Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque formation.Therefore,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's disease.Microtubule acetylation/deacetylation plays a central role in lysosomal acidification.Here,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's disease.Fu rthermore,we found that treatment with valproic acid markedly enhanced autophagy.promoted clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's disease.Our findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

Effects of dietary ratio of n-6 to n-3 polyunsaturated fatty acids on immunoglobulins, cytokines, fatty acid composition, and performance of lactating sows and suckling piglets

This experiment was conducted to investigate the effects of dietary ratios of n-6：n-3 polyunsaturated fatty acids （PUFA） on the performance of lactating sows and their piglets. Thirty pregnant Landrace sows were assigned to one of three treatments from d 108 of gestation until weaning （26-29 d） and were fed diets containing different ratios of n-6：n-3 PUFA including 3：1,9：1 and 13：1. The effects on sow and litter production traits were examined together with an assessment of sow body condition. No differences were detected among the treatments for the daily feed intake of sows or changes in sow weight and back-fat levels during lactation （P 〉 0.05）. Litter size at d 14 and d 21 were tended to increase in 3：1 treatment compared with 9：1 and 13：1 treatments （P 〈 0.10）. Litter weight gain （1.77 kg/d） from d 0 to d 14 was tended to increase in 9：1 groups compared with the other two treatments （P 〈 0.10）. A significant difference was observed for the content of a -linolenic acid, total n-3 PUFA, and the ratio of n-6：n-3 PUFA in the colostrum, milk, and piglets plasma （P 〈 0.01）. The effects of different ratios of n-6：n-3 PUFA in sow diets on colostrum, milk and piglet plasma immunoglobulin concentrations are studied. No difference was observed among treatments in the concentrations of IgM, and IgA in colostrum （P 〉 0.05）. A great significant difference for IgG concentration was observed among 3 group in colostrum. A great significant difference for IgA, and IgM （P〈 0.01） concentrations in piglet plasma at d14 and a significant difference for IgG（P 〈 0.05） was observed at d14. Furthermore, at d 21 of lactation, piglet plasma IgG and IgA concentration were greater in 3：1 compared with 13：1 group （P 〈 0.01）. In summary, the current study demonstrated that altering the ratio of n-6：n-3 PUFA in lactating sow diet had an effect on the immune component including immunoglobulin and cytokines, and it tended to increase the litter average daily gain and improve the immune status of piglets when dietary ratio of n-6：n-3 PUFA was 9：1.

Efficacy of Topical versus Oral 5-Aminosalicylate for Treatment of 2,4,6-Trinitrobenzene Sulfonic Acid-induced Ulcerative Colitis in Rats

5-aminosalicylic acid（5-ASA） is drug of choice for the treatment of ulcerative colitis（UC）. In this study, the efficacy of topical versus oral 5-ASA for the treatment of UC was examined as well as the action mechanism of this medication. A flexible tube was inserted into the rat cecum to establish a topical administration model of 2,4,6-trinitrobenzene sulfonic acid（TNBS）-induced UC. A total of 60 rats were divided into sham operation group（receiving an enema of 0.9% saline solution instead of the TNBS solution via the tube）, model group, topical 5-ASA group, oral Etiasa group（a release agent of mesalazine used as positive control） and oral 5-ASA group（n=12 each）. Different treatments were administered 1 day after UC induction. The normal saline（2 mL） was instilled twice a day through the tube in the sham operation group and model group. 5-ASA was given via the tube in the topical 5-ASA group（7.5 g/L, twice per day, 100 mg/kg）, and rats in the oral Etiasa group and oral 5-ASA group intragastrically received Etiasa（7.5 g/L, twice per day, 100 mg/kg） and 5-ASA（7.5 g/L, twice per day, 100 mg/kg）, respectively. The body weight was recorded every day. After 7 days of treatment, blood samples were drawn from the heart to harvest the sera. Colonic tissues were separated and prepared for pathological and related molecular biological examinations. The concentrations of 5-ASA were detected at different time points in the colonic tissues, feces and sera in different groups by using the high pressure liquid chromatography（HPLC）. The results showed that the symptoms of acute UC, including bloody diarrhea and weight loss, were significantly improved in topical 5-ASA-treated rats. The colonic mucosal damage, both macroscopical and histological, was significantly relieved and the myeloperoxidase activity was markedly decreased in rats topically treated with 5-ASA compared with those treated with oral 5-ASA or Etiasa. The mRNA and protein expression of IL-1β, IL-6, and TNF-α was down-regulated in the colonic tissue of rats topically treated with 5-ASA, significantly lower than those from rats treated with oral 5-ASA or Etiasa. The concentrations of 5-ASA in the colonic tissue were significantly higher in the topical 5-ASA group than in the oral 5-ASA and oral Etiasa groups. It was concluded that the topical administration of 5-ASA can effectively increase the concentration of 5-ASA in the colonic tissue, decrease the expression of proinflammatory cytokines, alleviate the colonic pathological damage and improve the symptoms of TNBS-induced acute UC in rats.

