Exosomes from artesunate-treated bone marrow-derived mesenchymal stem cells transferring SNHG7 to promote osteogenesis via TAF15-RUNX2 pathway.

Aim: Effect of artesunate (ART)-treated bone marrow-derived mesenchymal stem cells-derived exosomes (BMSC-Exos) on osteogenesis and its underlying mechanisms were investigated. Materials & methods: Proliferation, alkaline phosphatase activity and calcified nodule formation of osteoblasts were determined. A mouse model of osteoporosis was established by ovariectomy. Results: SNHG7 was upregulated in BMSC-Exos by twofold, which was further enhanced in ART-BMSC-Exos by about twofold. ART intensified BMSC-Exos-induced proliferation, alkaline phosphatase activity by about fourfold, calcified nodule formation by about threefold and upregulation of osteogenesis related molecules RUNX2 (by 50%), BMP2 (by 30%) and ATF4 (by 40%) via delivering SNHG7. Mechanistically, SNHG7 recruited TAF15 to facilitate RUNX2 stability. Conclusion: ART-BMSC-Exos facilitated osteogenesis via delivering SNHG7 by modulating TAF15/RUNX2 axis.

Osteoporosis is the most common and complex skeletal disorder worldwide. Exosomes derived from bone marrow-derived mesenchymal stem cells (BMSC-Exos) have been recognized as an ideal seed source for bone tissue regeneration. We aimed to explore the effect of artesunate (ART)-BMSC-Exos on osteogenesis and its underlying mechanisms. The results showed that ART-BMSC derived exosomal SNHG7 facilitated osteoblast activity and attenuated osteogenesis in mice by modulating TAF15/RUNX2 pathway. Our findings contribute to a better understanding of the therapeutic mechanisms of ART-BMSCs-Exos for osteoporosis and suggest ART-BMSC-Exos as a novel therapeutic option for osteoporosis.

The neural stem cell properties of Pkd2l1+ cerebrospinal fluid-contacting neurons in vivo.

The neural stem cells (NSCs) in the ventricular-subventricular zone of the adult mammalian spinal cord may be of great benefit for repairing spinal cord injuries. However, the sources of NSCs remain unclear. Previously, we have confirmed that cerebrospinal fluid-contacting neurons (CSF-cNs) have NSC potential in vitro. In this study, we verified the NSC properties of CSF-cNs in vivo. In mouse spinal cords, Pkd2l1+ CSF-cNs localized around the central canal express NSC markers. In vitro, Pkd2l1+ CSF-cNs form a neurosphere and express NSC markers. Activation and proliferation of CSF-cNs can be induced by injection of the neurotrophic factors basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) into the lateral ventricle. Spinal cord injury (SCI) also induces NSC activation and proliferation of CSF-cNs. Collectively, our results demonstrate that Pkd2l1+ CSF-cNs have NSC properties in vivo and may be involved in SCI recovery.

Artesunate inhibits osteoclastogenesis through the miR-503/RANK axis.

Osteoporosis is a metabolic bone disease that is characterized by decreased bone density and strength due to excessive loss of bone protein and mineral content, which can be induced by increased osteoclast activity. Developing agents targeting osteoclast activation is considered to be the most effective method to reverse bone destruction and alleviate the pain caused by osteoporosis. MTT assay was conducted to detect the cell viability after artesunate treatment of RAW264.7 cells. TRACP staining and pit formation assays were performed to examine the TRACP-positive cells and pit-forming activity of osteoclasts. qRT-PCR and Western blot analysis were performed to assess the mRNA and protein expression levels of the osteoclastogenesis-related genes NFATc1, TRAP, and cathepsin k. The protein levels of RANK, p-Akt, p-p38, and p-ERK were examined by Western blotting. Luciferase reporter assay was conducted to determine whether miR-503 targeted RANK directly. Artesunate inhibited TRACP-positive cells and the pit-forming activity of osteoclasts. However, artesunate increased the expression of miR-503. Artesunate suppressed osteoclastogenesis-related gene expression and RANKL-induced activation of MAPKs and the AKT pathway. In addition, miR-503 inhibited RANK expression by directly targeting RANK during osteoclast differentiation. Artesunate inhibited osteoclastogenesis and osteoclast functions in vitro by regulating the miR-503/RANK axis and suppressing the MAPK and AKT pathways, which resulted in decreased expression of osteoclastogenesis-related markers.

