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Abstract: The stable structures of (AgBr) n (n ⩽6) are optimized by using density functional method, and the basis set effect is also investigated. Our initial structures are the stable structures of (AgX) n (X=Cl, Br, I, n ⩽6) obtained from the results of genetic algorithm. It is found that the most stable structures of (AgBr) n are planar rings for n ⩽4 and three-dimensional structures for n >4, with (AgBr)3 the most stable one. For the ground state structures of (AgBr) n , the chemical bonds are studied and electronic structures also explored. [ABSTRACT FROM AUTHOR]

During the study of anti-HIV-1 active components of the aqueous extracts of the roots of Salvia yunnanensis, three new derivatives of polyphenols, namely: methyl salvianolate A (2), ethyl salvianolate A (3) and cis-lithospermic acid (5) were isolated along with two known polyphenols, salvianolic acid A (1) and lithospermic acid (4) their structures were elucidated on the basis of NMR and MS spectral analyses. The anti-HIV-1 activities of the 5 polyphenols were tested for the inhibition of P24 antigen in HIV-1 infected MT-4 cell cultures and HIV-1 replicative enzymes in vitro. [ABSTRACT FROM AUTHOR]

A new polyphenol, designated as salvianolic acid N, was isolated from the aqueous extracts of the roots of Salvia yunnanensis. Its chemical structure was elucidated as 3-(3,4-dihydroxylphenyl)-2-{(E)-3-(1,8,9-trihydroxyl-dibenzo[b,f]oxpin-3-yl)acryloxloxy}propanoic acid (1) on the basis of NMR and MS spectral analyses. The new polyphenol inhibited both HIV-1 IN in vitro and also reduced HIV-1 p24 antigen in MT-4 cell lines. [ABSTRACT FROM AUTHOR]

Abstract: Genetic algorithm was combined with the semi-empirical quantum chemical PM3 method (GA+PM3) to scan the potential energy surface of cluster. The resulting isomers found by the GA+PM3 approach were then further optimized at the first principle level using Density Functional Theory (DFT) to obtain the optimal geometry and electronic structure for each cluster. This methodology was applied to investigate Si6N8 clusters. The electric charges and bond properties, along with the IR and Raman frequencies, polarizabilities and hyperpolarizabilities, of Si6N8 clusters were analyzed in detail. [Copyright &y& Elsevier]

A 32-bp deletion on the CCR5 gene (ccr5Δ32) confers resistance to HIV-1 infection. This deletion is common in Caucasians, but rare in Asians. Since the frequency of the ccr5Δ32 allele of Chinese in mainland China has been unknown we investigated the ccr5Δ32 mutation in a cohort of 407 Chinese people in this area. A 225-bp fragment of CCR5 encompassing the 32-bp region was analysed by PCR, hybridization and sequencing. Only 1 out of 407 subjects was heterozygous for ccr5Δ32 and no homozygotes were detected. The frequency of ccr5Δ32 in this cohort is thus 0.00123, i.e. much lower than that of Caucasians. The ccr5Δ32 heterozygote is a healthy young man. To our knowledge this is the first ccr5Δ32 mutant found in Chinese people. The results indicate that ccr5Δ32 does exist in Chinese people, but at very low frequency. This suggests that ccr5Δ32 is not a significant factor for the genetic resistance to HIV-1 in Chinese people. [ABSTRACT FROM AUTHOR]

The morphology of donor‐acceptor heterojunction interface significantly affects the electron/hole processes in organic solar cells, including charge transfer (CT), exciton dissociation (ED), and charge recombination (CR). Here, to investigate interface molecular configuration effects, the donor‐acceptor complexes with face‐on, edge‐on, and end‐on configurations were constructed as model systems for the p‐SIDT(FBTTh2)2/C60 heterojunction. The geometries, electronic structures, and excitation properties of monomers and the complexes with three configurations were studied based on density functional theory (DFT) and time‐dependent DFT calculations with optimally tuned range separation parameters and solid polarization effects. In terms of Marcus theory, the rate constants of ED and CR processes were analyzed. The results show that most of the excited states for p‐SIDT(FBTTh2)2 exhibit an intramolecular CT character, and the similarity of the excitation characters (CT and local excitation) and energies among three complexes with different configurations indicate that the electronic structure and excitation properties are insensitive to the interfacial molecular configurations. However, the rates of ED and CR processes heavily depend on it. These results underline the importance of controlling molecular configuration and then the morphology at the heterojunction interface in organic solar cells. [ABSTRACT FROM AUTHOR]

