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Five novel bisindole alkaloids, hunzeylanines A-E (1-5), with an unprecedented skeleton were isolated from the roots of Hunteria zeylanica. Compounds 1-5 represent the first examples of akuammine-pleioarpamine-type bisindole alkaloids fused with a dihydropyran unit. Their structures including absolute configurations were established through comprehensive spectroscopic data analyses and computational calculation methods. The plausible biogenetic pathway of 1 was also proposed. Alkaloids 1 and 2 displayed moderate cytotoxicity toward three human cancer cell lines (MDA-MB-231, AV3, and Huh7).

This study explored the protective effect of atractylenolide Ⅰ(AO-Ⅰ) against acetaminophen(APAP)-induced acute liver injury(ALI) in mice and its underlying mechanism. C57 BL/6 J mice were randomly divided into a control group, an APAP group(500 mg·kg~(-1)), a low-dose combination group(500 mg·kg~(-1) APAP + 60 mg·kg~(-1) AO-Ⅰ), and a high-dose combination group(500 mg·kg~(-1) APAP + 120 mg·kg~(-1) AO-Ⅰ). ALI was induced by intraperitoneal injection of APAP(500 mg·kg~(-1)). AO-Ⅰ by intragastric administration was performed 2 hours before APAP treatment, and the control group received the same dose of solvent by intragastric administration or intraperitoneal injection. The protective effect of AO-Ⅰ against APAP-induced ALI was evaluated by detecting alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in the plasma and Hamp;E staining in liver tissues of mice. The malondialdehyde(MDA) and glutathione(GSH) content and catalase(CAT) activity in mouse liver tissues were detected to evaluate the effect of AO-Ⅰ on APAP-induced oxidative stress in the liver. The proteins in the liver p38 mitogen-activated protein kinase(p38 MAPK), c-jun N-terminal kinase(JNK), and nuclear factor kappa-B p65(NF-κB p65) signaling pathways were measured by Western blot, and the liver inflammatory cytokines interleukin-1β(IL-1β) and interleukin-6(IL-6) were detected by real-time PCR. Compared with the APAP group, the combination groups showed reduced APAP-induced ALT level and liver MDA content, potentiated liver CAT activity, and elevated GSH content. Mechanistically, AO-Ⅰ treatment significantly inhibited APAP-up-regulated MAPK phosphorylation and NF-κB p65, and significantly reduced the transcriptional activities of IL-1β and IL-6, downstream targets of NF-κB p65. AO-Ⅰ can improve APAP-induced ALI and the underlying mechanism is related to the inhibition of the MAPK/NF-κB p65 signaling pathway in APAP-challenged mice.

Background Pulmonary arterial hypertension (PAH), characterized by pulmonary artery constriction and vascular remodeling, has a high mortality rate. New drugs for the treatment of PAH urgently need to be developed. Purpose This study was designed to investigate the vasorelaxant activity of OTNA in isolated pulmonary arteries, and explore its molecular mechanism. Methods Pulmonary arteries and thoracic aortas were isolated from mice, and vascular tone was tested with a Wire Myograph System. Nitric oxide levels were determined with DAF-FM DA and DAX-J2™ Red. Cellular thermal shift assays, microscale thermophoresis, and molecular docking were used to identify the interaction between OTNA and aryl hydrocarbon receptor (AhR). The levels of PI3K, p-PI3K, Akt, p-Akt, eNOS, p-eNOS, and AhR were analyzed by Western blotting. Results OTNA selectively relaxed the isolated pulmonary artery rings in an endothelium-dependent manner. Mechanistic study showed that OTNA induced NO production through activation of the PI3K/Akt/eNOS pathway in endothelial cells. Furthermore, we also found that OTNA directly bound to AhR and activated the PI3K/Akt/eNOS pathway to dilate pulmonary arteries by inhibiting AhR. Conclusions OTNA relaxes pulmonary arteries by antagonizing AhR. This study provides a new natural antagonist of AhR as a promising lead compound for PAH treatment.

Five novel bisindole alkaloids, hunzeylanines A-E (

Ervadivamines A (1) and B (2), two unprecedented trimeric monoterpenoid indole alkaloids, were isolated from Ervatamia divaricata. They are the first examples of vobasine-iboga-vobasine-type alkaloid with both C-C and C-N linkage patterns. Their structures including absolute configurations were fully accomplished by extensive spectroscopic analysis, single-crystal X-ray diffraction, and electric circular dichroism methods. The plausible biogenetic pathways of these trimeric alkaloids were also proposed. In addition, compound 1 exhibited significant cytotoxicity against four cancer cells.

