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Severe uterine injury is a major cause of endometrial scar formation and female infertility. Currently, the methods for accelerating injured uterine healing are still lacking. Genetic engineering modification of mesenchymal stem cells (MSCs) has been shown great promise in preclinical studies on regeneration. Here, we constructed a type of UC-MSCs with overexpressed bFGF (UC-MSCbFGF) and investigated the effects of the UC-MSCbFGF/scaffold on functional regeneration of the full-thickness defect uterus of the rat model. At day 7, 14, 30 after treatments, the rats were euthanized and the injured uterus were observed. The structural and functional change of uterine were assessed by hematoxylin and eosin (HE) staining, immunohistochemical staining and fertility experiment. The UC-MSCbFGF/scaffold group exhibited anti-inflammatory effect, and the number of CD45+ cell in the UC-MSCbFGF/scaffold group was significantly less than that in UC-MSCs/scaffold group and scaffold group, but higher than sham-operated group at day 7 post-mending. At day 14, the UC-MSCbFGF/scaffold group exhibited dramatically pro-angiogenesis efficacy compared with UC-MSCs/scaffold group and scaffold group. At day 30, the endometrial thickness, structure of myometrium and blood vessels in the UC-MSCbFGF/scaffold were better than those of the UC-MSCs/scaffold group and scaffold group, even close to sham-operated group. Implantation rate at injury region post-operation 30 days in the UC-MSCbFGF/scaffold group (8/16) was significantly higher than that in UC-MSCs/scaffold group (1/16) and scaffold group (0/16). Taken together, the UC-MSCbFGF/scaffold system suppressed local inflammation, promoted angiogenesis and accelerated regeneration of the defected uterine wall, and thereby greatly shortened the healing time of the injured uterus.

Anorexia nervosa (AN) is a psychiatric illness with the highest mortality. Current treatment options have been limited to psychotherapy and nutritional support, with low efficacy and high relapse rates. Hypothalamic AgRP (agouti-related peptide) neurons that coexpress AGRP and neuropeptide Y (NPY) play a critical role in driving feeding while also modulating other complex behaviors. We have previously reported that genetic ablation of Tet3 , which encodes a member of the TET family dioxygenases, specifically in AgRP neurons in mice, activates these neurons and increases the expression of AGRP, NPY, and the vesicular GABA transporter (VGAT), leading to hyperphagia and anxiolytic effects. Bobcat339 is a synthetic small molecule predicted to bind to the catalytic pockets of TET proteins. Here, we report that Bobcat339 is effective in mitigating AN and anxiety/depressive-like behaviors using a well-established mouse model of activity-based anorexia (ABA). We show that treating mice with Bobcat339 decreases TET3 expression in AgRP neurons and activates these neurons leading to increased feeding, decreased compulsive running, and diminished lethality in the ABA model. Mechanistically, Bobcat339 induces TET3 protein degradation while simultaneously stimulating the expression of AGRP, NPY, and VGAT in a TET3-dependent manner both in mouse and human neuronal cells, demonstrating a conserved, previously unsuspected mode of action of Bobcat339. Our findings suggest that Bobcat339 may potentially be a therapeutic for anorexia nervosa and stress-related disorders.

Background: Preeclampsia is a complicated syndrome with marked heterogeneity. The biomarker-based classification for this syndrome is more constructive to the targeted prevention and treatment of preeclampsia. It has been reported that preeclamptic patients had elevated microRNA-155 (miR-155) in placentas or circulation. Here, we investigated the characteristics of patients with high placental miR-155 (pl-miR-155). Methods: Based on the 95th percentile (P95) of pl-miR-155 in controls, preeclamptic patients were divided into high miR-155 group (≥P95) and normal miR-155 group ( Results: About one-third of preeclamptic patients had high pl-miR-155 expression, which was positively correlated with circulating miR-155 levels. These patients could be clustered as 1 group, according to clinical manifestation, placental pathology, or transcriptomes by t-distributed stochastic neighbor embedding and hierarchical clustering analysis. Further, the pregnant mice with placental restricted miR-155 overexpression could simulate the changes of clinical signs, pathology, and transcriptome of placentas in patients with high pl-miR-155. AntagomiR-155 treatment relieved the preeclampsia-like phenotype and improved the placental vascular development in mice. Conclusions: There is at least 1 type of preeclampsia with upregulated miR-155 presenting more severe clinical manifestations. MiR-155 may be a potential therapeutic target in patients with high pl-miR-155.

