Illihenin A: An Antiviral Sesquiterpenoid with a Cage-like Tricyclo[6.2.2.01,5]dodecane Skeleton from Illicium henryi.

Illihenin A (1), a novel sesquiterpenoid, was isolated from the roots of Illicium henryi. The structure was determined by spectroscopic analyses, ECD calculation, and single-crystal X-ray diffraction. Compound 1 represents a class of novel 5/7/6 tricyclic sesquiterpenoids featuring a rare cage-like tricyclo[6.2.2.01,5]dodecane core. A plausible biosynthetic pathway of 1 by rearrangement of allo-cedrane is proposed. Additionally, 1 showed potent antiviral activity against coxsackievirus B3 with an IC50 value of 2.87 µM.

[Comparison on driving mechanism of county ecological efficiency: With three counties in the mountainous area of southern Ningxia, China as an example]. / 县域生态效率驱动机制对比­­ä»¥å®å—山区3县为例.

With Tongxin, Xiji, and Longde counties in the mountainous area of southern Ningxia as the research area, we used extended-exergy analysis (EEA) to compare their ecological efficiency driving mechanism in 2008-2017 to explore the causes of their variation in ecological degradation. The results showed that the overall difference of ecological efficiency in the three counties was significant during the study period. The ecological efficiency of Tongxin was low, with large inter-annual variation. The ecological efficiency of Xiji was stable, and the overall efficiency of Longde was the highest. The difference of exergy scale was small among the three counties. The exergy proportion in the economic sectors was not coordinated, which were dominated by agricultural and residential sectors. The economic sectors presented significant capital-pull-type and labor-intensive characteristics, indicating the driving force for ecological degradation mainly came from agricultural production and residents' lives in underdeveloped regions. The system's internal exergy conversion rate and the external energy exchange rate of the three counties were extremely low, constituting a simple network circulation path with high input, low storage, low opening and low conversion, which weakened the endogenous development of social economic subsystem and threatened the fragile ecosystem.

Effects of Androgen on Social Behavior of Mice and Underlying Mechanisms / 中国药学杂志

OBJECTIVE: To investigate the effect of androgen on social behavior of male mice and underlying mechanisms. METHODS: After sham or gonadectomy (GDX) operation under deep anesthesia, adolescent (4-week-old) ICR male mice were divided into sham operation group (Sham), gonadectomy group (GDX), and gonadectomy with testosterone propionate (TP, 0.5, 1 mg•kg-1•d-1) supplementation group (GDX+TP)(TP supplementation was continued until the end of the experiment). By 13-week-old, social behaviors were tested. Testosterone levels in serum and the brain as well as arginine vasopressin (AVP) level in the brain were analyzed by ELISA. Androgen receptor (AR) level in the brain was analyzed by Western blot. Morphology of accessory olfactory bulb was detected by paraffin section. AVP expression in amygdala was detected by immunofluorescence. RESULTS: TP supplementation reversed GDX-induced inhibition of sexual behavior and invasive aggressive behavior. TP improved the social recognition ability rather than the general sense of smell of GDX mice. TP supplementation increased the level of testosterone in the brain and in serum and the expression of AR in the brain of GDX mice. TP increased the cell density of mitral cell layer, a projecting neuron in accessory olfactory bulb and elevated the level of AVP in the amygdala brain area. CONCLUSION: Androgen promotes social recognition by increasing the expression of AR in the brain, cell density in the mitral cell layer in accessory olfactory bulb, and AVP level in the amygdala, thus affecting social behavior of adult male mice.

[Jasmonate signal pathway involved in phytoalexin biosynthesis in Sorbus aucuparia cell elicited by Hpa1].

The Harpin protein Hpa1 can induce defense responses in plant. This study aimed at investigating the role of jasmonate (JA) signal pathway in the process of biosynthesis of secondary metabolite in Sorbus aucuparia cell eliciting by Hpa1 crude extract (Hpa1 CE). The results showed that Hpa1 crude extract (Hpa1 CE) could induce phytoalexin synthesis in S. aucuparia cell， most of which was noraucuparin and its glycosides. Meanwhile Hpa1 CE treatment resulted in methyl jasmonate (MeJA) production increased and noraucuparin was de novo synthesized in large quantities. Combination of Hpa1 CE and salicylhydroxamic acid (SHAM, JA signaling inhibitor) caused the decreased MeJA and noraucuparin in the S. aucuparia cell compared with that in Hpa1 CE group. Real-time PCR results indicated that Hpa1 CE treatment caused down-regulation of JAZ and up-regulation of mcy2 in transcription level. Therefore Hpa1 CE elicited defense mechanism and JA signaling pathway involved in phytoalexin biosynthesis in S. aucuparia cell. It presented information to elucidate the role of JA signal pathway in stress response in the perspective of secondary metabolism of plant.

