Human AKR1A1 involves in metabolic activation of carcinogenic aristolochic acidⅠ

OBJECTIVE To investigate whether aldo-keto reductases(AKRs)can act as a nitrore⁃ductase(NR)and bioactivate aristolochic acidⅠ(AA-Ⅰ)to produce AA-Ⅰ-DNA adducts.METHODS①Human-induced hepatocytes(hiHeps)and human bladder RT4 cells were used as tool cells and treated with AA-Ⅰ0,0.5,1.0 and 2μmol·L^(-1)for 24 h.Cell viability was detected using the CCK-8 method,and the half maximal inhibition concentration(IC_(50))was calculated using the CCK-8 method and the level of DNA adduct production was calculated.②hiHeps and RT4 cells were treated with AKR inhibitor luteotin(0,5,10 and 25μmol·L^(-1))+AA-Ⅰ0.2 and 1.0μmol·L^(-1)for 24 h,respectively,and the levels of DNA adducts were detected by a liquid chromatography-tandem mass spectrometer(LC-MS/MS).③hiHeps cells were incubated with 80 nmol·L^(-1)small interfering RNAs(si-AKRs)for 48 h and treated with AA-Ⅰ1.0μmol·L^(-1)for 24 h.Real-time qualitative PCR(RT-qPCR)method was used to detect the mRNA expression of AKRs gene and LC-MS/MS technology was used to investigate the effect of specific AKR gene knockdown on DNA adduct levels.④500 nmol·L^(-1)human AKR recombinant proteins AKR1A1 and AA-Ⅰwere incubated in vitro under anaerobic conditions and the formation of AA-Ⅰ-DNA adducts was detected.RESULTS①The IC_(50)of AA-Ⅰto hiHeps and RT4 cells was 1.9 and 0.42μmol·L^(-1),respec⁃tively.The level of DNA adduct production of the two cell lines was significantly different(P<0.01).②Luteolin≥5μmol·L^(-1)significantly inhibited the production of AA-Ⅰ-DNA adducts in both cells(P<0.05),and there was a concentration-dependent effect in hiHeps cells(P<0.01,R=0.84).③In the AKR family,the knockdown of AKR1A1 gene up to 80%inhibited the generation of AA-Ⅰ-DNA adducts by 30%-40%.④The AA-Ⅰ-DNA adducts were detected in the incubation of recombinant protein AKR1A1 and AA-Ⅰunder anaerobic conditions in vitro,approximately 1 adduct per 107 nucleotides.CONCLU⁃SION AKR1A1 is involved in AA-Ⅰbioactivation,providing a reference for elucidation of the carcino⁃genic mechanism of AA-Ⅰ.

Analysis of Environmental Endocrine Disrupting Activities in Wastewater Treatment Plant Effluents Using Recombinant Yeast Assays Incorporated with Exogenous Metabolic Activation System

Objective To measure the endocrine disrupting chemicals （EDCs） in wastewater and evaluate the EDCs removal efficiencies in the municipal wastewater treatment plants （WWTP）. Methods A battery of in vitro recombinant yeast bioassays incorporated with exogenous metabolic activation system （rat liver preparation, S9 mix） was conducted to assess the estrogen receptor （ER）, androgen receptor （AR）, progesterone receptor （PR）, and thyroid receptor （TR） ant/agonistic activities of effluents collected from Datansha WWTP. Results The indirect estrogenic, anti‐androgenic, anti‐progesteronic, and anti‐thyroidic activities were observed in the influent. The removal efficiencies of EDCs were above 74%, suggesting that the present wastewater treatment processes were good enough to remove most of these indirect endocrine disrupting chemicals. Conclusion The incorporation of exogenous metabolic capacity into the test system was valid for the study of indirect effects on ER, AR, PR, and TR.