Preeclampsia (PE) is a pregnancy-related syndrome characterized by new-onset hypertension and proteinuria after gestational 20 weeks. Oxidative stress, resulting from the imbalance between the production of oxidants and antioxidants in placentas, is recognized as a key pathology of PE. To date, the molecules that regulate antioxidants production remain unclear. CD151, a member of tetraspanins, is an important regulator of many physiological functions. However, the function of CD151 in oxidative stress and its association with pregnancy-related complications are currently unknown. In the present study, we have demonstrated that CD151 was a key regulator of antioxidants in placentas. Compared with the placentas of the controls, the placentas of PE patients exhibited decreased CD151 expression accompanying with decreased antioxidant gene expression (HO-1, NQO-1, GCLC and SOD-1). In vitro, overexpression of CD151 in trophoblast cells could enhance HO-1, NQO-1, GCLC and SOD-1 expression but downregulation of CD151 decreased those antioxidant genes expression, which indicates CD151 is the upstream of antioxidants. Importantly, the phenotype of PE (hypertension and proteinuria) was mimicked in the downregulating CD151 induced mouse model. Moreover, the beneficial effect of CD151 in trophoblast cells was hindered when ERK and Nrf2 signaling were blocked. Overall, our results revealed CD151 might be a new target for PE treatment.

Thin endometrium has been widely recognized as a critical cause of infertility, recurrent pregnancy loss, and placental abnormalities; however, access to effective treatment is a formidable challenge due to the rudimentary understanding of the pathogenesis of thin endometrium. Here, we profiled the transcriptomes of human endometrial cells at single-cell resolution to characterize cell types, their communications, and the underlying mechanism of endometrial growth in normal and thin endometrium during the proliferative phase. Stromal cells were the most abundant cell type in the endometrium, with a subpopulation of proliferating stromal cells whose cell cycle signaling pathways were compromised in thin endometrium. Both single-cell RNA sequencing and experimental verification revealed cellular senescence in the stroma and epithelium accompanied by collagen overdeposition around blood vessels. Moreover, decreased numbers of macrophages and natural killer cells further exacerbated endometrial thinness. In addition, our results uncovered aberrant SEMA3, EGF, PTN, and TWEAK signaling pathways as causes for the insufficient proliferation of the endometrium. Together, these data provide insight into therapeutic strategies for endometrial regeneration and growth to treat thin endometrium.

Emerging evidence demonstrates the important role of circular RNAs (circRNAs) in regulating pathological processes in various diseases including organ fibrosis. Endometrium fibrosis is the leading cause of uterine infertility, but the role of circRNAs in its pathogenesis is largely unknown. Here, we provide the evidence that upregulation of circPTPN12 in endometrial epithelial cells (EECs) of fibrotic endometrium functions as endogenous sponge of miR-21-5p to inhibit miR-21-5p expression and activity, which in turn results in upregulation of ΔNp63α to induce the epithelial mesenchymal transition (EMT) of EECs (EEC-EMT). In a mouse model of endometrium fibrosis, circPTPN12 appears to be a cofactor of driving EEC-EMT. Our findings reveal the novel mechanism in the pathogenesis of endometrium fibrosis and the potential therapeutic strategy for endometrium fibrosis via targeting circPTPN12/miR-21-5p/ΔNp63α pathway.

Epithelial homeostasis plays an essential role in maintaining endometrial function. But the epithelial role in endometrial fibrosis has been less studied. Previously, we showed that ectopic expression of ΔNp63α is associated with fibrosis process and epithelial dysfunction in endometria of patients with intrauterine adhesions (IUAs). Since ΔNp63α is profoundly involved in maintaining the epithelial homeostasis, we hereby focused on its roles in regulating the function and phenotype of endometrial epithelial cells (EECs) in context of endometrial fibrosis. We identified a typical type 2 epithelial-to-mesenchymal transition (EMT) in EECs from IUA patients and this process was induced by the forced expression of ΔNp63α in EECs. In transcriptomic analysis, we found that diverse signaling pathways regulated by ΔNp63α were involved in pro-EMT. We demonstrated that the DUSP4/GSK-3β/SNAI1 pathway was critical in transducing the pro-EMT signals initiated by ΔNp63α, while bFGF reversed ΔNp63α-induced EMT and endometrial fibrosis both in vitro and in vivo by blocking DUSP4/GSK3β/SNAI1 pathway. Taken together, our findings are important to understand the molecular mechanisms of endometrial fibrosis and to provide potential therapeutic targets.

In this paper, the effect of top heave motion frequency on the global dynamic responses of a deep sea mining system is presented. The excitation of different frequencies is induced by time-varying heave motion of the surface vessel. First the numerical model of the system is established which can be solved by the lump mass method. Then three different scenarios caused by harmonic heave motion corresponding to different heave motion frequencies are introduced. On these basis, the pipe tension at bottom, deflection and bending force of the system are presented and discussed. Amplitude spectrum through FFT and the phase plots for the time histories of pipe bottom motion are made to analysis the possible different motion modes.