The amino acid transporter SLC6A14 in cancer and its potential use in chemotherapy

Tumor cells have an increased demand for glucose and amino acids to support their rapid growth,and also exhibit alterations in biochemical pathways that metabolize these nutrients.Transport across the plasma membrane is essential to feed glucose and amino acids into these tumor cell-selective metabolic pathways.Transfer of amino acids across biological membranes occurs via a multitude of transporters;tumor cells must upregulate one or more of these transporters to satisfy their increased demand for amino acids.Among the amino acid transporters,SLC6A14 stands out with specific functional features uniquely suited for the biological needs of the tumor cells.This transporter is indeed upregulated in tumors of epithelial origin,including colon cancer,cervical cancer,breast cancer,and pancreatic cancer.Since normal cells express this transporter only at low levels,blockade of this transporter should lead to amino acid starvation selectively in tumor cells,thus having little effect on normal cells.This offers a novel,yet logical,strategy for the treatment of cancers that are associated with upregulation of SLC6A14.In addition,a variety of amino acid-based prodrugs are recognized as substrates by SLC6A14,thus raising the possibility that anticancer drugs can be delivered into tumor cells selectively via this transporter in the form of amino acid prodrugs.This strategy allows exposure of SLC6A14-positive tumor cells to chemotherapy with minimal off-target effects.In conclusion,the amino acid transporter SLC6A14 holds great potential not only as a direct drug target for cancer therapy but also for tumor cell-selective delivery of anticancer drugs.

Effects of the Ratio of n-6∶n-3 Polyunsaturated Fatty Acids in the Maternal Diet on Immunoglobulins,Fatty Acid Composition,and Performance of Lactating Sows and Suckling Piglets under Conditions of Low Maternal Energy Intake

This experiment was conducted to investigate the effects of different ratios of n-6 ∶ n-3 polyunsaturated fatty acids （PUFA） in sow diets on the performance of lactating sows and their piglets at low digestible energy intakes. Twenty-one pregnant Landrace sows were assigned to one of three diets from day 108 of gestation until weaning （26 to 29 d） ,containing n-6∶n-3 PUFA ratios of 3 ∶1,8 ∶1 and 11 ∶1. The effects on sow and litter production traits and on sow body condition were examined. There were no differences among treatments in daily feed intakes or in changes in sow weight and back-fat levels during lactation. Litter size,litter weight at birth and weaning and litter average daily weight gain were also unaffected by treatment. As expected, large differences were observed in n-6 and n-3 fatty acids in the colostrum and plasma of sows and piglets （P 〈 0. 01） . The ratio of n6 ∶ n-3 PUFA the diet was positively correlated with those in colostrum,sow plasma and piglet plasma （R 2= 0. 55,0. 80 and 0. 80,respectively） . Sow plasma insulin and IGF-I levels at weaning were unaffected by the treatments. Plasma leptin （P 〈 0. 05） concentrations were increased in sows fed the diet with a n-6∶n-3 ratio of 8 ∶ 1. Immunoglobulin concentrations in colostrum were not altered by dietary treatment. Plasma IgG concentrations at d 14 were highest in piglets from sows fed the 8 ∶ 1 ratio of n-6∶n-3. Furthermore,this group had the highest IgA concentrations at day 21 of lactation compared with the other two groups （P 〈 0. 05） . In summary,our study demonstrated that at low digestible energy levels,altering the ratio of n-6 ∶ n-3 PUFA in the diets for lactating sows affected immune components and the fatty acid composition of lactating sows and their piglets. Further studies are needed to examine whether higher levels of fat supplementation than those used in the present study （1. 5%） can successfully enhance performance.