With the development of wireless communication technology and computer technology, more and more smart technologies have been applied in electricity distribution networks. This paper presents an adaptive current differential protection and fast auto-closing system for application in 10 kV distribution networks in China Southern Power Grid. The current differential protection can adaptively change its settings according to the topology change of the primary distribution networks, thus the system effectively reduces the operation and maintenance cost of the power distribution network. In order to restore the power supply for the healthy part of the 10 kV networks quickly after a power system fault is cleared, the protection and control system provides wide area control function for automatic fault isolation and automatic switching. The traditional overcurrent protection and control system have no fault location function, it may take several minutes or even hours to manually locate a fault and then restore the power supply. Compared with the protection and control system of the traditional 10 kV distribution networks, the system developed can locate and isolate faults within 900 ms (assuming that the operating time of the load switch is 700 ms), and can quickly restore power supply in less than one second after a power system fault is cleared. [ABSTRACT FROM AUTHOR]

The optoelectronic properties of formamidinium CH(NH2)2+ (FA) doped double perovskite Cs2AgBiBr6 with corresponding formula Cs1.875FA0.125AgBiBr6 were investigated based on electronic structures and supercell models. The dopant formation energies, tolerance and octahedral factors support the doped structures are stable. FA dopant increases band gap about 0.15 eV without introducing dopant states in gap, but also increases the reduced effective masses, exciton binding energies, and elastic constants. However, it decreases exciton energies and charge carrier mobilities. Though the energy barriers among the different FA orientations in Cs1.875FA0.125AgBiBr6 are quite small (<30 meV), FA orientations in doped systems can remarkably impact on electron and hole mobilities. [ABSTRACT FROM AUTHOR]

The cross combination of dry-method(network pharmacology analysis) and wet-method(high-resolution mass spectro-metry with antioxidation experiment) was used to predict antioxidant quality markers(Q-markers) of Hippophae tibetana. Ultra-high performance liquid chromatography coupled with hybrid quadrupole-orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) was developed to rapidly separate and identify the chemical constituents in H. tibetana. Then in DPPH free radicals and superoxide anion scavenging experiment, the antioxidant activity of the four different polar parts with extracts of petroleumether, ethyl acetate, n-butanol and water was evaluated. Network pharmacology method was used for functional enrichment and pathway analysis to screen antioxidant-related components and preliminarily explain the mechanism of action. On this basis, multi-source information was integrated to predict the antioxidant Q-markers. The results showed that 51 components in H. tibetana were identified, including 18 flavonoids, 14 terpenoids, 6 alkaloids, 4 coumarins and phenylpropanoids, 3 volatile components and 2 polyphenols. The antioxidant capacity of different fractions: ethyl acetate &gt; n-butanol &gt; water &gt; petroleum ether. The medicine mainly acted on PI3 K-Akt and FoxO signaling pathways to perform antioxidant effects through flavonoids such as quercetin, luteolin and kaempferol. According to the results of dry-method and wet-method, quercetin, luteolin and kaempferol, the representatives of poly-hydroxy flavone, may be the antioxidant Q-markers of H. tibetana. In this study, with the antioxidant Q-markers of H. tibetana as an example, an investigation model of predicting Q-marker was discussed based on the ternary system of composition, function and informatics, providing a scientific basis for the establishment of quality evaluation standards for H. tibetana.

Molecular engineering is significantly important for developing electron donor and acceptor materials of active layers in organic photovoltaics (OPVs). The OPVs based on halogenated donors frequently produced high power conversion efficiencies. Here, based upon density functional theory calculations with optimally tuned range separation parameters and solid polarization effects, we studied the effects of donor halogenation on molecular geometries, electronic structures, excitation, and spectroscopic properties for F n ZnPc ( n = 0, 4, 8, 16) and Cl n SubPc ( n = 0, 6) monomers and the complexes with C 60 as well as the photoinduced direct charge transfer (CT), exciton dissociation (ED), and charge recombination (CR) processes that were described by rate constants calculated using Marcus theory. The tiny differences of the molecular orbital energy gap, excitation, and spectroscopic properties of F n ZnPc ( n = 0, 4, 8, 16) and Cl n SubPc ( n = 0, 6) monomers suggest that halogenation cannot effectively tune the electronic and optical gap but the significant decrease of molecular orbital energies support the idea that halogenation has a remarkable influence on the energy level alignment at heterojunction interfaces. The halogenation also enhances intermolecular binding energies between C 60 and donors and increases the CT excitation energies of donor/C 60 complexes, which are favorable for improving open circuit voltage. Furthermore, for F n ZnPc/C 60 ( n = 0, 4, 8, 16) and SubPc/C 60 ( n = 0, 6) complexes, the CR rates dramatically decrease (several orders) with increasing number of halogen atoms (except for F 16 ZnPc/C 60 ), meaning suppression of CR processes by halogenation. As for the special case of F 16 ZnPc/C 60 , it underlines the importance of fluorination degree in molecular design of donor materials. This study provides a theoretical understanding of the halogenation effects of donors in OPVs and may be helpful in molecular design for electron donor materials.

