Control of the spider-like interference structure in photoelectron momentum distributions of a helium atom in a few-cycle nonlinear chirped laser pulse.

We investigate theoretically the photoelectron momentum distributions (PMDs) of the helium atom in the few-cycle nonlinear chirped laser pulse. The numerical results show that the direction of the spider-like interference structure in PMDs exhibits periodic variations with the increase of the chirp parameter. It is illustrated that the direction of the spider-like interference structure is related to the direction of the electron motion by tracking the trajectories of the electrons. We also demonstrate that the carrier-envelope phase can precisely control the opening of the ionization channel. In addition, we investigate the PMDs when a chirp-free second harmonic (SH) laser pulse is added to the chirped laser field, the numerical results show that the interference patterns can change from only spider-like interference structure to both spider-like and ring-like interference structures.

Inhibitory Effect and Mechanism of Ursolic Acid on Cisplatin-Induced Resistance and Stemness in Human Lung Cancer A549 Cells.

The survival rate of lung cancer patients remains low largely due to chemotherapy resistance during treatment, and cancer stem cells (CSCs) may hold the key to targeting this resistance. Cisplatin is a chemotherapy drug commonly used in cancer treatment, yet the mechanisms of intrinsic cisplatin resistance have not yet been determined because lung CSCs are hard to identify. In this paper, we proposed a mechanism relating to the function of ursolic acid (UA), a new drug, in reversing the cisplatin resistance of lung cancer cells regulated by CSCs. Human lung cancer cell line A549 was selected as the model cell and treated to become a cisplatin-resistant lung cancer cell line (A549-CisR), which was less sensitive to cisplatin and showed an enhanced capability of tumor sphere formation. Furthermore, in the A549-CisR cell line expression, levels of pluripotent stem cell transcription factors Oct-4, Sox-2, and c-Myc were increased, and activation of the Jak2/Stat3 signaling pathway was promoted. When UA was applied to the cisplatin-resistant cells, levels of the pluripotent stem cell transcription factors were restrained by the inhibition of the Jak2/Stat3 signaling pathway, which reduced the enrichment of tumor stem cells, and in turn, reversed cisplatin resistance in lung cancer cells. Hence, as a potential antitumor drug, UA may be able to inhibit the enrichment of the lung CSC population by inhibiting the activation of the Jak2-Stat3 pathway and preventing the resistance of lung cancer cells to cisplatin.

Overexpression of Stat3 increases circulating cfDNA in breast cancer.

PURPOSE: Current studies on circulating cell-free DNA (cfDNA) have been focusing on its potential as biomarkers in liquid biopsy by detecting its content or genetic and epigenetic changes for the evaluation of tumor burden and therapeutic efficacy. However, the regulatory mechanism of cfDNA release remains unclear. Stat3 has been documented as an oncogene for the development and metastasis of breast cancer cells. In this study, we investigated whether Stat3 affects the release of cfDNA into blood and its association with the number of circulating tumor cells (CTCs). METHODS: The cfDNA level in plasma of patients with breast cancer and healthy volunteers were determined by quantitative real-time PCR. Three mouse breast cancer models with different Stat3 expression were generated and used to established three breast cancer orthotopic animal models to examine the effect of Stat3 on cfDNA release in vivo. Stat3 mediated Epithelial-mesenchymal phenotype transition of CTCs was determined by immunofluorescence assay and Western blot assay. RESULTS: The data showed that Stat3 increased circulating cfDNA, which is correlated with the increased volume of primary tumors and number of CTCs, accompanied with the dynamic EMT changes regulated by Snail induction. Furthermore, the high level of total circulating cfDNA and Stat3-cfDNA in patients with breast cancer were detected by quantitative real-time PCR using GAPDH and Stat3 primers. CONCLUSION: Our results suggested that Stat3 increases the circulating cfDNA and CTCs in breast cancer.

