Phytochemical Composition, Antioxidant Activity, and Enzyme Inhibitory Activities (α-Glucosidase, Xanthine Oxidase, and Acetylcholinesterase) of Musella lasiocarpa.

In this study, we aimed to investigate the chemical components and biological activities of Musella lasiocarpa, a special flower that is edible and has functional properties. The crude methanol extract and its four fractions (petroleum ether, ethyl acetate, n-butanol, and aqueous fractions) were tested for their total antioxidant capacity, followed by their α-glucosidase, acetylcholinesterase, and xanthine oxidase inhibitory activities. Among the samples, the highest total phenolic and total flavonoid contents were found in the ethyl acetate (EtOAc) fraction (224.99 mg GAE/g DE) and crude methanol extract (187.81 mg QE/g DE), respectively. The EtOAc fraction of Musella lasiocarpa exhibited the strongest DPPH· scavenging ability, ABTS·+ scavenging ability, and α-glucosidase inhibitory activity with the IC50 values of 22.17, 12.10, and 125.66 µg/mL, respectively. The EtOAc fraction also showed the strongest ferric reducing antioxidant power (1513.89 mg FeSO4/g DE) and oxygen radical absorbance capacity ability (524.11 mg Trolox/g DE), which were higher than those of the control BHT. In contrast, the aqueous fraction demonstrated the highest acetylcholinesterase inhibitory activity (IC50 = 10.11 µg/mL), and the best xanthine oxidase inhibitory ability (IC50 = 5.23 µg/mL) was observed from the crude methanol extract as compared with allopurinol (24.85 µg/mL). The HPLC-MS/MS and GC-MS analyses further revealed an impressive arsenal of compounds, including phenolic acids, fatty acids, esters, terpenoids, and flavonoids, in the most biologically active EtOAc fraction. Taken together, this is the first report indicating the potential of Musella lasiocarpa as an excellent natural source of antioxidants with possible therapeutic, nutraceutical, and functional food applications.

Microalgal-bacterial granular sludge process outperformed aerobic granular sludge process in municipal wastewater treatment with less carbon dioxide emissions.

The aerobic granular sludge (AGS) process and microalgal-bacterial granular sludge (MBGS) process were comparably applied for municipal wastewater treatment in sequencing batch reactors with a height to diameter ratio of eight. For morphological appearances, the yellow aerobic granules were strip-shaped (4.0 mm × 0.62 mm) while the green microalgal-bacterial granules were elliptical-shaped (2.0 mm × 0.75 mm). The dominated rod-shaped bacteria (e.g., Acidobacteria and Bacteroidetes) and the slender configuration might be associated with the strip shape of aerobic granules under weak acid conditions. The nutrients removal performances by MBGS process were generally slightly better than AGS process. In addition, nutrients removal mechanisms were identified to elucidate how organics, ammonia, and phosphorus were removed by AGS process and MBGS process, respectively. Mass balance calculation estimated that MBGS process appeared to achieve much less CO2 emission (5.8%) compared with AGS process (44.4%). Overall, it proved that MBGS process, with the merits of potentially low energy cost, limited CO2 emission, and excellent performance, showed more prospects in municipal wastewater treatment than AGS process.

Intracellular Trapping of the Selective Phosphoglycerate Dehydrogenase (PHGDH) Inhibitor BI-4924 Disrupts Serine Biosynthesis.

Phosphoglycerate dehydrogenase (PHGDH) is known to be the rate-limiting enzyme in the serine synthesis pathway in humans. It converts glycolysis-derived 3-phosphoglycerate to 3-phosphopyruvate in a co-factor-dependent oxidation reaction. Herein, we report the discovery of BI-4916, a prodrug of the co-factor nicotinamide adenine dinucleotide (NADH/NAD+)-competitive PHGDH inhibitor BI-4924, which has shown high selectivity against the majority of other dehydrogenase targets. Starting with a fragment-based screening, a subsequent hit optimization using structure-based drug design was conducted to deliver a single-digit nanomolar lead series and to improve potency by 6 orders of magnitude. To this end, an intracellular ester cleavage mechanism of the ester prodrug was utilized to achieve intracellular enrichment of the actual carboxylic acid based drug and thus overcome high cytosolic levels of the competitive cofactors NADH/NAD+.

