Guided Isolation of New Cytotoxic Cassane Diterpenoids from Caesalpinia sappan.

Guided by an MS/MS-based molecular networking, six undescribed cassane diterpenoids and three known ones were isolated and identified from the seeds of Caesalpinia sappan. Their structures were unequivocally elucidated by extensive spectroscopic analyses and electronic circular dichroism (ECD) calculations. Cytotoxic evaluation showed that phanginin JA exhibited significant antiproliferative activities against human non-small cell lung cancer (A549) cells with IC50 values of 16.79±0.83 µM. Further flow cytometry analysis revealed that phanginin JA could exert apoptotic effect of A549 cells by arresting cell cycle in G0/G1 phase.

Pushing the boundary of seasonal prediction with the lever of varying annual cycles.

Predicting climate anomalies months in advance is of tremendous socioeconomic value. Facing both theoretical and practical constraints, this realm of "seasonal prediction" progressed slowly in recent decades. Here we devise an innovative scheme that pushes the boundary of seasonal prediction by recognizing and isolating distinct spatiotemporal footprints left by modes of climate variability that cause varying annual cycles in response to the solar forcing. The predictive power harnessed from these spatiotemporal footprints results in a prediction skill surpassing existing models for seasonal forecasts of eastern China rainfall, which is one of the most challenging seasonal prediction problems. By considering varying annual cycles explicitly, the new scheme is able to predict multi-provincial flood and/or drought occurrences seamlessly over an entire year. This novel scheme is generically applicable for improving seasonal forecasts over other monsoon regions and for critical climate variables such as surface temperature and Arctic sea-ice extent.

Spatiotemporal propagating decadal signal of ocean heat content and thermocline depth identified in the tropical Pacific.

Tropical Pacific decadal variability (TPDV) and its mechanisms are essential for understanding long-term variations in global climate. The spatiotemporal pattern of this decadal variation has yet to be clarified. Here, on the basis of observational data with the help of the adaptive data analysis method, we extracted and investigated the spatiotemporal evolution of the tropical Pacific decadal variability in upper ocean heat content (UOHC) and thermocline depth. The tropical decadal signal propagated eastward along the equator from the western Pacific to the eastern Pacific after the 1970s, with a speed of 4-5 cm s-1 yielding a decadal oscillation of approximately 11-13 years. This decadal variability of the thermocline fluctuations (UOHC) was proven to be closely correlated with western wind anomalies since the 1970s and may have been induced by the regime shift of the Pacific decadal oscillation. These peaks of decadal signals corresponded well with the strong El Niño-Southern Oscillation (ENSO) events, reflecting nonlinear rectification of ENSOs on TPDV. Moreover, the TPDV showed a modulating signal on moderate and weak ENSO events.

Seasonal to decadal spatiotemporal variations of the global ocean carbon sink.

The global ocean has absorbed approximately 30% of anthropogenic CO2  since the beginning of the industrial revolution. However, the spatiotemporal evolution of this important global carbon sink varies substantially on all timescales and has not yet been well evaluated. Here, based on a reconstructed observation-based product of surface ocean pCO2 and air-sea CO2  flux (the MPI-SOMFFN method), we investigated seasonal to decadal spatiotemporal variations of the ocean CO2  sink during the past three decades using an adaptive data analysis method. Two predominant variations are modulated annual cycles and decadal fluctuations, which account for approximately 46% and 25% of all extracted components, respectively. Although the whole summer to non-summer seasonal difference pattern is determined by the Southern Ocean, the non-summer CO2  sink at mid-latitudes in both hemispheres shows an increasing trend (a total increase of approximately 1.0 PgC during the period 1982-2019), while it is relatively stable in summer. On decadal timescales for the global ocean carbon sink, unlike the weakening decade (1990-1999) and the reinvigoration decade (2000-2009) in which the Southern Ocean plays the dominant role, the reinforcement decade (2010-2019) is mainly the result from the weakening source effect in the equatorial Pacific Ocean. Our results suggest that except for the Southern Ocean's role in the global ocean carbon sink, the strengthening non-summer's sink at mid-latitudes in both hemispheres and the decadal or longer timescales of equatorial Pacific Ocean dynamics should be fully considered in understanding the oceanic carbon cycle on a global scale.

ENSO and Southeast Asian biomass burning modulate subtropical trans-Pacific ozone transport.

