Aquaporin 5 maintains lens transparency by regulating the lysosomal pathway using circRNA.

The lens is transparent, non-vascular, elastic and wrapped in a transparent capsule. The lens oppacity of AQP5-/- mice was increased more than that of wild-type (AQP5+/+ ) mice. In this study, we explored the potential functional role of circular RNAs (circRNAs) and transcription factor HSF4 in lens opacity in aquaporin 5 (AQP5) knockout (AQP5-/- ) mice. Autophagy was impaired in the lens tissues of AQP5-/- mice. Autophagic lysosomes in lens epithelial cells of AQP5-/- mice were increased compared with AQP5+/+ mice, based on analysis by transmission electron microscopy. The genetic information of the mice lens was obtained by high-throughput sequencing, and then the downstream genes were analysed. A circRNA-miRNA-mRNA network related to lysosomal pathway was constructed by the bioinformatics analysis of the differentially expressed circRNAs. Based on the prediction of the TargetScan website and the validation by dual luciferase reporter assay and RNA immunoprecipitation-qPCR, we found that circRNA (Chr16: 33421321-33468183+) inhibited the function of HSF4 by sponging microRNA (miR-149-5p), and it downregulated the normal expression of lysosome-related mRNAs. The accumulation of autophagic lysosome may be one of the reasons for the abnormal development of the lens in AQP5-/- mice.

Discovery of selective N-[3-(1-methyl-piperidine-4-carbonyl)-phenyl]-benzamide-based 5-HT1 F receptor agonists: Evolution from bicyclic to monocyclic cores.

Preclinical experiments and clinical observations suggest the potential effectiveness of selective 5-HT1F receptor agonists in migraine. Identifying compounds with enhanced selectivity is crucial to assess its therapeutic value. Replacement of the indole nucleus in 2 (LY334370) with a monocyclic phenyl ketone moiety generated potent and more selective 5-HT1F receptor agonists. Focused SAR studies around this central phenyl ring demonstrated that the electrostatic and steric interactions of the substituent with both the amide CONH group and the ketone CO group play pivotal roles in affecting the adopted conformation and thus the 5-HT1F receptor selectivity. Computational studies confirmed the observed results and provide a useful tool in the understanding of the conformational requirements for 5-HT1F receptor agonist activity and selectivity. Through this effort, the 2-F-phenyl and N-2-pyridyl series were also identified as potent and selective 5-HT1F receptor agonists.

[Analysis of soil components along water channel of east route of South-to-North Water Diversion Project].

OBJECTIVE: To explore the relationship between the soil components along the areas of the east route of the Southto-North Water Diversion Project and the survival situation of Oncomelania hupensis snails. METHODS: Four study sites were selected along the project, and soil samples were collected to analyze the components. The amounts of components among the different study sites were compared statistically. RESULTS: Except zinc, sodium, and phosphorus, the contents of the soil components where the snails survived were different from those where snails were dead (t = -19.150 to 12.810, all P < 0.01). However, the logistic regression analysis did not obtain a model with statistical significance. CONCLUSIONS: O. hupensis snails live in the soil with adequate organic matter and neutral pH value. Along with the global warming and the operation of the South-toNorth Water Diversion Project, O. hupensis snails may survive in the northern area, and therefore, the surveillance work should be strengthened.

Pachyelasides A-D, novel molluscicidal triterpene saponins from Pachyelasma tessmannii.

This is the first report for secondary metabolites in an African medicinal plant, Pachyelasma tessmannii (Leguminosae). Four novel saponins, pachyelasides A-D, were isolated from the methanol extract of the root bark by using recycling HPLC. These compounds showed molluscicidal activity (LD(50) < or =8.0 mug/mL) against the South American snail, Biomphalaria glabratus. The structures were determined on the basis of extensive nuclear magnetic resonance spectroscopic and matrix-assisted laser desorption/ionization time-of-flight mass spectrometric studies.

Oxidative C-C bond-forming reaction of electron-rich alkylbenzyl ether with trimethylvinyloxysilane.

Treatment of an electron-rich benzyl ether with DDQ at ambient temperature followed by addition of a silyl enol ether undergoes a C-C bond-forming reaction to afford 3-alkoxy-3-phenyl-propionyl compound. This is a general reaction and works well with a variety of silyl enol ethers to give carbonyl products in yields ranging from 10 to 85%.

