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An alternative method for the synthesis of brevetoxin B uses the heptacyclic phosphonium iodide and the tricyclic aldehyde as the basic materials for the brevetoxin B framework. The production of the tricyclic lactone and the dioxepane region of the molecule are carried out by Yamaguchi lactonization. Murai coupling which involves the addition of a higher order organocuprate to the lactone-derived enol triflate attaches the essential appendage on ring E. Fetizon cyclization produces the pentacyclic lactone while Cr/Ni coupling reaction produces allylic alcohol as a precursor to the pentacyclic lactol.

The purpose of this study is to investigate hydrometeorology changing patterns impacts on erosive landforms evolution in Loess Plateau in the past 60 years (1950–2010). We firstly describe hydrometeorology changing patterns (rainfall-runoff-soil erosion response) at different time scales (daily, monthly, and yearly) in perspective of river basins and then further investigate hydrometeorology impacts on erosive landform through combined analysis of statistical quantification and proposed conceptual model of rainfall-runoff-soil erosion landform. Through the above investigations, the following findings are achieved. Firstly, it shows that annual runoff and sediment discharges decreased obviously although precipitation remained at the same level in the past 50 years (1960–2010). Discharges of annual runoff and sediment decreased by 30%–80% and 60%–90%, respectively. Secondly, contributors of soil erosion are determined by integrated factors such as precipitation, river network, and topography characteristics of river basins. The strong soil erosion area existed in the middle hilly-gully region, while the high precipitation was in southern mountains. Thirdly, erosion landform development was largely shaped by hydrometeorology characteristics in comparison with other contributors. It shows that there is strong positive relationship between precipitation and erosion. [ABSTRACT FROM AUTHOR]

The Asian corn borer, Ostrinia furnacalis enters diapause as fully grown larvae. Owing to geographical variation in photoperiodic control of diapause, the subtropical strain from Hefei city (HF) enters diapause in response to short daylengths, whereas the tropical strain from Ledong county (LD) exhibits almost no diapause under the same conditions. The two strains were used in crosses to study the inheritance of diapause. The HF strain showed a typical long-day response with a critical daylength of approximately 14.97 h at 22 °C, 14.60 h at 25 °C and 13.68 h at 28 °C. The LD strain showed weak photoperiodic responses at 22 and 25 °C; and the F1 progeny also showed a long-day response with significantly shorter critical daylength compared with the HF strain. However, the LD × HF (F × M) crosses had significantly longer critical daylengths than HF × LD crosses, indicating a sexual bias in the inheritance of diapause induction, with the male parent having more influence on the F1 progeny. The critical daylength in a backcross to HF was significantly longer than a backcross to LD. Whether the inheritance of diapause fits an additive hypothesis or not depended on photoperiod, with results from different photoperiods showing additive inheritance or incomplete dominance of either diapause or non-diapause. Unlike diapause induction, the duration of diapause for reciprocal crosses was equally influenced by each parent, suggesting that diapause incidence and maintenance are controlled by separate systems in O. furnacalis.

As a consequence of geographical variation in diapause mechanism in the cabbage beetle, Colaphellus bowringi, the southern strains enter diapause as an adult in response to long photoperiod, whereas the northern strains enter diapause in response to temperature. In the present study, we examined the inheritance of diapause by crossing a southern Xiushui strain (XS) with a most-northern Harbin strain (HB). The southern XS strain showed a clear short-day response for the induction of diapause, whereas the most-northern strain entered diapause regardless of photoperiod. Interestingly, the XS×HB progeny showed a short-day response, but the HB×XS progeny had no photoperiodic response, indicating that photoperiodic induction of diapause is influenced by maternal genotype. The incidence of diapause of F1 progeny was intermediate between their parents under short daylengths of 12 and 13 h. However, there was a sexual asymmetry, with the female parent exerting a greater effect on diapause incidence than the male parent, indicating a sex linkage in the inheritance of diapause induction. The χ2 test in C. bowringi revealed that the inheritance of diapause does not fit an additive hypothesis and also that the capacity for diapause is transmitted genetically (or possibly epigenetically) in a manner of incomplete dominance. These results suggest that a number of genetic factors are associated with differences in diapause capability in this beetle.