Contrast-enhanced ultrasound and real-time elastography in the differential diagnosis of malignant and benign thyroid nodules.

The diagnostic value of contrast-enhanced ultrasound (CEUS) or real-time elastography (RTE) alone, as well as a combination of CEUS and RTE, in distinguishing benign from malignant thyroid nodules was investigated. Between August 2012 and June 2014, a total of 97 consecutive patients (50 male and 47 female patients; mean age, 48.6±12.4; age range, 27-70 years) with thyroid nodules referred for surgical treatment were examined by CEUS and RTE. The final diagnosis was obtained based on histological findings. Image analysis of the CEUS and RTE scans was performed. Considering the postoperative pathological results as the golden standard, a receiver operating characteristic (ROC) curve was constructed. Subsequently, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy of CEUS alone, RTE alone and CEUS + RTE combination were calculated. Pathological examination showed 66 papillary carcinomas and 43 benign lesions, including 21 adenomas and 22 nodular goiters. The sensitivity, specificity, PPV, NPV and accuracy of CEUS were 81.82, 90.70, 93.10, 90.70 and 85.32%, respectively. In the case of RTE, the sensitivity, specificity, PPV, NPV and accuracy were 80.30, 88.37, 91.38, 88.37 and 83.49%, respectively. Furthermore, the combination of CEUS + RTE had a sensitivity of 95.45%, specificity of 95.35%, PPV of 96.92%, NPV of 95.35% and accuracy of 95.41%. Therefore, the CEUS + RTE combination showed a significantly higher sensitivity and specificity compared with CEUS or RTE alone (all P<0.05). Based on ROC analysis, the area under the curve (AUC) for CEUS, RTE and CEUS + RTE combination was 0.883, 0.863 and 0.959, respectively. The AUC of RTE alone was significantly lower compared with that of the CEUS + RTE combination. In conclusion, our results demonstrate that CEUS + RTE combination significantly increases the diagnostic performance for differential diagnosis of malignant and benign thyroid nodules compared with CEUS or RTE alone.

Combined effects of 50 Hz magnetic field and magnetic nanoparticles on the proliferation and apoptosis of PC12 cells.

OBJECTIVE: To investigate the bioeffects of extremely low frequency (ELF) magnetic field (MF) (50 Hz, 400 µT) and magnetic nanoparticles (MNPs) via cytotoxicity and apoptosis assays on PC12 cells. METHODS: MNPs modified by SiO2 (MNP-SiO2) were characterized by transmission electron microscopy (TEM), dynamic light scattering and hysteresis loop measurement. PC12 cells were administrated with MNP-SiO2 with or without MF exposure for 48 h. Cytotoxicity and apoptosis were evaluated with MTT assay and annexin V-FITC/PI staining, respectively. The morphology and uptake of MNP-SiO2 were determined by TEM. MF simulation was performed by Ansoft Maxwell based on the finite element method. RESULTS: MNP-SiO2 were identified as ~20 nm (diameter) ferromagnetic particles. MNP-SiO2 reduced cell viability in a dose-dependent manner. MF also reduced cell viability with increasing concentrations of MNP-SiO2. MNP-SiO2 alone did not cause apoptosis in PC12 cells; instead, the proportion of apoptotic cells increased significantly under MF exposure and increasing doses of MNP-SiO2. MNP-SiO2 could be ingested and then cause a slight change in cell morphology. CONCLUSION: Combined exposure of MF and MNP-SiO2 resulted in remarkable cytotoxicity and increased apoptosis in PC12 cells. The results suggested that MF exposure could strengthen the MF of MNPs, which may enhance the bioeffects of ELF MF.

New hybrid Cd(II) compounds: synthesis and structural characterization.