Problem Asherman's syndrome (AS) is characterized by endometrial fibrosis leading to intrauterine adhesions and symptoms like hypomenorrhea, infertility, and recurrent pregnancy loss. Macrophages are key regulators of inflammation, tissue repair, regeneration, and fibrosis. However, the role of macrophages in AS remains unclear. Method of study Endometrial biopsies of AS patients and controls were collected during the late proliferating phase of menstrual cycle. Fibrosis and proliferation markers were detected by Masson's trichrome staining and immunohistochemistry. Macrophages were examined by immunostaining and flow cytometry. The expression levels of CCL2, CSF1, CSF1R, and GM-CSF were detected by quantitative real-time polymerase chain reaction (q-PCR) and immunohistochemistry. A well-differentiated endometrial cell line Ishikawa (IK) was used for in vitro studies. Macrophages differentiating from THP-1 monocytic cells were polarized by IL-4/IL-13. Their culture supernatants (M(IL-4/13)-S) were applied to H2 O2 or bleomycin-damaged IK cells. Results In AS patients, endometrial stroma was replaced by fibrous tissue and cell proliferation was reduced. Macrophages in endometrial tissue were mainly alternative activated macrophages and their number was significantly decreased in AS patients. The CSF1 expression level was reduced in AS patients. M(IL-4/13)-S promoted the growth and migration of IK cells and inhibited H2 O2 -induced apoptosis. M(IL-4/13)-S protected IK cells from bleomycin-induced fibrosis. Conclusion Macrophages are critical cells involved in the process of endometrial repair and fibrosis. The decreased amount of endometrial macrophages may be attributed to the reduced expression level of CSF1. Manipulation of macrophage activation/function may provide a novel therapeutic target for AS.

Medulloblastoma (MB) and glioblastoma (GBM) are the most prevalent malignant brain tumors. The identification of novel therapeutic strategies is urgent for MB and GBM patients. Herein, we discovered 13a-(S)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b]-indolizidine (PF403) strongly exhibited inhibitory activity against Hedgehog (Hh) pathway-hyperactivated MB and GBM cells with a 50% inhibitory concentration (IC50) of 0.01 nM. CAT3 was designed and synthesized as the prodrug of PF403 and displayed significant in vivo efficacy against MB and GBM. Mechanistic study revealed that CAT3 inhibited MB and GBM primarily by interrupting the Hh signaling pathway. At the molecular level, PF403 inhibited the cell surface accumulation of the Smoothened (Smo) receptor by directly binding or enhancing the interaction of Smo with the repressor Ptch1. Furthermore, PF403 significantly repressed Gli1 nuclear accumulation and transcription by promoting Sufu-Gli1 and PKA-Gli1 interactions. Collectively, our studies support the hypothesis that CAT3 is a promising therapeutic agent for the treatment of Hh-driven MB and GBM.

Aims The mechanism of cough hypersensitivity induced by particulate matter 2.5 (PM2.5) remains elusive. The current study was designed to explore the effect of transient receptor potential vanilloid-1 (TRPV1) on cough hypersensitivity in airway and central nervous system. Main methods The PM2.5-induced chronic cough model of guinea pig was established by exposure to different doses of PM2.5 for three weeks. After exposure, the animals were microinjected with TRPV1 agonist capsaicine, antagonist capsazepine in the dorsal vagal complex respectively. Cough sensitivity was measured by determining the provocative concentration of citric acid inducing 5 or more coughs (C5). Airway inflammation was detected by hematoxylin eosin (HE) staining and Evans blue fluorescence, and substance P (SP) and TRPV1 expressions in airway were observed by immunohistochemical staining. TRPV1 expressions in the dorsal vagal complex were observed by immunofluorescence. Retrograde tracing by pseudorabies virus-Bartha (PRV-Bartha) was conducted to confirm the regulatory pathway between airway and central nervous system. Key findings PM2.5 induced TRPV1 expressions in both of airway and dorsal vagal complex and airway neurogenic inflammation. Airway vascular permeability increased after being exposed to PM2.5. The expressions of SP in the airway and airway inflammation was increased after microinjecting TRPV1 agonist, and decreased after microinjecting TRPV1 antagonist. PRV infected neurons in medulla oblongata mainly located in the dorsal vagal complex. Significance These findings show that TRPV1 in the dorsal vagal complex could promote airway neurogenic inflammation and cough reflex sensitivity through neural pathways of vagal complex-airways, which indicate the therapeutic potential of specific inhibition of TRPV1 for chronic cough induced by PM2.5.