Pharmacokinetic study of three different formulations of l-tetrahydropalmatine in brain tissues of rats.

l-Tetrahydropalmatine (l-THP), an active alkaloid compound isolated from Rhizoma Corydalis-yanhusuo, has been reported to possess biological activity for treating cocaine use. To enhance both oral bioavailability and brain penetration, three formulations of l-THP suspension, mixture of l-THP-puerarin and self-microemulsifying drug delivery systems (SMEDDS) were prepared. A sensitive and reliable ultra-high-performance liquid chromatography with tandem mass spectrometry method was developed and validated for the simultaneous determination of l-THP and its active metabolite l-isocorypalmine (l-ICP) in rat brain. Diazepam was used as the internal standard. The chromatographic separation was achieved on a Bonshell ASB C18 column at 30°C using acetonitrile-aqueous formic acid as mobile phase in gradient mode. The linearity was validated over the concentration ranges of 4.00-2,500 ng/ml for l-THP and 0.400-500 ng/ml for l-ICP. Full method validation was within the acceptance limits. The method was successfully used to determine the pharmacokinetics of two analytes following oral administration of these three formulations to rats. A significant difference was observed in the main pharmacokinetic parameters between SMEDDS and the suspension, and a 3.25- and 2.97-fold increase in the relative bioavailability of l-THP and l-ICP, respectively, was observed with the SMEDDS compared with the suspension formulation. It was concluded that SMEDDS enhanced the absorption of l-THP and l-ICP and delayed their release in brain.

YY1-induced lncRNA DSCR8 promotes the progression of ovarian cancer via miR-3192-5p/YY1 axis.

Ovarian cancer endangers the life of women worldwide. Plenty of lncRNAs have been found modulating the progression of ovarian cancer. Meanwhile, lncRNA DSCR8 (Down syndrome critical region 8) has been reported as an oncogene in hepatocellular carcinoma. In this study, we aimed to search the function of DSCR8 in ovarian cancer. qRT-PCR analysis assessed the expression of DSCR8 in ovarian cancer cells. EdU assay and colony formation assay was used to test cell proliferation. Flow cytometry analysis and TUNEL assay were conducted to investigate cell apoptosis. Wound healing assay and transwell invasion assay assessed cell migration and invasion. DSCR8 was significantly up-regulated in ovarian cancer cells. Inhibited DSCR8 could suppress the progression of ovarian cancer. Also, YY1 could activate the expression of DSCR8 in ovarian cancer cells. Meanwhile, DSCR8/miR-3192-5p/YY1 axis was identified in ovarian cancer cells. MiR-3192-5p could function as tumor suppresser in ovarian cancer cells. Furthermore, DSCR8 and YY1 (Yin Yang 1) transcription factor could play the regulatory network in ovarian cancer cells. In a word, YY1-induced lncRNA DSCR8 promotes the progression of ovarian cancer via miR-3192-5p/YY1 axis.

Resilience evaluation for UAV swarm performing joint reconnaissance mission.

The resilience of unmanned aerial vehicle (UAV) swarm is its joint capability to resist possible threat, adapt to disruptive events, and restore its intended performance under a specific time period. The quantitative assessment of the UAV swarm resilience requires a thorough understanding of its missions. In this paper, a mission-oriented framework is proposed to implement the resilience evaluation for the UAV swarm. Guided by the framework, the resilience evaluation for the UAV swarm performing joint reconnaissance mission is studied. A UAV swarm model is developed for joint reconnaissance mission based on complex networks and agent-based models. The following aspects of the UAV swarm are considered in the proposed model, namely, the mission orientation, UAV attributes, swarm topology, UAV cooperative strategy, UAV information exchange and fusion strategy, potential threats, recovery strategies, etc. Then, a novel performance metric is proposed to measure the mission capability of the UAV swarm performing joint reconnaissance mission. Results from the simulations show that, compared with existing studies, the proposed approach can provide more realistic and objective resilience evaluation for the mission-oriented UAV swarm. The above works can be used to support the decision making and the optimal design of the UAV swarm, given different missions.

