Search

Our previous study indicated that a chiral compound 071031B was a novel serotonin and noradrenaline reuptake inhibitor with superior antidepressant activity compared to duloxetine. The present study aimed to investigate chiral pharmacology differences of 071031B enantiomers, S-071031B and R-071031B, and disclose mechanisms underlying the behavioral differences based on target profiles and pharmacokinetic profiles. In vivo behavioral tests indicated that S-071031B was more potent than R-071031B in two depression models (the forced swimming test in mice and rats) and two pain models (the acetic acid-induced writhing and formalin tests in mice). In vitro assays revealed that both S-071031B and R-071031B showed high affinity for human serotonin transporters and norepinephrine transporters with equal potency, and showed consistently equipotent inhibitory effects on serotonin and norepinephrine uptake. Pharmacokinetic studies demonstrated that oral availability and hepatic metabolism, rather than pH stability, intestinal transport, and plasma binding, contributed to enantiomers’ behavioral differences. Based on these findings, it is suggested that S-071031B is a more active enantiomer, and the differential pharmacokinetic profiles, but not target affinity, contribute to differences of S-071031B and R-071031B in behavioral pharmacology. Moreover, current PK-PD study may provide positive exploration for chiral antidepressants development.

Rice false smut has become an increasingly serious disease in rice (Oryza sativa L.) production worldwide. The typical feature of this disease is that the fungal pathogen Ustilaginoidea virens (Uv) specifically infects rice flower and forms false smut ball, the ustiloxin‐containing ball‐like fungal colony, of which the size is usually several times larger than that of a mature rice seed. However, the underlying mechanisms of Uv‐rice interaction are poorly understood. Here, we applied time‐course microscopic and transcriptional approaches to investigate rice responses to Uv infection. The results demonstrated that the flower‐opening process and expression of associated transcription factors, including ARF6 and ARF8, were inhibited in Uv‐infected spikelets. The ovaries in infected spikelets were interrupted in fertilization and thus were unable to set seeds. However, a number of grain‐filling‐related genes, including seed storage protein genes, starch anabolism genes and endosperm‐specific transcription factors (RISBZ1 and RPBF), were highly transcribed as if the ovaries were fertilized. In addition, critical defense‐related genes like NPR1 and PR1 were downregulated by Uv infection. Our data imply that Uv may hijack host nutrient reservoir by activation of the grain‐filling network because of growth and formation of false smut balls.

As more and more oral formulations of nanoparticles are used in clinical contexts, a comprehensive study on the mechanisms of interaction between polymer nanoparticles and live cells seems merited. Such a study was conducted and the results were compared to the polymer itself in order to demonstrate different kinds of effects that are brought into the cell by polymer and its nanoparticles, especially the effects on the biomembrane. Several techniques, including surface plasmon resonance (SPR), Fourier transformed infrared spectroscopy (FTIR), Raman spectroscopy, fluorescence polarization spectroscopy (FP), flow cytometry (FCM) with quantitative analysis, and confocal images with antibody staining were employed toward this end. The cytotoxicity in vitro was also evaluated. Chitosan (CS), a polycationic polymer, was used to prepare the nanoparticles. We demonstrate that chitosan nanoparticles (CS-NP) induce strong alterations in the distribution of membrane proteins, fluidity of membrane lipids, and general membrane structure. Furthermore, the uptake of CS-NP into Caco-2 cells was found to have a similar mechanism to that of CS molecules, but the differences in degree were noted. These results indicate that positive charge and nanoscale size were the factors that most significantly affected the interactions between the nanoparticles of polycationic polymers and live cells. However, no difference in cytotoxicity toward the Caco-2 cells was found between CS and CS-NP. This supports the idea that CS-NP is an effective and safe carrier for oral drug delivery.