Under field conditions, the cabbage butterfly, Pieris melete, displays a pupal summer diapause in response to relatively low daily temperatures and gradually increasing day-length during spring and a pupal winter diapause in response to the progressively shorter day-length. To determine whether photoperiod is 'more' important than temperature in the determination of summer and winter diapause, or vice versa, the effects of naturally changing day-length and temperature on the initiation of summer and winter diapause were systematically investigated under field conditions for five successive years. Field results showed that the incidence of summer diapause significantly declined with the naturally increasing temperature in spring and summer generations. Path coefficient analysis showed that the effect of temperature was much greater than photoperiod in the determination of summer diapause. In autumn, the incidence of diapause was extremely low when larvae developed under gradually shortening day-length and high temperatures. The incidence of winter diapause increased to 60-90% or higher with gradually shortening day-length combined with temperatures between 20.0°C and 22.0°C. Decreasing day-length played a more important role in the determination of winter diapause induction than temperature. The eco-adaptive significance of changing day-length and temperature in the determination of summer and winter diapause was discussed.

The objective of this study was to describe trends in the incidence rates of primary lung cancer in a geographically defined Chinese population. Primary lung cancer cases (N=40,022) diagnosed between 1981 and 2000 were identified by the Tianjin Cancer Registry. Age-specific and age-adjusted incidence rates to the world standard population were examined in both males and females. Age-period-cohort (APC) model and Poisson regression were used to assess the cohort effects and incidence trends. Crude and age-adjusted incidence rates in the study period were: 66.2/100,000 and 45.2/100,000 in males; and 47.7/100,000 and 28.2/100,000 in females, respectively. The major birth cohort effect can be described as for those born before 1940, in every age group lung cancer incidence rate increased as the birth years advanced. For those born after 1940, age specific incidence rates decreased as the birth years advanced. Results from the Poisson regression analyses suggested a statistically significant increasing trend of incidence rates of lung cancer from 1981 to 1990 and changed little afterwards. Through first 10 years of the study period between 1981 and 2000, lung cancer incidence rates increased in both males and females. While the study results suggest that the age-adjusted incidence rates may have reached their peak and may even decline, as the Chinese population ages, and smoking prevalence remains high, the number of new lung cancer cases will continue to increase and overall burden of lung cancer will remain high.

Radioligand binding techniques were employed to determine the modulation by nucleotides of the specific [3H]glibenclamide (Gli) binding to rat aortic and cardiac ventricular preparations. Saturation analysis revealed a single binding site with K(D) value of 31.3 nM and Bmax of 180 fmol/mg wet weight in aortic preparations. We also observed that [3H]Gli bound reversibly and specifically to cardiac membranes. Unlabeled glibenclamide displaced [3H]Gli-specific binding of cardiac membranes completely with K(I) of 54.4 nM. In cardiac membranes, adenosine triphosphate (ATP), adenosine diphosphate (ADP), and uridine diphosphate (UDP) (from 0.01-5 mM) concentration dependently inhibited [3H]Gli binding independent of Mg2+. The values of K(I) were 0.47, 0.22, and 0.58 mM, respectively. However, in aortic preparations, [3H]Gli-specific binding was increased by ATP of 5 and 10 mM and showed a biphasic response to ADP. At concentrations to 1 mM, ADP inhibited binding; above 5 mM, the specific [3H]Gli binding was increased. UDP did not alter the binding up to 5 mM. In the presence of Mg2+ (20 mM), the inhibitory effects of ATP (0.01-1 mM) or ADP (0.01-5 mM) on the binding in cardiac membranes were abolished, whereas the facilitatory effects of ATP or ADP in aortic preparations were strengthened. Analysis of kinetics showed that the time of [3H]Gli association and dissociation in cardiac and aortic preparations was monophasic. The association was delayed with dissociation unchanged by ATP, ADP, and UDP of 1 mM, respectively, in cardiac membranes. In aorta, however, at the same concentration ATP accelerated association and retarded dissociation and vice versa for ADP. Association and dissociation were not changed by UDP of 5 mM. We conclude that ATP, ADP, and UDP are all major allosteric modulators of K(ATP) channels and they affect the antagonist binding to heart (sulfonylurea receptor 2A) and aorta (sulfonylurea receptor 2B) differently.