Medroxyprogesterone acetate affects eye growth and the transcription of associated genes in zebrafish.

Medroxyprogesterone acetate (MPA) is a widely used synthetic progestin in contraception pills and hormone replacement therapy. However, its effects on eye growth and development and function were largely unknown. In this study, the transcription of genes in the Notch signaling pathway and the visual cycle network were evaluated after chronic MPA exposure at 4.32 (L), 42.0 (M), and 424 (H) ng L-1 for 120 days in zebrafish. Meanwhile, the histology of the eyes was also examined. Transcriptional results showed that MPA at all three concentrations significantly increased the transcription of notch1a, dll4, jag1a, ctbp1 and rbpjb (key genes in the Notch signaling pathway) in the eyes of females. The up-regulation of noth1a, ctbp1 and kat2b was also observed in the eyes of males exposed to MPA at 424 ng L-1. In the visual cycle pathway, MPA increased the transcription of opn1sw1, opn1sw2, arr3a and rpe65a in the eyes of females from the M and H treatments. Histopathological analysis showed that exposure to 42.0 ng L-1 of MPA increased the thicknesses of inner nuclear layer in females and outer segment in males. Moreover, exposure to 424 ng L-1 of MPA increased the lens diameter in females. These results indicated that chronic MPA exposure affected the transcription of genes in the Notch signaling and in the visual cycle pathways, resulting in overgrowth of the eyes and interference of the eye functions. This study suggests that MPA pose a risk to fitness and survival of zebrafish in areas where MPA contamination exists.

Dydrogesterone affects the transcription of genes in visual cycle and circadian rhythm network in the eye of zebrafish.

Dydrogesterone (DDG) is a synthetic progestin used in contraception and hormone replacement therapy. Our previous transcriptome data showed that the response to light stimulus, photoperiodism and rhythm related gene ontology (GO) terms were significantly enriched in the brain of zebrafish after chronic exposure to DDG. Here we investigated the effects of DDG on the eye of zebrafish. Zebrafish were exposed to DDG at three concentration levels (3.39, 33.1, and 329 ng L-1) for 120 days. Based on our previous transcriptome data, the transcription of genes involved in visual cycle and circadian rhythm network was examined by qPCR analysis. In the visual cycle network, exposure to all concentrations of DDG significantly decreased transcription of grk7a, aar3a and guca1d, while increased the transcription of opn1mw4 and opn1sw2 at the low concentration. Importantly, exposure to all concentrations of DDG down-regulated the transcription of rep65a that encodes a critical enzyme to catalyze the conversion from all-trans-retinal to 11-cis-retinal in the eye of male zebrafish. In the circadian rhythm network, DDG enhanced the transcription of clocka, arntl2 and nifil3-5 at all three concentrations, while it decreased the transcription of cry5, per1b, nr1d2b and si:ch211.132b12.7. In addition, DDG decreased the transcription of tefa in both males and females. Moreover, histological analysis showed the exposure to 329 ng L-1 of DDG decreased the thickness of retinal ganglion cell in the eye of male zebrafish. These results indicated that DDG exposure could affect the transcription of genes in visual cycle and circadian rhythm network in the eyes of zebrafish. This suggests that DDG has potential negative impact on the normal eye function.

Effect of E-waste Recycling on Urinary Metabolites of Organophosphate Flame Retardants and Plasticizers and Their Association with Oxidative Stress.

In this study, three chlorinated (Cl-mOPs) and five nonchlorinated (NCl-mOPs) organophosphate metabolites were determined in urine samples collected from participants living in an electronic waste (e-waste) dismantling area (n = 175) and two reference areas (rural, n = 29 and urban, n = 17) in southern China. Bis(2-chloroethyl) phosphate [BCEP, geometric mean (GM): 0.72 ng/mL] was the most abundant Cl-mOP, and diphenyl phosphate (DPHP, 0.55 ng/mL) was the most abundant NCl-mOP. The GM concentrations of mOPs in the e-waste dismantling sites were higher than those in the rural control site. These differences were significant for BCEP (p < 0.05) and DPHP (p < 0.01). Results suggested that e-waste dismantling activities contributed to human exposure to OPs. In the e-waste sites, the urinary concentrations of bis(2-chloro-isopropyl) phosphate (r = 0.484, p < 0.01), BCEP (r = 0.504, p < 0.01), dibutyl phosphate (r = 0.214, p < 0.05), and DPHP (r = 0.440, p < 0.01) were significantly increased as the concentration of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of DNA oxidative stress, increased. Our results also suggested that human exposure to OPs might be correlated with DNA oxidative stress for residents in e-waste dismantling areas. To our knowledge, this study is the first to report the urinary levels of mOPs in China and examine the association between OP exposure and 8-OHdG in humans.

Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China.

Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑10OH-PAHs determined in e-waste recycling area (GM: 25.4µg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7µg/g Cre) and urban (10.9µg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6µg/g Cre) showed significantly higher (p<0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2µg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4µg/g Cre) and non-smokers (24.7µg/g Cre) were not significant (p>0.05) in e-waste dismantling sites, while these differences were significant (p<0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ10OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r=0.284, p<0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies.

Urinary Concentrations of Bisphenols and Their Association with Biomarkers of Oxidative Stress in People Living Near E-Waste Recycling Facilities in China.

In this study, concentrations of bisphenol A (BPA) and seven other bisphenols (BPs) were measured in urine samples collected from people living in and around e-waste dismantling facilities, and in matched reference population from rural and urban areas in China. BPA, bisphenol S (BPS), and bisphenol F (BPF) were frequently detected (detection frequencies: > 90%) in urine samples collected from individuals who live near e-waste facilities, with geometric mean (GM) concentrations of 2.99 (or 3.75), 0.361 (or 0.469), and 0.349 (or 0.435) ng/mL (or µg/g Cre), respectively; the other five BPs were rarely found in urine samples, regardless of the sampling location. The urinary concentrations of BPA and BPF, but not BPS, were significantly higher in individuals from e-waste recycling locations than did individuals from a rural reference location. Our findings indicated that e-waste dismantling activities contribute to human exposure to BPA and BPF. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured in urine as a marker of oxidative stress. In the e-waste dismantling location, urinary 8-OHdG was significantly and positively correlated (p < 0.001) with urinary BPA and BPS, but not BPF; a similar correlation was also observed in reference sites. These findings suggest that BPA and BPS exposures are associated with elevated oxidative stress.

[Effect of constructed wetland on the purification of industrial zone rainfall runoff contaminated with phenanthrene].

According to the water characteristics of industrial rainfall runoff in the catchment of Tongsha Reservoir, Dongguan City, a subsurface-flow constructed wetland (SSFCW) was used to treat simulated rainfall and the spatial variation of removal efficiency of contaminants in the wetland bed was analyzed. The longitudinal and vertical variation of removal efficiency of COD, NH4(+) -N, TN, TP and phenanthrene were examined. Enzyme activity of polyphenol oxidase (PPO) and nitrate reductase (NR) along the wetland bed were analyzed as well, meanwhile, four biogeochemical indexes of the wetland system, including DO, pH, ORP and water temperature, were monitored and their influences on the removal efficiency of contaminants and enzyme activity were analyzed. Results showed that DO, pH, ORP, water temperature all presented a decreasing tendency along the wetland bed, and the removal of COD, TP and phenanthrene occurred mainly in the front quarter of the wetland system; in the vertical direction, DO and ORP in the upper wetland bed were significantly higher than those in the ground floor, suggesting that the horizontal subsurface system was in an anaerobic or anoxic condition. The removal rates of COD, TP, TN, NH4(+) -N and phenanthrene were 1.17-1.36, 2.04-2.11, 1.40-1.92, 1.37-2.30, and 1.07-1.36 times higher than those at the bottom, respectively. Therefore, the vertical variation of purification efficiency was more significant than the longitudinal variation. A significant positive correlation was determined between the enzyme activity of NR and the NO3(-) -N concentration, but the longitudinal variation in the enzyme activity of NR and PPO was not obvious.

[Mechanism of reductive dechlorination of trichlorophenol with different electron donors].