C–S–H-PCE nanocomposites (CPNs) serving as nucleation sites are a promising material to accelerate the cement hydration and gain high early strength for cementitious materials. This study aimed to investigate the effects of CPNs on the properties and hydration of cement mortar under different water-to-cement (w/c) ratios. CPNs were prepared via the co-precipitation method in MAPEG-PCE solution and characterized by means of XRD, FT-IR, DLS, TEM , TGA, and TOC . The mechanism and effect of CPNs on the early hydration of cement mortar with w/c ratios of 0.50, 0.40, and 0.35 were assessed in terms of mechanical properties, isothermal calorimetry, setting time XRD, TGA, SEM, and MIP. The results showed that CPNs significantly promoted the early strength development of mortar and a higher enhancement ratio was brought at a lower w/c ratio. Calorimetry and setting results also showed a greater hydration acceleration of samples dosed CPNs with lower w/c ratio. From the analysis of XRD and TGA, the content of CH and C–S–H in the samples dosed CPNs increased with the decrease of w/c ratio in 6 h, while exhibited an opposite trend in 12 h and 3 d. MIP and SEM results showed that CPNs led to a refinement of pore structure and dense morphology, especially at a low w/c ratio. Moreover, the underlying acceleration mechanism of cement hydration versus w/c ratio was that the seeding ability was enhanced for the low distance between cement and CPNs at a low w/c ratio. According to this research, the use of CPNs may be more practical in high-strength concrete.

Tanshinone Ⅱ_A( Tan Ⅱ_A),the liposoluble constituents of Salvia miltiorrhiza,can not only ameliorate the lipidic metabolism and decrease the concentration of lipid peroxidation,but also resist oxidation damage,scavenge free radicals and control inflammation,with a protective effect on prognosis after liver function impairment. Therefore,the studies on the exact mechanism of Tan Ⅱ_A in protecting the liver can provide important theoretical and experimental basis for the prevention and treatment effect of Tan Ⅱ_A for liver injury. In the present study,the protective effects and mechanism of Tan Ⅱ_A on 4-hydroxynonenal( 4-HNE)-induced liver injury were investigated in vitro. Normal liver tissues NCTC 1469 cells were used to induce hepatocytes oxidative damages by 4-HNE treatment. The protective effect of Tan Ⅱ_A on hepatocytes oxidative damages was detected by release amount of lactate dehydrogenase( LDH) analysis and hoechst staining. The protein expression changes of peroxisome proliferator-activated receptor α( PPARα) and peroxisome proliferator response element( PPRE) were analyzed by Western blot analysis in NCTC 1469 cells before and after Tan Ⅱ_A treatment. The gene expression changes of fatty aldehyde dehydrogenase( FALDH) were analyzed by Real-time polymerase chain reaction( PCR) analysis. The results showed that 4-HNE increased the release amount of LDH,lowered the cell viability of NCTC 1469 cells,and Tan Ⅱ_A reversed 4-HNE-induced hepatocyte damage. Western blot analysis and RT-PCR analysis results showed that 4-HNE decreased the expression of PPARα and FALDH and increased the expression of 4-HNE. However,the expression of PPARα and FALDH were increased significantly and the expression of 4-HNE was decreased obviously after Tan Ⅱ_A treatment. This study confirmed that the curative effect of Tan Ⅱ_A was obvious on hepatocytes damage,and the mechanism may be associated with activating PPARα and FALDH expression as well as scavenging 4-HNE.

The atom occupied sites, structures, tetragonal transformation and magnetic properties are studied by the first principles calculations. From least energy principle, the calculated equilibrium lattice parameter is 6.03 Å and 6.00 Å for Cu2MnAl type Ni2YIn (Y=Fe, Co) alloys, respectively. The Ni2YIn (Y=Fe, Co) alloys show steady martensitic phases at c/a=1.29 and c/a=1.36 based on the EBP’s method. Ni atoms and Y (Y=Fe, Co) contribute to the total magnetic moments, and keep parallel aligned in martensitic and austenitic phases. The Ni2YIn (Y=Fe, Co) alloys are the candidates for Ferromagnetic Shape Memory Alloys.