Insights into the bacterial species and communities of a full-scale anaerobic/anoxic/oxic wastewater treatment plant by using third-generation sequencing.

For the first time, full-length 16S rRNA sequencing method was applied to disclose the bacterial species and communities of a full-scale wastewater treatment plant using an anaerobic/anoxic/oxic (A/A/O) process in Wuhan, China. The compositions of the bacteria at phylum and class levels in the activated sludge were similar to which revealed by Illumina Miseq sequencing. At genus and species levels, third-generation sequencing showed great merits and accuracy. Typical functional taxa classified to ammonia-oxidizing bacteria (AOB), nitrite-oxidizing bacteria (NOB), denitrifying bacteria (DB), anaerobic ammonium oxidation bacteria (ANAMMOXB) and polyphosphate-accumulating organisms (PAOs) were presented, which were Nitrosomonas (1.11%), Nitrospira (3.56%), Pseudomonas (3.88%), Planctomycetes (13.80%), Comamonadaceae (1.83%), respectively. Pseudomonas (3.88%) and Nitrospira (3.56%) were the most predominating two genera, mainly containing Pseudomonas extremaustralis (1.69%), Nitrospira defluvii (3.13%), respectively. Bacteria regarding to nitrogen and phosphorus removal at species level were put forward. The predicted functions proved that the A/A/O process was efficient regarding nitrogen and organics removal.

The Discovery of LML134, a Histamine H3 Receptor Inverse Agonist for the Clinical Treatment of Excessive Sleep Disorders.

Histamine H3 receptor (H3R) inverse agonists that have been in clinical trials for the treatment of excessive sleep disorders, have been plagued with insomnia as a mechanism-based side effect. We focused on the identification of compounds that achieve high receptor occupancy within a short time, followed by rapid disengagement from the receptor, a target profile that could provide therapeutic benefits without the undesired side effect of insomnia. This article describes the optimization work that led to the discovery of 1-(1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)piperidin-4-yl 4-cyclobutylpiperazine-1-carboxylate (18 b, LML134).

Bacterial communities of four adjacent fresh lakes at different trophic status.

Knowing the microbial compositions in fresh lakes is significant to explore the mechanisms of eutrophication and algal blooms. This study reported on the bacterial communities of the four adjacent fresh lakes at different trophic status by Illumina MiSeq Platform, which were Tangxun Lake (J1), Qingling Lake (J2), Huangjia Lake (J3) and Niushan Lake (J4) in Wuhan, China. J1 had the highest salinity and phosphorus. J2 was abundant in TC (Total Carbon)/TOC (Total Organic Carbon.), calcium and magnesium. J3 had the highest content of nitrogen, iron and pollution of heavy metals. High-throughput sequencing analysis of the 16S rRNA gene revealed that the eutrophic lakes (J1, J2 and J3) were dominated by Cyanobacteria (46.1% for J1, 40.8% for J2, 33.4% for J3) and the oligotrophic lake (J4) was dominated by Actinobacteria (34.2%). An increase of Cyanobacteria could inhibit the growth of Proteobacteria, Actinobacteria and Bacteroidetes. Functional inferences from 16S rRNA sequences suggested that J4 had more abundant bacteria with regard to substrate metabolism than J1, J2, and J3. Burkholderia and Fluviicola might be a suggestion of good water quality. The results demonstrated that the bacterial community could well reflect the water quality of the four lakes.

Mechanism Underlying Acupuncture-Ameliorated Depressive Behaviors by Enhancing Glial Glutamate Transporter in Chronic Unpredictable Mild Stress (CUMS) Rats.