Synthesis and Structural Characterization of a New Cadmium(Ⅱ) Complex Bridged by Endo-norbornene-cis-5,6-dicarboxylic Acid

A polynuclear complex [Cd（endc）（H20）]n·nH2O （endc = endo-norbornene-cis- 5,6-dicarboxylate anion） has been synthesized by the hydrothermal reaction of cadmium nitrate tetrahydrate with endo-norbornene-cis-5,6-dicarboxylic acid in 1：1 molar ratio, and structurally characterized by single-crystal X-ray diffraction. It crystallizes in monoclinic, space group P21/c with α = 1.16471（7）, b = 0.95334（7）, c = 0.91109（9） nm, Z= 4, V= 1.01035（14） nm^3, D, = 2.160 g/cm^3,μ = 2.172 mm^-1, F（000） = 648, R = 0.0302 and wR = 0.0752. According to structural analysis, each Cd（II） ion is coordinated to six O atoms from three endc anions and one water molecule, giving a distorted octahedral geometry. Two- dimensional layer arrangement of the title complex is constructed from the bridging nature of endc. It is worth notice that adjacent two-dimensional layers are joined together to form a three-dimensional supramolecular framework via intermolecular hydrogen bonding interactions.

Design,Synthesis,and Biological Evaluation of 5H-Thiazolo[3,2-a]pyrimidine-6-carboxylic Acid Ethyl Ester Derivatives as a Novel Series of Acetylcholinesterase Inhibitors

Acetylcholinesterase inhibitors are the most frequently prescribed anti-Alzheimer＇s drugs. A series of 5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester derivatives as the novel acetylcholinesterase inhibitors was designed based on virtual screening methods. The target compounds were synthesized with Biginelli reaction and Hantzsch-type condensation of dihydropyrimidines with substituted phenacyl chlorides, and were characterized with elemental analysis, IR, MS, ^1H NMR, and ^13C NMR. The biological evaluation against human acetylcholinesterase in vitro indicated all the target compounds show more than 50% inhibition at 10μmol/L by means of the Ellman method. The results provide a starting point for the development of novel drugs to treat Alzheimer＇s disease and lay the foundation of searching for improved acetylcholinesterase inhibitors with the novel scaffolds.

Different n-6/n-3 polyunsaturated fatty acid ratios affect postprandial metabolism in normal and hypertriglyceridemic rats

Postprandial metabolism plays major roles in many pathological conditions.The n-6/n-3 polyunsaturated fatty acid(PUFA)ratio is closely related to various physiological disorders.This study aimed to investigate the effects of high fat meals with different n-6/n-3 PUFA ratios on postprandial metabolism in normal control(NC)and hypertriglyceridemia(HTG)rats.The postprandial response of triglyceride(TG)in HTG groups was higher than that in NC groups after different n-6/n-3 PUFA ratio meals.The HTG groups showed higher postprandial total cholesterol(TC)responses than NC groups after 1:1 and 20:1 ratio meals.The 5:1 n-6/n-3 PUFA ratio elicited lower postprandial responses of tumor necrosis factorα(TNF-α)than 1:1 and 10:1 ratios in HTG groups.The postprandial malondialdehyde(MDA)response was lower after a 5:1 n-6/n-3 PUFA ratio meal than 1:1 and 20:1 ratio meals in HTG groups.The 1:1 ratio resulted in a lower postprandial reactive oxygen species(ROS)level than 5:1 and 10:1 n-6/n-3 PUFA ratios in NC groups.The results showed that a low n-6/n-3 PUFA ratio improved postprandial dysmetabolism induced by a high fat meal in NC and HTG rats.A high n-6/n-3 PUFA ratio increased the difference in postprandial metabolism between NC and HTG rats.

