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.

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.

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.

A 3D-QSAR Study on C-3 Substituted 4,6-Dichloroindole-2- Carboxylic Acids with Comparative Molecular Field Analysis

Aim and Method Comparative molecular field analysis (CoMFA), a threedimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a novelseries of C-3 substituted 4, 6-dichloioindole-2-carboxylic acids to study the relationship betweentheir structure and the affinity for the glycine site of the NMDA receptor. Result Hie coefficientsof cross-validation q^2 and non cross-validation r^2 for the model established by the study are0.744 and 0.993, respectively, the value of variance ratio F is 261.343, and standard error estimate(SE) is 0.039. Conclusion These values indicate that the CoMFA model may have a good prediction forthe activity of C-3 substituted 4, 6-dichloroin-dole-2-carboxylic acids. As a consequence, thepredicted activity values of new designed compounds supports our conclusion from the model.

Gallic acid与DA-6强化黑麦草修复复合重金属(Cd、Pb、Cu、Zn)污染土壤的研究

用盆栽实验研究了Gallic acid与DA-6单独及耦合使用对黑麦草修复复合重金属污染土壤的影响。结果表明,Gallic acid与DA-6单独及耦合使用,能使黑麦草对重金属污染土壤中Cd、Zn的修复产生明显的促进作用,但对Pb、Cu的修复没有明显变化。当添加5 mmol/kg的Gallic acid时,黑麦草对Cd、Zn的富集量分别达到了15.9 mg/kg与1 660.8 mg/kg,富集系数较未添加Gallic acid时提高了93.9%,233.9%;同时添加10μmol/kg DA-6与5 mmol/kg Gallic Acid之后,黑麦草对Cd、Zn的富集量分别达到了18.8 mg/kg,1 680.5 mg/kg,富集系数较未添加DA-6时提高了18.2%与1.2%。

非小细胞肺癌组织中circBIRC6、APPBP2表达及临床预后意义

目的 探讨非小细胞肺癌(NSCLC)组织中环状核糖核酸杆状病毒IAP重复序列6(circBIRC6)、β淀粉样蛋白前体蛋白结合蛋白2(APPBP2)表达及临床预后意义。方法 收集2018年6月~2020年1月90例在河北北方学院附属第一医院行手术切除的NSCLC组织及癌旁组织,采用实时荧光定量聚合酶链式反应检测circBIRC6、APPBP2表达,并分析二者与NSCLC患者临床病理特征的关系。通过Pearson相关性分析NSCLC组织中circBIRC6与APPBP2 mRNA表达的相关性,Kaplan-Meier法绘制不同表皮生长因子受体(EGFR)基因突变、TNM分期和circBIRC6、APPBP2 mRNA表达的NSCLC患者生存曲线,多因素Cox回归分析NSCLC患者预后的影响因素。结果 与癌旁组织比较,NSCLC组织中circBIRC6、APPBP2 mRNA表达升高(P<0.05)。NSCLC组织中circBIRC6与APPBP2 mRNA表达呈正相关(r=0.817,P<0.001)。NSCLC患者不同分化程度、TNM分期、淋巴结转移组织中circBIRC6、APPBP2 mRNA表达比较有差异(P<0.05)。随访3年,90例NSCLC患者总生存率为55.56%(50/90)。EGFR基因突变阳性/阴性NSCLC患者总生存率比较无差异(P>0.05);TNM分期Ⅰ~Ⅱ期NSCLC患者总生存率高于Ⅲ期NSCLC患者(P<0.05);circBIRC6、APPBP2 mRNA高表达组生存率低于circBIRC6、APPBP2 mRNA低表达组(P<0.05)。低分化、TNM分期Ⅲ期、淋巴结转移和circBIRC6≥10.97、APPBP2 mRNA≥2.48为NSCLC患者死亡的独立危险因素[OR(95%CI)=3.586(1.080~11.909)、3.632(1.193~11.057)、3.197(1.060~9.640)、3.223(1.086~9.570)、2.767(1.022~7.492)]。结论 NSCLC组织中circBIRC6、APPBP2 mRNA高表达,与分化程度、TNM分期、淋巴结转移和预后有关。

