Acetyl-CoA-mediated autoacetylation of fatty acid synthase as a metabolic switch of de novo lipogenesis in Drosophila.

De novo lipogenesis is a highly regulated metabolic process, which is known to be activated through transcriptional regulation of lipogenic genes, including fatty acid synthase (FASN). Unexpectedly, we find that the expression of FASN protein remains unchanged during Drosophila larval development from the second to the third instar larval stages (L2 to L3) when lipogenesis is hyperactive. Instead, acetylation of FASN is significantly upregulated in fast-growing larvae. We further show that lysine K813 residue is highly acetylated in developing larvae, and its acetylation is required for elevated FASN activity, body fat accumulation, and normal development. Intriguingly, K813 is autoacetylated by acetyl-CoA (AcCoA) in a dosage-dependent manner independent of acetyltransferases. Mechanistically, the autoacetylation of K813 is mediated by a novel P-loop-like motif (N-xx-G-x-A). Lastly, we find that K813 is deacetylated by Sirt1, which brings FASN activity to baseline level. In summary, this work uncovers a previously unappreciated role of FASN acetylation in developmental lipogenesis and a novel mechanism for protein autoacetylation, through which Drosophila larvae control metabolic homeostasis by linking AcCoA, lysine acetylation, and de novo lipogenesis.

The association of potentially inappropriate medications, polypharmacy and anticholinergic burden with readmission and emergency room revisit after discharge: A hospital-based retrospective cohort study.

AIMS: While certain drug-use indicators are known to be associated with clinical outcomes, the relationship is unclear for some highly prevalent conditions in in patients aged ≥65 years. We examine correlations between 3 drug-use indicators and postdischarge healthcare services use by older patients according to the presence of dementia, advanced age and frailty. METHODS: This retrospective cohort study analysed data collected from hospital electronic health records between April and December 2017. Potentially inappropriate medications (PIMs) and anticholinergic burden were assessed using the 2015 Beers Criteria and anticholinergic cognitive burden scale (ACBS) score. Minor and major polypharmacy were defined as the use of 5-9 and ≥10 drugs, respectively. Outcomes were set as emergency room revisits and readmissions at 1, 3 and 6 months postdischarge. The correlation between drug-use indicators and outcomes was analysed by multivariable logistic regression. RESULTS: The final cohort included 3061 patients for the analysis, and 2930, 2671 and 2560 patients were followed up to 1, 3 and 6 months after discharge. After controlling for confounders, all 3 drug-use indicators were significantly associated with readmission and emergency room revisits except for the relationship between PIMs and readmission within 6 months. These associations were significantly observed among patients without dementia, aged >80 years and with frailty. CONCLUSION: PIMs, polypharmacy and anticholinergic burden are common at discharge and correlate with future use of healthcare services. In older patients, the absence of dementia, advanced age and frailty should be given extra consideration with regard to medication safety.

Ultra-High Sensitivity Terahertz Microstructured Fiber Biosensor for Diabetes Mellitus and Coronary Heart Disease Marker Detection.

Diabetes Mellitus (DM) and Coronary Heart Disease (CHD) are among top causes of patient health issues and fatalities in many countries. At present, terahertz biosensors have been widely used to detect chronic diseases because of their accurate detection, fast operation, flexible design and easy fabrication. In this paper, a Zeonex-based microstructured fiber (MSF) biosensor is proposed for detecting DM and CHD markers by adopting a terahertz time-domain spectroscopy system. A suspended hollow-core structure with a square core and a hexagonal cladding is used, which enhances the interaction of terahertz waves with targeted markers and reduces the loss. This work focuses on simulating the transmission performance of the proposed MSF sensor by using a finite element method and incorporating a perfectly matched layer as the absorption boundary. The simulation results show that this MSF biosensor exhibits an ultra-high relative sensitivity, especially up to 100.35% at 2.2THz, when detecting DM and CHD markers. Furthermore, for different concentrations of disease markers, the MSF exhibits significant differences in effective material loss, which can effectively improve clinical diagnostic accuracy and clearly distinguish the extent of the disease. This MSF biosensor is simple to fabricate by 3D printing and extrusion technologies, and is expected to provide a convenient and capable tool for rapid biomedical diagnosis.