Objective: To evaluate the effect of combined use of stanazolol (ST) on the final adult height (FAH) in girls with idiopathic central precocious puberty (ICPP) and apparently decreased linear growth during gonadotropin-releasing hormone analog (GnRHa) therapy., Method: Sixty-three girls with ICPP and decreased velocity of growth of height (HV<4 cm/yr) during GnRHa therapy were divided into 3 groups based on the following types of interventions:group 1 (n = 20), GnRHa+ST [25-30 µg/(kg·d) every 3-month followed by 3-month discontinuation], group 2 (n = 21), GnRHa+recombinant human growth hormone [rhGH, 1-1.1 U/(kg·w)], group 3 (n = 22), GnRHa alone.HV, the advancement of bone age (BA) for chronological age (CA) (ΔBA/ΔCA) and FAH were compared among groups., Result: (1)Total duration of ST combination therapy was (12.22 ± 3.62) months, while total duration of combination of rhGH was (13.22 ± 6.80) months. (2)HV increased significantly in both group 1 [ (2.79 ± 0.60) cm/yr vs. (6.27 ± 1.98) cm/yr, P < 0.01] and in group 2 [(2.80 ± 0.50) cm/yr vs. (6.25 ± 1.98) cm/yr, P < 0.01] during combined therapy, but maintained at low levels in group 3 [(3.95 ± 1.10) cm/yr vs. (3.34 ± 0.95) cm/yr, P > 0.05].No significant differences of ΔBA/ΔCA were found among the three groups [0.25(0.11∼0.28), 0.22(0.15∼0.31),0.19(0.10∼0.32), P > 0.05]. (3)FAH was significantly higher than predicted adult height (PAH) before combined therapy, as well as higher than target height (THt) in both group 1 [(156.25 ± 2.90) cm vs. (150.78 ± 3.70) cm, P < 0.01, (156.25 ± 2.90) cm vs. (153.94 ± 2.62) cm, P < 0.01], and in group2 [ (157.33 ± 4.69) cm vs. (152.61 ± 3.92) cm, P < 0.01, (157.33 ± 4.69) cm vs. (154.39 ± 4.72) cm, P = 0.01].In group 3, FAH was similar to PAH [(153.88 ± 2.6) cm vs. (152.54 ± 5.86) cm, P > 0.05], and was less than THt [(153.88 ± 2.6) cm vs. (155.60 ± 4.52) cm, P = 0.02]. (4)In girls treated with ST, no hirsutism, clitorism or hoarse voice was recorded.No polycystic ovary syndrome was found by B-mode ultrasound., Conclusion: Intermittent combined use of low dose ST therapy can increase HV and thus improve FAH in girls with ICPP and apparently decreased linear growth during GnRHa therapy.

Objective: To assess the utility of serum steroids measurement in monitoring the treatment of children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD)., Method: Nineteen Patients with CAH 21OHD aged (3.67±1.54) years treated with hydrocortisone and fluorocortisone replacement were followed up at an intervals of 0.33 - 1.0 years over a period of (1.47±0.7) years. At each visit, roentgenograms of the hands and wrists were taken, fasting peripheral blood were collected to test serum dehydroepiandrosterone sulfate, progesterone, 17-hydroxyprogesterone (17-OHP), androstenedione (Δ4-A), testosterone, free testosterone, estrone, and estradiol concentrations at 8 AM in the morning before the first dose of glucocorticoid. Then the patients were classified as being in "Good Control" or in "Poor Control" based on clinical criteria including signs of androgen excess, growth velocity and bone age increment at each interval. Comparisons were carried out between the serum steroid concentrations of the two groups. The receiver operating characteristic (ROC) curves were used to determine the cut-off values for diagnosing "Poor Control"., Result: Both of serum Δ4-A and 17-OHP concentrations were higher in "Poor Control" group than those in "Good Control" group [5.95 (2.23-11.2) nmol/L versus 1.05 (1.05-9.89) nmol/L, t=2.19; 13.85 (6.06-20) µg/L versus 3.67 (0.42-21.1) µg/L, t=2.17; P<0.05, respectively]. The ROC curves for serum Δ4-A concentrations, serum 17-OHP concentrations, serum Δ4-A in combination with 17-OHP concentrations were constructed with areas under the ROC curves (95%CI) of 0.76 (0.62, 0.90), 0.75 (0.62, 0.88), 0.69 (0.54, 0.84), P<0.05, respectively. Serum Δ4-A of 3.9 nmol/L had 0.78 of sensitivity and 0.75 of specificity in diagnosing "Poor Control". Serum 17-OHP of 7.1 µg/L has 0.67 of sensitivity and 0.71 of specificity in diagnosing "Poor Control"., Conclusion: Each of serum 17-OHP or/and Δ4-A concentration was of significance in diagnosing "Poor Control" during the glucocorticoid replacement treatment of CAH 21OHD, with the diagnostic efficacy being serum Δ4-A concentration, serum 17-OHP concentration and serum Δ4-A in combination with 17-OHP concentration in descending order. Serum Δ4-A and 17-OHP concentrations may be used as the biochemical indicators to monitor the therapy of CAH 21OHD.