血清ADMA、IL-6、内毒素及乳酸在新生儿败血症所致感染性休克中的表达及临床意义

目的探讨血清不对称二甲基精氨酸(ADMA)、白细胞介素-6(IL-6)、内毒素及乳酸在新生儿败血症所致感染性休克中的表达及临床意义。方法选取我院收治的58例新生儿败血症所致感染性休克患儿为休克组,62例新生儿败血症未发生感染性休克患儿为败血症组,60例无感染新生儿为对照组。检测所有研究对象血清中的ADMA、IL-6、内毒素及乳酸水平。比较三组研究对象的ADMA、IL-6、内毒素及乳酸水平;分析ADMA、IL-6、内毒素及乳酸水平对新生儿败血症所致感染性休克患儿的诊断价值;分析ADMA水平与IL-6、内毒素及乳酸水平的关系;分析ADMA、IL-6、内毒素及乳酸水平与休克组预后的关系。结果休克组的ADMA、IL-6、内毒素及乳酸水平均高于败血症组及对照组(P<0.05);败血症组的ADMA、IL-6、内毒素水平均高于对照组(P<0.05);败血症组和对照组的乳酸水平无显著差异(P>0.05)。受试者工作特征曲线(ROC)结果显示,ADMA、IL-6、内毒素及乳酸诊断新生儿败血症所致感染性休克的曲线下面积(AUC)分别为0.93、0.89、0.89、0.92。Pearson相关性分析结果显示,ADMA水平与IL-6、内毒素及乳酸水平呈正相关(P<0.05)。ADMA、IL-6、内毒素及乳酸高水平与新生儿败血症所致感染性休克预后不良有关。结论血清ADMA、IL-6、内毒素及乳酸在新生儿败血症所致感染性休克中表达水平较高,可作为该疾病诊断的生物标志物并预测预后。

Lactic Acid Reduces LPS-Induced TNF-a and IL-6 mRNA Levels Through Decreasing I?Ba Phosphorylation

This study explored the effects over time of lactic acid （LA） on IκBα phosphorylation and nuclear factor-kappa B （NF-κB） p65 protein expression, and on tumor necrosis factor a （TNF-α） and interleukin-6 （IL-6） mRNA levels in rat intestinal mucosa microvascular endothelial cells （RIMMVECs） stimulated by lipopolysaccharide （LPS）. I？Ba, phosphorylated IκBa （p-IκBa） and p65 protein levels were monitored by Western blot analysis, and TNF-a and IL-6 mRNA levels were analyzed using real-time PCR. LA treatment reduced TNF-a and IL-6 mRNA levels in LPS-stimulated RIMMVECs, with the greatest effect being after 3 h. The highest inhibitory effect of LA on IκBa phosphorylation to prevent activation of NF-κB was after 6 h. These results suggest that LA reduces TNF-a and IL-6 mRNA levels through decreasing IκBa phosphorylation and blocking the dissociation of IKK complex, which prevents activation of NF-κB.

Influence of gallic acid on porcine neutrophils phosphodiesterase 4,IL-6,TNF-α and rat arthritis model

Our previous studies showed that the anti-inflammatory effects of Paeonia lactiflora roots extract may be mediated, at least in part, through its gallic acid content, and this effect may be regulated in part by an inhibition on c AMP-phosphodiesterase（PDE）. To explore the anti-inflammatory effect and mechanism, the influence of gallic acid on neutrophils PDE4 activity and expression, TNF-α and IL-6 content and rat arthritis model were further studied. PDE4 activity and gene express were calculated respectively by substrate c AMP change examined with HPLC and real-time RT-PCR. The concentration of IL-6 and TNF-α in supernatant were assayed by ELISA method. Model of rat arthritis was caused by complete Freund＇s adjuvant. Results showed that gallic acid had a dose-dependent restraint on PDE4 activity of neutrophils in vitro, promoted significantly PDE4 A expression（P〈0.01）, and had no influence on the expressions of PDE4 B and 4D. However, PDE4 C expression was not detected. Gallic acid could promote IL-6 release（P〈0.05）, and inhibit TNF-α release of neutrophils（P〈0.05）. The experiment in vivo showed that gallic acid had obvious restraint on local inflammation of animal model（P〈0.05）. Therefore, the anti-inflammatory effect of gallic acid may be mediated in part through an inhibition on PDE4 activity and further an increase of IL-6 and a decrease of TNF-α of neutrophils, and this effect seemed to have no relationship with PDE4 expression.