Characterization and screening of cyclooxygenase-2 inhibitors from Zi-shen pill by affinity ultrafiltration-ultra performance liquid chromatography mass spectrometry.

ETHNOPHARMACOLOGICAL RELEVANCE: Zi-shen pill (ZSP) is a classical Chinese herbal formula used for treatment of benign prostatic hyperplasia (BPH). AIM OF THE STUDY: To characterize and screen cyclooxygenase-2 (COX-2) inhibitors from ZSP extract. MATERIALS AND METHODS: The ZSP extract was incubated with COX-2 and the potential ligands were screened out by affinity ultrafiltration. Celecoxib and glipizide were chosen as positive control and negative control drug, respectively. Affinity ultrafiltration-ultra performance liquid chromatography-mass spectrometry (UPLC-MS) method was used. In addition, in vitro COX-2 inhibitory assay and in silico molecular docking technique were used for further validation. RESULTS: A total of 20 components were discovered and identified from ZSP ultrafiltrate by high resolution Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS), among which 8 compounds were deduced as potential COX-2 inhibitors by their high specific binding values (>1.5). Inhibitory activities of demethyleneberberine, palmatine, berberine and timosaponin A-I were confirmed by an enzyme assay of COX-2, which validated the reliability of our approach. Molecular docking simulation investigated potential mechanism of action for these compounds. CONCLUSION: The results revealed that affinity ultrafiltration UPLC-MS could successfully screen out the potential COX-2 inhibitors from complex Chinese herbal formula ZSP extract, indicating that its therapeutic effect on BPH was partly based on the enzyme active ingredients.

Metabolite profiling of l-isocorypalmine in rat urine, plasma, and feces after oral administration using high performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry.

l-Isocorypalmine, an active alkaloid compound isolated from Rhizoma Corydalis yanhusuo, has been reported to possess biological activity for treating cocaine use disorder. A high-performance liquid chromatography coupled to Fourier transform ion cyclotron resonance mass spectrometry method was established for identification of the metabolites of l-isocorypalmine in urine, plasma and feces samples of rats after a single intragastric gavage of l-isocorypalmine at a dose of 15 mg/kg. As a result, a total of 21 metabolites (six phase І metabolites and fifteen phase II metabolites) were detected and tentatively identified by mass spectrometry and fragment ions from tandem mass spectrometry spectra. All metabolites were present in the urine samples, nine metabolites were found in the plasma samples and three metabolites were found in the feces samples. Results indicated that metabolic pathways of l-isocorypalmine included oxidation, dehydrogenation, demethylation, sulfate conjugation, and glucuronide conjugation. In addition, glucuronidation was the major metabolic reaction. Results of this investigation could provide significant experimental basis for efficacy, safety and action mechanism of l-isocorypalmine, which will be advantageous to new drug development for treating cocaine addiction.

Stat3/Oct-4/c-Myc signal circuit for regulating stemness-mediated doxorubicin resistance of triple-negative breast cancer cells and inhibitory effects of WP1066.