Optimizing the Schoenemann Reaction for Colorimetric Assays of VX and GD.

The analysis of nerve agents is the focus of chemical warfare agent determination because of their extreme toxicity. A classical chemical colorimetric method, namely, the Schoenemann reaction, has been developed to detect G agents; however, it has not been utilized for VX analysis mainly because of its low peroxyhydrolysis rate. In this study, based on the mechanism of the Schoenemann reaction, a novel rapid quantitative determination method for VX was developed by optimizing the reaction conditions, such as concentrations of peroxide and the indicator, temperature, and reaction time. Using 2 ml 0.5 wt% sodium perborate as the peroxide source, 1 ml 0.1 wt% benzidine hydrochloride as the indicator, and 1 ml acetone as the co-solvent, VX and GD in ethanol or water solutions could be quantitatively analyzed within 15 min at 60°C. Further experiments based on 31P NMR spectroscopy confirmed the existence of a peroxyphosphate intermediate during the GD assay. This quantitative colorimetry system for VX and GD analysis can be developed as a portable device for the water samples in fieldwork applications.

Involvement of spinal cannabinoid receptor type 2 in the analgesia effect of hyperbaric oxygen treatment on paclitaxel-induced neuropathic pain.

BACKGROUND: Chemotherapy-induced neuropathic pain (CINP) is intractable, and spinal cannabinoid receptors (CBRs) are potential therapeutic targets for CINP. Previous studies demonstrated that hyperbaric oxygen (HBO2) may contribute in alleviating specific peripheral neuropathic pain. However, neither CINP nor CBR have been clarified. We hypothesized that HBO2 is capable of alleviating CINP, and the effect could be explained by the activation of spinal CBRs. METHODS: A series of paclitaxel-induced CINP models were established on male Sprague-Dawley rats. Then HBO2 treatment was administered for seven consecutive days at 2.5 atmospheres absolute. Two groups were treated with AM251 (an antagonist of CBR type-1, CBR1) or AM630 (an antagonist of CBR type-2, CBR2) respectively 30 minutes before each HBO2 treatment. The mechanical withdrawal threshold was assessed before, during and at two weeks after HBO2 treatment. Lumbar spinal cords were collected for Western blot analysis of CBR1, CBR2, GFAP and CD11b, and ELISA analysis of proinflammatory cytokines IL-1ß and TNF-α. RESULTS: A mechanical allodynia was successfully exhibited and the spinal GFAP, CD11b, IL-1ß and TNF-α significantly increased after the modeling, and these effects could be further reversed by HBO2 treatment, which could be blocked by AM630, other than AM251. CONCLUSION: HBO2 treatment can alleviate paclitaxel-induced neuropathic pain, and be mediated by CBR2. Spinal glial cells and proinflammatory cytokines are involved in this process.

Pretreatment Method for Chloramine-T Decon Sample Before GC Analysis of HD and VX.

Chloramine-T, especially its solution in weak acidity, is one of the decontaminants for chemical warfare agents (CWAs), HD, and VX. A high CWAs recovery from decontamination (decon) sample via pretreatment was essential for evaluating decontamination effects. This paper performed experiments to optimize pretreatment methods to extract residual CWAs from chloramine-T decon samples before GC analysis. Effects of two neutralization methods, destroying decon activity by 15% Na2SO3 or decreasing decon activity by 3% NH3·H2O or 4% NaOH, were studied. Results showed they were all suitable for the HD decon sample, but only 4% NaOH was ideal for the VX decon sample. As for extractant, compared with dichloromethane, petroleum ether was more suitable for recovering CWAs from decon samples. A high recovery above 80% could be obtained for HD and VX samples ranging from 10 mg/L to 10,000 mg/L when optimized neutralization and extraction methods were simultaneously carried out.

Sulfur-Induced Growth of Coordination Polymer Derived-Straight Carbon Nanotubes on Carbon Nanofiber Network for Zn-Air Batteries.

