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Triterpenoids and saponins have a broad range of pharmacological activities. Unlike most legumes which contain mainly oleanane-type scaffold, Astragalus membranaceus contains not only oleanane-type but also cycloartane-type saponins, for which the biosynthetic pathways are unknown.This work aims to study the function and catalytic mechanism of oxidosqualene cyclases (OSCs), one of the most important enzymes in triterpenoid biosynthesis, in A. membranaceus.Two OSC genes, AmOSC2 and AmOSC3, were cloned from A. membranaceus. Their functions were studied by heterologous expression in tobacco and yeast, together with in vivo transient expression and virus-induced gene silencing. Site-directed mutagenesis and molecular docking were used to explain the catalytic mechanism for the conserved motif.AmOSC2 is a β-amyrin synthase which showed higher expression levels in underground parts. It is associated with the production of β-amyrin and soyasaponins (oleanane-type) in vivo. AmOSC3 is a cycloartenol synthase expressed in both aerial and underground parts. It is related to the synthesis of astragalosides (cycloartane-type) in the roots, and to the synthesis of cycloartenol as a plant sterol precursor. From AmOSC2/3, conserved triad motifs VFM/VFN were discovered for β-amyrin/cycloartenol synthases, respectively. The motif is a critical determinant of yield as proved by 10 variants from different OSCs, where the variant containing the conserved motif increased the yield by up to 12.8-fold. Molecular docking and mutagenesis revealed that Val, Phe and Met residues acted together to stabilize the substrate, and the cation-π interactions from Phe played the major role.The study provides insights into the biogenic origin of oleanane-type and cycloartane-type triterpenoids in Astragalus membranaceus. The conserved motif offers new opportunities for OSC engineering.

Using mass spectrometry-based high-throughput proteomics, we identified a membrane protein on extracellular vesicles (EVs), 90 K, which predicts poor overall survival of patients with head and neck cancer. 90 K levels in serum EVs could serve as an independent factor for poor prognosis of patients with head and neck cancer. Pre-treatment of immune competent mice with tumor-derived EVs (TDEs) elicited an immune-suppressive microenvironment for tumor cells, which was regulated by 90 K. The immunosuppressive function of TDE-90 K depends on the presence of myeloid derived suppressor cells (MDSCs) rather than regulatory T cells. The immune regulatory role of TDEs on MDSCs depends on miR-21 which is encapsulated in TDEs. Moreover, 90 K is required for the internalization of TDE cargo though interacting with integrin-β1 and anti-siglec-9 rather than directly affecting the immune function of MDSCs. 90 K modification of γδT cell-derived EVs (γδTEVs) could increase the delivery efficiency and therapeutic effect of PD-L1 siRNA by γδTEVs. We concluded that as a secreted protein modulating cell-cell and cell-matrix interactions, 90 K can be carried by TDEs to mediate the internalization and delivery of TDEs cargo by recipient cells. This function of 90 K could be utilized to improve the efficiency of EV-based drug delivery.

Chitosan (CTS)/chitosan oligosaccharide (COS) and whey protein isolate (WPI) have been frequently used as food supplements, but notably, the interaction between the carbohydrate and the protein may affect the digestibility of protein. Thus, the present study focused on effects of the interaction between CTS/COS and WPI on the protein digestibility. A series of chemical and spectroscopic techniques including gel electrophoresis, gel permeation chromatography, Fourier transform-infrared (FT-IR) spectroscopy, intrinsic fluorescence (IF) spectroscopy, and circular dichroism (CD) spectroscopy were applied. According to the findings, both CTS and COS dramatically reduced intestinal digestibility of WPI, resulting in a decrease of DH by 43.33 % and 52.31 %, respectively. The substitution degree of WPI on CTS was 0.87 g WPI/g CTS, and the electrostatic interaction between amine groups of CTS and carboxyl groups of WPI caused changes in WPI's stability, microstructure, and fluorescence intensity. Notably, CTS affected the digestibility of WPI by precipitating protein and enzyme, whereas COS altered WPI's digestibility by decreasing or inactivating enzyme activity. The present study offered a solid scientific foundation for the rational formulations of carbohydrates and proteins in food industry.