Graphical abstract, The development of new therapeutic agents against the coronavirus causing Middle East Respiratory Syndrome (MERS) is a continuing imperative. The initial MERS-CoV epidemic was contained entirely through public health measures, but episodic cases continue, as there are currently no therapeutic agents effective in the treatment of MERS-CoV, although multiple strategies have been proposed. In this study, we screened 30,000 compounds from three different compound libraries against one of the essential proteases, the papain-like protease (PLpro), using a fluorescence-based enzymatic assay followed by surface plasmon resonance (SPR) direct binding analysis for hit confirmation. Mode of inhibition assays and competition SPR studies revealed two compounds to be competitive inhibitors. To improve upon the inhibitory activity of the best hit compounds, a small fragment library consisting of 352 fragments was screened in the presence of each hit compound, resulting in one fragment that enhanced the IC50 value of the best hit compound by 3-fold. Molecular docking and MM/PBSA binding energy calculations were used to predict potential binding sites, providing insight for design and synthesis of next-generation compounds.

CAT3, one of the (+)-deoxytylophorinine-based phenanthroindolizidine alkaloids, is a promising therapeutic agent for the treatment of hedgehog (Hh)-driven glioblastoma and is currently being evaluated in preclinical studies. In this paper, a novel and practical synthetic route for CAT3 was firstly demonstrated with 10% overall yield in 11 steps and has been successfully validated for pilot-plant scale preparation. Investigation of the substitution at the 3-position of phenanthrene revealed that the electron-donating functionality can well preserve the S configuration. In particular, the excellent enantiomeric excess of CAT3 (≥99% ee) was achieved by introducing the strongly electron-donating tert-butyldimethylsilyl (TBS) group.

Nine new grayanoids (1-9), together with 11 known compounds, were isolated from the roots of Rhododendron molle. The structures of the new compounds (1-9) were determined on the basis of spectroscopic analysis, including HRESIMS, and 1D and 2D NMR data. Compounds 4, 6, 12, and 14-20 showed significant antinociceptive activities in an acetic acid-induced writhing test. In particular, 14 and 15 were found to be more potent than morphine for both acute and inflammatory pain models and 100-fold more potent than gabapentin in a diabetic neuropathic pain model.

Neuroblastoma is the most common cancer in infants and the fourth most common cancer in children. Our previous study showed that PF403 had a potent antitumor ability. In the present study, we evaluated the anti-neuroblastoma property of PF403 and investigated the underlying mechanisms. MTT assay, colony formation assay and flow cytometry assay were used to assess cytotoxicity of PF403 on SH-SY5Y cells. Transwell assay was chosen to estimate the anti-invasion ability of PF403 on neuroblastoma cells. The protein expression was detected by western blot analysis. The SH-SY5Y brain xenograft model was used to assess in vivo antitumor activity of PF403. PF403-mediated SH-SY5Y cell death was found to be dose- and time-dependent, and PF403 was able to limit invasion and metastasis of neuroblastoma cells. MRI and pathology analysis proved that the pro-drug of PF403, CAT3, inhibited SH-SY5Y cells in vivo. PF403 decreased expression of phosphorylated FAK, MMP-2 and MMP-9 proteins, and downregulated the activity of PI3K/AKT and Raf/ERK pathways, followed by regulation of the proteins expression of Bcl-2 family, activated caspase-3, -9 and PARP and initiation of apoptosis of neuroblastoma cells. PF403 exerted cytotoxicity against SH-SY5Y neuroblastoma cell both in vitro and in vivo, and inhibited its invasion ability, suggesting PF403 has potential as a new anticancer drug for the treatment of neuroblastoma.

A novel asymmetric synthesis of a phenanthroindolizidine alkaloid, (+)-deoxytylophorinine, is reported, which uses a chiral nickel(II) complex of a glycine Schiff base to synthesize a substituted ( R )-3-phenanthrylalanine as a key intermediate and Meldrum’s acid to construct the E ring.

CAT ((+)-(13aS)-deoxytylophorinine) is a novel anticancer drug belonging to phenanthroindolizidine alkaloids. A sensitive and reliable liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for simultaneous quantification of CAT and its pharmacologically active 3-O-desmethyl metabolite (S-4) was developed and validated in rat plasma using rotundine as the internal standard (IS). CAT, S-4 and IS were extracted by acetonitrile protein precipitation and separated on an Eclipse XDB-C18 column (1.8 μm, 4.6 mm × 50 mm) with acetonitrile–water (27:73, v/v) mobile phase containing 0.1% formic acid at a 0.4 mL/min flow rate. Positive ion electrospray ionization in multiple reaction monitoring mode was employed to measure CAT, S-4 and IS by monitoring the transitions m/z 364.2 → 70.1 for CAT, 350.1 → 70.1 for S-4 and 356.2 → 192.2 for IS. Good linear correlation ( r 2 > 0.991) was achieved for CAT and S-4 over the range of 0.214–128.16 and 0.044–11.00 ng/mL, respectively. The lower limit of quantification was 0.214 ng/mL for CAT and 0.044 ng/mL for S-4, using 50 μL rat plasma samples. The intra- and inter-day precisions were not exceed 15% and the accuracy ranged between 94.80% and 108.22%. The average extraction recoveries of both analytes were greater than 94.62%. The method was successfully applied to the pharmacokinetic study of CAT and S-4 in rats after oral administration.