Genetic and ecologic characteristics of Bartonella communities in rodents in southern China.

Ecologic and bacteriologic observations of small mammals captured in Yunnan Province in the People's Republic of China indicated that Bartonella infections occurred at a high prevalence among some rodent species. Sequence analyses of the citrate synthase genes of these Bartonella demonstrated that rodents in this region harbored a diverse assemblage of strains. The Bartonella isolates obtained from Apodemus, Eothenomys, and Rattus typically clustered separately by genus of rodent host. Cultures obtained from Rattus rats were genetically related to Bartonella elizabethae, a recognized human pathogen. The finding of Bartonella species in a high proportion of the rodent samples from Yunnan suggests the need to investigate whether these agents might be responsible for cases of febrile illnesses of unknown etiology in southern China and elsewhere in southeastern Asia.

Molecular complexes of antipsychotic pharmaceutical parent molecule phenothiazine and unsaturated acid anhydrides.

The charge-transfer complexes (CTC) between a parent molecule of antipsychotic pharmaceuticals, phenothiazine, and seven unsaturated acid anhydrides, 1,4,5,8-naphtalenetetracarboxylic dianhydride, diphenic anhydride, maleic anhydride (MA), 3,4,5,6-tetrahydrophthalic anhydride (THPA), 3-hydroxy-1,8-naphthalic anhydride (HONA), 4-chloro-1,8-naphthalic anhydride (ClNA), and 1,8-naphthalic anhydride (NA) were studied using IR and UV spectroscopy. Stability constants (K) at different temperatures were measured, and based on the K's DeltaH and DeltaS were calculated. The values of electron affinity (E(A)) of anhydrides were obtained according to Mulliken's theory. The results show that phenothiazine is an excellent donor and has strong ability to complex with the carbonyl group, and the E(A) values have good linear relationships with DeltaH and K, respectively. The solvent effect on CTCs was also determined and explained. The CTC of phenothiazine-succinic anhydride (SA) was studied under the same conditions. It was deduced from the results obtained that there were two charge-accepting centers in the unsaturated acid anhydrides when they formed CTCs with phenothiazine. The first one was carbon atom of the two carbonyl groups and the second one was their -C=C- in the molecules.

[Effects of Dendrolimus punctatus feeding and methyl jasmonate (MeJA)--or terpenes fumigation on abscisic acid and jasmonic acid contents in Pinus massoniana seedling needles].

Abscisic acid (ABA) and Jasmonic acid (JA) play an important role in inducing the stress-resistance of plants. In this study, parts of the needles on a ring of Pinus massoniana seedling shoots were subjected to 4 hours Dendrolimus punctatus feeding or 4 hours fumigation with 10 micromol x L(-1) of methyl jasmonate (MeJA) or terpenes, and the ABA and JA contents in treated needles, untreated neighboring sister needles, and untreated needles above and below the ring were determined by GC/MS. An obvious increase of ABA and JA contents was observed in all of the needles, whether they were treated or not, illustrating that ABA and JA were the vital signaling molecules in the wound signal transduction pathway, and participated in the formation of systematic resistance of P. massoniana seedlings.

Structure-activity relationships of SERMs optimized for uterine antagonism and ovarian safety.

Structure-activity relationship studies are described, which led to the discovery of novel selective estrogen receptor modulators (SERMs) for the potential treatment of uterine fibroids. The SAR studies focused on limiting brain exposure and were guided by computational properties. Compounds with limited impact on the HPO axis were selected using serum estrogen levels as a biomarker for ovarian stimulation.

Design, synthesis and evaluation of bicyclic benzamides as novel 5-HT1F receptor agonists.

Several fused bicyclic systems have been investigated to serve as the core structure of potent and selective 5-HT1F receptor agonists. Replacement of the indole nucleus in 2 with indazole and 'inverted' indazole provided more potent and selective 5-HT1F receptor ligands. Indoline and 1,2-benzisoxazole systems also provided potent 5-HT1F receptor agonists, and the 5-HT1A receptor selectivity of the indoline- and 1,2-benzisoxazole-based 5-HT1F receptor agonists could be improved with modification of the benzoyl moiety of the benzamides. Through these studies, we found that the inherent geometries of the templates, not the nature of hybridization of the linking atom, were important for the 5-HT1F receptor recognition.