Low-cost heteroatom-doped carbon nanomaterials have been widely studied for efficient oxygen reduction reaction and energy storage and conversion in metal-air batteries. A Masson pine twigs-like 3-dimensional network construction of carbon nanofibers (CNFs) with abundant straight long Co, N, and S-doped carbon nanotubes (CNTs) is developed by thermal treatment of Co-based polymer coated onto polyacrylonitrile nanofiber network together with thiourea at 900 °C, denoted as CNFT-Co9 S8 -900. It is interesting to note that the introduction of a high concentration of sulfur does not lead to the complete toxicity of catalysts, but promotes the axial growth to selectively form straight CNTs instead of curly bamboo-like CNTs. The highly graphitized in-situ grown Co, N, S-doped CNTs and the 3-dimensional N-doped CNF network provide both active catalytic sites and highly conductive paths, which are beneficial for oxygen reduction reaction (ORR). Thus, the optimal CNFT-Co9 S8 -900 performs the excellent ORR catalytic activity with a half-wave potential of 0.84 V and a diffusion-limited current density of 5.49 mA cm-2 . Furthermore, the CNFT-Co9 S8 -900-based Zn-air devices also possess a high power density of 136.9 mW cm-2 better than commercial Pt/C.

Developing an Integrated Electronic Medication Reconciliation Platform and Evaluating its Effects on Preventing Potential Duplicated Medications and Reducing 30-Day Medication-Related Hospital Revisits for Inpatients.

The aims were to develop an integrated electronic medication reconciliation (ieMR) platform, evaluate its effects on preventing potential duplicated medications, analyze the distribution of the potential duplicated medications by the Anatomical Therapeutic and Chemical (ATC) code for all inpatients, and determine the rate of 30-day medication-related hospital revisits for a geriatric unit. The study was conducted in a tertiary medical center in Taiwan and involved a retrospective quasi pre-intervention (July 1-November 30, 2015) and post-intervention (October 1-December 31, 2016) study design. A multidisciplinary team developed the ieMR platform covering the process from admission to discharge. The ieMR platform included six modules of an enhanced computer physician order entry system (eCPOE), Pharmaceutical-care, Holistic Care, Bedside Display, Personalized Best Possible Medication Discharge Plan, and Pharmaceutical Care Registration System. The ieMR platform prevented the number of potential duplicated medications from pre (25,196 medications, 2.3%) to post (23,413 medications, 3.8%) phases (OR 1.71, 95% CI, 1.68-1.74; p < .001). The most common potential duplicated medications classified by the ATC codes were cardiovascular system (28.4%), alimentary tract and metabolism (26.4%), and nervous system (14.9%), and by chemical substances were sennoside (12.5%), amlodipine (7.5%), and alprazolam (7.4%). The rate of medication-related 30-day hospital revisits for the geriatric unit was significantly decreased in post-intervention compared with that in pre-intervention (OR = 0.12; 95% CI, 0.03-0.53; p < .01). This study indicated that the ieMR platform significantly prevented the number of potential duplicated medications for inpatients and reduced the rate of 30-day medication-related hospital revisits for the patients on the geriatric unit.

The impact of a medication reconciliation programme at geriatric hospital admission: A pre-/postintervention study.

AIMS: The aim of this study was to improve medication reconciliation and reduce the occurrence of duplicate prescriptions by pharmacists and physicians within 72 hours of hospital admission using an intelligent prescription system combined with the National Health Insurance PharmaCloud system to integrate the database with the medical institution computerized physician order entry (CPOE) system. METHODS: This 2-year intervention study was implemented in the geriatric ward of a hospital in Taiwan. We developed an integrated CPOE system linked with the PharmaCloud database and established an electronic platform for coordinated communication with all healthcare professionals. Patients provided written informed consent to access their PharmaCloud records. We compared the intervention effectiveness within 72 hours of admission for improvement in pharmacist medication reconciliation, increased at-home medications documentation and decreased costs from duplicated at-home prescriptions. RESULTS: The medication reconciliation rate within 72 hours of admission increased from 44.0% preintervention to 86.8% postintervention (relative risk = 1.97, 95% confidence interval [CI]: 1.69-2.31; P < .001). The monthly average of patients who brought and took home medications documented in the CPOE system during hospitalization increased by 7.54 (95% CI 5.58-20.49, P = .22). The monthly average of home medications documented increased by 102.52 (95% CI 38.44-166.60; P = .01). Savings on the monthly average prescription expenditures of at-home medication increased by US$ 2,795.52 (95% CI US$1310.41-4280.63; P < .01). CONCLUSION: Integrating medication data from PharmaCloud to the hospital's medical chart system improved pharmacist medication reconciliation, which decreased duplicated medications and reduced in-hospital medication costs.