Microbial community structure and functional metabolic diversity are associated with organic carbon availability in an agricultural soil

Exploration of soil environmental characteristics governing soil microbial community structure and activity may improve our understanding of biogeochemical processes and soil quality. The impact of soil environmental characteristics especially organic carbon availability after 15-yr different organic and inorganic fertilizer inputs on soil bacterial community structure and functional metabolic diversity of soil microbial communities were evaluated in a 15-yr fertilizer experiment in Changping County, Beijing, China. The experiment was a wheat-maize rotation system which was established in 1991 including four different fertilizer treatments. These treatments included： a non-amended control（CK）, a commonly used application rate of inorganic fertilizer treatment（NPK）; a commonly used application rate of inorganic fertilizer with swine manure incorporated treatment（NPKM）, and a commonly used application rate of inorganic fertilizer with maize straw incorporated treatment（NPKS）. Denaturing gradient gel electrophoresis（DGGE） of the 16 S r RNA gene was used to determine the bacterial community structure and single carbon source utilization profiles were determined to characterize the microbial community functional metabolic diversity of different fertilizer treatments using Biolog Eco plates. The results indicated that long-term fertilized treatments significantly increased soil bacterial community structure compared to CK. The use of inorganic fertilizer with organic amendments incorporated for long term（NPKM, NPKS） significantly promoted soil bacterial structure than the application of inorganic fertilizer only（NPK）, and NPKM treatment was the most important driver for increases in the soil microbial community richness（S） and structural diversity（H）. Overall utilization of carbon sources by soil microbial communities（average well color development, AWCD） and microbial substrate utilization diversity and evenness indices（H＇ and E） indicated that long-term inorganic fertilizer with organic amendments incorporated（NPKM, NPKS） could significantly stimulate soil microbial metabolic activity and functional diversity relative to CK, while no differences of them were found between NPKS and NPK treatments. Principal component analysis（PCA） based on carbon source utilization profiles also showed significant separation of soil microbial community under long-term fertilization regimes and NPKM treatment was significantly separated from the other three treatments primarily according to the higher microbial utilization of carbohydrates, carboxylic acids, polymers, phenolic compounds, and amino acid, while higher utilization of amines/amides differed soil microbial community in NPKS treatment from those in the other three treatments. Redundancy analysis（RDA） indicated that soil organic carbon（SOC） availability, especially soil microbial biomass carbon（Cmic） and Cmic/SOC ratio are the key factors of soil environmental characteristics contributing to the increase of both soil microbial community structure and functional metabolic diversity in the long-term fertilization trial. Our results showed that long-term inorganic fertilizer and swine manure application could significantly improve soil bacterial community structure and soil microbial metabolic activity through the increases in SOC availability, which could provide insights into the sustainable management of China＇s soil resource.

Elevated metabolic rate during passive stretching is not a sufficient aerobic warm-up

Purpose： The purpose of this study was to determine the extent that a static stretching program could increase heart rate （HR） and oxygen consumption （VO2）, and if the increases were sufficient to serve as a warm-up for aerobic activity. Methods： The HR and VO2 of 15 male and 16 female college students were measured after either 12 min of passive static stretching （SS）, or 12 rain pseudo-stretching （PS）, which consisted of moving through the stretching positions without placing the muscles on stretch. Four different lower body stretches were used with each stretch held for 30 s before the participant moved to a different position, with the circuit being repeated four times. VO2 was determined by averaging breath-by-breath measures over the total 12 min. HR was obtained every 30 s and the 24 values were averaged. Warm-up benefit was determined from the 02 deficit accrued during 7-min cycling at 60% VOzmax. Results： HR （beats/rain, mean 4. SD） for SS （84 ± 11） was a significant （p 〈 0.05） 9% greater than PS （78 ± 12）. Similarly, VO2 （mL/min, mean 4. SD） for SS （0.53 ± 0.13） was a significant 44% greater than PS （0.38 ± 0.11）. The O2 deficit （L, mean 4, SD） for SS （0.64 ± 1.54） was not different from PS （0.72 ± 1.61）. Conclusion： These data indicate that passive static stretching increases both HR and VO2, indicating that metabolic activity can be increased without muscle activation. The magnitude of the increases, however, is not sufficient to elicit a warm-up effect.