Trans-Pacific transport of enhanced ozone plumes has been mainly attributed to fossil fuel combustion in Asia in spring, but less attention has been paid to vegetation fires in Asia. Here we show that the El Niño-Southern Oscillation (ENSO)-modulated fires in Southeast Asia, rather than Asian fossil fuel plumes, dominate the interannual variability of springtime trans-Pacific transport of ozone across the entire North Pacific Ocean. During El Niño springs, the intensified fires from both the Indochinese Peninsula and Indonesia, together with large-scale circulation anomalies, result in enhanced ozone plumes that stretch over 15 000 km in both the lower-middle and upper troposphere. This enhancement is also observed in the in situ measurements of ozone concentration, with an almost 10% increase at Mauna Loa Observatory, Hawaii, a unique site to monitor the long-distance transport over the North Pacific. This study reports an unexpectedly strong influence of vegetation fires, linked with climate variability, on global tropospheric chemistry and proves once more how complex the interactions in the climate system are.

Data concerning statistical relation between obliquity and Dansgaard-Oeschger events.

Data presented are related to the research article entitled "Using Holo-Hilbert spectral analysis to quantify the modulation of Dansgaard-Oeschger events by obliquity" (J. Deng et al., 2018). The datasets in Deng et al. (2018) are analyzed on the foundation of ensemble empirical mode decomposition (EEMD) (Z.H. Wu and N.E. Huang, 2009), and reveal more occurrences of Dansgaard-Oeschger (DO) events in the decreasing phase of obliquity. Here, we report the number of significant high Shannon entropy (SE) (C.E. Shannon and W. Weaver, 1949) of 95% significance level of DO events in the increasing and decreasing phases of obliquity, respectively. First, the proxy time series are filtered by EEMD to obtain DO events. Then, the time-varying SE of DO modes are calculated on the basis of principle of histogram. The 95% significance level is evaluated through surrogate data (T. Schreiber and A. Schmitz, 1996). Finally, a comparison between the numbers of SE values that are larger than 95% significance level in the increasing and decreasing phases of obliquity, respectively, is reported.

Pharmacokinetic and tissue distribution studies of cassane diterpenoids, in rats through an ultra-high-performance liquid chromatography-Q exactive hybrid quadrupole-Orbitrap high-resolution accurate mass spectrometry.

Cassane diterpenoids (CA) are considered as the main active constituents of medicinal plants belonging to the Caesalpinia genus. Three cassane derivatives, bonducellpin G (BG), 7-O-acetyl-bonducellpin C (7-O-AC) and caesalmin E (CE), isolated from Caesalpinia minax Hance seeds, showed strong anti-inflammatory activity. In this paper, pharmacokinetics (BG, 7-O-AC, CE) and tissue distribution (7-O-AC, CE) properties were studied for the first time using a reliable, sensitive and rapid UHPLC-Q-Orbitrap HR-MS to develop new anti-inflammatory agents. A novel quantitative method with full scan in positive ion mode was used to determine the contents of compounds. They were separated using acetonitrile-water (0.1% formic acid) as gradient mobile phase. The calibration curve displayed good linearity and the lower limit of quantitation was 0.005-0.02 µg/mL for all analytes. Meanwhile, the absorption, distribution, metabolism, excretion (ADME) property was predicted using PreADMET web. The pharmacokinetic parameters indicated that they were absorbed quickly, eliminated rapidly together with high blood concentration. The results of tissue distribution demonstrated that CE was distributed rapidly and widely among tissues, and stomach was the main tissue site of CE and 7-O-AC, followed by small intestine/liver. This study indicates that the structures and dosages of active CA should be modified to help improve the absorption rate and residence time, and the findings are helpful for the pharmaceutical design of CA derivatives.

Length-dependent dual-mechanism-controlled failure modes in silver penta-twinned nanowires.

A series of molecular dynamics simulations on silver penta-twinned nanowires are performed to reveal the tensile failure mechanisms that are responsible for the different failure modes and morphologies of fracture surfaces observed in various experimental reports. The simulations show that a ductile-to-brittle transition in failure mode occurs with increasing length of the nanowires. Short nanowires have ductile-like plasticity with flat-like fracture surfaces, while long nanowires show brittle-like fractures with cone-like failure surfaces. These two seemingly counterintuitive scenarios can be attributed to two sets of mechanisms: (1) stable dislocation nucleation-controlled incipient plasticity followed by stable dislocation motion-mediated plasticity assisted by pores for short nanowires, (2) unstable dislocation nucleation-controlled incipient plasticity followed by rapid necking for long nanowires. These two sets of failure mechanisms are distinguished by fitted lines using phased strain data. We propose a general strategy to build a necking-based model for predicting the critical nanowire aspect ratio while distinguishing the fracture modes. A mechanism map of silver penta-twinned nanowire is constructed to delineate the predominant failure behaviours. Our findings reveal a correlation between the failure mode and the resulting morphology of the fracture surface and provide a paradigm for the design and engineering of mechanical properties of nanowires.