The aim of this study was to investigate the effects of melatonin on oxidative stress, the expression of transient receptor potential melastatin-2 (TRPM2) in guinea pig brains, and the influence of melatonin on oxidative stress in lungs and airway inflammation induced by particulate matter 2.5 (PM2.5). A particle suspension (0.1 g/ml) was nasally administered to the guinea pigs to prepare a PM2.5 exposure model. Cough frequency and cough incubation period were determined through RM6240B biological signal collection and disposal system. Oxidative stress markers, including malondialdehyde (MDA), total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and glutathione peroxidase (GSH-Px), in the medulla oblongata were examined through spectrophotometer. Reactive oxygen species (ROS) were detected in the hypoglossal nucleus, cuneate nucleus, Botzinger complex, dorsal vagal complex, and airway through dihydroethidium fluorescence. Hematoxylin-eosin (HE) staining and substance P expression via immunohistochemistry revealed the inflammatory levels in the airway. TRPM2 was observed in the medulla oblongata through immunofluorescence and Western blot. The ultrastructure of the blood-brain barrier and neuronal mitochondria was determined by using a transmission electron microscope. Our study suggests that melatonin treatment decreased PM2.5-induced oxidative stress level in the brains and lungs and relieved airway inflammation and chronic cough. TRPM2 might participate in oxidative stress in the cough center by regulating cough.

Nine new prenylbisabolane diterpenoids, claoxylones A–I (1–9), were isolated from the branches and leaves of Claoxylon polot. This is the first example of prenylbisabolane diterpenoids with furan and tetrahydrofuran rings. Their structures and relative configurations were established by spectroscopic and conformational analysis, and the absolute configurations were determined by single-crystal X-ray diffraction and electronic circular dichroism (ECD) analysis. Compounds 1–9 exhibited antiviral activity against Coxsackie B3 virus, with IC50 values of 6.0–33.3 μM.

In the presence of Pt catalyst, α,ω-hydrogenpolysiloxane reacted with allyl glycidyl ether, and an intermediate α,ω-diepoxysiloxane was formed. The epoxy cyclic-opening reaction was conducted between the intermediate and polyetheramine in isopropanol solution, the silicone polyetheramine block copolymer (BPEAS) was thus made. The chemical structures of BPEAS were characterized using IR and 1H-NMR separately. Then cotton fabric was treated with BPEAS for application purpose. The finishing effects were tested in terms of film morphology, hydrophilic ability, softness and mechanical properties. The recorded results showed that BPEAS can be used directly to treat cotton fabrics without adding any emulsifier at the viscosity of 6700 mPa·s and amino value of 0.6009 mmol/g. Bending rigidity and hysteresis of the treated fabric decreased by 53.53 % and 67.39 %, the drape coefficient dropped by 15 %, whereas the wrinkle recovery angle increased by 57.14 %. The treated cotton fabric is hydrophilic, and has a bulky soft hand, better anti-wrinkle property compared to the untreated one.

Penicillactones A-C (1-3) are structurally related natural products with a spirocyclic anhydride structure and were isolated from the endophytic fungus Penicillium dangeardii Pitt. Penicillactones B and C showed inhibition of the release of β-glucuronidase from polymorphonuclear leukocytes with ED50 values of 2.58 and 1.57 μM. A 2D INADEQUATE experiment of 1 was performed at natural abundance to confirm the arrangement of its carbon skeleton. The configurations of 1-3 were established through extensive NMR spectroscopic analysis, selective structural modifications, and CD analysis.

Mollolide A (1), a diterpenoid featuring a new 1,10:2,3-disecograyanane skeleton, was isolated from the roots of Rhododendron molle. Its structure was elucidated through extensive MS, IR, and NMR spectroscopy analyses. The absolute configuration was determined by single-crystal X-ray diffraction of its p-bromobenzoate derivative (1b). Compound 1 exhibits a significant analgesic effect at a dose of 20 mg/kg and antiviral activity against the Coxsackie B3 virus with an IC50 value of 27.7 μM.

Whole-body molecular imaging is able to directly map spatial distribution of molecules and monitor its biotransformation in intact biological tissue sections. Imaging mass spectrometry (IMS), a label-free molecular imaging method, can be used to image multiple molecules in a single measurement with high specificity. Herein, a novel easy-to-implement, whole-body IMS method was developed with air flow-assisted ionization in a desorption electrospray ionization mode. The developed IMS method can effectively image molecules in a large whole-body section in open air without sample pretreatment, such as chemical labeling, section division, or matrix deposition. Moreover, the signal levels were improved, and the spatial assignment errors were eliminated; thus, high-quality whole-body images were obtained. With this novel IMS method, in situ mapping analysis of molecules was performed in adult rat sections with picomolar sensitivity under ambient conditions, and the dynamic information of molecule distribution and its biotransformation was provided to uncover molecular events at the whole-animal level. A global view of the differential distribution of an anticancer agent and its metabolites was simultaneously acquired in whole-body rat and model mouse bearing neuroglioma along the administration time. The obtained drug distribution provided rich information for identifying the targeted organs and predicting possible tumor spectrum, pharmacological activity, and potential toxicity of drug candidates.

