final three-phase product distribution. The catalyst addition slightly increased the activation energy but greatly increased the pre-exponential factor.

Microwave pyrolysis of rice straw: products, mechanism, and kinetics.

Rice straw is an abundant resource for the production of biofuels and bio-based products. How to convert the recalcitrant lignocellulose effectually is a critical issue. The objective of this study was to investigate the products, mechanism, and kinetics of rice straw pyrolysis by using microwave heating. The highest energy densification ratio of solid residues was achieved at the microwave power level of 300 W. The atomic H/C and O/C ratios of solid residues were much lower than those of rice straw. The primary components of gaseous product were CO, H2, CO2, and CH4, whose molecular fractions were 57%, 21%, 14%, and 8%, respectively. The more gaseous product and the less solid residues were obtained at higher microwave power levels, while the liquid production remained the same and showed a maximum of about 50 wt.%. The kinetic parameters of rice straw pyrolysis were increased with increasing microwave power level.

Catalytic and atmospheric effects on microwave pyrolysis of corn stover.

Corn stover, which is one of the most abundant agricultural residues around the world, could be converted into valuable biofuels and bio based products by means of microwave pyrolysis. After the reaction at the microwave power level of 500W for the processing time of 30min, the reaction performance under N2 atmosphere was generally better than under CO2 atmosphere. This may be due to the better heat absorbability of CO2 molecules to reduce the heat for stover pyrolysis. Most of the metal-oxide catalysts effectively increased the maximum temperature and mass reduction ratio but lowered the calorific values of solid residues. The gas most produced was CO under N2 atmosphere but CO2 under CO2 atmosphere. Catalyst addition lowered the formation of PAHs and thus made liquid products less toxic. More liquid products and less gas products were generated when using the catalysts possibly due to the existence of the Fischer-Tropsch synthesis.

pH-dependent mechanisms of methylene blue reacting with tunneled manganese oxide pyrolusite.

This study examined the reaction of methylene blue (MB) with tunneled manganese oxide pyrolusite regarding pH and reaction time. MB was cleaved through N-demethylation, in which reaction azure B (AB), azure A (AA), azure C (AC), and thionin (TH) were stepwise generated at all tested pH. Pyrolusite predominantly serves as the oxidant in the oxidative degradation of MB at a pH under the pHiep of pyrolusite (4.70) while playing the role of the catalyst at pH higher than pHiep. Among all oxidative products and original MB molecule, TH is the alone compound adsorbed onto the pyrolusite surface at all tested pH. However, the quantity of adsorbed TH increases with pH because of the stronger affinity between the cationic TH molecule and the more negatively charged surface of pyrolusite with pH increasing. Because the lattice oxygen and surface hydroxyl groups form excited oxygen firstly to cause the oxidation of MB, the tunneled pyrolusite with less constrained corner and edge oxygen catalytically promote the oxidation reaction at pH beyond pHiep. The vacancy of the consumed lattice oxygen forms the active sites for the other oxidation and could be replenished by molecular oxygen to complete a catalytic cycle.

Removal of hexavalent Cr by coconut coir and derived chars--the effect of surface functionality.

The Cr(VI) removal by coconut coir (CC) and chars obtained at various pyrolysis temperatures were evaluated. Increasing the pyrolysis temperature resulted in an increased surface area of the chars, while the corresponding content of oxygen-containing functional groups of the chars decreased. The Cr(VI) removal by CC and CC-derived chars was primarily attributed to the reduction of Cr(VI) to Cr(III) by the materials and the extent and rate of the Cr(VI) reduction were determined by the oxygen-containing functional groups in the materials. The contribution of pure Cr(VI) adsorption to the overall Cr(VI) removal became relatively significant for the chars obtained at higher temperatures. Accordingly, to develop a cost-effective method for removing Cr(VI) from water, the original CC is more advantageous than the carbonaceous counterparts because no pyrolysis is required for the application and CC has a higher content of functional groups for reducing Cr(VI) to less toxic Cr(III).

Energy life cycle assessment of rice straw bio-energy derived from potential gasification technologies.

To be a viable alternative, a biofuel should provide a net energy gain and be capable of being produced in large quantities without reducing food supplies. Amounts of agricultural waste are produced and require treatment, with rice straw contributing the greatest source of such potential bio-fuel in Taiwan. Through life-cycle accounting, several energy indicators and four potential gasification technologies (PGT) were evaluated. The input energy steps for the energy life cycle assessment (ELCA) include collection, generator, torrefaction, crushing, briquetting, transportation, energy production, condensation, air pollution control and distribution of biofuels to the point of end use. Every PGT has a positive energy benefit. The input of energy required for the transportation and pre-treatment are major steps in the ELCA. On-site briquetting of refused-derived fuel (RDF) provides an alternative means of reducing transportation energy requirements. Bio-energy sources, such as waste rice straw, provide an ideal material for the bio-fuel plant.

Adsorption mechanism of selenate and selenite on the binary oxide systems.

Removal of selenium oxyanions by the binary oxide systems, Al- or Fe-oxides mixed with X-ray noncrystalline SiO(2), was previously not well understood. This study evaluates the adsorption capacity and kinetics of selenium oxyanions by different metal hydroxides onto SiO(2), and uses X-ray absorption spectroscopy (XAS) to assess the interaction between selenium oxyanions and the sorbents at pH 5.0. The binary oxide systems of Al(III)- or Fe(III)-oxides mixed with SiO(2) were prepared, and were characterized for their surface area, point of zero charge (PZC), pH envelopes, X-ray diffraction analysis (XRD), and then macro-scale adsorption isotherm and kinetics of selenite and selenate, micro-scale adsorption XAS. The adsorption capacity of selenite and selenate on Al(III)/SiO(2) is greater than on Fe(III)/SiO(2). Adsorption isothermal and kinetic data of selenium can be well fitted to the Langmuir isotherm and pseudo-second-order kinetic models. Based on simple geometrical constraints, selenite on both the binary oxide systems forms bidentate inner-sphere surface complexes, and selenate on Fe(III)/SiO(2) forms stronger complexes than on Al(III)/SiO(2).

Stabilization of copper-contaminated sludge using the microwave sintering.

A sintering with a microwave process was considered to stabilize copper-contaminated sludge and transform it into a sinter because microwave can provide uniform and quick heating. The parameters of addition of iron powder and ferric oxide, crucible modification, and air-forced leading were used in the microwave sintering. The results showed that reduced copper was present and some holes, caused by the high copper-contaminated synthetic sludge passing through the microwave sintering, were distributed throughout the sinters. However, when microwave sintering with the modification of parameters (improved microwave sintering) was used, the phenomena of copper reduction and hole formation were dispelled. Moreover, the improved microwave sintering of synthetic sludge with iron powder at 800W at 30 min formed cuprospinel with peaks of 2theta degrees of 18.508 and 57.05 shifting to 18.9 and 56.55 and the leaching concentration from this sinter passed the limit of toxicity characteristic leaching procedure (TCLP) for copper.