Doxorubicin (Dox) is widely used in the treatment of triple-negative breast cancer cells (TNBCs), however resistance limits its effectiveness. Cancer stem cells (CSCs) are associated with Dox resistance in MCF-7 estrogen receptor positive breast cancer cells. Signal transducer and activator of transcription 3 (Stat3) may functionally shift non-CSCs towards CSCs. However, whether Stat3 drives the formation of CSCs during the development of resistance in TNBC, and whether a Stat3 inhibitor reverses CSC-mediated Dox resistance, remains to be elucidated. In the present study, human MDA-MB-468 and murine 4T1 mammary carcinoma cell lines with the typical characteristics of TNBCs, were compared with estrogen receptor-positive MCF-7 cells as a model system. The MTT assay was used to detect cytotoxicity of Dox. In addition, the expression levels of CSC-specific markers and transcriptional factors were measured by western blotting, immunofluorescence staining and flow cytometry. The mammosphere formation assay was used to detect stem cell activity. Under long-term continuous treatment with Dox at a low concentration, TNBC cultures not only exhibited a drug-resistant phenotype, but also showed CSC properties. These Dox-resistant TNBC cells showed activation of Stat3 and high expression levels of pluripotency transcription factors octamer-binding transcription factor-4 (Oct-4) and c-Myc, which was different from the high expression of superoxide dismutase 2 (Sox2) in Dox-resistant MCF-7 cells. WP1066 inhibited the phosphorylation of Stat3, and decreased the expression of Oct-4 and c-Myc, leading to a reduction in the CD44-positive cell population, and restoring the sensitivity of the cells to Dox. Taken together, a novel signal circuit of Stat3/Oct-4/c-Myc was identified for regulating stemness-mediated Dox resistance in TNBC. The Stat3 inhibitor WP1066 was able to overcome the resistance to Dox through decreasing the enrichment of CSCs, highlighting the therapeutic potential of WP1066 as a novel sensitizer of Dox-resistant TNBC.

Quantitative assessment of soil productivity and predicted impacts of water erosion in the black soil region of northeastern China.

As Northeastern China is the country's most significant grain production base, soil productivity in this region has consistently attracted attention. National food security is threatened by an ongoing drain of soil nutrients and decline in soil productivity. Black soil is the key natural resource in this region of China, which is thus known as the "black soil region". It is necessary to study the impact of soil erosion on black soil and its productivity to protect this important resource and ensure its sustainable productivity. Through a field investigation and laboratory analysis, the physicochemical properties in 112 soil profiles from a typical black soil sub-region were measured to assess soil productivity using a soil productivity index (PI) model. The soil PI in the study area was relatively high and showed an increasing trend from southwest to northeast. PI values and their spatial distribution were affected by soil organic matter, soil clay content, soil thickness, slope and geomorphological position. Soil productivity and cluster analysis revealed that the southern and northwestern areas of the typical black soil sub-region under study were subject to the greatest risk. To maintain the region's soil productivity, it is vital to prevent the black soil layer, especially the topsoil, from being destroyed.

Compatibility effects of herb pair Phellodendri chinensis cortex and Anemarrhenae rhizoma on benign prostatic hyperplasia using targeted metabolomics.

Phellodendri chinensis cortex (P. C. cortex) and Anemarrhenae rhizoma (A. rhizoma) herb pair is a core component of traditional Chinese medicines used to treat inflammation and benign prostatic hyperplasia (BPH). The present study was designed to profile the arachidonic acid (AA) metabolomic characteristics in rat plasma and prostate after being treated with P. C. cortex and A. rhizoma as well as their combination. Plasma and prostate samples from sham group, BPH model group, herb pair group and two single herb groups were collected on days 7, 14, 21 and 28. Then, a systemic metabolomic analysis based on UFLC-MS/MS was employed to quantify AA and its cyclooxygenase and lipoxygenase pathway metabolites (15-HETE, 12-HETE, 5-HETE, AA, PGI2 , PGF2α , 8-HETE, PGD2 , PGE2 and LTB4 ). The results demonstrated that BPH led a significant increase of 10 biomarkers in plasma and tissue (p < 0.05). The clusters of herb pair group and single herb groups showed a tendency to return to the initial space, and the AA and its metabolites from those groups were differently downregulated to a healthier level, with the combination of single herbs most obvious. The present study demonstrated that P. C. cortex-A. rhizoma herb pair might produce synergistic or complementary compatibility effects on suppressing inflammatory processes occurring in BPH.