Aim: To study the relationship between adenosine (Ade) receptors and adenosine 5'-triphosphate (ATP)-sensitive potassium (KATP) channels in rat aorta., Methods: Isolated rat aorta rings were suspended for isometric force recording. The vascular effects of Ade were assessed in the presence or absence of functional endothelium. The interactions of Ade and pinacidil (Pin) or glibenclamide (Gli) were investigated., Results: In isolated aorta preconstricted with KCl 20 mmol.L-1, Ade 3-300 mumol.L-1 induced relaxation in a concentration-dependent manner; and in 48/99 preparations from 32 rats, Ade induced initial transient constriction followed by sustained relaxation. When the functions of KATP channels were blocked with Gli 1 or 100 mumol.L-1, effects of Ade were characterized by vasoconstriction rather than vasorelaxation. The combination of Pin 1 mumol.L-1 with Ade 100 mumol.L-1 showed no synergic vasodilatory effects and did not affect Ade-induced vasoconstriction. After the removal of endothelium, Ade still induced vasoconstriction and vasorelaxation, and the constrictive effects showed no difference from those in the presence of endothelium, but the potency of vasodilatory effects became weaker with slower decrease in tension., Conclusion: The activation of KATP channels is involved in Ade receptor-induced vasodilation.

Aim: To study the role of clonidine (Clo) on the myocardial beta-adrenergic receptor (beta-AR)-adenyl cyclase (AC)-cAMP system after the scalds in rats., Methods: A 30% skin-full-thickness scald was produced by immersing rats in 95 degrees C water for 9 s. Clo 0.1-3.0 mg.kg-1 was injected i.p. to rats at 30 min before scalds, yohimbine (Yoh) 0.05 mg.kg-1 or prazosin (Pra) 0.03 mg.kg-1 to rats at 30 min before i.p. Clo. beta-AR density and affinity, AC activity, phosphoric diester hydrolases (PDH) activity, and cAMP content were determined with radioreceptor assay, indirect method, enzymeradiochemical assay, and radioimmunoassay, respectively., Results: Clo inhibited the decrease of the myocardial beta-AR density, the attenuation of AC activity, and the reduction of cAMP content at 12 h after the scalds. Yoh partially reversed the effects of Clo on the three parameters. But Pra did not., Conclusion: Clo reversed the changes of the myocardial beta-AR-AC-cAMP system resulted from the scalds in rats.

In order to define the structural parameters associated with the antitubulin activity and cytotoxicity of 2-methoxyestradiol, a mammalian metabolite of estradiol, an array of analogs was synthesized and evaluated. The potencies of the new congeners as inhibitors of tubulin polymerization and colchicine binding were determined using tubulin purified from bovine brain, and the cytotoxicities of the new compounds were studied in a variety of cancer cell cultures. Maximum antitubulin activity was observed in estradiols having unbranched chain substituents at the 2-position with three non-hydrogen atoms. 2-Ethoxyestradiol and 2-((E)-1-propenyl)-estradiol were substantially more potent than 2-methoxyestradiol itself. The tubulin polymerization inhibitors in this series displayed significantly higher cytotoxicities in the MDA-MB-435 breast cancer cell line than in the other cell lines studied. The potencies of the analogs as cytotoxic and antimitotic agents in cancer cell cultures correlated with their potencies as inhibitors of tubulin polymerization, supporting the hypothesis that inhibition of tubulin polymerization is the mechanism of the cytotoxic action of 2-methoxyestradiol and its congeners. Several of the more potent analogs were tested in an estrogen receptor binding assay, and their affinities relative to estradiol were found to be very low.

A model of pleurisy was established with an intrapleural injection of carrageenan (Car, 10 mg.kg-1) in rats to explore the anti-inflammatory action of tetrandrine (Tet) and its mechanism. After the injection of Car, the exudate, protein and neutrophils appeared in the pleural cavity of rats at 2 h, then increased progressively, and reached a peak level at 12 h and remained high up to 48 h. The phospholipase A2(PLA2) activity of neutrophils (Neu-PLA2) and of the acellular component (ACC-PLA2) in the pleural exudate intensified at 2 h, rose to maximal intensity at 8 h, and started to decline at 48 h. The changes of the amount of exudate, protein content and neutrophil count, and parameters indicating the inflammatory response, were closely related to that of the PLA2 activity (r = 0.749-0.928, P < 0.05 or 0.01). By ig gavage of Tet (10-80 mg.kg-1) to rats at 30 min before and 4 h after the injection of Car, the inflammatory parameters were reduced and the PLA2 activity was inhibited, dose-dependently. The reductions of the inflammatory parameters were significantly associated with the inhibition of the PLA2 activity (r = 0.928-0.993, P < 0.05 or 0.01). These results indicate that Tet has a fine anti-inflammatory action and its mechanism may involve the inhibition on the activation and release of PLA2 of inflammatory cells.