Objective: To study the clinical manifestations of germinoma in children with precocious puberty and to evaluate the diagnostic value of serum levels of β-human chorionic gonadotropin (β-hcG) combined with detections of β-hcG in cerebrospinal fluid (CSF)., Method: Twelve male children with germinomas confirmed by pathology from Jan. 2005 to Dec. 2009, aged from 4.2 to 10.2 years, were enrolled in this study. Patients were classified into two groups according to tumor locations: intracranial group and non-intracranial group. Levels of β-hcG in serum as well as in CSF were detected before the initiation of therapy. Age and gender matched 5 children undergoing lumbar puncture for other diseases were set as control group for the determinations of β-hcG in CSF. Levels of β-hcG and testosterone in serum and CSF were compared between intracranial group and non-intracranial group, and levels of β-hcG in CSF were compared between non-intracranial group and control group., Result: The 12 children showed elevated serum levels of testosterone: 10.43 (1.70-254.00) µg/L, 11 children had testicular volume > 4 ml, while response to LHRH stimulation tests were low; 6 children had gynecomastia. Serum levels of β-hcG were elevated in both intracranial and non-intracranial group and no significant differences were found between groups 63.75 (8.50-309.50) IU/L vs. 59.00 (25.10-71.77) IU/L, P = 0.644. No correlations were found between serum levels of β-hcG and ages, tumor locations, and courses of the patients. Levels of β-hcG in CSF were significantly higher in intracranial group than that in non-intracranial group 488.99 (17.30-1048.53) IU/L vs. 1.20 (1.20-1.50) IU/L, P = 0.009. Children with non-intracranial germinomas had similar levels of β-hcG in CSF as that in control group (P = 0.571)., Conclusion: The main clinical manifestations in boys suffered from germinoma included pseudo-precocious puberty, disproportionate testicular volume and gynecomastia. Detection of serum levels of β-hcG combined with β-hcG levels in CSF may be useful for determination of the locations of germinomas in children with precocious puberty.

For obtaining new structural compounds with unique resistance profiles or novel mechanisms of action on HIV-1 from natural products, anti-HIV-1 drug screening models were used in vitro. Norcantharidin (NCTD), a derivative from cantharidin, was found to have inhibitory activities on HIV-1(IIIB) p24 antigen in lymphocyte lines MT-4, CEM and H9. It inhibited HIV-1 strain 018a (sensitive to zidovudine) from replicating with EC50 (50% effective concentration) of 14.9 micromol L(-1) and also inhibited HIV-1 strain 018c (resistant to zidovudine) from replicating with EC50 of 20.2 micromol L(-1) in primary lymphocytes peripheral blood mononuclear cells (PBMC). Norcantharidin showed synergistic activity with zidovudine on HIV-1(IIIB) in MT-4 cells, the combination index was less than 0.3. But, it was not active on HIV-1 integrase, reverse transcriptase or protease in vitro. As the structure of norcantharidin is unique and different from that of all clinic drugs approved, it would be possible to obtain new and effective compounds against HIV-1 with low toxicities after modification of norcantharidin.

Plant active components characterized of many different structures and activities on multiple targets, have made them to be the important sources of inhibitors on HIV-1. For finding leading compounds with new structure against HIV-1, three key HIV-1 replicative enzymes (reverse transcriptase, protease and integrase) were used as screening models. The in vitro activities of 45 plant derived components isolated from Schisandraceae, Rutaceae and Ranunculaceae were reported. Within twelve triterpene components isolated, eight compounds were found to inhibit HIV-1 protease, in these eight active compounds, kadsuranic acid A (7) and nigranoic acid (8), inhibited both HIV-1 protease and integrase; Among fifteen lignans, meso-dihydroguaiaretic acid (15) and kadsurarin (16) were active on HIV-1 reverse transcriptase, and 4, 4-di(4-hydroxy-3-methoxyphenly)-2, 3-dimethylbutanol (13) active on HIV-1 integrase. All of the six alkaloids, seven flavones, and five others compounds were not active or only with low activities against HIV-1 replicative enzymes. Further studies of the triterpene components showing strong inhibitory activities on HIV-1 were warranted.

