Integrative Analysis of Metabolomics and Transcriptomics Reveals Molecular Mechanisms of Anthocyanin Metabolism in the Zikui Tea Plant (Camellia sinensis cv. Zikui).

In this study, we performed an association analysis of metabolomics and transcriptomics to reveal the anthocyanin biosynthesis mechanism in a new purple-leaf tea cultivar Zikui (Camellia sinensis cv. Zikui) (ZK). Three glycosylated anthocyanins were identified, including petunidin 3-O-glucoside, cyanidin 3-O-galactoside, and cyanidin 3-O-glucoside, and their contents were the highest in ZK leaves at 15 days. This is the first report on petunidin 3-O-glucoside in purple-leaf tea. Integrated analysis of the transcriptome and metabolome identified eleven dependent transcription factors, among which CsMYB90 had strong correlations with petunidin 3-O-glucoside, cyanidin 3-O-galactoside, and cyanidin 3-O-glucoside (PCC > 0.8). Furthermore, we also identified key correlated structural genes, including two positively correlated F3'H (flavonoid-3'-hydroxylase) genes, two positively correlated ANS (anthocyanin synthase) genes, and three negatively correlated PPO (polyphenol oxidase) genes. Overexpression of CsMYB90 in tobacco resulted in dark-purple transgenic calluses. These results showed that the increased accumulation of three anthocyanins in ZK may promote purple-leaf coloration because of changes in the expression levels of genes, including CsMYB90, F3'Hs, ANSs, and PPOs. These findings reveal new insight into the molecular mechanism of anthocyanin biosynthesis in purple-leaf tea plants and provide a series of candidate genes for the breeding of anthocyanin-rich cultivars.

Tumor necrosis factor receptor-associated factor (TRAF) 6 inhibition mitigates the pro-inflammatory roles and proliferation of rheumatoid arthritis fibroblast-like synoviocytes.

BACKGROUND: Rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) play a crucial role in RA through producing inflammatory cytokines and proteases which could cause cartilage destruction. We showed previously that elevated expression of tumor necrosis factor receptor-associated factor 6 (TRAF6) in RA synovium correlated significantly with the severity of synovitis and the number of infiltrated inflammatory cells. The aims of this study are to detect the roles of TRAF6 in RA-FLSs. METHODS: Synovium were collected by closed needle biopsy from inflamed knees of active RA patients, and FLSs were isolated by modified tissue culture method. Expression of TRAF6 and CD55 in RA synivium was tested by double immunofluorescence (IF) staining. TRAF6 in RA-FLSs was inhibited using Lentiviral-TRAF6-shRNA transfection. Real-time PCR and ELISA were used to detect the mRNA expression and secretion of matrix metalloproteinase (MMP) and pro-inflammatory cytokines. Cell Counting Kit-8 was used to detect cell proliferation, flow cytometry was used to detect cell cycle, and Annexin V assay was used to detect cell apoptosis. RESULTS: We showed that in the intimal and subintimal area of RA synovium, TRAF6 was expressed obviously not only in CD55+ cells, but also in some other CD55- cells. TRAF6 expression in RA-FLSs was suppressed effectively by Lentiviral-TRAF6-shRNA transfection. Inhibition of TRAF6 in RA-FLSs mitigated the mRNA levels and secretion of pro-inflammatory cytokines and MMPs, such as IL-1ß, IL-8, IL-6, TNF-α, MMP-13, and MMP-3. In addition, it decreased the proliferation of RA-FLSs, blocked RA-FLSs in G0/G1-phase, and inhibited the cells to go into S-phase and G2/M-phase, but not facilitated apoptosis of RA-FLSs. CONCLUSION: TRAF6 plays direct roles in the pro-inflammatory effects and proliferation of RA-FLSs. TRAF6 may serve as a potential treatment target in RA.

CW dual-frequency MOPA laser with frequency separation of 45 GHz.