S100 calcium binding protein A6 and associated long noncoding ribonucleic acids as biomarkers in the diagnosis and staging of primary biliary cholangitis

BACKGROUND Primary biliary cholangitis(PBC)is a chronic and slowly progressing cholestatic disease,which causes damage to the small intrahepatic bile duct by immunoregulation,and may lead to cholestasis,liver fibrosis,cirrhosis and,eventually,liver failure.AIM To explore the potential diagnosis and staging value of plasma S100 calcium binding protein A6(S100A6)messenger ribonucleic acid(mRNA),LINC00312,LINC00472,and LINC01257 in primary biliary cholangitis.METHODS A total of 145 PBC patients and 110 healthy controls(HCs)were enrolled.Among them,80 PBC patients and 60 HCs were used as the training set,and 65 PBC patients and 50 HCs were used as the validation set.The relative expression levels of plasma S100A6 mRNA,long noncoding ribonucleic acids LINC00312,LINC00472 and LINC01257 were analyzed using quantitative reverse transcription-polymerase chain reaction.The bile duct ligation(BDL)mouse model was used to simulate PBC.Then double immunofluorescence was conducted to verify the overexpression of S100A6 protein in intrahepatic bile duct cells of BDL mice.Human intrahepatic biliary epithelial cells were treated with glycochenodeoxycholate to simulate the cholestatic environment of intrahepatic biliary epithelial cells in PBC.RESULTS The expression of S100A6 protein in intrahepatic bile duct cells was up-regulated in the BDL mouse model compared with sham mice.The relative expression levels of plasma S100A6 mRNA,log10 LINC00472 and LINC01257 were upregulated while LINC00312 was down-regulated in plasma of PBC patients compared with HCs(3.01±1.04 vs 2.09±0.87,P<0.0001;2.46±1.03 vs 1.77±0.84,P<0.0001;3.49±1.64 vs 2.37±0.96,P<0.0001;1.70±0.33 vs 2.07±0.53,P<0.0001,respectively).The relative expression levels of S100A6 mRNA,LINC00472 and LINC01257 were up-regulated and LINC00312 was down-regulated in human intrahepatic biliary epithelial cells treated with glycochenodeoxycholate compared with control(2.97±0.43 vs 1.09±0.08,P=0.0018;2.70±0.26 vs 1.10±0.10,P=0.0006;2.23±0.21 vs 1.10±0.10,P=0.0011;1.20±0.04 vs 3.03±0.15,P<0.0001,respectively).The mean expression of S100A6 in the advanced stage(III and IV)of PBC was up-regulated compared to that in HCs and the early stage(II)(3.38±0.71 vs 2.09±0.87,P<0.0001;3.38±0.71 vs 2.57±1.21,P=0.0003,respectively);and in the early stage(II),it was higher than that in HCs(2.57±1.21 vs 2.09±0.87,P=0.03).The mean expression of LINC00312 in the advanced stage was lower than that in the early stage and HCs(1.39±0.29 vs 1.56±0.33,P=0.01;1.39±0.29 vs 2.07±0.53,P<0.0001,respectively);in addition,the mean expression of LINC00312 in the early stage was lower than that in HCs(1.56±0.33 vs 2.07±0.53,P<0.0001).The mean expression of log10 LINC00472 in the advanced stage was higher than those in the early stage and HCs(2.99±0.87 vs 1.81±0.83,P<0.0001;2.99±0.87 vs 1.77±0.84,P<0.0001,respectively).The mean expression of LINC01257 in both the early stage and advanced stage were up-regulated compared with HCs(3.88±1.55 vs 2.37±0.96,P<0.0001;3.57±1.79 vs 2.37±0.96,P<0.0001,respectively).The areas under the curves(AUC)for S100A6,LINC00312,log10 LINC00472 and LINC01257 in PBC diagnosis were 0.759,0.7292,0.6942 and 0.7158,respectively.Furthermore,the AUC for these four genes in PBC staging were 0.666,0.661,0.839 and 0.5549,respectively.The expression levels of S100A6 mRNA,log10 LINC00472,and LINC01257 in plasma of PBC patients were decreased(2.35±1.02 vs 3.06±1.04,P=0.0018;1.99±0.83 vs 2.33±0.96,P=0.036;2.84±0.92 vs 3.69±1.54,P=0.0006),and the expression level of LINC00312 was increased(1.95±0.35 vs 1.73±0.32,P=0.0007)after treatment compared with before treatment using the paired t-test.Relative expression of S100A6 mRNA was positively correlated with log10 LINC00472(r=0.683,P<0.0001);serum level of collagen type IV was positively correlated with the relative expression of log10 LINC00472(r=0.482,P<0.0001);relative expression of S100A6 mRNA was positively correlated with the serum level of collagen type IV(r=0.732,P<0.0001).The AUC for the four biomarkers obtained in the validation set were close to the training set.CONCLUSION These four genes may potentially act as novel biomarkers for the diagnosis of PBC.Moreover,LINC00472 acts as a potential biomarker for staging in PBC.