Objective: To investigate the effects and the mechanisms of stanozolol (ST) on the proliferation, maturation and differentiation of in vitro cultured growth plate chondrocyte isolated from gonadotropin releasing hormone analogue (GnRHa)-treated adolescent rats, to study if ST mediates the proliferation of chondrocytes via the estrogen receptor alpha (ERalpha), androgen receptor (AR) and/or insulin-like growth factor-1 receptor (IGF-1R) and interactions of the two receptor and IGF-1R receptor signaling pathway, to investigate the mechanism of the biological effects in ST promoting bone growth/maturity at molecular level., Method: The rats were weaned at the end of 3 weeks and intramuscular injection of triptorelin of GnRHa preparations, qow x 2 was started. The rats were sacrificed at the end of 7 weeks, and then the tibiae growth plates were taken out with sterile procedure. The chondrocytes were obtained by two-time enzyme digestion method, and the experiments were carried out with the primary chondrocytes. Immunohistochemical staining of proliferating cell nuclear antigen (PCNA) and Western blot analysis were applied., Result: The results of PCNA demonstrated that stanozolol enhanced the proliferation of the chondrocytes, time-course studies showed that the proliferation were maximally stimulated by stanozolol after 2 days of incubation and decreased again after longer periods of incubation. The expression of p-ERalpha, p-IGF-1R and p-extracellular-signal regulated kinase 1/2 (ERK1/2) increased with the incubation period of ST treatment, and reached the peak value at a certain time, and then gradually decreased. The expression of p-ERalpha, p-IGF-1R and p-ERK1/2 increased with the elevation of ST concentration, and reached the peak value at 10(-9) - 10(-8) mol/L, then gradually decreased. ST induced-p-ERalpha expression was partially blocked by ERalpha and mitogen-activated protein kinase kinase inhibitors. ST induced-p-IGF-1R expression was partially blocked by ERalpha and IGF-1R inhibitors. ST induced-p-ERK1/2 expression was partially blocked by mitogen-activated protein kinase kinase and IGF-1R inhibitors., Conclusion: As an androgen derivation, ST exerts its biological effects of promoting proliferation of the long bone growth plate chondrocytes via activating the classic ERalpha receptor pathway and mitogen-activated protein kinase pathway, and at the same time, by activation of IGF-1R. Both IGF-1R and ERalpha can promote "cross-talk" of two systems' receptor signal through mitogen-activated protein kinase signal pathway.

Objective: To investigate the pattern of pubertal development in healthy Cantonese schoolgirls., Method: From 1992 to 2001, 311 normal Cantonese schoolgirls, ages from 6.25 to 8.83 yrs (7.24 +/- 0.38) at baseline, were followed up until they reached their final adult height (age 15.72 +/- 0.84 yrs, n = 238). Annual physical examinations including height and weight measurement were performed. From the 3rd visit, pubertal maturations (breast and pubic hair development) were also assessed annually until they were 14.5 years. Age of menarche was recorded., Result: (1) Median age at the entry of puberty (age at reaching B2) was 9.83 years (9.33-10.33). Median age at initiation of pubic hair development (PH2) was 10.67 (9.92-11.38) years. Menarche occurred at (12.35 +/- 1.30) years. The age at reaching B2, age at reaching PH2 and age of menarche were all later than that observed in the cross-section study performed in 2003, Guangzhou, China. Peak height velocity (PHV) was reached at (10.52 +/- 1.07) years, 1.00 (0.50-1.50) years after B2 was reached. Interval between "age at onset of breast development" and "age at menarche" was 2.92 (2.08-3.67) years. Duration of pubertal growth (defined as the time from age at B2 to age at which adult height was attained) was (4.80 +/- 0.85) years. (2) Average final adult height (FAH) was (158.74 +/- 5.74) cm. As compared with the cross-section studies held in Guangzhou, China, the FAH in our study was higher than that observed in 1985 but was lower than that observed in 2003. (3) Multiple linear regression analyses showed that the age reaching B2 was an independent factor associated with the age of menarche. (4) Durations of breast stages, interval between B2 and menarche and duration of pubertal growth were similar to that reported in the longitudinal studies in the United Kingdom (1969), Senegal (1995-2000), the United States (1986-1996)., Conclusion: In healthy Cantonese schoolgirls, the timing of sexual maturation was in a trend of decline in the past 20 years, however it may have no significant impacts on the tempo of pubertal development and FAH.