Gametophyte development is an important process in flowering plants. Seeds are the primary organs for harvesting, and therefore spikelet fertility is especially vital for rice yield. Here, we report the characterization and genetic mapping of a novel rice male and female sterile mutant, mfs1, which was generated from a transgenic line of japonica rice variety Zhonghua 9. Anther transverse sections indicate that the microspores in these plants were abnormally degenerated at the meiotic leptotene stage, while the tapetum layer was not degenerated and remained present; therefore, no functional pollen grains formed in the mutant anther locules. In addition, the majority of mutant embryo sacs did not undergo differentiation or the differentiation was incomplete, resulting in the absence of functional embryo sac formation. Genetic analysis of three F2 populations indicated that the mutant phenotype was controlled by a single recessive gene. The mutant phenotype was confirmed by linkage analysis to be not due to a foreign T-DNA insertion. A map-based cloning strategy was employed to map the mutant gene, and, finally, the mfs1 locus was mapped to a 99-kb physical interval between simple sequence repeat markers RM12585 and D051 on rice chromosome 2. Sequence analysis indicates that 11 rice candidate genes are located in this region, including three encoded putative proteins and eight encoded known proteins, such as transcription factors having WRKY and zinc finger domains, a ubiquitin fusion degradation protein, chaperone protein clpB 1, a two-component response regulator, the ZOS2-04-C2H2 zinc finger protein, a peptidase of the T1 family and a protein kinase.

Thymopentin, a potent immunomodulating drug, was incorporated into pH-sensitive chitosan nanoparticles prepared by ionic gelation of chitosan with tripolyphosphate anions and then coated with Eudragit S100 to improve the stability and the oral bioavailability. Nanoparticles particle size and zeta potential were measured by photo correction spectroscopy and laser Dopper anemometry. Its morphology was examined by environment scan electron microscope. The encapsulation efficiency and the release in vitro were determined by HPLC. Enzymatic stabilization was expressed by the enzymatic degradation of aminopeptidase. Biological activity of TP5 loaded in nanoparticles was assayed by lymphocyte proliferation test in vitro and the immune function (CD4+/CD8+) of irradiated rat in vivo. The results obtained demonstrated that the average sizes of pH-sensitive chitosan nanoparticles were 175.6 ± 17 nm, the zeta potential was 28.44 ± 0.5 mV and the encapsulation efficiency was 76.70 ± 2.6%. The cumulative release percentages of thymopentin from the pH-sensitive nanoparticles were 24.65%, 41.01%, and 81.44% incubated in different medium, 0.1 N HCl, pH 5.0 PBS, and pH 7.4 PBS, respectively. The pH-sensitive chitosan nanoparticles could efficiently protect TP5 from enzymatic degradation and prolong the degradation half-time of TP5 from 1.5 min to 15 min. It was demonstrated from the lymphocyte proliferation test that the nanoparticle-encapsulated TP5 still kept its biological activity. In immunosuppression rats, the lowered T-lymphocyte subsets values were significantly increased and the raised CD4+/CD8+ ratio was evidently reduced. These results indicated that pH-sensitive chitosan nanoparticles may be used as the vector in oral drug delivery system for TP5.

Novel microreactors have been fabricated on silicon in order to dehydrogenate cyclohexane to benzene. There are 12 reactor chips on one single silicon wafer. The microreactor consists of three chips, which are reaction chamber, separation membrane and reactor cap. The whole dimension of the reactor is 20 mm long, 14 mm wide and 3 mm high. As for reaction chamber, 80 microchannels 50 μm wide, 400 μm deep and 8 mm long have been etched. We use silicon 〈110〉 wafers to obtain high-aspect-ratio microstructures. Twenty nanometer Ti is sputtered and oxidized as the adhesion layer and catalyst carrier. Twenty nanometer Pt is sputtered as the catalyst. For the separation membrane, it is 6 mm by 8 mm, with 80 folded rectangular 4 μm thick Pd foil structures 50 μm wide, 200 μm high and 6 mm long anchored on silicon. This utilizes the combination of silicon 〈110〉 wet etching and dry etching together. These folded Pd microstructures contribute to increase the separation area of hydrogen. The reactor cap for inlet and outlet gas pipes is made of PDMS, which is a kind of relatively new material for MEMS applications. Finally, the reaction chamber, separation membrane and reactor cap have been bonded using Polyimide with very good contact strength between chips. The microreactors have been tested using a GC with a conversion value of 18.4%.