A test was conducted to examine the degradation effect and reductive dechlorination pathway of 2, 4, 6-trichlorophenol (2,4,6-TCP) in the presence of different electron donors, such as glucose, sodium lactate, sodium pyruvate and sodium acetate. The results showed that, compared with the effect of glucose, sodium lactate, sodium pyruvate and sodium acetate enhanced the dechlorination of 2, 4, 6-TCP effectively, among which sodium lactate could serve as a kind of hydrogen release compound, and the electrons required for reductive dechlorination were released in a sustained way. Substrate metabolism dehydrogenase activity was improved by the external electron donor; after reaction for 240 h, the activity of dehydrogenase was increased in the four electron donor systems, by 21.49%, 25.78%, 136.85% and 139.3%, respectively. The main reductive dechlorination products of 2,4,6-TCP included 2,4-dichlorophenol (2,4-DCP), 4-chlorophenol (4-CP) and phenol; when sodium acetate was used as the electron donor, 4-CP was the main degradation product, and the transformation ratio from 2,4,6-TCP to 4-CP was more than 22%.

[Influences of pH and complexing agents on degradation of reactive brilliant blue KN-R by ferrous activated persulfate].

The influences of pH and complexing agents on degradation of reactive brilliant blue KN-R by ferrous activated persulfate were investigated, and finally the complexed and the uncomplexed system were compared. Because the lower the pH the more quickly will be the dissociation of S2O8(2-) to the SO4(-*) and the ORP of the dominant radical SO4(-*) in the acidic condition is higher than the dominant radical *OH in the alkaline condition, KN-R degradation rates in acidic condition are far outweigh in the neutral and alkaline conditions. When pH value was 3, the residual rate of KN-R was 17.0% within 3 hours by EDTA system with the lowest PS consumption rate 32.3%, so EDTA was the best complexing agent choice in acidic condition. When pH value was 7, the residual rates of KN-R were 11.3%, 12.4% within 3 days by EDTA, citric acid system with the PS residual rates 28.9%, 28.0% respectively, so EDTA, citric acid were the better choices in the neutral condition. When pH value was 10, glucose acid, citric acid, EDTA and tartaric acid systems all had the similar KN-R degradation rates and PS residual rates, so all could acted as the complexing agents, when the system contained trace amounts of ferrous, the addition of complexing agent would greatly improve the degradation rate of pollutant, from original 52.5% to 79.3% of 3 d, so PS is suitable for in situ chemical oxidation (ISCO).

[Degradation of azo dye acid orange 7(AO7) by heat, ZVI and heat/ZVI activated persulfate].

Effects of temperatures, PS concentrations and ZVI dosages on AO7 decomposition were investigated in sole heat and ZVI activating systems. The degradation results of two systems were compared for selecting a better activating way for AO7 degradation and finally the two activating ways were combined for getting the optimal AO7 degradation efficiency. The degradation of AO7 by Heat/PS systems followed pseudo first-order kinetics. The reaction rates increased with increasing reaction temperatures (elevated from room temperature to 90 degrees C) and also increased when initial PS concentrations varied from 1 to 12 mmol x L(-1). For ZVI activating systems (ZVI/PS systems), the degradation rate of AO7 was the highest when ZVI dose was 0.2 g, and it reached to 95.6% within 90 min. Comparing ZVI/PS systems with Heat/PS systems, the results showed that the ZVI activation was a more effective way to activate PS than the heat activation for AO7 degradation. AO7 degradation processes by ZVI/heat/PS systems were two-stage pseudo first-order kinetic processes, and the combining of two activating ways significantly increased the reaction rates. By the addition of ZVI to the Heat/PS system, the apparent activation energy E(a) of AO7 degradation reduced from the original 130.26 kJ x mol(-1) to 27.70 kJ x mol(-1).

The fate of di-n-butyl phthalate in a laboratory-scale anaerobic/anoxic/oxic wastewater treatment process.