Gossypol acetic acid regulates leukemia stem cells by degrading LRPPRC via inhibiting IL-6/JAK1/STAT3 signaling or resulting mitochondrial dysfunction

BACKGROUND Leukemia stem cells(LSCs)are found to be one of the main factors contributing to poor therapeutic effects in acute myeloid leukemia(AML),as they are protected by the bone marrow microenvironment(BMM)against conventional therapies.Gossypol acetic acid(GAA),which is extracted from the seeds of cotton plants,exerts anti-tumor roles in several types of cancer and has been reported to induce apoptosis of LSCs by inhibiting Bcl2.AIM To investigate the exact roles of GAA in regulating LSCs under different microenvironments and the exact mechanism.METHODS In this study,LSCs were magnetically sorted from AML cell lines and the CD34+CD38-population was obtained.The expression of leucine-rich pentatricopeptide repeat-containing protein(LRPPRC)and forkhead box M1(FOXM1)was evaluated in LSCs,and the effects of GAA on malignancies and mitochondrial RESULTS LRPPRC was found to be upregulated,and GAA inhibited cell proliferation by degrading LRPPRC.GAA induced LRPPRC degradation and inhibited the activation of interleukin 6(IL-6)/janus kinase(JAK)1/signal transducer and activator of transcription(STAT)3 signaling,enhancing chemosensitivity in LSCs against conventional chemotherapies,including L-Asparaginase,Dexamethasone,and cytarabine.GAA was also found to downregulate FOXM1 indirectly by regulating LRPPRC.Furthermore,GAA induced reactive oxygen species accumulation,disturbed mitochondrial homeostasis,and caused mitochondrial dysfunction.By inhibiting IL-6/JAK1/STAT3 signaling via degrading LRPPRC,GAA resulted in the elimination of LSCs.Meanwhile,GAA induced oxidative stress and subsequent cell damage by causing mitochondrial damage.CONCLUSION Taken together,the results indicate that GAA might overcome the BMM protective effect and be considered as a novel and effective combination therapy for AML.

EXPRESSION OF IL-6, sgp130, IL-8 AND THEIR RECEPTORS INACUTE PROMYELOCYTIC LEUKEMIA DURING ALL-TRANSRETINOIC ACID INDUCTION TREATMENT