Unlabelled: It has been proved that to analyze the factors that determine responsiveness to rhGH and to develop growth prediction models can help doctors to individualize the treatment and maximize the effect., Objectives: To set up and validate the predictive models of growth responses to rhGH treatment in the first year in prepubertal short stature children with various GH secretary statuses., Methods: Growth responses to rhGH treatment in the first year, height velocities (HV) and increases in height SDS (DeltaHtSDS), in 62 prepubertal short stature children with various GH secretary statuses were analyzed retrospectively. There were 27 patients with complete growth hormone deficiency (cGHD), 23 with partial GHD (pGHD) and 12 with idiopathic short stature (ISS) in the model group. According to the peak GH value in GH provocative test, the group of pGHD was divided into pGHD-1 (5 - 6.9 microg/L, 12 patients) and pGHD-2 (7 - 9.9 microg/L, 11 patients). All the cases in model group were used for setting up Model-total and the cases of growth hormone deficiency for Model-GHD. Predictive models, including Model-GHD and Model-total, to HV and DeltaHtSDS were set up by the way of multiple regression analysis, based on the results of simple correlation analysis. Other 14 children were included according to the same criteria with the model group, the validation group. The validation group was analyzed prospectively. The actual growth responses were compared with the predicted values calculated by different models so that the predictive models could be validated., Results: The simple correlation analysis showed that HV and DeltaHtSDS in the first year were negatively correlated with the same group factors at baseline: chronological age, bone age, height SDS, differences between the height SDS and the target height SDS, peak value in GH provocative test and IGF-1SDS. All the 4 predictive models were found to be significant at a level of P < 0.05, R(2) ranged from 0.244 to 0.519. The two models predicted HV and Model-GHD for DeltaHtSDS were proved to be validated. The observed and predicted responses positively and significantly correlated with each other, r value ranged from 0.753 to 0.996. And there was no significant difference between them when tested by paired t test., Conclusions: The availability of the predictive model will help to individualize the growth hormone treatment in prepubertal short stature children with various growth hormone secretary status.

Achyranthes bidentata polysaccharide sulfate (ABPS) was a sulfated derivate derived from Achyranthes bidentata polysaccharide (ABP) which was isolated and identified from Chinese herb Achyranthes bidentata. The anti human immunodeficiency virus type 1 (HIV-1) activities were studied in vitro and in vivo. ABPS was found to inhibit HIV-1 reverse transcriptase and integrase with the 50% inhibiting concentration (IC60) of (2.948 +/- 0.556) micromol x L(-1) and (0.155 +/- 0.030) micromol x L(-1), respectively, but the parent compound ABP was not effective. ABPS inhibited HIV-1 P24 antigen with IC50 of (0.082 +/- 0.044) micromol x L(-1) and selective index (SI) of > (358 +/- 148) in MT-4 cell cultures acutely infected with HIV-1 IIIB virus, and with IC50 of (11.80 +/- 5.90) micromol x L(-1) and SI of > (24.2 +/- 12.1) in PBMC cell cultures acutely infected with clinical isolated zidovudine resistant HIV-1 virus, but there was no activity even at its concentration of 500 micromol x L(-1) in latent infection of H9/HIV-1 IIIB cell cultures. 5% sera taken from rats after intraperitoneal injection from rats with ABPS 125 mg x kg(-1) once or mice with 3 mg x kg(-1) qd for 20 days effectively inhibited HIV-1 P24 in MT-4 cell cultures, but those had no inhibitory effect when given orally. The results suggested that ABPS is a promising HIV-1 inhibitor, active on HIV-1 reverse transcriptase, integrase in vitro and HIV-1 P24 antigens in cell cultures, it was well absorbed by intraperitoneal injection but poor in oral bioavailability. It warrants further study.

An improved and practical synthesis of racemic 11-demethylcalanolide A [(+/-)-1] was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5,7,-dihydroxy4-n-propylcoumarin (3). Poly phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone (4). A microwave assisted synthetic method preparing chromene (6) using chromenynation of chromanone (4) with 1, 1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH4 with CeCl3 x 7H2O preferably gave (+/-)-1. The overall yield of this four step synthesis of (+/-)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (+/-)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD50 of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65 mg kg(-1) and 525.10 mg x kg(-1), respectively. The Cmax and AUC(0-infinity) were 0.54 microg x mL(-1) and 1.08 (microg x mL(-1) x h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100 mg x kg(-1 (+/-)-1 once intraperitoneally were similar to that of 5 mg x kg(-1) of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (+/-)-1 was warranted.