Therapeutic effects of Caesalpinia minax Hance on complete Freund's adjuvant (CFA)-induced arthritis and the anti-inflammatory activity of cassane diterpenes as main active components.

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Caesalpinia minax Hance called 'Ku-Shi-Lian' (KSL) in China have been used as Zhuang or Dai folk medicines for treatment of common cold, fever, rheumatoid arthritis and dysentery for hundred years. AIM OF THE STUDY: This study aimed to investigate therapeutic efficacy of KSL extract using complete Freund's adjuvant (CFA) induced arthritis in a rat model and the anti-inflammatory activity of cassane diterpenes as the main active material basis of this herb. MATERIALS AND METHODS: Arthritis was induced in male Wistar rats (200-220 g) by immunization with CFA. Dexamethasone (DXMS) and Tripterygium glycosides (TG) were chosen as the positive drugs. Water soluble fraction (CMW, 1000 and 2000 mg/kg) and chloroform soluble fraction (CMC, 400 and 800 mg/kg) of KSL were orally administered from day 1 and continued for 21 days. Change of paw swelling perimeter, arthritics score, body weight growth, were observed, and the production of TNF-α, IL-1ß and IL-6 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The histological changes in the ankle joint were analyzed in adjuvant induced arthritis rats. Moreover, the inhibitory effect on mRNA expression of proinflammatory cytokine IL-1ß, IL-6 and TNF-α of fourteen cassane diterpenes obtained from CMC extract were valued using the RAW 264.7 macrophages cell stimulated by lipopolysaccharide (LPS) assay. RESULTS: The chloroform soluble fraction (CMC) showed the significantly suppressed change of paw swelling perimeter, arthritics score and increased body weight loss. The overproduction of TNF-α, IL-1ß and IL-6 were remarkably suppressed in the serum. Fourteen cassane derivatives as the main constituents of CMC extract showed the promising activity on the expression mRNA of cytokine IL-1ß, IL-6 and TNF-α produced by macrophages cells. CONCLUSIONS: In this study, the chloroform soluble fraction of 'KSL' (seeds of C. minax) was found to exert an anti-RA activity significantly in vivo for the first time, which indicted this fraction might be used as a powerful therapeutic agent for arthritis treatments. Cassane diterpenes, as the main constituents in this fraction, showed the anti-inflammation activity through the regulation of cytokine expression, which might be developed as target-agents for this national herb further developing.

Analysis of the interaction among rice, weeds, inorganic fertilizer, and a herbivore in a composite farming paddy ecosystem.

As one of the Globally Important Agricultural Heritage Systems (GIAHS), rice field composite farming is an ecological measure in rice production, which can reduce the amount of chemical fertilizers, pesticides and herbicides. This research studies the interaction among rice, weed, inorganic fertilizer and herbivore in a composite farming paddy ecosystem. We develop a differential equation model to analyze the relations and interactions among those components. Results show the existence of an equilibrium for paddy and weed extinction, one or two equilibria for rice extinction, an equilibrium for weed extinction, and an equilibrium for rice and weed coexistence. Based on the obtained stability conditions of these equilibria, measures are proposed to avoid the existence or the stability of equilibria for rice extinction. Other measures are proposed to lead to a stable equilibrium for weed extinction, which is the most desirable result in rice production. Conditions for maximizing the yield of rice are also obtained by taking the relative mortality of rice as variable. In addition, we discover the existence of Hopf bifurcation phenomenon in the system, and develop the critical value of Hopf bifurcation by taking the artificial fertilizer rate as the bifurcation parameter. Our findings provide effective guidance and insights for rice production in a composite farming paddy ecosystem.

Spatiotemporal evolution of the chlorophyll a trend in the North Atlantic Ocean.

Analyses of the chlorophyll a concentration (chla) from satellite ocean color products have suggested the decadal-scale variability of chla linked to the climate change. The decadal-scale variability in chla is both spatially and temporally non-uniform. We need to understand the spatiotemporal evolution of chla in decadal or multi-decadal timescales to better evaluate its linkage to climate variability. Here, the spatiotemporal evolution of the chla trend in the North Atlantic Ocean for the period 1997-2016 is analyzed using the multidimensional ensemble empirical mode decomposition method. We find that this variable trend signal of chla shows a dipole pattern between the subpolar gyre and along the Gulf Stream path, and propagation along the opposite direction of the North Atlantic Current. This propagation signal has an overlapping variability of approximately twenty years. Our findings suggest that the spatiotemporal evolution of chla during the two most recent decades is part of the multidecadal variations and possibly regulated by the changes of Atlantic Meridional Overturning Circulation, whereas the mechanisms of such evolution patterns still need to be explored.