Synthesis and biological evaluation of novel N-(piperazin-1-yl)alkyl-1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential MEK inhibitors.

In this paper, a series of novel 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid bearing different N-(piperazin-1-yl)alkyl side chains were designed, synthesised and evaluated for their in vitro anticancer activities against three human hepatocarcinoma cell lines (SMMC-7721, HepG2 and Hep3B). Among them, compound 10g exhibited the most potent activity against three cancer cell lines with IC50 values of 1.39 ± 0.13, 0.51 ± 0.09 and 0.73 ± 0.08 µM, respectively. In the kinase inhibition assay, compound 10g could significantly inhibit MEK1 kinase activity with IC50 of 0.11 ± 0.02 µM, which was confirmed by western blot analysis and molecular docking study. In addition, compound 10g could elevate the intracellular ROS levels, decrease mitochondrial membrane potential, destroy the cell membrane integrity, and finally lead to the oncosis and apoptosis of HepG2 cells. Therefore, compound 10g could be a potent MEK inhibitor and a promising anticancer agent worthy of further investigations.

Secretory expression of ß-mannanase in Saccharomyces cerevisiae and its high efficiency for hydrolysis of mannans to mannooligosaccharides.

Degradation of mannans is a key process in the production of foods and prebiotics. ß-Mannanase is the key enzyme that hydrolyzes 1,4-ß-D-mannosidic linkages in mannans. Heterogeneous expression of ß-mannanase in Pichia pastoris systems is widely used; however, Saccharomyces cerevisiae expression systems are more reliable and safer. We optimized ß-mannanase gene from Aspergillus sulphureus and expressed it in five S. cerevisiae strains. Haploid and diploid strains, and strains with constitutive promoter TEF1 or inducible promoter GAL1, were tested for enzyme expression in synthetic auxotrophic or complex medium. Highest efficiency expression was observed for haploid strain BY4741 integrated with ß-mannanase gene under constitutive promoter TEF1, cultured in complex medium. In fed-batch culture in a fermentor, enzyme activity reached ~ 24 U/mL after 36 h, and production efficiency reached 16 U/mL/day. Optimal enzyme pH was 2.0-7.0, and optimal temperature was 60 °C. In studies of ß-mannanase kinetic parameters for two substrates, locust bean gum galactomannan (LBG) gave Km = 24.13 mg/mL and Vmax = 715 U/mg, while konjac glucomannan (KGM) gave Km = 33 mg/mL and Vmax = 625 U/mg. One-hour hydrolysis efficiency values were 57% for 1% LBG, 74% for 1% KGM, 39% for 10% LBG, and 53% for 10% KGM. HPLC analysis revealed that the major hydrolysis products were the oligosaccharides mannose, mannobiose, mannotriose, mannotetraose, mannopentaose, and mannohexaose. Our findings show that this ß-mannanase has high efficiency for hydrolysis of mannans to mannooligosaccharides, a type of prebiotic, suggesting strong potential application in food industries.

Synthesis and in vitro cytotoxic evaluation of new 1H-benzo[d]imidazole derivatives of dehydroabietic acid.

A series of new 1H-benzo[d]imidazole derivatives of dehydroabietic acid were designed and synthesized as potent antitumor agents. Structures of the target molecules were characterized using MS, IR, 1H NMR, 13C NMR and elemental analyses. In the in vitro cytotoxic assay, most compounds showed significant cytotoxic activities against two hepatocarcinoma cells (SMMC-7721 and HepG2) and reduced cytotoxicity against noncancerous human hepatocyte (LO2). Among them, compound 7b exhibited the best cytotoxicity against SMMC-7721 cells (IC50: 0.36±0.13µM), while 7e was most potent to HepG2 cells (IC50: 0.12±0.03µM). The cell cycle analysis indicated that compound 7b caused cell cycle arrest of SMMC-7721 cells at G2/M phase. Further, compound 7b also induced the apoptosis of SMMC-7721 cells in Annexin V-APC/7-AAD binding assay.