With the output of an OPG/OPA pumped by the third harmonic output 355 nm of a pulsed Nd·YAG laser as radiation source, the emission spectrum of laser induced coal sample plasma is created. The emission spectral line shows the character of Lorenz profile. So Stark broadening is the main widening way of this plasma system. The spatial distribution of the plasma temperature and electron density is measured from the intensity and Stark broadening of the spectral lines. It is found that in the direction from vertical to plasma luminous flame, both plasma temperature and electron density are symmetrically relative to the center. While in the direction of parallel to plasma luminous flame, they are asymmetrically relative to the center. Plasma temperature and electron density is maximized in the centre of the flame, and the emission intensity of the plasma in the centre is also strong. So we ought to collect the emission spectrum in the plasma centre when using the technique of spectroscopy for the diagnosis of plasma characteristics. It is also found that there is a dip in the centre of some spectral lines. This indicates that there exists strong self-absorption in the plasma. The appearance of self-absorption varies with laser wavelength. It is most obvious when the wavelength is near to the center of the profile, because the transition probability is the largest at the center of the profile. Both emission intensity and self-absorption increase with laser energy. These experimental results can be interpreted as the increase of the particle density with laser energy. Thus we ought to select spectral lines with no self-absorption when measuring the parameters of the plasma with the technique of laser spectroscopy. This can ensure higher detection accuracy.

Telechelic polymers have been explored widely because they are precursors for preparing multi-block copolymers, grafted polymers, star polymers, and polymer networks [1-2]. A variety of telechelic polymers with terminals like hydroxy, carboxylic, epoxy groups and carbon–carbon double bond have been prepared by controlled radical polymerization (CRP) techniques including nitroxide-mediated polymerization (NMP), atom transfer radical polymerization (ATRP) and reversible addition-fragmentation chain transfer polymerization (RAFT)[3-5].The CRP techniques can not only control the molecular weight but also can be carried out in the presence of many functional groups from monomers, initiators, or chain transfer agents (CTA).

This study introduced a prototype of an axial-stress bioreactor system that supports long-term growth and development of engineered tissues. The main features of this bioreactor are an integrated substance exchanger and feedback control of pH and PO₂. A 21-day study was conducted to validate the system's ability to maintain a stable environment, while remaining sterile. Our results showed that the pH, PO₂, and nutrient (glucose) remained balanced at appropriate levels, while metabolic waste (lactic acid) was removed. No bacteria or fungi were detected in the system or tissue; thus, demonstrating that it was sterile. These data indicate the bioreactor's strong potential for long-term tissue culture. To explore this idea, the effect of dynamic culture, including cyclic compression and automatic substance exchange, on mouse bone-marrow mesenchymal stem cells (BMSCs) seeded in decalcified bone matrix was studied using the bioreactor prototype. Histological sections of the engineered tissues showed higher cell densities in scaffolds in dynamic culture compared to those in static culture, while cell cycle analysis showed that dynamic culture promoted BMSC proliferation (proliferation index, PI=34.02±1.77) more effectively than static culture (PI=26.66±1.81). The results from a methyl thiazolyl tetrazolium assay were consistent with the loading experimental data. Furthermore, elevated alkaline phosphatase activity and calcium content were observed in dynamic condition compared to static culture. In conclusion, this bioreactor system supplies a method of modulating the pH and PO₂ in defined ranges with only small fluctuations; it can be used as a physiological or pathological analog. Automatic control of the environment is a practical solution for long-term, steady-state culture for future commercialization.

Dexamethasone (Dex) causes osteoblast cell injuries. In the present research, we tested the potential effect of SC79, a novel and specific Akt activator, against Dex in osteoblasts. In primary murine osteoblasts and osteoblastic MC3T3-E1 cells, pretreatment with SC79 significantly attenuated Dex-induced cell death. Further, Dex-induced mitochondrial permeability transition pore (mPTP) opening, cytochrome C release and apoptosis activation were dramatically alleviated with SC79 pretreatment in above cells. At the molecular level, SC79 activated Akt, which was indispensable for subsequent osteoblast protection against Dex. Akt inhibitors (LY294002, perifosine and MK-2206) blocked SC79-induced Akt activation and abolished its anti-Dex actions in osteoblasts. Further, SC79 activated Akt downstream Nrf2 (NF-E2-related factor 2) signaling and attenuated Dex-induced oxidative stress in osteoblasts. Nrf2 shRNA knockdown or S40T mutation almost reversed SC79-mediated anti-oxidant and cytoprotective activities in osteoblasts. Together, these results suggest that SC79 activates Akt-Nrf2 signaling to protect osteoblasts from Dex.

Polyethersulfone (PES) flat sheet membranes were prepared via phase inversion induced by immersion precipitation from a novel lower critical solution temperature (LCST) system containing PES, 1-butanol and N, N-dimethylacetamide. And the effect of coagulation bath temperature on the properties and structure of PES membranes were investigated. The results show that the pure water flux increases and the tensile strength decreases as the coagulation temperature increases form 20°C to 50°C. Besides, the SEM images shows that all of the membranes prepared from a LCST system at different CBT own sponge-like structures.