A CW dual-frequency master oscillator power amplifier (MOPA) laser system with dozens of gigahertz (GHz) frequency separation is presented. The MOPA system consists of a monolithic microchip seed laser and a double-end pumped traveling wave power amplifier. The short length of seed laser cavity guarantees the seed signal with a large frequency separation (above 53 GHz) but low output power (below 247.8 mW). By adding a long and low-doped active medium laser amplifier stage, a significant increase in laser power and an improvement in beam quality are obtained. After fine temperature tuning of seed laser cavity for "spectra matching", a 2.40 W dual-frequency laser signal with 45 GHz frequency separation is achieved.

Establishment of an efficient regeneration system of 'ZiKui' tea with hypocotyl as explants.

Zikui (Camellia sinensis cv. Zikui) is a recently discovered cultivar of local purple tea in Guizhou, China. It is a purple leaf bud mutation material of Meitan Taicha (Camellia sinensis cv. 'Meitan-taicha') 'N61' strain, which is an important local germplasm resource in Guizhou. It is also a model plant for the study of anthocyanins, but the limited germplasm resources and the limitation of traditional reproduction hinder its application. Here, an efficient regeneration system is established by using hypocotyl as explants for the first time. Different plant growth regulators (PGRs) are evaluated during different regeneration processes including callus and root induction. According to our findings, using the optimal disinfection conditions, the seed embryo contamination rate is 17.58%. Additionally, the mortality rate is 9.69%, while the survival rate is measured as 72.73%. Moreover, the highest germination rate of 93.64% is observed under MS + 2.40 mg/L GA3 medium conditions. The optimal callus induction rate is 95.19%, while the optimal adventitious bud differentiation rate is 20.74%, Medium with 1.6 mg/L IBA achieved 68.6% rooting of the adventitious shoots. The survival rate is more than 65% after 6 days growth in the cultivated matrix. In summary, our research aims to establish a regeneration system for Zikui tea plants and design a transformation system for tea plant tissue seedlings. This will enable transfer of the target gene and ultimately facilitate the cultivation of new tea varieties with unique characteristics.

LiuweiDihuang improved cognitive functions in SAMP8 mice by inhibiting COX-2 expression and subsequent neuroinflammation.

ETHNOPHARMACOLOGICAL RELEVANCE: LiuweiDihuang (LW) pills was mainly used to treatment of children's fontanelle incomplete closure, enuresis and nervous system development delays and other diseases.Following the deepening of pharmacological research, LW has a good effect on neurological diseases include senile dementia. However, the neuroprotection mechanism of LW on Alzheimer's disease (AD) through regulation of inflammation remains unclear. AIM OF THE STUDY: Here, we aimed to explore the effects and mechanism of LW on learning and memory deficits in SAMP8 mice. MATERIALS AND METHODS: Mice aged 6 months were treated with LW for 2 months and BV2, C6 and HT22 cells were treated with LW pharmaceutic serum and Lipopolysaccharide (LPS) continuously. Then, cognitive tests were performed, including the Morris water maze and Y maze tests. The mRNA level of cyclooxygenase 2 (COX-2) and pro-inflammatory factors (IL-1ß, IL-6 and TNF-α) were examined in cells and the cortex and hippocampus by quantitative RT-PCR. The expression of postsynaptic density protein 95, synaptophysin and various inflammatory factors were detected in the cortex and hippocampus by Western blot. Furthermore, Ionized calcium binding adapter molecule 1, glial fibrillary acidic protein and Aß were examined in the brain of AD mice by immunofluorescence staining and immunohistochemistry. And synaptic loss and neuronal ultrastructure were observed by transmission electron microscope. RESULTS: We found that LW suppressed LPS-induced COX-2 expression in vitro. Importantly, LW dramatically improved spatial learning and memory in SAMP8 mice through inhibiting Aß accumulation and restoring structural synaptic integrity. Furthermore, LW inhibited the glial activation and neuroinflammation (COX-2, IL-1ß, IL-6 and TNF-α) in the cortex and hippocampus of SAMP8 mice. CONCLUSION: Taken together, the present data not only indicated that LW is an effective agent on improving the learning and memory deficits through mitigating neuroinflammation but highlighted the LW can be a potential therapeutic drug for AD therapy.