Size-dependent melting modes and behaviors of Ag nanoparticles: a molecular dynamics study.

The size-dependent melting behaviors and mechanisms of Ag nanoparticles (NPs) with diameters of 3.5-16 nm were investigated by molecular dynamics (MD). Two distinct melting modes, non-premelting and premelting with transition ranges of about 7-8 nm, for Ag NPs were demonstrated via the evolution of distribution and transition of atomic physical states during annealing. The small Ag NPs (3.5-7 nm) melt abruptly without a stable liquid shell before the melting point, which is characterized as non-premelting. A solid-solid crystal transformation is conducted through the migration of adatoms on the surface of Ag NPs with diameters of 3.5-6 nm before the initial melting, which is mainly responsible for slightly increasing the melting point of Ag NPs. On the other hand, surface premelting of Ag NPs with diameters of 8-16 nm propagates from the outer shell to the inner core with initial anisotropy and late isotropy as the temperature increases, and the close-packed facets {111} melt by a side-consumed way which is responsible for facets {111} melting in advance relative to the crystallographic plane {111}. Once a stable liquid shell is formed, its size-independent minimum thickness is obtained, and a three-layer structure of atomic physical states is set up. Lastly, the theory of point defect-pair (vacancy-interstitial) severing as the mechanism of formation and movement of the solid-liquid interface was also confirmed. Our study provides a basic understanding and theoretical guidance for the research, production and application of Ag NPs.

Fast multidimensional ensemble empirical mode decomposition for the analysis of big spatio-temporal datasets.

In this big data era, it is more urgent than ever to solve two major issues: (i) fast data transmission methods that can facilitate access to data from non-local sources and (ii) fast and efficient data analysis methods that can reveal the key information from the available data for particular purposes. Although approaches in different fields to address these two questions may differ significantly, the common part must involve data compression techniques and a fast algorithm. This paper introduces the recently developed adaptive and spatio-temporally local analysis method, namely the fast multidimensional ensemble empirical mode decomposition (MEEMD), for the analysis of a large spatio-temporal dataset. The original MEEMD uses ensemble empirical mode decomposition to decompose time series at each spatial grid and then pieces together the temporal-spatial evolution of climate variability and change on naturally separated timescales, which is computationally expensive. By taking advantage of the high efficiency of the expression using principal component analysis/empirical orthogonal function analysis for spatio-temporally coherent data, we design a lossy compression method for climate data to facilitate its non-local transmission. We also explain the basic principles behind the fast MEEMD through decomposing principal components instead of original grid-wise time series to speed up computation of MEEMD. Using a typical climate dataset as an example, we demonstrate that our newly designed methods can (i) compress data with a compression rate of one to two orders; and (ii) speed-up the MEEMD algorithm by one to two orders.

New triterpenoids from the latex of Euphorbia resinifera Berg.

Nine novel compounds, six euphane triterpenes, Euphorol A-D (1-4), H (8) and I (9), and three tirucallane triterpenes, Euphorol E-G (5-7) including four nortriterpenes, together with seven known compounds (10-16) have been isolated from the methanol extraction of Euphorbium. Their structures were established on the basis of extensive analyses of their HR-ESI-MS, UV, IR, 1D and 2D NMR methods. A putative biogenetic relationship to these compounds was proposed. The cytotoxicity of all these isolates against MCF-7, U937 and C6 cancer cell lines was evaluated. Compounds 1-3, 10, 11 and 13-16 exhibited moderate cytotoxic activities.

Simultaneous identification and analysis of cassane diterpenoids in Caesalpinia minax Hance by high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

Cassane diterpenoids were successfully and simultaneously identified in Caesalpinia minax Hance by high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A total of 59 peaks were detected, and among them 51 compounds, including 41 furanocassane diterpenoids, 10 furanolactone cassane diterpenoids were simultaneously identified and characterized on the basis of the protonated molecule, retention behavior, and fragments in MS(2) . Ten compounds, including seven novel compounds, were identified or tentatively identified for the first time in C. minax. In a positive ion mode, the fragmentation pathways of cassane diterpenoids were also analyzed for the first time. The relative amounts of the five main diterpenoids (caesalpinin L, caesalpinin F2 , bondcellpin C, caesalpinin E, and ξ-caesalmin) were simultaneously quantified by high-performance liquid chromatography. Results showed that the newly discovered and known components of C. minax can be used to determine the material basis of bioactivity; this method can also be applied to analyze cassane diterpenoids in herbal medicines from the genus Caesalpinia belonging to the family Fabaceae.