齐刺环跳穴干预坐骨神经损伤大鼠海马IL-1β、IL-6、TNF-α及GFAP表达影响的实验研究

目的 通过观察齐刺环跳穴对坐骨神经损伤大鼠海马白细胞介素-1β(Interleukin-1β,IL-1β)、白细胞介素-6(Interleukin-6,IL-6)、肿瘤坏死因子-α(Tumor Necrosis Factor-alpha, TNF-α)及胶质纤维酸性蛋白(Glial Fibrillary Acidic Protein, GFAP)表达的影响,探讨齐刺环跳穴治疗坐骨神经痛的中枢镇痛机制。方法 60只SD大鼠随机分为假手术组、模型组、齐刺组、单刺组及药物组,每组12只,采用钳夹法制备大鼠坐骨神经损伤模型。造模第2天开始进行针刺及药物干预,连续14 d。观察各组大鼠干预前后坐骨神经功能指数(Sciatic nerve Function Index, SFI)、热缩足反射潜伏期(Paw Withdrawal Latency, PWL)的变化,ELISA法检测海马组织IL-1β、IL-6、TNF-α蛋白表达水平,实时定量PCR法及免疫组化法检测海马组织GFAP表达水平。结果 干预前,与假手术组比较,其余各组大鼠PWL值、SPI值显著降低(P<0.01),与模型组比较,齐刺组干预后大鼠PWL值、SPI值显著改善(P<0.01)。ELISA法、RT-PCR法及免疫组化检测结果显示,模型组、齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达较假手术组显著升高(P<0.01);与模型组相比,齐刺组、单刺组、药物组IL-1β、IL-6、TNF-α、GFAP表达显著下降,齐刺组表达低于单刺组及药物组(P<0.01)。结论 齐刺环跳穴缓解坐骨神经痛的镇痛机制可能与下调海马炎症因子表达,抑制星形胶质细胞活化,从而降低中枢痛觉敏化程度有关。

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.

A New Synthetic Route for Preparation of 2-Chloro-6-fluoro- benzonitrile and 2-Chloro-6-fluorobenzoic Acid

An effective synthetic route for preparation of 2-chloro-6-fluorobenzonitrile, 2-chloro-6-fluorobenzamide and 2-chloro-6-fluorobenzoic acid has been described. It includes diazotization, fluorination, ammoxidation and hydrolysis reactions.

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.

A new solid acid SO_4^(2-)/TiO_2 catalyst modified with tin to synthesize 1,6-hexanediol diacrylate

A new solid acid catalyst,SO4^2-/TiO2 modified with tin,was prepared using a sol-gel method and its physicochemical properties were revealed by nitrogen adsorption-desorption,X-ray powder diffraction,scanning electron microscopy,Fourier transform infrared spectroscopy,infrared spectroscopy of adsorbed pyridine,temperature-programmed desorption of ammonia and thermal gravimetric analysis.The structure,acidity and thermal stability of the SO4^2-/TiO2-SnO2 catalyst were studied.Incorporating tin enlarged the specific surface area and decreased crystallite size of the SO4^2-/TiO2 catalyst.The total acid sites of the modified catalyst increased and Bronsted acid strength remarkably increased with increasing tin content.The decomposition temperature of sulfate radical in the modified catalyst was 100 ℃ greater and its mass loss was more than twice that of the SO4^2-/TiO2 catalyst.The SO4^2-/TiO2-SnO2 catalyst was designed to synthesize 1,6-hexanediol diacrylate by esterification of 1,6-hexanediol with crylic acid.The yield of 1,6-hexanediol diacrylate exceeded 87% under the optimal reaction conditions：crylic acid to 1,6-hexanediol molar ratio = 3.5,catalyst loading = 7%,reaction temperature = 130 ℃ and reaction time = 3 h.The modified catalyst exhibited excellent reusability and after 10 cycles the conversion of 1,6-hexanediol was above 81%.

Meclofenamic acid represses spermatogonial proliferation through modulating m^6A RNA modification

Background: N6-Methyladenosine(m^6A), the most prevalent modification in mammalian m RNA, plays important roles in numerous biological processes. Several m^6A associated proteins such as methyltransferase like 3(METTL3),methyltransferase like 14(METTL14), α-ketoglutarate-dependent dioxygenase Alk B homolog 5(ALKBH5) and YTH domain containing 2(YTHDC2) are involved in the regulation of spermatogenesis and oogenesis. However, the role of the first detected m^6A demethylase, fat mass and obesity associate protein(FTO), in germ cells remains elusive.Elucidation of FTO roles in the regulation of germ cell fate will provide novel insights into the mammalian reproduction.Methods: Mouse GC-1 spg cells were treated with the ester form of meclofenamic acid(MA2) to inhibit the demethylase activity of FTO. The cellular m^6A and m^6Amlevel were analyzed through high performance liquid chromatography combined with tandem mass spectrometry(HPLC/MS-MS). The cell apoptosis was detected via TUNEL and flow cytometry. The cell proliferation was detected through Ed U and western blot. The m RNA level of core cyclin dependent kinases(CDKs) was quantified via q-PCR. RNA decay assay were performed to detect RNA stability. Dual fluorescence assay was conducted to study whether MA2 affects the expression of CDK2 dependent on the m^6A modification at 3’UTR.Results: MA2 significantly increased the cellular m^6A level and down-regulated the expression of CDK1, CDK2, CDK6 and Cd C25 a, resulting in arrest of G1/S transition and decrease of cell proliferation. MA2 downregulated CDK2 m RNA stability. Additionally, mutation of the predicted m^6A sites in the Cdk2–3’UTR could mitigated the degradation of CDK2 m RNA after MA2 treatment.Conclusion: MA2 affected CDKs expression through the m^6A-dependent m RNA degradation pathway, and thus repressed spermatogonial proliferation.