Influences of V5-epitope tag on the metabolic activation of AFB1 by human cytochrome P450 2A13

Objective： To explore the impact of V5-epitope tag inserted in the commercial pcDNA5/FRT/V5-His TOPO expression vector on the metabolic activation of AFB1 by human CYP2A13. Methods ： A C-terminal 6 × Histag was first introduced into CYP2A13 cDNA by PCR and subsequently transferred into the expressing vector pcDNA5/FRT. Another commercial pcDNA5/FRT/V5-His TOPO expression vector was used to develop the construct directly via PCR. Both of the constructs were then transfected into Flp-In CHO and allowed for the stable expression of CYP2A13. The mouse CYP2A5 and the vector alone were used as positive and negative control, respectively. The presence of CYP2A5 and CYP2A13 cDNA and their protein expression in the stable transfectant cells were deterrrfined by immunoblotting assay using a monoclonal antibody against 6 × Histag. The AFBl-induced cytotoxicity in these tranfected CHO cells were conducted by MTS assay and the IC50 of cell viability was used to compare the CYP enzyme metabolic activity in AFB1 metabolism among these cells. Results： In accordance with the Flp-In system working mechanism, all the transfectant cells presented same protein expression level. The CHO cells expressing CYP2A5 was more sensitive to AFB1 treatment than those cells expressing CYP2A13, there was about 30-fold ICs0 difference between the two cells （2.1 nmol/L vs 58 nmol/L）. Interestingly, CYP2A13 fused with V5-Histag had the lost of metabolic activity to AFB1 than that fused with Histag alone, the ICa, of the viability in CHO-2A13-His-V5 cells was about 20-fold less than CHO-2A13- His （〉 1 000 nmol/L vs 58 nmol/L）. However, there was no change between CYP2A5 fused with V5-Histag and Histag alone （2.4 nmol/L vs 2.1 nmol/L）. Conclusion： The results demonstrate that CYP2A13 fused with V5-epitope has a significant impact on its metabolic activation to AFB1, which indicated that it should be careful to select a new expressing vector for evaluating the enzyme activity in carcinogen metabolism.

Variation in soil organic matter accumulation and metabolic activity along an elevation gradient in the Santa Rosa Mountains of Southern California, USA

Variations in soil organic matter accumulation across an elevation can be used to explain the control of substrate supply and variability on soil metabolic activity. We investigated geographic changes in soil organic matter and metabolic rates along an elevation gradient（289–2,489 m） in the Santa Rosa Mountains, California, USA from subalpine and montane pine forests through chaparral to desert. From base（289 m） to summit（2,489 m）, 24 sites were established for collecting soil samples under canopies and inter-canopy spaces, at 0–5 and 5–15 cm soil depths increments. Soil organic matter（SOM） content was determined using weight loss on ignition at 550°C and soil CO2 efflux（R） was measured at day 5（R5） and day 20（R20） of incubation. Changes in SOM content along the elevation gradient showed a significant relationship（P〈0.05） but R5 and R20 were not related to either elevation or SOM content. However, the ratio of R and SOM（R5/SOM） showed a strong relationship across the mountains at both soil depths. R5/SOM, as an indicator of carbon use efficiency, may be applicable to other semi-arid transects at larger scale modeling of soil metabolic processes.

Hemoglobin Adducts as Biomarkers of Exposure to and metabolic Activation of Carcinogenic Tobacco-Specific Nitrosamines

The carcinogenic tobacco-specific nitrosamines N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-l-(3-pyridyl)-l-butanone (NNK) form hemoglobin adducts in laboratory animals and humans. These adducts release 4-hydroxy-l-(3-pyridyl)-l-butanone (HPB) upon mild base hydrolysis. HPB released from human hemoglobin can be quantified by gas chromatography-mass spectrometry. It is the only available biochemical marker for determination of exposure to, and metabolic activation of, carcinogens present only in tobacco. Levels of HPB were highest in snuff-dippers, followed by smokers and nonsmokers. Large interindividual variations in adduct levels were observed. The relationship between HPB levels in globin and DNA of rats treated with NNK has been investigated in order to aid in interpretation of the data from humans. These studies have provided the initial database for understanding the metabolic activation of tobacco-specific nitrosamines in humans.