To compare the anti-HIV-1 activities of (+/-)-11-demethyl-calanolide A and its mother compound (+/-)-calanolide A in vitro and in vivo, the inhibitory activities of the two compounds on HIV-1 reverse transcriptase (RT) were detected in vitro with isotope 3H assay. The cytotoxicity and inhibition of cytopathic effect (CPE) were studied in HIV-1 IIIB infected MT-4 cell cultures by MTT staining method; Mice were given with the two compounds 100 mg x kg(-1) once intraperitoneally, then the mouse sera taken on 30 min and 60 min after administration were detected for the inhibition of HIV-1 RT in vitro. The data showed that (+/-)-11-demethyl-calanolide A and (+/-)-calanolide A inhibited HIV-1 RT in vitro with 50% inhibitory concentration (IC50) of (3.028 +/- 2.514) micromol x L(-1) and (3.965 +/- 5.235) micromol x L(-1), and also inhibited CPE in HIV-1 IIIB infected MT-4 cell cultures with IC50 of (1.081 +/- 0.337) micromol x L(-1) and (1.297 +/- 0.076) micromol x L(-1), respectively. After intraperitoneal injection of 100 mg x kg(-1) of the two compounds in mice, all the mice sera taken 30 and 60 min afterward inhibited HIV-1 RT in vitro. In comparison with control mice sera, the inhibitory rates of the sera for (+/-)-11 -demethyl-calanolide A were (42.7 +/- 1.5)% at 30 min (P < 0.01) and (32.2 +/- 6.1)% at 60 min (P < 0.05), separately, while the inhibitory rates of the sera for (+/-)-calanolide A were (40.7 +/- 6.3)% at 30 min (P < 0.01) and (29.2 +/- 6.7)% at 60 min. The results suggested that (+/-)-11-demethyl-calanolide A is a new non-nucleoside HIV-1 RT inhibitor, its anti-HIV-1 activities in vitro, in cell cultures and in mice were slightly higher than that of its mother compound (+/-)-calanolide A and warrants further studies.

Objective: To study the chemical constituents in the root of Salvia yunnansis., Method: Compounds were isolated and purified by Diaion HP20, Sephadex LH - 20, ODS chromatography. Their structures were determined by spectral analysis and chemical evidence., Result: Twelve compounds were isolated and identified from the root of S. yunnansis protocatechaldehyde (1), caffeic acid (2), ferulic acid (3), rosmarinic acid (4), salvianolic acid A (5), salvianolic acid C (6), lithospermicacid (7), lithospermicacid B (8), 9'-methyl lithospermate B (9), 9"'-methyl lithospermate B (10), 9',9'''-dimethyl lithospermate B (11), 9'-ethyl lithospermate B (12)., Conclusion: The compounds 1, 2, 3, 5, 6, 9, 10, 11 and 12 were first isolated from S. yunnanensis.

Aim: To observe the Lamivudine resistance character of a DHBV strain in vitro and in vivo, and to analyze if the Lamivudine resistance character is caused by gene mutation or by abnormity of the Lamivudine metabolism., Methods: Congenitally DHBV-negative Guangdong brown ducks and duck embryo liver cells were respectively taken as animal and cell model. The Lamivudine-susceptive DHBV and Lamivudine-resistant DHBV (LRDHBV) were infected and Lamivudine was administrated according to the divided groups. The changes of DHBV quantity in the animal and cell model were tested. Three Lamivudine-resistant and two Lamivudine-susceptive DHBV complete genomes were successfully amplified, sequenced and then submitted to GenBank. All the DHBV complete sequences in the GenBank at present were taken to align with the three LRDHBV to analyze the mutational points related to the Lamivudine-resistant mutation., Results: Both the animal and cell model showed that the large and the small dosage Lamivudine have no significant inhibitory effect on the LRDHBV. Five sequences of DHBV complete genomes were successfully cloned. The GenBank accession numbers of the three sequences of LRDHBV are AY521226, AY521227, and AY433937. The two strains of Lamivudine-susceptive DHBV are AY392760 and AY536371. The correlated mutational points are KorR86Q and AorE591T in the P protein., Conclusion: The Lamivudine resistance character of this DHBV strain is caused by genome mutation; the related mutational points are KorR86Q and AorE591T and have no relations with the YMDD motif mutation.

Objective: To investigate the effect of Chinese herbal medicine Xin-kang oral liquid on interferon (IFN)-induction and its antiviral activity in Coxsackievirus B3 virus strain (CVB3) infected mice., Methods: The Xin-kang oral liquid was given orally to mice two days prior to the challenge of CVB3 virus to induce myocarditis. Two dosages of Xin-kang oral liquid crude herbal medicine 30 g x kg(-1) x d(-1) and 12 g x kg(-1) x d(-1) were given to the mice of different treatment groups respectively, sterilized water was given to the mice of virus control group. IFN-alpha 10(6) U x kg(-1) x d(-1) S.C was given to the infected mice as positive drug control group. The mice were sacrificed on 5th, 10th and 20th day of infection for evaluation, the levels of serum interferon (IFN) were titrated with vesicular stomatitis virus (VSV) and cardiac tissue was fixed and sectioned. The quantitative histological changes at various stages of myocarditis were observed., Results: In the infected mice fed with 30 g x kg(-1) x d(-1) or 12 g x kg(-1) x d(-1) of Xin-kang oral liquid orally for 5, 10 and 20 days, the mean titer of serum IFN of Xin-Kang oral liquid treated group was markedly higher (29.3 U/0.1 ml) than that of virus control group (12.6 U/0.1 ml). The level of serum IFN in IFN treated positive control mice was lower than that of Xin-kang treatment groups. The histological examination showed extensive myocardial necrosis and cellular infiltration in virus control group, but necrosis and cellular infiltration were less severe in Xin-kang treatment goups of mice. It is demonstrated that there were close correlation between the degree of myocardial lesions and the level of IFN-induction in treated mice., Conclusion: Xin-kang oral liquid could facilitate the induction of endogenous interferon that exerted its antiviral activity in CVB3 infected mice. This can help us to understand better the mechanism of anti-CVB3 effect of Xin-Kang oral liquid.