Three major monodesmethyl metabolites of (+)-13a-(S)-deoxytylophorinine were synthesized stereospecifically and their configurations at C-13a were determined. Biological assays revealed that one of the metabolites, 3-O-desmethyl-13a-(S)-deoxytylophorinine, had a higher cytotoxic potency than the parent compound or the positive controls doxorubicin (Adriamycin) and paclitaxel (Taxol).

Investigated is the coupled response of a tension leg platform (TLP) for random waves. Inferred are the mass matrix, coupling stiffness matrix, damping matrix in the vibration differential equation and external load of TLP in moving coordinating system. Infinitesimal method is applied to divide columns and pontoons into small parts. Time domain motion equation is solved by Runge-Kutta integration scheme. Jonswap spectrum is simulated in the random wave, current is simulated by linear interpolation, and NPD spectrum is applied as wind spectrum. The Monte Carlo method is used to simulate random waves and fluctuated wind. Coupling dynamic response, change of tendon tension and riser tension in different sea conditions are analyzed by power spectral density (PSD). The influence of approach angle on dynamic response of TLP and tendon tension is compared.

An integrated approach combining data acquisition using MS(E) and multi-period product ion scan (mpMS/MS), with high-resolution characteristic extracted ion chromatograms (hcXIC) as a data mining method, was developed for in vivo drug metabolites screening and identification. This approach is illustrated by analyzing metabolites of a potential anticancer agent, 3,6,7-trimethoxyphenanthroindolizidine (CAT) in rat urine based on rapid resolution liquid chromatography combined with tandem mass spectrometry (RRLC-MS/MS). Untargeted full-scan MS(E) enabled the high-throughput acquisition of potential metabolites, and targeted mpMS/MS contributed to the sensitivity and specificity of the acquisition of molecules of interest. The data processing method hcXIC, based on the structure of CAT, was shown to be highly effective for the metabolite discovery. Through the double-filtering effect of the characteristic ion and accurate mass, conventional extracted ion chromatograms that contained a substantial number of false-positive peaks were simplified into chromatograms essentially free of endogenous interferences. As a result, 21 metabolites were detected in rat urine after oral administration of CAT. Based on the characteristic fragmentation patterns of the phenanthroindolizidine alkaloid, the structures of 9 metabolites were identified. Furthermore, the interpretation of the MS/MS spectra of these metabolites enabled the determination of demethylation position as well as the differentiation between N-oxidized and hydroxylated metabolites.

Six new cardenolides, periforosides D–E ( 1 – 2 ), periforgenin C ( 3 ) and periforosides F–H ( 4 – 6 ), as well as 10 previously identified cardenolides ( 7 – 16 ) were isolated from the ethanol extract of the stems of Periploca forrestii . The structures of the new compounds were determined using extensive spectroscopic analyses including HRESI-MS, 1D and 2D NMR data. Evaluation of the cytotoxic activity of all the isolated compounds in five different human cancer cell lines indicated that compounds 2 – 6 , 8 , 9 and 12 – 16 have potent activity.

Background: Phenanthroindolizidine alkaloids are a family of plant-derived compounds with significant antineoplastic activity. The specific biomolecular targets of these alkaloids have not yet been clearly identified. (+)-(13aS)-deoxytylophorinine is a new phenanthroindolizidine alkaloid originally extracted from the roots of Tylophora atrofolliculata and Tylophora ovata in our institute. (+)-(13aS)-deoxytylophorinine exerts both in vitro and in vivoanticancer activities. Methods: The in vivo anticancer effects and toxicity of this compound were investigated in mice, and interactions between this compound and double-helical DNA sequences were studied in detail with circular dichroic spectroscopy and fluorescence spectroscopy. Viscosity measurements were applied to check the interactive mode between this compound and DNA. Results: Potent anticancer effects were observed in vivo. Also, concentration-dependent interactions were observed and this compound seemed to interact in a sequence-specific manner with AT-repeated sequences of double-helical DNA. Such interactions were proved to be intercalating by viscosity measurements. Conclusions: Anticancer alkaloid (+)-(13aS)-deoxytylophorinine can have sequence-specific interactions with DNA in an intercalating manner.