Microbial Remediation of Heavy Metal(loid)Contaminated Soil: A Review

Because of the rapid development of industrial processes, increased urban pollution and agricultural chemicals applied in recent years, heavy metal(loid) pollution in soil has been very serious, and there is an urgent need for fast and efficient removal of heavy metal(loid) pollution. Currently, environmental microorganisms are always used to perform biological alteration or improvement of soils and sewage. Using functional microorganisms that are resistant to toxic heavy metal(loid) ions for alteration and transformation of heavy metal(loid)s in ionic form is an effective measure for microbial remediation of heavy metal(loid)contaminated soil. This paper reviewed the microbial remediation mechanism of heavy metal(loid) contaminated soils, and the approaches for breeding bacteria those can be used for highly efficient removal of heavy metal(loid)s, as well as the application examples of microbial remediation and transformation of heavy metal(loid) contaminated soil, and finally described the future trends and further research work of heavy metal(loid) contaminated soils by microbial remediation.

Biological process of soil improvement in civil engineering:A review

The concept of using biological process in soil improvement which is known as bio-mediated soil improvement technique has shown greater potential in geotechnical engineering applications in terms of performance and environmental sustainability. This paper presents a review on the soil microorganisms responsible for this process, and factors that affect their metabolic activities and geometric compatibility with the soil particle sizes. Two mechanisms of biomineralization, i.e. biologically controlled and biologically induced mineralization, were also discussed. Environmental and other factors that may be encountered in situ during microbially induced calcite precipitation （MICP） and their influences on the process were identified and presented. Improvements in the engineering properties of soil such as strength/stiffness and permeability as evaluated in some studies were explored. Potential applications of the process in geotechnical engineering and the challenges of field application of the process were identified.

Effects of Copper on the Photosynthesis and Oxidative Metabolism of Amaranthus tricolor Seedlings

The objective of the present study was to gain better insight into the physiological mechanisms on the effects of copper （Cu） on photosynthesis and active oxygen metabolism in three-colored amaranth plant （Amaranthus tricolor）. Three- colored amaranth seedlings were subjected to different Cu levels in soils during the entire experimental period. The parameters of growth, photosynthesis, mineral elements contents, and active oxygen metabolism were investigated using plant physiological methods. The results showed that 2.0 and 4.0 mmol Cu kg^-1 treatments decreased the whole plant biomass to 91 and 73% of the control, respectively. The net photosynthetic rate （Pn） and the stomatal conductance （gs） were similarly reduced in the third leaves of three-colored amaranth seedlings treated with 2.0 and 4.0 mmol Cu kg^-1 soil, respectively. None of the investigated Cu levels decreased the internal CO2 concentration （Ci）. The effect of Cu on the potential efficiency of photosystem Ⅱ （Fv/Fm） was negligible, whereas the effect of Cu on the PS Ⅱ quantum efficiency （ΦPS Ⅱ） after plant adaptation in actinic irradiation was more noticeable. On the other hand, decreases in water percentage, contents of photosynthetic pigments and mineral elements including Fe, K, and Mg, and significant increase in the Cu content were observed in the third leaves of Cu-treated plants. Superoxide dismutase （SOD） and peroxidase （POD） activities as well as the proline （Pro） content significantly increased in the third leaves of the three-colored amaranth seedlings treated with 2.0 and 4.0 mmol Cu kg^-1 soil, while catalase （CAT） and ascorbate peroxidase （APX） activities as well as the contents of carotenoid （Car）, glutathione （GSH）, and ascorbic acid （AsA） decreased, and accompanied by the increases in the contents of hydrogen peroxide （H2O2）, superoxide anion （O2^-）, and malondialdehyde （MDA）, and electrolyte leakage. As a result of the imbalance of active oxygen metabolism, Pn and ΦPS Ⅱ decreased, and peroxidization enhanced under levels of 2.0 and 4.0 mmol Cu kg^-1 soil. Finally, the growth of three-colored amaranth plant was significantly inhibited.