In an acidic solution, the room-temperature reactions of CdX2 (X(-) = Cl(-), Br(-) or CH3COO(-)) and organic N-heterocyclic molecules with or without SCN(-)/SeCN(-)/dca(-) (dca(-) = dicyanamide) created the five new hybrid Cd(ii) compounds [H2(4,4'-dtdpy)]2[CdBr4]SO4·2.5H2O (dtdpy = dithiodipyridine) 1, [H(2,2'-dtdpy)]2[CdBr4] 2, [(Hbim)2CdCl2(SCN)2] (bim = 2,2'-biimidazole) 3, [H2(pip)][Cd(SCN)4] (pip = piperazine) 4 and [CdL2] (L = HNC(OH)N(-)CN) 5. X-ray single-crystal diffraction analysis revealed that: (i) compound 1 is a double salt of [H2(4,4'-dtdpy)]SO4 and [H2(4,4'-dtdpy)][CdBr4], [H2(4,4'-dtdpy)]SO4 shows a two-dimensional (2D) supramolecular layer structure and [H2(4,4'-dtdpy)][CdBr4] is distributed in the space between the supramolecular layers; (ii) compounds 2 and 3 are mononuclear molecular entities. Of those, 2,2'-dtdpy and bim were only in situ monoprotonated; (iii) compound 4 contains a 2D supramolecular layered structure which is based on [Cd(SCN)4](2-) chains H2(pip)(2+)via NSCNNpip interactions; (iv) the three-dimensional (3D) compound 5 exhibits a rutile-related (4·6(2))2(4(2)·6(10)·8(3))-topology. The ligand L originates from the in situ nucleophilic addition of H2O with one -CN group of dca(-). Upon excitation, the solid-state compounds 3 and 4 emit blue light, and the solid-state compound 5 emits violet light.

Imaging of bronchioloalveolar carcinoma in the mice with the αâ ¤ß3 integrin-targeted tracer (99m)Tc-RGD-4CK.

Receptor-based imaging agents have shown improved specificity and sensitivity of cancer diagnosis by targeting the specific features of cancer. Here we reported the (99m)Tc-labeling of a cyclic polypeptide RGD-4CK and the characterization of this agent in vitro and in bronchioloalveolar carcinoma (BAC) xenograft model. The αⅤß3 integrin receptor binding affinity of (99m)Tc-RGD-4CK was determined in BAC. The cancer targeting properties of (99m)Tc-RGD-4CK were determined in NCI-H358 xenografted nude mice. Moreover, the BAC uptake of (99m)Tc-RGD-4CK was blocked with nonradiolabeled RGD-4CK in xenografts. The competitive assay showed that (99m)Tc-RGD-4CK exhibited high specificity to BAC cell line NCI-H358. Biodistribution studies indicated that (99m)Tc-RGD-4CK exhibited high tumor uptake (4.12 ± 1.21% injected dose/g 120 minutes after injection) and prolonged tumor retention (2.08 ± 0.33% injected dose/g 240 minutes after injection) in NCI-H358 xenografted nude mice. Moreover, (99m)Tc-RGD-4CK produced a good tumor-to-lung ratio (2.38) because of low lung activity accumulation 120 minutes postinjection. BAC on the flank of xenografted mice was clearly visualized by single photon emission computed tomography/computed tomography imaging using (99m)Tc-RGD-4CK. In conclusion, this study provides evidence that (99m)Tc-RGD-4CK is a promising agent for noninvasive determination of αⅤß3 integrin status and therapy monitoring in BAC.

New Cd2+, Pb2+ complexes with acylhydrazidate molecules from in situ acylation reactions.

Through employing the hydrothermal in situ acylation of N2H4 with aromatic dicarboxylic acids, four new acylhydrazidate-coordinated complexes, [Cd2(pth)4(phen)2(H2O)2]·H2O (pth = phthalhydrazidate; phen = 1,10-phenanthroline) 1, [Cd3(dcpth)6(phen)2(H2O)2] (dcpth = 4,5-dichlorophthalhydrazidate) 2, [Cd(pdh)2(H2O)2] (pdh = pyridine-2,3-dicarboxylhydrazidate) 3 and [Pb(sdpth)(phen)] (sdpth = 4,4'-sulfoyldiphthalhydrazidate) 4, were obtained. X-ray analysis revealed that (i) isomerization and deprotonation of acylhydrazide molecules also occurred; (ii) compound 2 possesses a one-dimensional (1-D) double-chain structure, in which dcpth exhibits three types of coordination modes; (iii) compound 4 shows a 1-D castellated single-chain structure; (iv) the adjacent uncoordinated acylamino groups form a hydrogen-bonded dimer, via which compounds 2-4 self-assemble into different two-dimensional (2-D) supramolecular networks. In the solid state, only compound 3 emits green light (λ(em) = 525 nm), while in an aqueous solution, compounds 1, 3 and 4 all emit light. Density functional theory (DFT) calculations indicate that the emission at 470 nm for compound 1 corresponds to a charge transfer within the phen molecule, whereas the emission at 400 nm for compound 3 corresponds to a charge transfer within the pdh molecule.