Chromosome rearrangements involving NUP98 at 11p15 are rare but recurring abnormalities in acute myeloid leukemia (AML). Here we described 12 cases of myeloid neoplasms with t(v; 11p15); NUP98 rearrangement and characterized their pathologic features. Our patient cohort included 10 adults and 2 children with a median age of 51 years. They were predominantly AML (n = 10) including de novo AML, therapy-related AML, chronic myeloid leukemia with myeloid blast crisis, and mixed phenotype acute leukemia, as well as therapy-related myelodysplastic syndrome (MDS) and MDS/myeloproliferative neoplasm with increased blasts. The blasts shared some common features including pink/red cytoplasmic granules, presence of a perinuclear hof, Auer rods, and occasional bilobed nuclei, mimicking acute promyelocytic leukemia (APML). Flow cytometric studies showed blasts positive for MPO, CD117, CD13 and CD33, with a subset of cases negative for CD34 and/or HLA-DR and a subset of cases expressing monocytic markers. The translocations of 11p15 included t(7; 11) (p15; p15), t(2; 11) (q31; p15), t(9; 11) (p22; p15), t(5; 11) (q32; p15), and t(11; 12) (p15; q13). Three cases showed cryptic NUP98 rearrangement. These patients showed incomplete response to therapy with median overall survival of 17.5 months, a complete remission rate of 25% following chemotherapy induction and primary refractory disease of 58%. It is clinically important to recognize this group of diseases because the blasts can be misclassified as promyelocytes, and NUP98 rearrangement may be cryptic requiring fluorescence in situ hybridization (FISH) study. This case series highlights that NUP98-rearranged myeloid neoplasms are clinically, morphologically, and cytogenetically distinct and could be considered as a separate entity in the WHO classification defined by cytogenetic abnormality.

The role of alkali metals in the development of neural tube defects (NTDs) is little known. We examined the associations between placental concentrations of lithium (Li), sodium (Na), potassium (K), rubidium (Rb), and cesium (Cs), and the occurrence of NTDs in fetuses.408 women who had NTD-affected pregnancies and 593 women who delivered healthy infants were included. Logistic regression, weight quantile sum regression (WQSR), and Bayesian kernel machine regression (BKMR) were applied to assess whether these metals are associated with the occurrence of NTDs.Cs showed an inverse association with the odds of NTDs [adjusted odds ratio (aOR): 0.58, 95% confidence interval (CI): 0.36-0.91] in single-metal logistic model. Estimates did not change much in the multiple-metal logistic model. In WQSR, the WQS index was inversely associated with the odds of NTDs (aOR: 0.62, 95%CI: 0.51-0.75), in which Cs (weighted 0.45) had the highest weight. In BKMR, the odds of NTDs decreased with the levels of the five-metal mixtures. Cs was associated with decreased odds of NTDs when the remaining four metals were fixed at their 25A high concentration of Cs and Na in placental tissue was respectively associated with decreased and increased odds of NTDs. In addition, the occurrence of NTDs decreased with the levels of the five-metal mixtures.

Li transient concentration distribution in spherical active material particles can affect the maximum power density and the safe operating regime of the electric vehicles (EVs). On one hand, the quasi-exact/exact solution obtained in the time/frequency domain is time-consuming and just as a reference value for approximate solutions; on the other hand, calculation errors and application range of approximate solutions not only rely on approximate algorithms but also on discharge modes. For the purpose to track the transient dynamics for Li solid-phase diffusion in spherical active particles with a tolerable error range and for a wide applicable range, it is necessary to choose optimal approximate algorithms in terms of discharge modes and the nature of active material particles. In this study, approximation methods, such as diffusion length method, polynomial profile approximation method, Pade approximation method, pseudo steady state method, eigenfunction-based Galerkin collocation method, and separation of variables method for solving Li solid-phase diffusion in spherical active particles are compared from calculation fundamentals to algorithm implementation. Furthermore, these approximate solutions are quantitatively compared to the quasi-exact/exact solution in the time/frequency domain under typical discharge modes, i.e., start-up, slow-down, and speed-up. The results obtained from the viewpoint of time-frequency analysis offer a theoretical foundation on how to track Li transient concentration profile in spherical active particles with a high precision and for a wide application range. In turn, optimal solutions of Li solid diffusion equations for spherical active particles can improve the reliability in predicting safe operating regime and estimating maximum power for automotive batteries.