The effects of phenolic acid on nitrogen metabolism in Populus 3 euramericana ‘Neva’

The declines in soil fertility and productivity in continuously cropped poplar plantations axe related to phenolic acid accumulation in the soil. Nitrogen is a vital life element for poplar and whether the accumulation of phenolic acid could influence nitrogen metabolism in poplar and thereby hinder continuous cropping is not clear. In this study, poplar cuttings of Populus × euramericana ‘Neva＇ were potted in vermiculite, and phenolic acids at three concentrations （032, 0.5X and 1.0X） were added according to the actual content （1.0X） in the soil of a second-generation poplar plantation. Each treatment had eight replicates. We measured gas exchange parameters and the activities of key enzymes related to nitrogen metabolism in the leaves. Leaf photosynthetic parameters varied with the concentration of phenolic acids. The net photosynthetic rate （PN） significantly decreased with increasing phenolic acid concentration, and non-stomatal factors might have been the primary limitation for PN- The activities of nitrate reductase （NR）, glutamine synthetase （GS） and glutamate synthase （GOGAT）, as well as the contents of nitrate nitrogen, ammonium nitrogen, and total nitrogen in the leaves decreased with increasing phenolic acid concentration. This was significantly and positively related to PN （P 〈 0.05）. The low concentration of phe- nolic acids mainly affected the transformation process of NO3- to NO2-, while the high concentration of phenolic acids affected both processes, where NO3- was transferred to NO2- and NH4＋ was transferred to glutamine （Gln）. Overall, phenolic acid had significant inhibitory effects on the photosynthetic productivity of Populus x euramericana ＇Neva＇. This was probably due to its influence on the activities of nitrogen assimilation enzymes, which reduced the amount of amino acids that were translated into protein and enzymes. Improving the absorption and utilization of nitrogen by plants could help to overcome the problems caused by continuous cropping.

Effects of salt-alkali stress on active oxygen metabolism in roots of Spiraea × bumalda 'Gold Mound' and Spiraea × bumalda 'Gold Flame'

Under artificially-simulated complex salt-alkali stress, the levels of active oxygen metabolism in roots were studied using three-year-old cutting seedlings of Spiraea × bumalda ‘Gold Mound＇ and Spiraea × bumalda ‘Gold Flame＇. The present study aimed at exploring the antioxidant capacity in roots of spiraeas and revealing their adaptability to salt-alkali stress. Results indicate that the oxygen free radicals contents, electrolyte leakage rates and MDA contents in roots of Spiraea × bumalda ＇Gold Mound＇ and Spiraea × bumalda ＇Gold Flame＇ show an increasing tendency with the increases of the salinity and pH value, whereas the activities of superoxide dismutase （SOD）, peroxidase （POD） and catalase （CAT） all increased firstly and then decreased. With the increase in intensity of salt-alkali stress, the CAT activity in roots of Spiraea × bumalda ‘Gold Flame＇ is higher and the increasing extents in the oxygen free radicals contents, electrolyte leakage rates as well as MDA contents are lower compared with Spiraea × bumalda ‘Gold Mound＇, indicating that Spiraea × bumalda ‘Gold Flame＇ has a stronger antioxidant capacity.

Immunometabolism: A target for the comprehension of immune response toward transplantation

Organ transplantation is a life-saving procedure, however predicting graft survival is still challenging. Understanding immune-cell pathobiology is critical to the development of effective therapies to prevent rejection. Over the recent years it has become progressively evident that the complex nature of immune cell behavioral dynamics is strongly dependent on cellular metabolism, which in turn, relies on competition for nutrients, oxygen and metabolites with other immune cells and microbiota. Furthermore, the influence of the inflammatory state can lead to substantial changes in conditions within the tissue microenvironment. Considering the context of immunity, alterations in metabolic pathways (glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway, the fatty acid oxidation and synthesis, and the amino acid metabolic pathways) will influence the production of different sets of cytokines and affect transplantation outcome. It is now known that na?ve, resting and effector cells acquire different metabolic profiles and studies have shown that specifically targeting some of these metabolic routes can prevent differentiation of effector T cells in favor of Tregs. Ultimately, to develop effective therapies that will prevent graft loss and understanding how cell metabolism impacts the fate and function of immune cells is now a critical point of discussion. The distinct metabolic features and requirements observed in effector and suppressive cell subsets offer promising opportunities for selective regulation of the immune responses in transplantation and will be discussed in this review.