Arachidonic acid metabonomics study for understanding therapeutic mechanism of Huo Luo Xiao Ling Dan on rat model of rheumatoid arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Huo Luo Xiao Ling Dan (HLXLD), a traditional Chinese medicine (TCM), is commonly used for the treatment of rheumatoid arthritis (RA). AIM OF THE STUDY: To explore the potential therapeutic mechanism of HLXLD on anti-inflammatory activity. MATERIALS AND METHODS: A metabolomic approach based on UFLC-MS/MS to profile arachidonic acid (AA) metabolic changes was used. The cyclooxygenase (COX) and lipoxygenase (LOX) catalyzed metabolites in plasma were quantified on 7, 14, 21, and 28 days after the rats injected with Complete Freund's adjuvant and orally administrated with HLXLD, methotrexate and dexamethasone in parallel as the positive control drugs. RESULTS: Nineteen metabolites involved in COX and LOX pathways in RA model group were significant increased compared with normal group (P < 0.05), including 12-hydroxyeicosatetraenoic acid (12-HETE), 15-HETE, 8-HETE, leukotriene B4(LTB4), prostaglandin E2 (PGE2), PGI2, PGD2, PGF2α, thromboxane B2 (TXB2), etc. From day 7 to day 28, the trajectory direction of HLXLD group and positive control groups gradually moved towards the initial space, and the concentrations of AA and its metabolites after HLXLD treatment were significantly reduced in dual pathways compared to control groups. CONCLUSION: HLXLD induced a substantial change in the AA metabolic profiles through refrain the expression of COX and LOX. The present investigation also highlights that distinct ingredients of this formula tend to inhibit different target to achieve a therapeutic effect.

Identification of the absorbed components and metabolites of modified Huo Luo Xiao Ling Dan in rat plasma by UHPLC-Q-TOF/MS/MS.

To reveal the material basis of Huo Luo Xiao Ling Dan (HLXLD), a sensitive and selective ultra-high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) method was developed to identify the absorbed components and metabolites in rat plasma after oral administration of HLXLD. The plasma samples were pretreated by liquid-liquid extraction and separated on a Shim-pack XR-ODS C18 column (75 × 3.0 mm, 2.2 µm) using a gradient elution program. With the optimized conditions and single sample injection of each positive or negative ion mode, a total of 109 compounds, including 78 prototype compounds and 31 metabolites, were identified or tentatively characterized. The fragmentation patterns of representative compounds were illustrated as well. The results indicated that aromatization and hydration were the main metabolic pathways of lactones and tanshinone-related metabolites; demethylation and oxidation were the major metabolic pathways of alkaloid-related compounds; methylation and sulfation were the main metabolic pathways of phenolic acid-related metabolites. It is concluded the developed UHPLC-Q-TOF/MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of HLXLD, and the results will provide essential data for further studying the relationship between the chemical components and pharmacological activity of HLXLD.

Increasing trends in rainfall-runoff erosivity in the Source Region of the Three Rivers, 1961-2012.

As the head source of the two longest rivers in China and the longest river in Southeast Asia, the East Qinghai-Tibetan Plateau (QTP) is experiencing increasing thaw snowmelt and more heavy precipitation events under global warming, which might lead to soil erosion risk. To understand the potential driving force of soil erosion and its relationship with precipitation in the context of climate change, this study analyzed long-term variations in annual rainfall-runoff erosivity, a climatic index of soil erosion, by using the Mann-Kendall statistical test and Theil and Sen's approach in the Source Region of the Three Rivers during 1961-2012. The results showed the followings: (i) increasing annual rainfall-runoff erosivity was observed over the past 52years, with a mean relative trend index (RT1) value of 12.1%. The increasing trend was more obvious for the latest two decades: RT1 was nearly three times larger than that over the entire period; (ii) more precipitation events and a higher precipitation amount were the major forces for the increasing rainfall-runoff erosivity; (iii) similar rising trends in sediment yields, which corresponded to rainfall-runoff erosivity under slightly increasing vegetation coverage in the study area, implied a large contribution of rainfall-runoff erosivity to the increasing sediment yields; and (iv) high warming rates increased the risk of soil destruction, soil erosion and sediment yields. Conservation measures, such as enclosing grassland, returning grazing land to grassland and rotation grazing since the 1980s, have maintained vegetation coverage and should be continued and strengthened.