[Effect of electroacupuncture on laparoscope postoperative shivering in patients undergoing general anesthesia].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on laparoscope postoperative shivering in patients undergoing general anesthesia and explore its effect mechanism. METHODS: A total of 80 patients with elective laparoscopic resection of intestinal tumor under general anesthesia were randomly divided into an EA group and a tramadol group, 40 cases in each group. Thirty min prior to the end of the operation, in the EA group, EA was exerted at Neimadian and Zusanli (ST 36), with disperse-dense wave, 2 Hz/100 Hz in frequency, 1 mA in intensity, and lasting 30 min. In the tramadol group, tramadol hydrochloride injection was dropped intravenously, 1 mg/kg. The conditions of shivering, dizziness, nausea, vomiting and agitation were observed in the post-anesthesia care unit (PACU). Heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were observed before treatment (T0), at the moment of extubation (T1), in 3 min of extubation (T2) and 1 h after operation (T3). Using ELISA, at T0 and T3, the expression levels of interleukin 6 (IL-6) and 5-hydroxytryptamine (5-HT) in plasma were detected separately. Choking and agitation were recorded during extubation. RESULTS: ① In the EA group, the incidence of shivering, dizziness, nausea, vomiting and agitation in the PACU was lower than that in the tramadol group (P<0.05). ②Compared with T0, HR, SBP and DBP were increased at T1 and T2 in the tramadol group (P<0.05). HR, SBP and DBP in the EA group were lower than the tramadol group at T1 and T2 (P<0.05). ③Compared with T0, the expression levels of IL-6 and 5-HT in plasma were increased at T3 in the tramadol group (P<0.05). The expression levels of IL-6 and 5-HT in the EA group were lower than the tramadol group at T3 (P<0.05). ④The incidence of choking and agitation during exudation in the EA group was lower than that in the tramadol group (P<0.05). CONCLUSION: Electroacupuncture can reduce the incidence of laparoscopic postoperative shivering under general anesthesia. The potential mechanism mays related to the modulation of the expression levels of IL-6 and 5-HT caused by surgical trauma.

Influence of stacking fault energy on defect structures and microhardness of Cu and Cu alloys.

Nano-structured Cu, Cu-10 wt%Zn and Cu-2 wt%Al with stacking fault energies (SFE) of 78, 35 and 37 mJ/m2, respectively, were preprared through high energy ball milling. X-ray diffraction and Vickers microharness test were used to investigate the microstructure and microhardness of all the samples after ball milling. X-ray diffraction measurements indicate that lower SFEs lead both to decrease in grain size and increase in microstrain, dislocation and twin densities for Cu-10 wt%Zn and Cu-2 wt%Al after 5 h of ball milling. The microhardnesses of Cu-10 wt%Zn and Cu-2 wt%Al reach to nearly the same values of 2.5 GPa after 5 h of ball milling, which is higher than that of Cu of 2.0 GPa. Two factors are considered to contribute to the finer grian size and higher microhardness of Cu-10 wt%Zn and Cu-2 wt%Al: (1) the effect of solid solution strengthening, which result in the interaction of solute atoms with screw dislocations; (2) the introduction of deformation twins during ball milling process by the decreasing of SFE, which results in the grain refinement.

Recursive partitioning analysis classification and graded prognostic assessment for non-small cell lung cancer patients with brain metastasis: a retrospective cohort study.