Objective: To evaluate the expression and its clinical significance of interleukin 6 (IL-6), soluble glycoprotein 130 (sgp130), interleukin 8 (IL-8) and type A interleukin 8 receptor (IL-8RA) in acute promyelocytic leukemia (APL) patients during all-trans retinoic acid (ATRA) induction treatment. Methods: Plasma and bone marrow mononuclear cell (MNC) culture supernatant IL-6, sgp130, IL-8 concentration of 18 cases with APL were kinetically measured in vivo and in vitro (ELISA). Bone marrow MNC IL-8RA was measured by flow cytometry after being cultured with ATRA (10?6mmol/L). Results: Plasma IL-6, sgp130, IL-8 levels were higher than normal (P<0.05), IL-6, spg130 levels correlated with white blood cell (WBC) counts (P<0.05) while IL-8 levels correlated with body temperature (P<0.05) at initial diagnosis. After 72-hour incubation with ATRA, concentration of IL-6 of bone marrow MNC culture supernatant did not change, that of sgp130 mildly decreased, and IL-8 significantly decreased while the positive rate of IL-8RA on bone marrow MNC increased. During ATRA treatment, plasma IL-6 changes were correlated with WBC counts. Peak levels of IL-6 and WBC were lower in patients who received intermittent therapy than those who received continuous therapy. Plasma IL-6 and IL-8 were increased when complicated with infection and IL-8 seemed more sensitive. Conclusion: Plasma IL-6, sgp130, IL-8 levels may reflect patients' responsiveness to ATRA treatment, and could be used to predict hyperleukocytosis and intercurrent infection. ATRA induces APL cell differentiation possibly via sgp130 signal transducer chain. Measurement of sgp130 had certain meaning to prognosis.

Facile and Efficient Syntheses of (±)-2,6-Dimethyl-6-hydroxy-2,7-octadienoic Acid and Its Methyl Ester

The facile and efficient total syntheses of monoterpenoid acid 7a and its ester 7b, isolated from Artemisia siebert and Piper aduncum respectively, can be completed in four steps with an overall yield 41%.

Spectrofluorimetric Determination of Magnesium (Ⅱ) with 7-(8-Hydroxy-3, 6-Disulfonaphthylazo)-8-Hydroxyquinoline-5-Sulfonic Acid

A new fluorescent reagent, 7 (8 hydroxy 3, 6 disulfonaphthylazo) 8 hydroxyquinoline 5 sulfonic acid (HDNHQ) for the determination of magnesium has been developed. It reacted with magnesium to form a 1∶1 fluorescent complex with λ ex / λ em =356/495 nm immediately at room temperature in ammonia ammonium chloride buffer (pH 10.7). A linear relationship was obtained in the magnesium concentration range of 0 160 ng·mL -1 with the detection limit of 0.04 ng·mL -1 . The proposed method was simple, rapid and sensitive. It has been successfully applied to the determination of trace magnesium in blood serum with recoveries of 103.75% and 98.16%, respectively.

6-(N,N-Dimethylamino)-2-naphthoylacryl Acid:a Highly Selective and Sensitive Fluorescent Sensor of Copper(Ⅱ)

A novel fluorescent probe,6-（N,N-dimethylamino）-2-naphthoylacryl acid（ACADAN） was designed and synthesized as a fluorescent sensor for Cu^2＋ in aqueous media.Significant amplification of fluorescence signals without causing any discernible change of maximum fluorescence emission wavelength（λ max） was observed upon the addition of Cu^2＋.Importantly,ACADAN is capable of recognizing Cu^2＋ selectively in aqueous media in the presence of various biologically relevant metal ions and the prevalent toxic metal ions in the environment with high sensitivity（detection limit was 0.1 μmol/L）.

Hydroxylation of nigranoic acid to 6β-hydroxynigranoic acid by Caryospora carllicarpa YMF1.01026

Microbial transformation of nigranoic acid by Caryospora carllicarpa YMF1.01026 afforded the new derivative 6β-hydroxynigranoic acid. Its structure was elucidated by spectroscopic methods.