Influence of Phenobarbital and Carbon tetrachloride on the Modulation of Tissue Retention Profile of Hexachlorocyclohexane in Rats

The study was designed to investigate the role of hepatic metabolic activity on body burden of HCH residue. Male albino rats were orally administered 0, 5, and 10 mg/kg HCH for 90 days, followed by either sodium phenobarbital or carbon tetrachloride treatment for 0, 15 and 30 days after withdrawal of their respective HCH administration. The liver weight was significantly increased at 30 days after the administration of phenobarbital and carbon tetrachloride in both 5 mg and 10 mg/kg HCH withdrawal groups when compared to control. HCH residue was maximun in fat followed by adrenal>thymus>liver>kidney>spleen>testes>brain>plasma. Carbon tetrachloride caused an accumul-ation of HCH residues in the liver 15 and 30 days after administration of both doses of HCH. Phenobarbital did not show significant variation in HCH residues in hepatic tissue. Phenobarbital treatment caused significant induction of hepatic RED, APD, AHH, GST and QR activities. Significant decreases in activities were observed by carbon tetrachloride when compared to animals treated with HCH alone. The overall results clearly suggest the role of P450 protein on the body burden of HCH residues.

Role of positron emission tomography in primary carcinoma ex pleomorphic adenoma of the bronchus: A case report

BACKGROUND Primary carcinoma ex pleomorphic adenoma arising from the tracheobronchial system is rarely reported.CASE SUMMARY We present a patient with primary carcinoma ex pleomorphic adenoma of the bronchus and review the associated literature for further comparison,including age,clinical manifestations,and diagnostic process.This patient had no history of neoplasms of the salivary gland.CONCLUSION Positron emission tomography played an important role in the staging work-up of primary carcinoma of ex pleomorphic adenoma.Long-term follow-up was necessary for further prognosis analysis.

Study of the Protective Effects in PEPC Transgenic Rice

The diurnal course of chlorophyll fluorescence parameter and active oxygen metabolism of flag leaves in PEPC transgenic and untransformed rice Kitaake were studied. The results showed that the photosynthetic rate under high light intensity has been increased by 50% and photoinhibition of photosynthesis in PEPC transgenic was alleviated after the introduction of PEPC gene from maize into rice. It was demonstrated that the increment of photosynthesis in PEPC transgenic was related to the introduction of PEPC gene using specific inhibitor of PEPC. Photoinhibition of photosynthesis in different genotypes exists at noon under natural condition. PEPC transgenic rice exhibited a less decrease in Fv/Fm, a less photoinhibition and a higher efficiency of light energy conversion to chemical energy and lower thermal energy dissipation. These results provided the physiological basis on the mechanism of tolerance to photoinhibition and rice breeding with high photosynthetic efficiency.

The Effects of Antibiotics, Metals, and Biotic Interactions on the Assembly of Taxonomically Diverse Single and Mixed Species Biofilms

To better understand the assembly of the sturgeon egg microbiome, we purified six bacterial isolates from eggs and characterized their ability to form biofilms under the stress of tobramycin, with and without exogenous protein. In experiments with single species biofilms, tobramycin reduced the metabolic activity of all isolates and increased biofilm biomass of three. The addition of exogenous protein to the assay countered the inhibition of biofilm and metabolic activity by tobramycin of Pseudomonas sp., Brevundimonas sp., Flavobacterium columnare and mixed biofilms of Pseudomonas-F. columnare and Brevundimonas-Hydrogenophaga. Two of the isolates (Pseudomonas spp.) that produced antimicrobial activity, were effective at reducing biofilm formation by Brevundimonas, but enhanced biofilm formation in other isolates. Increasing concentrations of Mg2+ had no effect on biofilm formation but Ca2+ enhanced biofilm formation of Pseudomonas aeruginosa PA01 (positive control) and Brevundimonas. Biofilm assembly by these two bacteria was inhibited by low concentrations of Ni2+. Mixed biofilms of Brevundimonas and Hydrogenophage consistently produced more robust biofilm than the strains in isolation, suggesting synergism. Established Brevundimonas biofilm appeared adept at recruiting pelagic Acidovorax and Hydrogenophaga into biofilm, suggesting that it plays an important role in the selection of species into the microbiome.