Synthesis of hybrid carbon materials with core-shell structure and robust catalytic performance is of great research interest, and remains a great challenge in catalytic dehydrogenation of hydrocarbons reaction. In this paper, few-layer sp2 carbon decorated SiC nanocrystals with core-shell structure (SiC@C) were fabricated through a dual-confined magnesiothermic method by employing glucose and SiO2 as precursors. The SiC@C nanocrystals were further crosslinked to be a three dimensional (3D) mesoporous hybrid by the in situ generated carbon as binders and exhibiting a 410.30 m2 g−1 large surface area. The as-prepared SiC@C hybrid materials as metal-free catalysts were evaluated in the steam-free direct dehydrogenation of ethylbenzene to styrene. Benefiting from the abundant surface carbonyl groups on the graphite carbon layers, the optimized yield rate of styrene normalized by carbon mass was as high as 11.58 mmol g−1carbon h−1, nearly 4 times that of nanodiamonds. Considering the low cost and excellent catalytic activity, the hybrid 3D SiC@C material may be a promising candidate for direct dehydrogenation of hydrocarbons.

In general, although the climate during the Holocene has been warm, nine well-recognized cold events with an average time interval of more than one thousand years have been highlighted. The forcing mechanism of these cold events with millennial-scale cycles is still widely discussed. In the present study, two different Solar System dynamical processes collectively driven by all eight planets were considered together: the solar inertial motion and the combined planetary tidal force acting on the Sun. In this context, an attempt was made to analyze their effects on solar activity and Holocene North Atlantic cold events at the millennial-scale. These two Solar System dynamical processes were proxied by the distance between the Sun and the Solar System barycenter (DS–S) and the intensity of the combined planetary tidal force (IP–S), respectively. Using the ensemble empirical mode decomposition (EEMD) method, time series data of Solar System dynamics proxies (i.e., DS–S, and IP–S), solar activity proxies (i.e., 14C and 10Be), and a proxy of Holocene North Atlantic cold events (i.e., hematite-stained grains) were decomposed into several intrinsic mode functions (IMFs). After extracting IMF components containing millennial-scale cycles, a correlation analysis was performed. As a result, it was found that the solar inertial motion had ~2,300- and ~1,000-year cycles and the combined planetary tidal force had a ~1,500-year cycle, while the solar activity and Holocene North Atlantic cold events proxies had ~2,300-, ~1,500-, and ~1,000-year cycles, respectively. The correlation analysis revealed that the millennial-scale periodic components of the two Solar System dynamics proxies were largely correlated with that of solar activity and Holocene North Atlantic cold events, suggesting that the solar inertial motion and combined planetary tidal force may work together to impact solar activity, and thus the climate in the North Atlantic. Consequently, solar activity was weaker and the North Atlantic temperature was cooler when the Sun was far from the Solar System barycenter and/or the combined planetary tidal force was weakened. This might indicate the involvement of Solar System dynamics on Holocene North Atlantic cold events at the millennial-scale.

Backgrounds Adsorption by adsorbents is accepted as a promising technology that can efficiently separate CO2 from flue gas. Optimal adsorption performance can be obtained by specific solid adsorbents with excellent CO2 adsorption capacity. Methods In this work, N, S co-doped porous carbons were synthesized from polyacrylonitrile fiber by a facile synthesis process i.e. hydrothermal treatment followed by KOH activation. N, S enriched hydrochar was obtained after hydrothermal treatment of polyacrylonitrile fiber and ammonium sulfide. Further KOH activation of hydrochar obtained N, S co-doped carbons with advanced porous structure. Significant findings This series of sorbents has the highest CO2 uptake of 3.37 and 5.23 mmol g−1 at 1 bar, 25 °C and 0 °C, respectively. Detailed investigation revealed that the mutual effects of narrow microporostiy, N and S content are responsible for the CO2 uptake of these adsorbents. Additionally, these adsorbents also show various good CO2 capture properties such as excellent recyclability, reasonable CO2/N2 selectivity, moderate heat of adsorption, fast adsorption kinetics, and good dynamic adsorption capacity. These findings suggest that N, S co-doped porous carbons derived from polyacrylonitrile fiber are potential promising sorbents for CO2 capture.