OBJECTIVE: To assess prognostic factors and validate the effectiveness of recursive partitioning analysis (RPA) classes and graded prognostic assessment (GPA) in 290 non-small cell lung cancer (NSCLC) patients with brain metastasis (BM). METHODS: From Jan 2008 to Dec 2009, the clinical data of 290 NSCLC cases with BM treated with multiple modalities including brain irradiation, systemic chemotherapy and tyrosine kinase inhibitors (TKIs) in two institutes were analyzed. Survival was estimated by Kaplan-Meier method. The differences of survival rates in subgroups were assayed using log-rank test. Multivariate Cox's regression method was used to analyze the impact of prognostic factors on survival. Two prognostic indexes models (RPA and GPA) were validated respectively. RESULTS: All patients were followed up for 1-44 months, the median survival time after brain irradiation and its corresponding 95% confidence interval (95% CI) was 14 (12.3-15.8) months. 1-, 2- and 3-year survival rates in the whole group were 56.0%, 28.3%, and 12.0%, respectively. The survival curves of subgroups, stratified by both RPA and GPA, were significantly different (P<0.001). In the multivariate analysis as RPA and GPA entered Cox's regression model, Karnofsky performance status (KPS) ≥ 70, adenocarcinoma subtype, longer administration of TKIs remained their prognostic significance, RPA classes and GPA also appeared in the prognostic model. CONCLUSION: KPS ≥70, adenocarcinoma subtype, longer treatment of molecular targeted drug, and RPA classes and GPA are the independent prognostic factors affecting the survival rates of NSCLC patients with BM.

Exploring the sulfate patterns of chondroitin sulfate/dermatan sulfate and keratan sulfate in human pancreatic cancer.

This study was designed to explore the sulfation patterns of chondroitin sulfate (CS)/dermatan sulfate (DS), and keratan sulfate (KS) and the expression of carbohydrate sulfotransferases (CHSTs) in 26 pancreatic tumor and normal tissues. CS/DS and KS profiles were simultaneously determined. Pancreatic tumor tissues exhibited increased ΔDi-0S, ΔDi-4S, and ΔDi-6S levels, with absolute ΔDi-4S content being highest, followed by ΔDi-6S. However, as for the contents of KS-6S and KS-6S,6'S, there were no significant regular change. The expression levels of CHST1 and CHST4 were 37 and 15 times higher than those in normal tissues. PCA and OPLS-DA revealed that ΔDi-4S and ΔDi-6S levels could be reliably used to differentiate between healthy and cancerous tissues. The up-regulation of CHST3, CHST12, CHST13, and CHST15 was directly correlated with C-4 and C-6 sulfation. These data provide a foundation for future studies of the role of ΔDi-4S and ΔDi-6S in the progression of pancreatic cancer.

Reduction-active Fe3O4-loaded micelles with aggregation- enhanced MRI contrast for differential diagnosis of Neroglioma.

Differential diagnosis between inflammatory mass and malignant glioma is of great significance to patients, which is the basis for developing accurate individualized treatment. Due to the lack of non-invasive imaging characterization methods in the clinical application, the current diagnosis grading of glioma mainly depended on the pathological biopsy, which is complicated and risky. This study aims to develop a non-invasive imaging differential diagnosis method of glioma based on the reduction activated strategy of intracellular aggregation of sensitive superparamagnetic Fe3O4 nanoparticles (SIONPs). In vitro and in vivo magnetic resonance imaging results indicated that SIONPs could specifically increase the T2 relaxation rate and enhance MR imaging in tumor with redox microenvironment by the response-aggregation in the tumorous site. In vivo experiments also demonstrate that the substantial improvement of T2-weighted imaging contrast could be used to differentiate inflammatory mass and malignant glioma. The reduction-active MR imaging contrast agent offers a new paradigm for designing "smart" MR imaging probes of differential diagnosis of the tumor.

Transient-axial-chirality controlled asymmetric rhodium-carbene C(sp2)-H functionalization for the synthesis of chiral fluorenes.