Two new diterpenes from the seeds of Caesalpinia minax Hance.

Molecules with diterpene skeletons often possess valuable medicinal properties. Two new diterpenes 1α,6α,7ß-triacetoxy-5α-hydroxy-14ß-ethyl-O-vouacapane (1) and 2α-acetoxy-14,15-cyclopimara-7ß,16-diol (2) were isolated from the seeds of Caesalpinia minax Hance. Their structures were established on the basis of extensive spectroscopic analyses, including HR-ESI-MS, UV, IR, 1D, and 2D NMR (HSQC, HMBC, NOESY) methods. The stereochemical structure of 1 was confirmed via the circular dichroism spectrum and calculated ECD experiment. The inhibitory activity of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide of compounds 1 and 2 was evaluated, and compound 1 was found to show significant inhibitory effect.

Anti-inflammation furanoditerpenoids from Caesalpinia minax Hance.

Cassane skeletons are rare in nature, but often possess valuable medicinal properties. A furanoditerpenoid with an unusual A-seco-rearranged cassane skeleton, neocaesalminin A, and five furanoditerpenoids were isolated from seeds of Caesalpinia minax Hance, along with six known cassane derivatives, 7-O-acetyl-bonducellpin C, caesalmin F, caesalmin C, ζ-caesalmin, caesalmin E1 and caesalpinin K. Compound structures were determined by spectroscopy (HR-ESI-MS, UV, IR, 1D NMR, 2D NMR), X-ray crystallography and quantum chemical computation of electronic circular dichroism). Three of the previously known compounds exhibited significant inhibition of nitric oxide production of RAW264.7 macrophages stimulated by lipopolysaccharide (LPS).

Seven new cassane furanoditerpenes from the seeds of Caesalpinia minax.

A bioassay-guided study led to the isolation of seven new cassane furanoditerpenes, designated as spirocaesalmin B (1), caesalpinin M1 (2), caesalpinin M2 (3), caesalmin E1 (4), caesalmin E2 (5), caesalmin E3 (6), caesalpinin F1 (7) and three known compounds neocaesalpin A(8), neocaesalpin L(9), neocaesalpin L1(10) from the seeds of Caesalpinia minax Hance. Compound structures were determined on the basis of extensive spectroscopic analyses, including X-ray crystallographic analysis, HRESI-MS, UV, IR, 1D and 2D NMR (HSQC, HMBC, NOESY) methods. Some absolute configurations were confirmed via the circular dichroism (CD) spectra. Compound 1 is the first example of an A-seco-rearranged cassane furanoditerpene with an unusual skeleton isolated from the genus Caesalpinia. All compound inhibitory effects on influenza virus neuraminidase (NA) in vitro were valued for the first time. Compared with the positive control (Zanamivir), new compounds were found to show moderate inhibitory activity.

Two new compounds with cytotoxic activity on the human melanoma A375-S2 cells from Daphne giraldii callus cells.

Four compounds were isolated from Daphne giraldii callus cells, and their structures were characterized as daphnenone (1), daphnolon (2), R-( - )-1-(4'-hydroxyphenyl)-3-hydroxy-5-phenyl-1,5-pentandione (3), and S-(+)-daphneolone-4'-O-ß-d-glucoside (4) on the basis of MS, NMR spectrographic analysis, and chemical methods. All of the four compounds possessed C6-C5-C6 carbon skeleton, and among them, 3 and 4 were two new compounds. In activity screening test, compounds 1, 2, 3, and 4 showed different degrees of cytotoxic activity against the tumor cells of human melanoma A375-S2 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium hydrobromide method, with IC(50) values of 29.8, 51.0, 41.0, and 150.0 µM, respectively. Furthermore, we found the important target which could explain the cytotoxic mechanism of the four compounds by using autodock 4.0, a structure-guided discovery approach, and the important residues CYS532, GLY534, and SER535 of B-Raf kinase have been discovered.

Three new cassane diterpenes from the seeds of Caesalpinia minax Hance.

Three new cassane-diterpene-lactones, methyl 1α,7ß-diacetoxy-5α,12α-dihydroxy-cass-13(15)-en-16,12-olide-17ß-carboxylate (1), methyl 7ß-acetoxy-1α,5α,12α-trihydroxy-cass-13(15)-en-16,12-olide-17ß-carboxylate (2), and 12α-ethoxyl-1α,6α,7ß-triacetoxy-5α,14ß-dihydroxy-cass-13(15)-en-16,12-olide (3), were isolated from the seeds of Caesalpinia minax Hance. Their structures were established on the basis of HR-ESI-MS, 1D and 2D NMR spectral analysis.