The aim of this work was to study the nasal route for the delivery of vasoactive intestinal peptide (VIP) to the brain and to evaluate the toxicity of VIP nasal spray. Mice were injected intracerebroventricularly with the aggregated Abeta25-35 to mimic Alzheimer's disease. Following administration, different groups of mice were treated over one week, and their spatial learning and memory capacities were evaluated by the Morris water maze test. The toxicity of VIP nasal spray was evaluated by examining the morphology of individual rat nasal mucosa cilia and the pathology of rat nasal mucosa. Rats receiving intranasal VIP (40 microg/ml) showed good spatial memory relative to the Abeta25-35 model group, but the escape latency did not show any statistically significant difference. Intranasal administration of VIP nasal spray (200 microg/ml) improved deficits in spatial memory to the point that test animals receiving intranasal VIP showed no statistically significant differences from the normal control group in escape latency. This indicated that the nasal spray method could increase the quantity of VIP entering the brain and protect the central nervous systems of mice. Toxicity evaluation showed that the preparation could cause minor irritation, which resolved spontaneously within a week at the end of treatment. In conclusion, VIP can be delivered successfully to the brain using the intranasal route.

Aimed at the puzzle of uncertainty resulted from qualitative selection for fracturing candidate of well and layer in oilfield, the paper proposed a sort of prediction model for fracturing candidate effect based on FNNS. In the paper, it was analyzed to the influence factors resulted in predictive precision being poor, discussed the FNNS and its fuzzy decision method, and also explored the modeling and forecasting of optimization layer in candidate wells. The application example shows that the well or layer of fracturing candidate can been optimized quantitatively by means of prediction model based on FNNS.

A Gram-negative bacterium, named LY402, was isolated from contaminated soil. 16S rDNA sequencing and measurement of the physiological and biochemical characteristics identified it as belonging to the genus Enterobacter. Degradation experiments showed that LY402 had the ability to aerobically transform 79 of the 91 major congeners of Aroclor 1242, 1254, and 1260. However, more interestingly, the strain readily degraded certain highly chlorinated and recalcitrant polychlorinated biphenyls (PCBs). Almost all the tri- and tetra-chlorobiphenyls (CBs), except for 3,4,3',4'-CB, were degraded in 3 days, whereas 73% of 3,4,3',4'-, 92% of the penta-, 76% of the hexa-, and 37% of the hepta-CBs were transformed after 6 days. In addition, among 12 octa-CBs, 2,2',3,3',5,5',6,6- CB was obviously degraded, and 2,2',3,3',4,5,6,6'- and 2,2',3,3',4,5,5',6'-CB were slightly transformed. In a metabolite analysis, mono- and di-chlorobenzoic acids (CBAs) were identified, and parts of them were also transformed by strain LY402. Analysis of PCB degradation indicated that strain LY402 could effectively degrade PCB congeners with chlorine substitutions in both ortho- and para-positions. Consequently, this is the first report of an Enterobacteria that can efficiently degrade both low and highly chlorinated PCBs under aerobic conditions.

The purpose of this work was to investigate distribution, transition, bioadhesion and release behaviors of insulin loaded pH-sensitive nanoparticles in the gut of rats, as well as the effects of viscosity agent on them. Insulin was labeled with fluorescein isothiocyanate (FITC). The FITC-insulin solution and FITC-insulin nanoparticle aqueous dispersions with or without hydropropylmethylcellulose (HPMC, 0.2%, 0.4%, or 0.8% (w/v)) were orally administered to rats, respectively. The amounts of FITC-insulin in both the lumen content and the intestinal mucosa were quantified by a spectrofluorimeter. The release profiles in the gut were plotted by the percentages of FITC-insulin released versus time. FITC-insulin nanoparticle aqueous dispersion showed similar stomach but lower intestine empty rates, and enhanced intestinal mucosa adhesion in comparison with FITC-insulin solution. Addition of the HPMC reduced the stomach and intestine empty rates, enhanced the adhesion of FITC-insulin to the intestine mucosa. The release of FITC-insulin from nanoparticles in the gut showed an S-shape profile, and addition of HPMC prolonged the release half-life from 0.77 to 1.51 h. It was concluded that the behaviors of pH-sensitive nanoparticles tested in gastrointestinal tract of rats and the addition of HPMC were favorable to the absorption of the drug loaded.