In catalytic asymmetric reactions, the formation of chiral molecules generally relies on a direct chirality transfer (point or axial chirality) from a chiral catalyst to products in the stereo-determining step. Herein, we disclose a transient-axial-chirality transfer strategy to achieve asymmetric reaction. This method relies on transferring point chirality from the catalyst to a dirhodium carbene intermediate with axial chirality, namely a transient-axial-chirality since this species is an intermediate of the reaction. The transient chirality is then transferred to the final product by C(sp2)-H functionalization reaction with exceptionally high enantioselectivity. We also generalize this strategy for the asymmetric cascade reaction involving dual carbene/alkyne metathesis (CAM), a transition-metal-catalyzed method to access chiral 9-aryl fluorene frameworks in high yields with up to 99% ee. Detailed DFT calculations shed light on the mode of the transient-axial-chirality transfer and the detailed mechanism of the CAM reaction.

Immersive virtual reality as analgesia for women during hysterosalpingography: study protocol for a randomized controlled trial.

BACKGROUND: Hysterosalpingography (HSG) is an accepted radiologic diagnostic modality for initial infertility workup, and is generally considered uncomfortable and painful. However, the management of pain related to HSG remains inefficient. As an emerging nonpharmacologic and noninvasive pain control strategy, virtual reality (VR) distraction has been successfully used in areas such as burns, blunt force trauma, hospital-based needle procedures, dental/periodontal procedures, and urological endoscopy patients. This study aims to evaluate the analgesic effect of VR during HSG. METHODS/DESIGN: A single-center, parallel-group, randomized controlled trial will be carried out in the Radiology Department of Yinchuan Women and Children Healthcare Hospital, Yinchuan. A total of 200 participants who are scheduled for HSG will be enrolled in this study. The participants will be randomized (1:1) into two groups: a VR group and a blank control group. The VR group will receive routine care plus immersive VR intervention and the blank control group will receive routine care. Outcomes will be monitored at baseline, immediately after HSG and 15 min after HSG for each group. The primary outcome is the worst pain score during HSG by a visual analog scale (VAS). The secondary outcomes include: affective pain, cognitive pain, and anxiety during the HSG procedure; worst pain within 15 min after HSG; patient satisfaction and acceptance with pain management; physiological parameters; adverse effects; HSG results; and immersion perception score of the VR system (for the VR condition only). DISCUSSION: This study will focus on exploring a simply operated, noninvasive and low-cost analgesia during the HSG procedure. The results of this trial will provide data on the feasibility and safety of VR distraction therapy during HSG. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR1900021342. Registered on 16 February 2019.

Effect of Poly(ethylene glycol) (PEG) Surface Density on the Fate and Antitumor Efficacy of Redox-Sensitive Hybrid Nanoparticles.

The effects of poly(ethylene glycol) (PEG) on improving the biological compatibility and circulation time of nanocarriers are determined by the surface density of PEG on nanoparticles. PEG with high surface density on nanocarriers has greater accumulation in tumor tissues. However, this impairs the release of drugs loaded in the nanoparticles in the tumor tissues. The relations and internal regularities between the controlled stripping of PEG of nanoparticles and its fate and antitumor efficacy in vivo remain unsolved. Redox-sensitive hybrid nanoparticles coated with varied PEG densities were prepared by blending a redox-sensitive polymer of DLPE-SS-MPEG. To keep identical nanoproperties, these nanoparticles were prepared with a similar size distribution of around 100 nm. The effects of controlled stripping of PEG on antitumor activities of nanoparticles were then investigated. As the PEG surface density increased, lower cellular internalization by tumor cells was observed. However, nanoparticles with higher controlled stripping of PEG showed greater accumulation in tumor tissues and advanced antitumor activities in vivo.

Extracellular matrix metalloproteinase inducer (EMMPRIN) is present in smooth muscle cells of human aneurysmal aorta and is induced by angiotensin II in vitro.