Objective: To provide some research clues from Chinese herbal medicine for SARS prevention and treatment., Method: According to the experience and information, to select several perspective candidates from anti-SARS effective TCM prescriptions and drugs., Result: A list of Chinese herbal medicine and more than 14 botanical taxa could be served for further anti-SARS investigation., Conclusion: This investigation indicated that Chinese herbal medicine will be an important source for ant-SARS new drug searching.

Objective: To study the effects of blocking transforming growth factor beta (TGF-beta) signalling on culture-activated rat hepatic stellate cells (HSCs)., Methods: After cultured in plastic dish for two days, HSCs were infected with adenovirus vector AdT beta-ExR or AdLacZ (control) at 10 multiplicity of infection (MOI) and incubated for four days. The expression of type I collagen, alpha-smooth muscle actin (alpha-SMA) and the proliferation of HSCs were analyzed by ELISA, western blot, immunocytochemistry and BrdU uptake respectively., Results: The expression level of type I collagen in HSCs infected with AdT beta-ExR was 42.99% of that in HSCs infected with AdLacZ (q = 9.100, P < 0.001). The expression of alpha-SMA in HSCs infected with AdTbeta-ExR was also inhibited evidently. But the BrdU uptake in HSCs infected with AdLacZ was 49.24% of that in HSCs infected with AdTbeta-ExR (q = 7.835, P < 0.001)., Conclusions: The blockade of TGF-beta signalling in cultured rat HSCs can inhibit their activation significantly, but promote their proliferation.

Aim: Synthesis of 1-(3-phthalimido-2-oxobutyl)-4-substituted- phenylpiperazines (5-15)., Methods: The starting material nitrogen mustard hydrochloride (16), reacted with the corresponding substituted anilines to afford piperazine hydrochlorides (17-27), which were then coupled with 1-bromo-3-phthalimidobutan-2-one (4) to give the target compounds., Results: Eleven target compounds (5-15) were synthesized, which were characterized by 1HNMR, IR and elemental analysis., Conclusion: Anti-HIV-1 RT using HIV reverse transcriptase P-66 protein test showed that compounds 11, 14, 10 and 13 possessed inhibitory effects against HIV-1 reverse transcriptase (RT), with IC50 29.80, 35.20, 43.77 and 63.76 mumol.L-1, respectively.

Aim: Three major enzymes of HIV-1, reverse transcriptase (RT), protease (PR), and integrase (IN), are important targets for anti-HIV drugs. Nine RT and five PR inhibitors have been effectively used in treatment of AIDS patients. In order to find active integrase inhibitors, twenty polyhydroxylated aromatic compounds were tested., Methods: ELISA method was used to test the integrase activity. The synthesized donor substrate oligonucleotide representing the HIV-1 U5LTR was immobilized onto Covalink polystyrene microtiter plates, and a synthesized biotinlated 20 bp oligonucleotide was used as the target substrate. The products were detected and quantified by a colorimetric avidin-linked alkaline phosphatase reporter system., Results: Compound NQ-2 was found to inhibit HIV-1 integrase with the IC50 of 78.5 mumol.L-1 by ELISA method. Its novel analogue NQ-3 was found to be 2 fold more potent on HIV intrgrase than NQ-2, IC50 was 37.2 mumol.L-1. The IC50s of NQ-2 and NQ-3 to inhibit the 3'-pro + assembly activity of integrase were 96.94 mumol.L-1 and 8.48 mumol.L-1; to inhibit assembly activity were 168 and 6.9 mumol.L-1 and to inhibit strand-transfer activity were 49.8 and 1.1 mumol.L-1, respectively. Compound NQ-2 mostly inhibited the strand transfer activity of HIV-1 integrase. Compound NQ-3 inhibited both the assembly and strand-transfer with high activities., Conclusion: Naphthoquinone compound NQ-3 was found to be a novel HIV integrase inhibitor which warrants further study. Uncoupled ELISA HIV integrase assay is shown to be useful to screen HIV-1 integrase inhibitors.