A laboratory-scale anaerobic/anoxic/oxic (AAO) wastewater treatment system was employed to investigate the effects of hydraulic retention time (HRT) and sludge retention time (SRT) on the removal and fate of di-n-butyl phthalate (DnBP). HRT had no significant effect on DNBP removal between 12 and 30 h. However, longer HRT increased DnBP accumulation in the system and DnBP retention in the waste sludge. When SRT was increased from 15 to 25 d, DnBP removal efficiency stayed above 95%. Compared to the removal of only 90% at SRT of 10d, longer SRT enhanced DnBP degradation efficiency. The optimal HRT and SRT for both nutrients and DnBP removal were 18 h and 15 d. At these retention times, about 72.66% of DnBP was degraded by the activated sludge process, 2.44% was released in the effluent, 24.44% was accumulated in the system, and 0.5% remained in the waste sludge. The anaerobic, anoxic and oxic reactors were responsible for 17.14%, 15.02% and 63.46% of the overall DnBP removal, respectively. Meanwhile a removal degradation model was formulated, and kinetic parameters were evaluated with batch experiments under anaerobic, anoxic, oxic conditions. The model can well forecast the effluent quality of anaerobic/anoxic/oxic reactors of the AAO process.

A fast predicting neural fuzzy model for on-line estimation of nutrient dynamics in an anoxic/oxic process.

In this paper a software sensor based on a fuzzy neural network approach was proposed for real-time estimation of nutrient concentrations. In order to improve the network performance, fuzzy subtractive clustering was used to identify model architecture, extract and optimize fuzzy rule of the model. A split network structure was applied separately for anaerobic and aerobic conditions was employed with dynamic modeling methods such as autoregressive with exogenous inputs and multi-way principal component analysis (MPCA). The proposed methodology was applied to a bench-scale anoxic/oxic process for biological nitrogen removal. The simulative results indicate that the learning ability and generalization of the model performed well and also worked well for normal batch operations corresponding to three data points inside the confidence limit determined by MPCA. Real-time estimation of NO(3)(-), NH(4)(+) and PO(4)(3-) concentration based on fuzzy neural network analysis were successfully carried out with the simple on-line information regarding the anoxic/oxic system.

Improved vitamin B(12) production by step-wise reduction of oxygen uptake rate under dissolved oxygen limiting level during fermentation process.

Effects of different oxygen transfer rates (OTR) on the cell growth and vitamin B(12) biosynthesis of Pseudomonas denitrificans were first investigated under dissolved oxygen limiting conditions. The results demonstrated that high OTR accelerated cell growth and initial vitamin B(12) biosynthesis rate, while lower OTR was critical for higher productivity in the late fermentation process. The oxygen uptake rates (OUR) corresponded well with OTR. Based on the metabolic intermediate analysis, a step-wise OUR control strategy was proposed. The strategy was successfully implemented in scale-up to an industrial fermenter (120,000 l). A stable maximum vitamin B(12) production of 208 + or - 2.5 mg/l was achieved, which was increased by 17.3% compared with the control. Furthermore, the glucose consumption coefficient to vitamin B(12) was 34.4% lower than that of the control. An efficient and economical fermentation process based on OUR criterion was established for industrial vitamin B(12) fermentation by P. denitrificans.

Synthesis and herbicidal activity of isoindoline-1,3-dione substituted benzoxazinone derivatives containing a carboxylic ester group.

A carboxylic ester group was introduced to three series of isoindolinedione substituted benzoxazinone derivatives. Some of these analogues exhibited good herbicidal activities, and the injury symptoms against weeds included leaf cupping, crinkling, bronzing, and necrosis, typical of protox inhibitor herbicides. Structurally, they were classified as Chemical Group A (4-carboxylic ester group-6-isoindolinyl-benzoxazinones), B (4-carboxylic ester group-7-isoindolinyl-benzoxazinones), and C (4-carboxylic ester group-6- tetrahydroisoindolinyl-benzoxazinones). All of the tested compounds were structurally confirmed by (1)H NMR, IR, mass spectroscopy, and elemental analysis. Preliminary bioassay data of these three classes of compounds showed that, in general, the order of the herbicidal effectiveness is C > A > B. Several of the lead compounds, for example, C10 (methyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2-methyl-3-oxo-2H-benzo[b][1,4] oxazin-4(3H)-yl) propano-ate), C12 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2- methyl-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl) propanoate), and C13 (ethyl 2-(6-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-7-fluoro-2-methyl-3-oxo-2H-benzo-[b][1,4]oxazin-4(3H)-yl) butanoate), exhibited greater than 80% control at 75 g a.i./ha in both pre- and postemergence treatments against dicotyledonous weeds, such as Abutilon theophrasti Medic, Chenopodium album L., and Amaranthus ascendens L., and monocotyledon weeds, such as Digitaria sanguinalis L., Echinochloa crus-galli L., and Setaria viridis L. On the basis of advanced screening tests and crop selectivity, compounds C10, C12, and C13 are safer to crops than flumioxazin. Compounds C10, C12, and C13 are potent to develop as pre-emergent herbicides used in peanut, soybean, maize, and cotton fields.