The aim of the present study was to determine whether EMMPRIN (extracellular matrix metalloproteinase inducer) is present and is up-regulated in human aneurysmal aortas, and to assess a possible association with AngII (angiotensin II)-induced aneurysm formation. The presence of EMMPRIN was assessed in 41 surgical specimens from patients with a TAA (thoracic aortic aneurysm) (Type A aortic dissection, n=12; Type B aortic dissection, n=7; and TAA without dissection, n=7) or an AAA (abdominal aortic aneurysm, n=15) by immunohistochemistry. EMMPRIN expression in aortic aneurysm tissues was compared with 12 aortas obtained during autopsy (free of any vascular diseases), and scored for both staining intensity and the percentage of vascular cells stained. EMMPRIN protein levels in cultured human aortic SMCs (smooth muscle cells) following stimulation of AngII were analysed by Western blotting. Significant EMMPRIN immunoreactivity was detected in aortic aneurysm lesions from patients with TAAs and AAAs. In the aneurysmal wall, alpha-actin-positive SMCs were the main source of EMMPRIN. The frequency of EMMPRIN overexpression was significantly higher (P=0.026) in TAAs with dissection (68.4%) than TAAs without dissection (14.3%). AngII stimulation up-regulated the expression of EMMPIRN in cultured human aortic SMCs, which was suppressed by the addition of the AT1R (AngII type 1 receptor) antagonist losartan. In conclusion, the present study is the first to report the expression of EMMPRIN in aortic aneurysmal diseases, and we speculate that EMMPRIN may be important in the pathogenesis of these diseases. Whether these abnormalities are potential therapeutic targets deserve further investigation.

Gold-Catalyzed Hydroalkoxylation/Povarov Reaction Cascade of Alkynols with N-Aryl Imines: Synthesis of Tetrahydroquinolines.

A one-pot gold-catalyzed hydroalkoxylation/Povarov reaction cascade of alkynols with N-aryl imines or in situ generated iminium has been developed. The protocol provides a facile access to a series of fused tricyclic tetrahydroquinolines with a broad substrate scope using readily available materials under mild conditions. The unique mechanistic feature is the dual function of the gold catalyst, which first catalyzed the intramolecular hydroalkoxylation of alkynols, and upon the formation of dihydrofuran species, promoted the following Povarov reaction with high stereoselectivity.

Gold-Catalyzed Oxidative Cyclization/Aldol Addition of Homopropargyl Alcohols with Isatins.

A novel gold-catalyzed oxidative cyclization/aldol addition of homopropargyl alcohols with isatins has been developed that provides an effective access to the 3-hydroxyoxindoles in high yields under mild reaction conditions with high diastereoselectivities. In comparison with disclosed transformations of alkyne oxidations via an α-oxo gold carbene route, this is the first example of an aldol-type interception of an ylide (or its enolate form) intermediate with alkyne as a safe and readily available nondiazo carbene precursor.

Single-Component Bismuth Nanoparticles as a Theranostic Agent for Multimodal Imaging-Guided Glioma Therapy.

Single-component nanomaterials such as bismuth (Bi) based on nanoparticles (NPs) intrinsically having both diagnostic and therapeutic capabilities are widely needed in biomedical fields. However, their design and fabrication still face enormous challenges. Here, a kind of pure Bi NPs with ultrahigh X-ray attenuation coeffcient was developed and evaluated as a simple but powerful theranostic nanomaterals and potent light-to-heat conversion efficiency for photoacuostic imaging (PAI)/photothermal therapy (PTT) in this study. The prepared pure Bi NPs showed excellent photothermal performance and the temperature of NPs solution (1 mg/mL) increased to 70 °C under near-infrared light irradiation within 4 min. The pure Bi NPs showed obvious enhancement effect both in X-ray computed tomography (CT) and PA imaging modalities in vivo. In addition, the glioma growth was efficiently suppressed by the pure Bi NPs after 808 nm laser irradiation, while maintained the biosafety and low toxicity. Thus, it is notable that this type of Bi nanomaterial has great potential in multi-imaging guided cancer treatment.