The performance of a reflective chiral-homeotropic (R-CH) liquid crystal (LC) is simulated by the dynamic parameter space method. The normally black reflective chiral-homeotropic display shows weak color dispersion, high contrast ratio, and fast response time.

Fuzzy system is known to predict model in the electrodialysis process. This paper aimed to study fitting effect by ANFIS in a laboratory scale ED cell. Separation percent of NaCl solution is mainly as a function of concentration, temperature, flow rate and voltage. Besides, ANFIS(Adaptive Neuro-Fuzzy Inference System) based on Sugeno fuzzy model, its structure was similar to neural network and could generate fuzzy rules automatically, using the error back propagation algorithm and least square method to adjust the parameters of fuzzy inference system. We obtained fitted values of separation percent by ANFIS. Separation percent from experiments compared with the fitted values of separation percent. The result is shown that the correlation coefficient is 0.988. Therefore, it is verified as a good performance in the electrodialysis process.

To discover new proteomic biomarkers of hepatocellular carcinoma. Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

Aim: To investigate the effects of peripheral orexins on myoelectric activity of the sphincter of Oddi (SO) in fasted rabbits, and carry out a preliminary investigation into the mechanisms underlying these effects. Methods: Myoelectric activity of SO in fasted rabbits was recorded before and after intravenous or local application of orexins. The effects of intravenous atropine on orexin-increased myoelectric activity of SO were tested. Results: Myoelectric activity of SO was activated by both intravenous and local injection of orexin-A or orexin-B. Intravenous application of atropine completely inhibited the excitatory effect of orexins on SO. Conclusion: Peripheral application of orexins can increase myoelectric activity of SO in fasted rabbits, which is partially associated with the activation of the cholinergic pathway.

To study the macroscopic, microscopic identification and chemical components of Cyperus rotundus growing in Wen-River area.The features of different parts of Cyperus rotundus were described by material morphology and microscopic identification, the chemical components of aerial part and rhizome of Cyperus rotundus were studied by chemical experiment and GC-MS analysis.Summarized the transverse section structure of rhizome, stem and leaf of Cyperus rotundus, the chemical components of aerial part and the components and relative content of volatile oil in rhizome were determined.This study provides reference for the drug identification and the daodi medicinal material exploitation of Cyperus rotundus.

To investigate the mechanism of Longchang Granule in the treatment of benign prostatic hyperplasia.Rat models of prostate hyperplasia were made by castration and testosterone propionate injection. After treated respectively with Longchang Granule and Longbishu by gastrogavage for 30 days, all the model rats were killed and their prostate glands harvested for the measurement of the wet weight and detection of the expression of bax in the prostatic hyperplastic tissues by RV 2-step method.The wet weight of the prostate was (0.61 +/- 0.03) g in the blank control group, (0.95 +/- 0.04) g in the model group, (0.73 +/- 0.02) g in the Longbishu group, (0.80 +/- 0.05) g in the low-dose Longchang group, (0.78 +/- 0.07) g in the medium-dose Longchang group and (0.68 +/- 0.03) g in the high-dose Longchang group, with significant differences between the model and the intervention groups (P0.05). The prostate indexes in the above groups were 0.143 +/- 0.006, 0.226 +/- 0.008, 0.172 +/- 0.004, 0.199 +/- 0.012, 0.181 +/- 0.010 and 0.168 +/- 0.003, respectively, and the expressions of bax by mean optical density were 0.226 +/- 0.010, 0.184 +/- 0.005, 0.206 +/- 0.015, 0.199 +/- 0.001, 0.202 +/- 0.003 and 0.211 +/- 0.003, respectively, both with significant differences between the model and the intervention groups (P0.05).Longchang Granule can effectively reduce the wet weight of the prostate and alleviate its pathological changes in BPH rats, the mechanism of which may be associated with its effect of upregulating the expression of bax and accelerating cell apoptosis in the prostate tissues.

To investigate the effects of peripheral orexins on myoelectric activity of the sphincter of Oddi (SO) in fasted rabbits, and carry out a preliminary investigation into the mechanisms underlying these effects.Myoelectric activity of SO in fasted rabbits was recorded before and after intravenous or local application of orexins. The effects of intravenous atropine on orexin-increased myoelectric activity of SO were tested.Myoelectric activity of SO was activated by both intravenous and local injection of orexin-A or orexin-B. Intravenous application of atropine completely inhibited the excitatory effect of orexins on SO.Peripheral application of orexins can increase myoelectric activity of SO in fasted rabbits, which is partially associated with the activation of the cholinergic pathway.