Three new phloroglucinols, named lysidicins F-H (1-3), were isolated from the roots of Lysidice rhodostegia. These compounds have a unprecedented benzyl benzo[b]furo[3,2-d]furan skeleton, and lysidicin F (1) is the first example of natural product with trans-fused furan rings. Their structures were established on the basis of extensive spectroscopic analysis, and the absolute configurations of them were determined by computational methods. A possible biosynthetic pathway for 1-3 was also postulated.

Cardiac glycosides are a class of naturally occurring compounds that are characterized by some interesting biological activities and are widely distributed in the plant kingdom and can also be found in some animals. There is an interest in the chemical characterization of these molecules due to their toxicity and their use in medicines. In the study reported here, a combination of electrospray ionization tandem mass spectrometry with high-performance liquid chromatography equipped with diode-array detector (HPLC-DAD/ESI-MS(n)), and hyphenation to both liquid chromatography and nuclear magnetic resonance spectroscopy (HPLC/NMR) were utilized for the on-line analyses of cardiac glycosides from Periploca forrestii. The fragmentation patterns and (1)H NMR spectra of nine isolated cardiac glycosides were investigated; their fragmentation rules and (1)H NMR spectral characteristics were summarized and applied to the structural identification of similar constituents in fractions from P. forrestii. As a result, a total of nine trace cardiac glycosides were tentatively determined by analyses of accurate molecular masses, representative fragment ions and characteristic (1)H NMR signals provided by HPLC/high-resolution mass spectrometry (HRMS), HPLC-DAD/ESI-MS(n) and HPLC/(1)H NMR experiments, respectively. Of these, eight (2-9) are new compounds and one (1) is reported from P. forrestii for the first time. Results of the present study can benefit the rapid identification and targeted isolation of new cardiac glycosides from crude plant extracts.

Elsholtzia rugulosa Hemsl. is known in China as a local herbal tea, medicinal herb and honey plant. Chemical examination of E. rugulosa led to the isolation of two new flavonoid glycosides, apigenin 4'-O-alpha-D-glucopyranoside (1) and 5,7,3',4'-tetrahydroxy-5'-C-prenylflavone-7-O-beta-D-glucopyranoside (2), together with nine known flavonoids. Their structures were elucidated on the basis of spectroscopic evidence.

A novel asymmetric synthesis of a phenanthroindolizidine alkaloid, (+)-deoxytylophorinine, is reported, which uses a chiral nickel(II) complex of a glycine Schiff base to synthesize a substituted ( R )-3-phenanthrylalanine as a key intermediate and Meldrum’s acid to construct the E ring.

Brusatol, a biologically active natural product, was modified in four distinct positions through the covalent attachment of a furoxan moiety, which acts as a nitric oxide (NO) donor. Forty derivatives were synthesized and evaluated for their inhibitory effects on excess NO biosynthesis in activated macrophages. Among them, compound 75 demonstrated inhibition (IC50 = 0.067 μM) comparable to that of brusatol but were less cytotoxic. More importantly, even at very low doses (2 μmol/kg/day), compound 75 also showed substantial inhibitory efficacy against chronic obstructive pulmonary disease (COPD)-like inflammation in the mouse model induced by cigarette smoke (CS) and lipopolysaccharide (LPS). Particularly, this compound was over 100-fold less toxic (LD50 > 3852 μmol/kg) than brusatol and could be a promising lead for further studies. Notably, the improved properties of this derivative are associated with its NO-releasing capability.

Rogue wave is a kind of wave that possesses concentrated energy, strong nonlinear and enormous devastating. When it interacts with the deep-sea structures, the structure will suffer a serious threat, and it may even cause significant harm to the offshore staff and property. Studies on the mechanism of rogue wave are of great significance to the platform design and security. It is also one of the hot issues on the waves of hydrodynamic studies. Some breather-type solutions of NLS equation have been considered as prototypes of rogue waves in ocean. They can appear from smooth initial condition only with a certain disturb given by the exact solution of NLS. In this paper, we have numerically studied rogue waves based on fourth order nonlinear Schrodinger equation. We show that the peaks of the largest amplitude of the resulting waves can be described in terms of the Peregrine breather-type solution as the solution of NLS equation.Copyright © 2014 by ASME

With the rapid development of the communication technology, the high quality of speech communication has become one of the main development trends. In order to solve the quality problem in the processing of communication, mixed excitation linear prediction speech coding algorithm (MELP) because of its higher compression rate and better security performance, is widely used in communication systems. In this paper pre-emphasis is used to improve the quality of the high frequency components in this algorithm. The speech enhancement of spectral subtraction is also applied in this speech coding algorithm to improve the ability of anti-noise. Adaptive difference pulse code improvement is also used in the quantization part of the speech algorithm to obtain the transmission rate that is much lower than before. Furthermore, the algorithm is transplanted into the digital signal processing system in order to validate the feasibility of this algorithm. At last, the speech quality will be proved by PESQ - MOS test and the spectrogram. Key words: underwater acoustic communication, MELP algorithm coding, speech coding

Five new diterpenoids (1-5), five new sesquiterpenoids (6-10), and three known compounds (11-13) were isolated from the roots of Illicium majus. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was assigned by X-ray crystallography, whereas those of the 1,2-diol moieties in 3 and 4 were determined using Snatzke's method. The abietane acids 1, 2, 11, 12, and 13 displayed antiviral activity against the Coxsackie B3 virus, with IC50 values of 3.3-51.7 μM/mL.