New thiocyanatocadmates templated by multi-dentate N-heterocyclic/diamine molecules.

With diverse multi-dentate N-heterocyclic/diamine molecules as the cations, the reactions between Cd(2+) and SCN(-) in C2H5OH/H2O solution acidified by H2SO4 created five new thiocyanatocadmates [H2(bim)][Cd(SCN)2(H2O)2]SO4 (bim = 2,2'-biimidazole) 1, [H2(pympip)]2[Cd2(SCN)4(SO4)2(H2O)4]·2H2O (pympip = 1-(2-pyrimidyl)piperazine) 2, [H2(tdpy)]2[Cd3(SCN)10] (tdpy = 4,4'-thiodipyridine) 3, [H2(badpm)][Cd(SCN)4] (badpm = 4,4'-biaminodiphenylmethane) 4 and [H2(pdma)][Cd2(SCN)4(SO4)] (pdma = 1,4-phenylenedimethanamine) 5. It is noteworthy that (i) in compounds 1, 2 and 5, SO4(2-) was incorporated into the organically templated thiocyanatocadmate frameworks; (ii) compound is a rare example, in which two types of chained thiocyanatocadmates are found, and (iii) compound shows an interesting layer structure, constructed up from the ribboned thiocyanatocadmates by µ2-mode SO4(2-). Photoluminescence analysis revealed that compounds 1, 2 and 5 in solid state emit blue light with the maximum at 425 nm for 1, 405 nm for 2 and 445 nm for 5, respectively.

[Comparison of the biodistribution of four contrast agents in nude mice bearing NCI-H358 human lung cancer and evaluation of their value in diagnostic imaging].

OBJECTIVE: To compare the uptake of four contrast agents: (99)Tc(m)-RGD-4CK, (99)Tc(m)-N(NOET)(2), (99)Tc(m)-MIBI and (18)F-FDG in Bal B/c nude mice bearing human non-small cell lung cancer NCI-H358 and evaluate their diagnostic value in low-metabolic lung cancer. METHODS: Human bronchioloalveolar carcinoma NCI-H358 cells were subcutaneously inoculated in Bal B/c nude mice to establish mouse models bearing human lung cancer. Twenty tumor-bearing nude mice were given injection of the four contrast agent, respectively, 5 mice in each group. SPECT imaging and biodistribution of the 4 tracers in the tumor-bearing nude mice were performed. The ratios of tumor to non-tumor (T/NT) of the tracers were compared. RESULTS: The results from semi-quantification of the planar image and assessment of biodistribution showed that tumor to contralateral muscle activity ratios (T/NT) of the four tracers had statistically significant difference between each two of the four tracer groups of tumor-bearing mice (P < 0.001), with a highest value of T/NT ratio in the (99)Tc(m)-RGD-4CK group. CONCLUSIONS: NCI-H358 tumors show a higher uptake of (99)Tc(m)-RGD-4CK than (18)F-FDG. It suggests that when diagnosing a well-differentiated lung cancer such as bronchioloalveolar carcinoma, the contrast agent (99)Tc(m)-RGD-4CK may be more sensitive than (18)F-FDG, and it may become a promising contrast agent in tumor imaging diagnosis.

Generation and characterization of monoclonal antibodies against botulinum neurotoxin type A (BoNT/A).

AIM: To generate the monoclonal antibodies(mAbs) against botulinum neurotoxin type A (BoNT/A). METHODS: BALB/c mice were intraperitoneally immunized with purified BoNT/A-Hc, and the splenocytes of immunized mice were fused with myeloma cells Sp2/0. Hybridoma cells were screened by indirect ELISA and monoclonal hybridoma cells was obtained using limited dilution. RESULTS: Three hybridomas, named 4A8, 2F7 and 4F2, producing the mAbs against BoNT/A, were successfully established, and the titer of ascitic mAbs ranged from 1x10(-4) to 1x10(-6). Identification of subclass showed that all the produced mAbs belonged to IgG1. 4A8 and 4F2 were stable in secreting anti-BoNT/A mAbs through three-month continuous culture and showed high specificity to recombinant BoNT/A-Hc and native BoNT/A. CONCLUSION: Anti-BoNT/A mAbs we generated have high specificity, which laid the foundation for the immunological detection of BoNT/A and clinical treatment of botulism in the future.