Although certain substituted cis-stilbenes have displayed potent tubulin polymerization inhibitory activity and significant cytotoxicities in cancer cell cultures, these compounds have limited aqueous solubility and are therefore difficult to formulate for in vivo evaluation. A series of water-soluble N-(3,4,5-trimethoxybenzyl)aniline salts has therefore been synthesized in which the olefinic bridge of the stilbenes is replaced by an aminomethylene hydrochloride moiety. A relationship was found between the size of the substituent in the 4-position of the aniline ring and both antitubulin activity and cytotoxicity, such that the smaller the substituent, the greater the potency. The most promising of the newly synthesized compounds was 4-methyl-N-(3,4,5-trimethoxybenzyl)aniline hydrochloride, with an IC50 value of 3.5 microM for inhibition of tubulin polymerization and cytotoxicity for a wide variety of cancer cell lines. The cytotoxicities of the benzylaniline hydrochlorides correlated remarkably well with their antitubulin activities.

A series of stilbenes has been prepared and tested for cytotoxicity in the five human cancer cell lines A-549 non-small cell lung, MCF-7 breast, HT-29 colon, SKMEL-5 melanoma, and MLM melanoma. The cis stilbenes 6a-f proved to be cytotoxic in all five cell lines, with potencies comparable to that of combretastatin A-4. These cytotoxic compounds were all potent inhibitors of tubulin polymerization. The corresponding trans stilbenes 7b-f were inactive as tubulin polymerization inhibitors and were significantly less cytotoxic in the five cancer cell lines. In the dihydro series, 8b, 8c, and 8f were inactive as tubulin polymerization inhibitors, while 8a, 8d, and 8e were less active than the corresponding cis compounds 6a, 6d, and 6e. The lack of tubulin polymerization inhibitory activity and cytotoxicity displayed by the phenanthrene 23b, which was synthesized as a conformationally rigid analogue of the lead compound 1, indicates that the activity of the stilbenes is not due to a totally planar conformation. Similarly, inactivity of the conformationally restricted analogue 26 suggests that the biologically active conformation of 1a resembles that of the cis alkene 1. Additional inactive compounds prepared include the benzylisoquinoline series 28-32 as well as the protoberberines 38 and 39. Shortening the two-carbon bridge of 1a to a one-carbon bridge in the diphenylmethane 20 resulted in a decrease in cytotoxicity and tubulin polymerization inhibitory activity. Although the corresponding benzophenone 18 was as active as 1a as a tubulin polymerization inhibitor, it was less cytotoxic than 1a, and the benzhydrol 19 was essentially inactive. With the exception of the amide 15c, which displayed low antitubulin activity, all of the phenylcinnamic acid derivatives 14a-c and 15a-f were inactive in the tubulin polymerization inhibition assay. The acid 14b and the ester 15a were cytotoxic in several of the cancer cell cultures in spite of their inactivity as tubulin polymerization inhibitors.

The C2 deoxy and C6 electron isosteric analogs of a new antiglaucoma agent, erycibe alkaloid II, were designed and synthesized. The main pharmacological results were as follows: 1. The C2-OH in erycibe alkaloid II was one of the key groups for its myotic activity; 2. It was worth noting that compounds 2 and 4 showed cholinergic and anticholinergic activities, respectively. This phenomenon in tropane alkaloids was not reported before; 3. The C6 electron isosteric compounds 16 and 17 showed neither anticholinergic nor cholinergic activities.

Lycobetaine (AT-1840), developed by our institute, is a new chemotherapeutic agent with relatively high percentage of remission on the treatment of ovary cancer and stomach cancer; no remarkable changes in blood picture, EKG and GPT, were observed. Early examination of the structure activity relationship of lycobetaine gave the following results: 1. A potential betaine and a methylenedioxy group in this compound may be critical for exhibiting antitumor activity; 2. Fission of the five membered ring of lycobetaine will not affect its antitumor activity. In order to see whether the distance between the phenolic oxygen and quaternary nitrogen affects its antitumor activity, compounds 7a-c, 8a-b were synthesized and screened against tumor in mice bearing EAC Preliminary experimental results showed that among the open ring analogs of lycobetaine, 7a, 7b and 8d possessed marked antitumor activity and 7c did not. The results indicate that changes in the distance of the betaine in lycobetaine obviously influence its antitumor activity.