[Chemical Constituents from Roots and Rhizome of Trillium tschonoskii( â £)].

Objective: To investigate the chemical constituents from the roots and rhizome of Trillium tschonoskii. Methods: The85% methanol elution parts from the roots and rhizome of Trillium tschonoskii were separated and purified by polyamide,silica gel,RPC18,Sephadex LH-20 column chromatography and the preparation of high performance liquid. Chemical structures were identified by MS,1D and 2D-NMR experiment. Results: Ten steroidal saponins compounds were isolated and identified as diosgenin-3-O-α-L-rhamnopyranosyl-( 1→4)-α-L-rhamnopyranosyl-( 1→4)-[α-L-rhamnopyranosyl( 1 →2) ]-ß-D-glucopyranoside( 1),trikamsteroside E( 2),deoxytrikamsteroside E( 3),( 23 S,24S,25S)-spirostan-5-ene-1ß,3ß,21,23,24-pentahydroxy-1ß-O-α-L-rhamnopyranosyl-( 1 →2)-[O-ß-D-xylopyranosyl( 1→3) ]-O-α-L-pyranarabinoside( 4),trikamsteroside B( 5),27-hydroxy-trikamsteroside B( 6),3-acetyl-pennogenin( 7),dioscoreanoside I( 8),sileneoside G( 9) and intergristerone B( 10). Conclusion: Compounds 8 ~ 10 are isolated from this genus for the first time,compounds 1,3,4,6,7 are isolated from this plant for the first time.

Synthesis, in vitro antimicrobial and cytotoxic activities of new carbazole derivatives of ursolic acid.

A series of new carbazole derivatives of ursolic acid were designed and synthesized in an attempt to develop potent antimicrobial or antitumor agents. Their structures were confirmed by using IR, HRMS and (1)H NMR analysis. All the synthesized compounds were evaluated for their antimicrobial activity against four bacterial and three fungal strains using serial dilution method. Compounds 3a, 3b, 4a, 4b and 5a-f exhibited significant antibacterial activity against at least one tested bacteria with MIC values of 3.9-15.6µg/ml. In addition, the in vitro cytotoxicity of these compounds were also assayed against two human tumor cell lines (SMMC-7721 and HepG2) using MTT colorimetric method. From the results, compounds 5a-e and 5h displayed pronounced cytotoxic activity with IC50 values below 10µM. Specially, compound 5e was found to be the most potent compound with IC50 values of 1.08±0.22 and 1.26±0.17µM against SMMC-7721 and HepG2 cells, respectively, comparable to those of doxorubicin. In addition, compound 5e showed reduced cytotoxicity against noncancerous LO2 cells with IC50 value of 5.75±0.48µM.

[Chemical Constituents from Saururus chinensis].

OBJECTIVE: To investigate the chemical constituents of active components of Saururus chinensis on anti-nicotine withdrawal symptoms. METHODS: Various column chromatography were used in the isolation and purification, and physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. RESULTS: Six chemical compounds were isolated from the active part of anti-withdrawal symptoms, and were identified as 4'-hydroxyl-3,3',4,5,5'-pentamethoxy-7,7'-epoxylignan (1) ,3-(2-nitroethyl)-1-methoxyindole(2), elemicin (3), erythro-(7R, 8S) - (-) - (3,4,5-trimethoxy-7-hydroxy-1'-allyl-3', 5'-dimethoxy)-8-O-4'-neolignan (4), 3,4,5-trimethoxy-phenylacrylaldehyde (5) and dibutyl phthalate (6). CONCLUSION: Compound 1 is a novel lignan, compounds 2 - 6 are firstly isolated from this plant.

[Study on Phenylpropanoids of Gardenia jasminoides].