BACKGROUND Major depressive disorder (MDD) is a recurrent mental illness worldwide. The glutamatergic neurotransmission system is now a target for antidepressant therapy because it takes part in synaptic plasticity and cognition in physical condition and has a potential excitatory neurotoxicity in pathological conditions. Glial glutamate transporter EAAT2 performs 90% of Glu neurotransmission. Therefore, the aim of the study was to evaluate the effect of acupuncture on depressive behaviors and EAAT2 in CUMS. MATERIAL AND METHODS We randomly divided 56 male SD rats into a normal group, a model group, an acupuncture group, and a riluzole group. Rats in the model group, acupuncture group, and riluzole group underwent chronic unpredictable mild stress (CUMS) exposure for 21 days. The acupuncture group received electro-acupuncture stimulation on LI4 and LR3 for 5 continuous days per week for 4 weeks, and rats in the riluzole group received 4 mg/kg of riluzole orally (Sanofi, J20140092) for 4 weeks after undergoing CUMS stimulation. RESULTS Rats showed significantly increased sucrose consumption in the sucrose preference test paradigm, and showed elevated food intake and shortened latency in the novelty-suppressed feeding test paradigm after undergoing acupuncture therapy and riluzole treatment. The amelioration of depressive behavioral actions was consistent with increasing number of positive cells, protein, and mRNA expression of glial glutamate transporter EAAT2 in the hippocampus and PFC. CONCLUSIONS The results suggest that acupuncture and riluzole are both effective in improving sucrose consumption, latency, and food intake in CUMS rats. However, acupuncture appears to achieve an antidepressant effect later than riluzole does because it might need accumulated stimulation by enhancing EAAT2 expression. Enhance glial glutamate transporter EAAT2 in the hippocampus and PFC is a mechanism underlying the antidepressant effect of acupuncture.

[Comparative study on effects between electroacupuncture and auricular acupuncture for methamphetamine withdrawal syndrome].

OBJECTIVE: To observe the efficacy difference of electroacupuncture and auricular acupuncture in the treatment of methamphetamine withdrawal syndrome. METHODS: Ninety male patients of methamphetamine addiction were randomized into an electroacupuncture group, an auricular acupuncture group and a control group, 30 cases in each one. In the electroacupuncture group, Neiguan (PC 6), Shenmen (HT 7), Zusanli (ST 36), Sanyinjiao (SP 6), Jiaji (EX-B 2) at T5 and L2 were selected bilaterally. In the auricular acupuncture group, jiaogan (AH(6a)), shenmen (TF4), fei (CO14) and gan (CO12) were selected unilaterally. The treatment was given 3 times a week, totally 12 treatments were required. In the control group, no any intervention was applied. Separately, before treatment and after 1, 2, 3 and 4 weeks treatment, the scores of methamphetamine withdrawal syndrome, Hamilton anxiety scale and Hamilton depression scale were observed in each group. RESULTS: The total score of methamphetamine withdrawal syndrome, anxiety score and depression score were obviously reduced in 2, 3 and 4 weeks of treatment as compared with those before treatment in the electroacupuncture group and the auricular acupuncture group (all P < 0.05), and showed a trend of gradual decline as the extension of treatment. In 1,2,3,4 weeks of treatment, the total score of withdrawal syndrome, anxiety score and depression score in the electroacupuncture group and auricular acupuncture group were lower significantly than those in the control group (all P < 0.05), in which, the total score of withdrawal syndrome in the electroacupuncture group was lower significantly than that in the auricular acupuncture group in the 4th week of treatment (3.69 +/- 2.446 vs 5.73 +/- 3.169, P < 0.05); the anxiety scores were lower significantly than those in the auricular acupuncture group in 3 and 4 weeks of treatment (8.19 +/- 4.57 vs 9.65 +/- 4.24, 5.27 +/- 2.89 vs 7.38 +/- 3.10, both P < 0.05); the depression scores were lower significantly than those in the auricular acupuncture group in 2, 3 and 4 weeks of treatment (15.35 +/- 5.64 vs 19.81 +/- 5.37, 10.96 +/- 4.52 vs 15.00 +/- 4.53, 7.96 +/- 2.69 vs 12.35 +/- 3.59, all P < 0.05). CONCLUSION: Electroacupuncture at the body points and auricular acupuncture play the therapeutic role in the treatment of methamphetamine withdrawal syndrome, anxiety and depression. The longer time the treatment is with electroacupuncture at the body points, the more obvious the efficacy will be on the above symptoms.