Novel glycyrrhizin (GL) derivatives were designed and synthesized by introducing various amine or amino acid residues into the carbohydrate chain and at C-30. Their inhibitory effects on high-mobility group box 1 (HMGB1) were evaluated using a cell-based lipopolysaccharide (LPS) induced tumor necrosis factor α (TNF-α) release study. Compounds 10, 12, 18–20, 23, and 24, which had substituents introduced at C-30, demonstrated moderate HMGB1 inhibition with ED50 values ranging from 337 to 141 μM, which are values comparable to that of the leading GL compound (1) (ED50 = 70 μM). Compounds 23 and 24 emerged as novel and interesting HMGB1 inhibitors. These compounds were able to extend the survival of mice with chronic heart failure (CHF) and acute heart failure (AHF), respectively. In addition, molecular modeling studies were performed to support the biological data.

Two new alkaloids, lycojaponicumins D (1) and E (2), were isolated from the club moss Lycopodium japonicum. Their structures were elucidated by spectroscopic methods, calculated ECD, CD experiments and X-ray diffraction analysis. Lycojaponicumin D (1) possesses an unprecedented 5/7/6/6 tetracyclic skeleton formed by an unusual C3–C13 linkage, which is first reported in Lycopodium alkaloids. The plausible biogenetic pathway of 1 is proposed.

Six compounds were isolated from the roots of Pithecellobium lucidum by various chromatograhic techniques such as column chromatography on silica gel and Sephadex LH-20, and preparative HPLC, and their structures were elucidated as julibroside A2 (1), 3-[ (2-acetamido-2-deoxy-beta-D-glucopyranosyl) oxy] -16alpha-hydroxyolean-12-en-28-oic acid (2), galloyl acid (3), ethyl gallate (4), (+)-catechin (5), (-)-gallocatechin gallate (6) on the basis of spectrascopic data analysis. Compounds 1-6 were isolated from Pithecellobium lucidum for the first time. Compound 2 showed selective cytoxic activity against the human cell lines A2780 with an IC50 value of 1.72 micromol x L(-1).

Phenanthroindolizidine alkaloids are a family of plant-derived compounds with significant antineoplastic activity as well as other effects like antiamebicidal, antiviral, and anti-inflammatory activities. The specific biomolecular targets of these compounds have not yet been clearly identified. S-(+)-Deoxytylophorinidine (CAT) is a new phenanthroindolizidine alkaloid, originally extracted from the roots of Tylophora atrofolliculata and Tylophora ovata. Potent anticancer activity was observed in vitro and in vivo. Neurotoxicity of CAT was also studied and it was far less serious than that of vinblastine. Interactions between this compound and DNA had been studied in detail in our laboratory previously, and we further studied its interactions with RNA.

Diarylheptanoids, natural products with a 1,7-diphenylheptane structural skeleton, are mainly distributed in the roots, rhizomes and bark of Alpinia, Zingiber, Curcuma and Alnus species. They have become of interest in natural product research over the past twenty years because of their remarkable anticancer, anti-emetic, estrogenic, antimicrobial and antioxidant activity. This paper compiles all 307 naturally occurring diarylheptanoids from 46 plants as reported in 137 references with their distributions, physiological activities and 13C-NMR spectral data.

Seven new stigmastane-type steroidal glycosides, vernocuminosides H–N, have been isolated from the stem bark of Vernonia cumingiana Benth. The structures of these compounds were determined by NMR spectrometric methods including HSQC, HMBC, 1H–1H COSY, and NOE, as well as circular dichroism experiments. Anti-inflammatory activities of vernocuminosides I and K–N were determined.

With the rapid development of the communication technology, the high quality of speech communication has become one of the main development trends. In order to solve the quality problem in the processing of communication, pre emphasis is used to improve the quality of the high frequency components in codec algorithm. The speech enhancement of spectral subtraction is also applied in this speech coding algorithm to improve the ability of anti noise. Repackaging the sending frames and redefining the length of the frame that need to be send in the algorithm in order to realize the low speed in speech communication process. At last, the speech quality will be proved by PESQ—MOS test and the spectrogram. From the test and the figure, the quality of the synthesized speech especially with background noise has been significantly improved.