OBJECTIVE: To investigate the phenylpropanoids constituents of Gardenia jasminoides. METHODS: Various column chromatography were used in the isolation and purification, physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. RESULTS: Eight compounds were isolated from Gardenia jasminoides, including 4-hydroxy-cinnamic acid methylester (1), 3, 5-dimethoxy-4-hydroxy-cinnamic acid methylester (2), pisoninol II (3), 7-hydroxy-orebiusin A (4), (E) -3-(4'-hydroxyphenyl) -acrylic acid n-butyl ester (5), (E) -3-(4'-methoxyphenyl) -acrylic acid n-butyl ester (6), 4-methoxyl-phenylpropanol n-butyl ether (7) and cycloolivil (8). CONCLUSION: All compounds are firstly isolated from this plant.

Synthesis and biological evaluation of novel N-substituted 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential antimicrobial agents.

A series of new N-substituted 1H-dibenzo[a,c]carbazole derivatives were synthesized from dehydroabietic acid, and their structures were characterized by IR, (1)H NMR and HRMS spectral data. All compounds were evaluated for their antibacterial and antifungal activities against four bacteria (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescens) and three fungi (Candida albicans, Candida tropicalis and Aspergillus niger) by serial dilution technique. Some of the synthesized compounds displayed pronounced antimicrobial activity against tested strains with low MIC values ranging from 0.9 to 15.6µg/ml. Among them, compounds 6j and 6r exhibited potent inhibitory activity comparable to reference drugs amikacin and ketoconazole.

[Study on chemical components of Tripterospermum chinense].

OBJECTIVE: To investigate the chemical components of the whole herb of Tripterospermum chinense. METHODS: Various column chromatography methods were used in the isolation and purification. Physio-chemical constant determination and spectral analysis were adopted to determine the chemical structures. RESULTS: Ten compounds were isolated and identified as 1, 7-dihydroxy-3,8-dimethoxyxanthone(1),1,3-dihydroxy-7,8-dimethoxyxanthone (2) 1,3,6,7-tetrahydroxyxanthone (3),1,8-dihydroxyxanthone(4),2'-deoxythymidine(5), 4-hydroxyphthalide(6),2,4-dihydroxy benzyl alcohol (7),2,5-dihydroxyphenetole (8), saponarin (9) and 4'-methoxysaponarin(10). CONCLUSION: Compounds 2 - 8 and 10 are isolated from this plant for the first time.

[Study on chemical constituents of Gardenia jasminoides(III)].

OBJECTIVE: To investigate the chemical constituents of Gardenia jasminoides fruits. METHODS: Various column chromatography were used in the isolation and purification, and physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. RESULTS: Twelve compounds were isolated from Gardenia jasminoides including jasminoside I (1), gardenoside (2), gardaloside (3), 3-hydroxy-urs-12-ene-11-ketone(4), 5, 4'-dihydroxyl-7, 3', 5'-trimethoxyflavone (5), 5, 7, 3', 4', 5'-pentamethoxyflavone(6), 3, 5, 6, 4'-tetrahydroxy-3', 5'-dimethoxyflavone (7), shikimic acid (8), 1, 2, 4-benzenetriol (9), 3, 4-dimethoxy-benzoic acid (10), dibutyl phthalate (11) and diisobutyl phthalate (12). CONCLUSION: Compounds 4 - 7 and 9 -10 were isolated from this plant for the first time.

[Study on chemical constituents of Eucommia ulmoides leaves].

OBJECTIVE: To investigate the chemical constituents of Eucommia ulmoides leaves. METHODS: Various column chromatography were used in the isolation and purification, physiochemical constant determination and spectral analysis were adopted to determine the chemical structures. RESULTS: Ten compounds were isolated and identified as borreriagenin (1), n-butyl-O-ß-D-fructopyranoside (2), α-D-glucopyranosyl-(1-->1')-3'-amino-3'-deoxy-ß-D-glucopyranoside (3), ß-D-fructofuranosyl-α-D-galactopyranoside (4), ß-D-fructose (5), diisobutyl phthalate (6), 5-hydroxy-9-isopropylether-guaiacylglycerol (7), 4-hydroxyphenylethanol-8-O-ß-D-apiofuranosyl(1-->6)-ß-D-glucopyranoside (8), lariciresinol (9), and (3S,5R,6R,9S)-tetrahydroxy-7-ene-megastigmane (10). CONCLUSION: All compounds are isolated from this genus for the first time.