Hydrothermal Syntheses and Crystal Structures of Six Complexes Constructed from 1,3,5-Benzenetricarboxylic Acid and 4'-(4-Pyridyl)-2,2':6',2''-terpyridine Mixed Ligands

Six new transition metal complexes, [Zn（HBTC）（PYTPY）]n·n PYTPY（1）, [Cu（HBTC）（PYTPY）]n·n PYTPY（2）, [Co（HBTC）（PYTPY）]n·n DMF（3）, [Mn（HBTC）（PYTPY）]n·n DMF（4）, [Cd（HBTC）（PYTPY）（H2O）]n·2nH2O（5）, and [Co（HBTC）（PYTPY）（H2O）2]（6）,（H3BTC = 1,3,5-benzenetricarboxylic acid, PYTPY = 4＇-（4-pyridyl）-2,2＇：6＇,2＇＇-terpyridine, DMF = N,N？-dimethylformamide）, have been synthesized and characterized by elemental analysis, IR and X-ray single-crystal diffraction. Complexes 1~5 all feature one-dimensional chain structures, and complex 6 exhibits a zero-dimensional structure. Complexes 1~5 present three-dimensional（3D） supramolecular frameworks via π-π stacking interactions, whenas 6 has also a 3D supramolecular structure assembled by hydrogen bonding. Meanwhile, complexes 1 ~ 6 exhibit the thermal stabilities and photoluminescent properties.

MoS2/Zn3In2S6 composite photocatalysts for enhancement of visible light-driven hydrogen production from formic acid

Enhancing the separation efficiency of photogenerated carriers is propitious for the promotion of photocatalytic hydrogen production from formic acid decomposition.Herein,MoS2/Zn3In2S6(MoS2/ZIS6)composite photocatalysts containing varying mass percentages of MoS2 were obtained by a straightforward synthetic method.The results confirmed that MoS2,as a cocatalyst,markedly promoted the photogenerated charge separation efficiency and visible light-driven hydrogen production activity of ZIS6(λ>400 nm).Specifically,the as-prepared 0.5%MoS2/ZIS6 photocatalyst exhibited the highest photocatalytic hydrogen production rate(74.25μmol·h^-1),which was approximately 4.3 times higher than that of ZIS6(17.47μmol·h^-1).The excellent performance of the 0.5%MoS2/ZIS6 photocatalyst may be due to the fact that MoS2 has a low Fermi energy level and can thus enrich photogenerated electrons from ZIS6,and furthermore reduce H+derived from formic acid,to form hydrogen.The structure and morphology of the MoS2/ZIS6 photocatalysts and the reactive species were determined by X-ray diffraction,transmission electron microscopy,and field emission scanning electron microscopy,among others;a plausible mechanistic rationale is discussed based on the results.

双标多测法在枣仁安神颗粒6个成分含量测定中的应用

目的建立枣仁安神颗粒中斯皮诺素、6'''-阿魏酰斯皮诺素、迷迭香酸、五味子醇甲、五味子乙素和丹酚酸B 6个成分的双标多测法,验证该方法在枣仁安神颗粒质量评价中应用的准确性和可行性。方法采用HPLC法,以乙腈为流动相A,0.2%冰醋酸溶液为流动相B,梯度洗脱,流速为1.0 mL·min^(-1),切换波长320 nm(斯皮诺素、6'''-阿魏酰斯皮诺素、迷迭香酸、丹酚酸B)、250 nm(五味子醇甲、五味子乙素),柱温28℃。采用5根不同的C_(18)色谱柱,测定枣仁安神颗粒6个成分的实际保留时间,计算各成分在各色谱柱保留时间的平均值,得到各成分的标准保留时间,选取斯皮诺素(峰1)、五味子乙素(峰6)作为双标化合物,使用双标线性校正法准确定位各成分色谱峰,预测成分在未知色谱柱的保留时间并进行方法学验证。以五味子乙素为参照物,计算其余各成分的相对校正因子,对各成分进行定量。结果双标线性校正法能够准确地预测待测组分在未知色谱柱上的保留时间;斯皮诺素、6'''-阿魏酰斯皮诺素、迷迭香酸、五味子醇甲和丹酚酸B相对于五味子乙素的相对校正因子分别为0.7342、0.6063、0.5664、0.9975及0.7773,其RSD均小于1%;各成分含量计算值和实测值无显著差异。结论双标多测法同时测定枣仁安神颗粒中6个成分可行且准确。