Bioactive conformation analysis of cyclic imides as protoporphyrinogen oxidase inhibitor by combining DFT calculations, QSAR and molecular dynamic simulations.

Bioactive conformation of drugs is one of the key points for understanding the ligand-receptor interactions. In the present study, by combining density functional theory-based (DFT-based) conformation analysis with quantitative structure-activity relationship analysis (QSAR), we developed successfully a new approach (DFT/QSAR) to carry out bioactive conformation analyses for a series of 25 cyclic imide derivatives as protoporphyrinogen oxidase (PPO) inhibitors. Further potential energy surface scan, molecular docking and molecular dynamic simulation calculations validated that the DFT/QSAR-derived conformation is indeed very similar to the 'real' bioactive conformation. We believe the DFT/QSAR approach provides a simple alternative for the bioactive conformation of small molecules, especially in the case that the three-dimensional structure of protein is unknown.

3-tert-Butyl-4-oxo-3,4-dihydro-phthalazin-1-yl 3,5-dimethyl-benzoate.

The title compound, C(21)H(22)N(2)O(3), was synthesized by the reaction of tert-butyl-hydrazine with phthalic anhydride and further O-benzoyl-ation of the resulting inter-mediate by 3,5-dimethyl-benzoyl chloride. Inter-molecular C-H⋯O=C inter-actions link the mol-ecules into layers.

Synthesis and herbicidal activity of 2-(7-fluoro-3-oxo- 3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)isoindoline-1,3-diones.

The mode of action of 2-(7-fluoro-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-4,5,6,7-tetrahydro-2H-isoindoline-1,3-diones, including the commercial herbicide flumioxazin, had been identified as inhibition of protoporphyrinogen oxidase (protox). As part of continuous efforts to search for new herbicides with high efficacy, broad-spectrum activity, and safety to crops, flumioxazin and its iodo analogue (B2055) were used as lead compounds for further optimization. Series of novel compounds were prepared by multistep synthetic procedures starting from 5-fluoro-2-nitrophenol. All of the test compounds were structurally confirmed by 1H NMR, IR, mass spectroscopy, and elemental analysis. Preliminary bioassay data showed that some of them possess commercial levels of herbicidal activity comparable to those of other protox-inhibiting herbicides. One of the best compounds, 5-fluoro-2-(7-fluoro-3-oxo-4-(prop-2-ynyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)isoindoline-1,3-dione (8e), has IC50 values for velvetleaf (Abutilon theophrasti Medic) and crabgrass (Digitaria sanguinalis) comparable to thos of B2055. With respect to crop selectivity, compound 8e is similar to flumioxazin. Compound 8e is safe to cotton and maize at a rate of 150 g of active ingredient (ai)/ha or less when applied at pre-emergent stage, and it has the best safety to wheat among the tested crops, showing no injury after post-emergent application at 7.5-30 g of ai/ha.

[Synthesis and spectral characterization of 10-hydroxycamptothecin].

10-hydroxycamptothecin was synthesized from camptothecin through oxidation and photo-activation. Grouping and optimizing the reaction conditions were as follows: in the oxidation condition: the reaction time 4 h, the reaction temperature 75 degrees C, the amount of H2O2 48 mL(w(H2O2) = 30%), the amount of HAc 350 mL(based on 0.01 mol CPT); in the photochemical reaction: the solvents V(1,4-dioxane): V(acetonitrile): V(H2O) = 6:2:1, bronsted acid catalyst 98% H2SO4. Purified by silica gel column, the total yield of HCPT is 49.9%, with 99.5% purity, m.p. 272-273 degrees C. The molecular structure of the title compound has been characterized by elemental analysis (EA), mass spectroscopy (MS), infrared spectrscopy(IR), and ID and 2D nuclear magnetic resonance spectrometry (NMR), and the main infrared absorption peaks and nuclear magnetic spectral bands of this conpound were assigned. The mass spectral fragmentations of the product's important fragment ions were elucidated. The result provides useful information for preparing the new derivatives of camptothecin.