Synthesis and DNA Cleavage Studies of 2,6-Dimethoxyhydroquinone-3-Mercaptoacetic Acid Conjugates

In an effort to investigate the use of short peptide chains as carriers of new anti-tumor agents, we synthesized four tripeptide-cytotoxic agent conjugates: DMQ-MA-Lys(DMQ-MA)-Phe -Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Ile-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Val-Arg-Ome, DMQ-MA-Lys(DMQ-MA)-Lys(Cbz)-Arg-Ome. The cytotoxic agent conjugated to the N-terminal and the xi -amino group of Lysine of the tripeptide is 2,6-dimethoxyhydroquinone-3-mercaptoacetic acid (DMQ-MA). The tripeptides were synthesized by coupling protected amino acid residues according to Pfp/DCC methods (Pfp: pentafluorophenol, DCC:N,N'-dicyclohexyl-carbodiimide) in solution. Agarose gel electrophoresis showed that these compounds can cleave supercoiled DNA into open-circular form in drug concentration as low as 4-50 mu M without H2O2 and UV irradiation. Further studies on their cytotoxicity for these conjugates are ongoing.

Human Sebaceous <i>Cis</i>-6-Hexadecenoic Acid: Possible Application of an Innate Antimicrobial Substance to Cosmetic Products for Mucous Membrane

The antimicrobial properties of cis-6-hexadecenoic acid (C16:1Δ6), a component of the innate human metabolome, were studied and its application to cosmetic products was investigated in detail. A variety of the resident and transient microbial flora of the skin, oral cavity, and intestine was applied to an investigation of the antimicrobial activity of C16:1Δ6. C16:1Δ6 showed selective antibacterial activity against human microbial pathogens such as Clostridium perfringens (one of the most common causes of food poisoning) and Streptococcus mutans (one of the tooth-decaying bacteria), as well as Staphylococcus aureus. C16:1Δ6 seemed to possess a “species-selective” antibacterial activity against bacteria belonging to the genera Staphylococcus and Clostridium. We performed a preliminary assessment of the application of C16:1Δ6 as an antimicrobial component in a liquid lip gloss by performing preservation efficacy and home-use tests. We noted that the amount of p-hydroxybenzoate was needed in an oily cosmetic, especially liquid lip gloss, could be reduced by replacing p-hydroxybenzoate with C16:1Δ6. We suggest that C16:1Δ6 may find application as a stable antimicrobial substance gentle enough for use in consumer products by its selective antimicrobial characteristics.

Silencing of the Nonspecific Phospholipase C6(NPC6)Gene Induces Ricinoleic Acid Accumulation in Castor Seeds

Castor,scientifically known as Ricinus communis L.,is among the top ten oil crops globally.It is considered a renewable resource and is commonly referred to as‘green oil’.Castor seeds contain castor oil as their main component,which is predominantly composed of ricinoleic acid.This study utilized RNAi technology to silence the NPC6 gene in NO.2129 castor,resulting in the creation of mutant plants L1 and L2.The weight of 100 dry seed kernels from L1 and L2 exceeds that from NO.2129.The crude fat and ricinoleic acid levels of L1 and L2 were higher than those of NO.2129 at various developmental stages.In the proteomics analysis of 60-day-old castor seeds,a total of 21 differentially expressed proteins were identified,out of which 19 were successfully recognized.Eleven of the differentially expressed proteins identified were legumins,which play a crucial role in nutrient storage within the seed.Silencing the NPC6 gene results in the accumulation of ricinoleic acid in castor seeds.The findings of this study not only enhance our knowledge of NPC6’s role in regulating castor seed oil synthesis but also offer fresh perspectives for investigating oil synthesis and accumulation in other plant species.

One-pot Synthesis of 6-Hydroxyhexanoic Acid from Cyclohexanone Catalyzed by Dealuminated HBEA Zeolite with Aqueous 30% H_2O_2 Solution

The one-pot synthesis of 6-hydroxyhexanoic acid from cyclohexanone via the integrated Baeyer-Villiger oxida-tion and ring opening reaction catalyzed by dealuminated HBEA zeolite has been developed. Under optimized conditions,the cyclohexanone conversion and 6-hydroxyhexanoic acid selectivity are over 95%, respectively. The excellent catalyticperformance is attributed to the activation of carbonyl group of cyclohexanone and the fast hydrolysis and ring opening ofs-caprolactone by both Lewis acid and Br0nsted acid sites under aqueous conditions.