To improve the cracking behavior of hydrocarbon, Ni–Mo/SiO2 bimetallic catalysts were synthesized by different preparation methods (sol-gel, co-impregnation and single-impregnation) and added the additives (citric acid, polyethylene glycol and cetyltrimethylammonium bromide) based on the most suitable method above. The cracking reaction of methylcyclohexane under supercritical conditions was performed as the probe reaction to estimate the catalytic performance, and the properties of Ni–Mo/SiO2 catalyst were characterized by N2 absorption-desorption, XRD, XPS, H2-TPR, NH3-TPD, in-situ IR of NH3 desorption, HRTEM and STEM-mapping so as to study the structure-activity relationship. The catalyst synthesized via sol-gel method showed the best conversion and heat sink, being 81.8% and 3.81 MJ/kg, which was closely related to strong mutual effect between active components and SiO2 as well as strong acid sites. Besides, the introduction of additives by sol-gel method has an affirmative influence on properties of Ni–Mo/SiO2 catalysts, being that the acidity (more L and B acid sites) was modulated and organic groups interact with metal to suppress the aggregation of metal species (Ni and Mo), thereby enhancing the catalytic activity. At 750 °C, the conversion (89.3%) as well as heat sink (3.99 MJ/kg) of MCH cracking obtained an optimum over Ni–Mo/SiO2 catalyst with addition of citric acid.

Background Effective dose to immune cell (EDIC), an estimated radiation dose to the circulating lymphocytes, is of significance for overall survival (OS) in non-small cell lung cancer. This study aimed to validate the EDIC’s OS effect on limited-stage small cell lung cancer (LS-SCLC). Method and materials This study included LS-SCLC patients received definitive chemo-radiation in one single center from 2012 to 2017. All patients had multiple complete-blood-count tests including lymphocyte count at pre-, during- and end- radiotherapy. EDIC, computed according to doses of the lung, heart, and the total body, was assessed for its correlation with lymphocyte nadir, OS and progression free survival (PFS). Results Of 503 eligible patients, the mean EDIC was 7.34 Gy. The mean lymphocyte nadir was 0.48 × 109 cells/L, significantly lower than 1.65 × 109 cells/L at pre-radiotherapy (p Conclusions This study demonstrated that EDIC is an independent predictor for lymphocyte nadir, PFS and OS. EDIC may serve as a predictor for lymphocyte nadir and a surrogate marker for OS in LS-SCLC. More attention should be paid to EDIC to decease the lymphocyte toxicity and improve survival.

Background: c-Jun N-terminal kinase 1 (JNK1) and JNK2 regulate distinct pathological processes in lung diseases. Here we discriminated the respective roles of these kinases in lung transplantation-induced ischemia-reperfusion injury (IRI). Methods Rat pulmonary microvascular endothelial cells were transfected with JNK1 small-interfering RNA (siRNA) and JNK2 siRNA and then subjected to in vitro IRI. For the isoform confirmed to aggravate IRI, the delivery of short-hairpin RNA (shRNA) plasmid was performed by intratracheal administration 48 hours before transplantation into donor rats. After a 3-hour reperfusion, the samples were collected. Results JNK1 siRNA decreased but JNK2 siRNA increased JNK phosphorylation and activity, phosphorylated and total c-Jun, and activator protein-1 activity. Although JNK1 siRNA decreased apoptosis and the levels of malondialdehyde, interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF-α), it increased the levels of superoxide dismutase, S-phase percentage, and cyclin D1; JNK2 siRNA had a converse effect. JNK1 siRNA decreased the level of lactate dehydrogenase and increased the levels of VE-cadherin, nitric oxide, phosphorylated nitric oxide synthase, and cell viability; JNK2 si RNA had a converse effect. Compared with the control group, the JNK1 shRNA group exhibited a higher lung oxygenation index and lower lung apoptosis index, injury score, wet weight:dry weight ratio, and levels of IL-1, IL-6, and TNF-α. Conclusions JNK1 aggravated, but JNK2 alleviated, IRI through differential regulation of the JNK1 pathway in in vitro ischemia-reperfusion. JNK1 silence attenuated lung graft dysfunction by inhibiting inflammation and apoptosis. These findings provide a theoretical basis for devising therapeutic strategies against IRI after lung transplantation.