Endophytic SR-15, SR-25 and SL-37 strains screened from rice hybrid D you 527 in Sichuan were analyzed. Through penetration and microscopic test, the strains were found be mainly located in the cell gap, vacuole and cytoplasm. PUC18 transferring and ERIC-PCR showed that the recombination strain SR-15 could grow in the plant stably. The strain was identified as Bacillus halmapalus based on its chemical components of cell wall, physiological and biochemical characters. It was also shown that the strain was not injurious to rice plant, instead, it promoted rice plant growth by penetration. The Cry1Ac gene was transferred into the stain and verified by Southern analysis. Cry1Ac-transferred SR-15 was toxic to the Chilo suppressalis, brought about death ratio as high as 84.2%.

To study the influence of seven different absorption enhancers on nasal mucosa.By testing last time of ciliary movement, velocity of ciliary movement, ciliary structural and specific cellular changes of nasal mucosa the influence of seven different absorption enhancers on nasal mucosa.The effect on lasting time of ciliary movement was 1%SDS1%SDC1%Brij355%Tween800.1%EDTA5%HP-beta-CD1%lecithin the effect on velocity of ciliary movement 1%Brij351%SDC1%SDS0.1%EDTA1%lecithin5%Tween805%HP-beta-CD,and the effect on ciliary structural and specific cellular changes of nasal mucosa 1%SDS approximately 1%SDC approximately 1%Brij355%Tween800.1%EDTA approximately 5% HP-beta-CD approximately 1%lecithin.The three methods have good correlation.

To study the preparation technique and release characteristic of 5-fluorouracil loaded chitosan microspheres for the intranasal administration.Using the liquid paraffin as the oil phase,and span-80 as the emuifier; 5-fluorouracil-loaded chitosan microspheres were achieved by emulsion-chemical crosslink technique. The orthogonal experimental design was applied to optimize the preparation procedure. Dynamic dialysis method was used to determine the releasing characteristic of microspheres in vitro and it influencing factors. Swelling behavior was expressed by swelling ratio. The degree of mucoadhesion was investigated by determining the mucociliary transport rate(MTR) of the microparticle across a frog palate.Microspheres with a good shape and narrow size distribution were prepared. The average diameter was (43+/-4) microm. The drug loading was 38.5%+/-1.0%. The entrapment efficiency was 79.0%+/-1.8%. The drug release profile in vitro could be described by Higuichi equation Q=0.1035t(1/2)+0.0284 (r=0.9965). Chitosan had good mucoadhesive property and caused a significant reduction in MTR(P0.01).The optimized preparation technique is stable and has a high entrapment efficiency. So it could be used to prepare 5-fluorouracil-loaded chitosan microspheres for the intranasal administration. Chitosan is a good material for nasal preparation and has prospective development in the pharmaceutical field.

Microreactors consisting of channels etched into silicon are used to dehydrogenate cyclohexane to benzene. These reactors are fabricated by wet etching into silicon. The reactors contain a system of 10 channels 10 micrometers deep, 500 micrometers wide, and 50 mm long. The surface of the channels is sputtered with platinum to catalyze the gas-solid heterogeneous reaction. This endothermic reaction is heated and kept isothermal at 200 degree(s)C. The level of conversion is linked to the details of the geometry, pressure, and fluid flow regime. Experiments and simulations show that conversion is higher in the Knudsen regime due to a higher level of molecule-wall collisions.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.