Immunoregulatory effects of ethyl-acetate fraction of extracts from Tetrastigma hemsleyanum Diels et. Gilg on immune functions of ICR mice.

OBJECTIVE: To evaluate the effects of ethyl-acetate fraction (EAF) of extracts from Tetrastigma hemsleyanum Diels et. Gilg (TDG) on immune functions of ICR mice. METHODS: ICR mice were exposed to different doses of EAF for 15 or 30 days and then their immune functions were analyzed, including ConA-induced splenic lymphocyte transformation, SRBC-induced delayed type hypersensitivity response, serum hemolysin analysis, antibody-producing cells, peritoneal macrophage phagocytized chicken red blood cells, natural killer cell activity, and serum level of cytokines. RESULTS: EAF of extracts from TDG at different doses had various effects on immune functions of ICR mice. As compared with the controls, it increased the mouse spleen lymphocyte transformation induced by ConA, the left-hind voix pedis thickness and the number of plague forming cells (PFCs) at the dose of 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the ink clearance ability at the dose of 0.91 mg/mL, 1.82 mg/mL, 5.48 mg/mL, and 9.12 mg/mL, respectively; increased the phagocytosis index of mononuclear-macrophages and production of serum interferon-gamma (IFN-gamma) at the dose of 5.48 mg/mL; and could promote the production of serum tumor necrosis factor-alpha (TNF-alpha) at the dose of 9.12 mg/mL. CONCLUSION: EAF of extracts from TDG can regulate mouse immune functions in vivo.

Renal protective activity of Hsian-tsao extracts in diabetic rats.

OBJECTIVE: To investigate the renal protective activity of Hsian-tsao Mesona procumbens Hemsl. water extracts in diabetic rats. METHODS: Thirty Sprague-dawley female rats were randomly divided into three groups (n = 10 each), "control group" with intraperitoneal saline injection, "diabetic group" with 60 mg of intraperitoneal streptozotocin injection per kg of body weight and "Hsian-tsao group" with intragastric administration of Hsian-tsao extraction everyday for 4 weeks after intraperitoneal streptozotocin injection. The body weight and blood sugar were measured before and after model induction in the three groups. Thrombospondin-1 (TSP-1) expressions in the kidney were monitored by immunohistochemistry. Kidney ultrastructural changes were also analyzed by using transmission electron microscopy. RESULTS: Before diabetic model induction, there were no significant differences among the three groups in body weight and blood sugar. Four weeks after the induction of diabetes, the differences became statistically significant. Electron microscopy also revealed disruption of the foot processes of the podocytes and other damages in diabetic group. These damages were significantly less severe in Hsian-tsao group when compared with the diabetic group. TSP-1 expressions in the kidney were significantly increased in both the diabetic group and Hsian-tsao group, but it was relatively lower in Hsian-tsao group than in diabetic group. CONCLUSION: Our results showed that Hsian-tsao treatment in the diabetic rats effectively prevented the pathological alterations in the kidney and decreased the TSP-1 expression. It was suggested that Hsian-tsao had protective effect on the kidneys of the diabetic rats.

Gold-catalyzed Bicyclization of Diaryl Alkynes: Synthesis of Polycyclic Fused Indole and Spirooxindole Derivatives.

An unprecedented gold-catalyzed bicyclization reaction of diaryl alkynes has been developed for the synthesis of indoles in good to high yields. Mechanistically, this alkyne bifunctionalization transformation was terminated by a stepwise formal X-H insertion reaction to furnish the corresponding polycyclic-frameworks with structural diversity, and the key intermediate 3 H-indole was isolated and characterized for the first time. In addition, further transformation of these generated tetracyclic-indoles with PCC as the oxidant provided straightforward access to the spirooxindoles in high yields.