Combined metabolic activators improve cognitive functions in Alzheimer’s disease patients:a randomised,double-blinded,placebo-controlled phase-II trial

Background Alzheimer’s disease(AD)is associated with metabolic abnormalities linked to critical elements of neurodegeneration.We recently administered combined metabolic activators(CMA)to the AD rat model and observed that CMA improves the AD-associated histological parameters in the animals.CMA promotes mitochondrial fatty acid uptake from the cytosol,facilitates fatty acid oxidation in the mitochondria,and alleviates oxidative stress.Methods Here,we designed a randomised,double-blinded,placebo-controlled phase-II clinical trial and studied the effect of CMA administration on the global metabolism of AD patients.One-dose CMA included 12.35 g L-serine(61.75%),1 g nicotinamide riboside(5%),2.55 g N-acetyl-L-cysteine(12.75%),and 3.73 g L-carnitine tartrate(18.65%).AD patients received one dose of CMA or placebo daily during the first 28 days and twice daily between day 28 and day 84.The primary endpoint was the difference in the cognitive function and daily living activity scores between the placebo and the treatment arms.The secondary aim of this study was to evaluate the safety and tolerability of CMA.A comprehensive plasma metabolome and proteome analysis was also performed to evaluate the efficacy of the CMA in AD patients.Results We showed a significant decrease of AD Assessment Scale-cognitive subscale(ADAS-Cog)score on day 84 vs day 0(P=0.00001,29%improvement)in the CMA group.Moreover,there was a significant decline(P=0.0073)in ADAS-Cog scores(improvement of cognitive functions)in the CMA compared to the placebo group in patients with higher ADAS-Cog scores.Improved cognitive functions in AD patients were supported by the relevant alterations in the hippocampal volumes and cortical thickness based on imaging analysis.Moreover,the plasma levels of proteins and metabolites associated with NAD+and glutathione metabolism were significantly improved after CMA treatment.Conclusion Our results indicate that treatment of AD patients with CMA can lead to enhanced cognitive functions and improved clinical parameters associated with phenomics,metabolomics,proteomics and imaging analysis.

Inhibiting Human Copper Transfer and Tumor Growth

Copper is a trace element that is required by almost all forms of life.Acting as cofactors for various key metabolism enzymes,copper takes part in many vital biological processes.Previous studies have found the concentration of copper is significantly higher in tumor cells than in normal cells.In addition,copper can promote angiogenesis by activating VEGF and FGF signaling.

Peracetic acid(PAA)-based pretreatment effectively improves medium-chain fatty acids(MCFAs)production from sewage sludge

Peracetic acid(PAA),known for its environmentally friendly properties as a oxidant and bactericide,is gaining prominence in decontamination and disinfection applications.The primary product of PAA oxidation is acetate that can serve as an electron acceptor(EA)for the biosynthesis of medium-chain fatty acids(MCFAs)via chain elongation(CE)reactions.Hence,PAA-based pretreatment is supposed to be beneficial for MCFAs production from anaerobic sludge fermentation,as it could enhance organic matter availability,suppress competing microorganisms and furnish EA by providing acetate.However,such a hypothesis has rarely been proved.Here we reveal that PAA-based pretreatment leads to significant exfoliation of extracellular polymeric substances(EPS)from sludge flocs and disruption of proteinic secondary structures,through inducing highly active free radicals and singlet oxygen.The production of MCFAs increases substantially to 11,265.6 mg COD L^(-1),while the undesired byproducts,specifically long-chain alcohols(LCAs),decrease to 723.5 mg COD L^(-1).Microbial activity tests further demonstrate that PAA pretreatment stimulates the CE process,attributed to the up-regulation of functional genes involved in fatty acid biosynthesis pathway.These comprehensive findings provide insights into the effectiveness and mechanisms behind enhanced MCFAs production through PAA-based technology,advancing our understanding of sustainable resource recovery from sewage sludge.