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In the study, the adjuvant features of the immunoregulatory polysaccharide component CARP2 isolated from cultivated Artemisia rupestris L. for influenza virus vaccine (IVV) and the mechanism responsible for its action in DCs were further explored. CARP2 showed a typical absorbance peak of polysaccharides in spectral analysis. At two doses of CARP2-adjuvanted IVV, IgG, hemagglutination inhibition (HI) titers, and effector/memory T cells were generated and lasted for 275 days without adverse events. CARP2 primed rapid HI and IgG, IgG2a/IgG1 ratio, splenocyte proliferation, and cytotoxic T lymphocyte (CTL), and facilitated the generation of INF-γ and IL-4 by activating DCs and regulatory T cells (Tregs). Additionally, CARP2 achieved the ten-fold dose-sparing effect. In vitro, CARP2 stimulated DCs to prime the production of Th1/Th2 cytokines and CCR7 and activated MyD88-dependent pathway by upregulating the expressions of TLR4, MyD88, TRAF-6, and p65. In contrast, MyD88, TRAF-6, and NF-κB inhibitors partially blocked the effect through reducing related cytokines and proteins. Overall, CARP2 promoted IVV efficacy, which was involved in the modulation of Th1/Th2 responses and shifted toward Th1-polarizing response via TLR4/MyD88/TRAF/NF-κB activation in DCs.

Screening and analysis of bioactive components from natural products is a fundamental part of new drug development and innovation. Two-dimensional (2D) chromatography has been demonstrated to be an effective method for screening and preparation of specific bioactive components from complex natural products.To collect details of application of 2D chromatography in screening of natural product bioactive components and to outline the research progress of different separation mechanisms and strategies.Three screening strategies based on 2D chromatography are reviewed, including traditional separation-based screening, bioactivity-guided screening and affinity chromatography-based screening. Meanwhile, in order to cover these aspects, selections of different separation mechanisms and modes are also presented.Compared with traditional one-dimensional (1D) chromatography, 2D chromatography has unique advantages in terms of peak capacity and resolution, and it is more effective for screening and identifying bioactive components of complex natural products.Screening of natural bioactive components using 2D chromatography helps separation and analysis of complex samples with greater targeting and relevance, which is very important for development of innovative drug leads.

The utilization of bamboo industry exhibits varied but still needs to be improved. Bamboo leaf flavonoid (BLF) is an important resource of bamboo which has become a research focus. However, the isolation and purification techniques of four flavonoid carbon glycosides (orientin, isoorientin, vitexin, and isovitexin) from BLF were still confronted with difficulties due to their complex and similar structures, which obstructed the development of bamboo utilization. In this article, a purification technology of four flavonoid carbon glycosides from BLF by Sephadex LH-20 was improved. The results were evaluated by HPLC and pharmacological activity. Specifically, the eluent, flow rate, and loading amount were investigated, respectively. According to the results, the eluent would dominate the isolation effect among three factors. High concentration of isoorientin and four flavonoid carbon glycosides would be obtained under the optimized condition (The eluent was 70 % methanol, the loading amount was 1.5 g, and the flow rate was 0.5 mL/min). Meanwhile, the link between flavonoid carbon glycosides content and their antioxidant activity in vitro was also revealed. Overall, the results suggested that BLF may serve as potential functional food additives and medicine.

Inactivated foot-and-mouth disease (FMD) vaccines generally require adjuvants to enhance the immunogenicity. To test whether the aqueous extracts of Cistanche deserticola (AECD) could be developed into a polysaccharide adjuvant for inactivated FMD vaccines in mice. Experimental vaccines were prepared with inactivated FMD viral antigen plus AECD or inactivated FMD vaccine plus AECD to subcutaneously immunize mice. AECD developed an FMDV-specific humoral response by increasing IgG antibodies and IL-4 in CD4+ T cells and enhanced lymphocyte proliferation and a balanced Th1/Th2 response. Importantly, AECD induced Th1 type immunity by augmenting the activation of T subsets (CD4+, CD8+, CD44+) and the induction of IFN-γ in T lymphocytes, especially CTL response and neutralizing antibodies in sera. In addition, AECD maintained the higher levels of CD80, CD40, MHC-II, CD86 on CD11c+ cells and decreased the Treg frequency. Our results suggested that AECD had the potential utility as an polysaccharide adjuvant for FMD vaccines.

Artemisia rupestris L. polysaccharides have immune enhancement effects with low toxicity in the previous studies. The effect of crude polysaccharides from cultivated Artemisia rupestris L. (CPCAR) on immunity has not been explored. Here, the adjuvant potential of CPCAR was investigated in vivo and its underlying mechanism in vitro was explored through activation of bone marrow-derived dendritic cells (BMDCs). After intramuscular immunizations, CPCAR elevated IgG levels with a TH1-biased response, lymphocyte proliferation and increased CD4 and CD8 T cells in spleen and lymph nodes. IFN-γ and IL-4 of CD8 or CD4 T cells were specifically increased. CPCAR improved DC maturation and diminished Treg frequency. BMDCs treated with CPCAR in vitro showed the up-regulation of CD40, CD86, IL-12 and TNF-α. BMDMs pretreated with TLR4 and NF-kB inhibitors decreased the expressions of CD40 and CD86 and produced less cytokines. These data demonstrated that CPCAR could boost TH1-biased response through DC activation in TLR4/NF-κB signalling.

Electrochemical water splitting technology is considered to be the most reliable method for converting renewable energy such as wind and solar energy into hydrogen. Here, a nanostructured RuO2/Co3O4–RuCo-EO electrode is designed via magnetron sputtering combined with electrochemical oxidation for the oxygen evolution reaction (OER) in an alkaline medium. The optimized RuO2/Co3O4–RuCo-EO electrode with a Ru loading of 0.064 mg cm−2 exhibits excellent electrocatalytic performance with a low overpotential of 220 mV at the current density of 10 mA cm−2 and a low Tafel slope of 59.9 mV dec−1 for the OER. Compared with RuO2 prepared by thermal decomposition, its overpotential is reduced by 82 mV. Meanwhile, compared with RuO2 prepared by magnetron sputtering, the overpotential is also reduced by 74 mV. Furthermore, compared with the RuO2/Ru with core–shell structure (η = 244 mV), the overpotential is still decreased by 24 mV. Therefore, the RuO2/Co3O4–RuCo-EO electrode has excellent OER activity. There are two reasons for the improvement of the OER activity. On the one hand, the core–shell structure is conducive to electron transport, and on the other hand, the addition of Co adjusts the electronic structure of Ru.

The literature documents the effects of monetary and macroprudential policies in controlling systemic risk, but empirical evidence of a systemwide framework that effectively coordinates the two policies is lacking. This study assesses the effectiveness, channels, and timeliness of monetary and macroprudential policies’ impacts on systemic risk in China from January 2009 to June 2018, and contributes to the discussion of how to coordinate these policies. Using an index synthesized from 28 indicators to proxy China’s systemic risk, we find the following: (1) A contractionary monetary (macroprudential) shock increases (reduces) systemic risk over the entire shock time period. (2) Macroprudential (monetary) policy is effective in the long (short) term. (3) The systemic risk intervention effect of monetary (macroprudential) policy is channeled through inflation control (asset price stability).

Thermogravimetric analysis and electrical resistivity were used to determine the hydration process of cement paste with rice husk ash (RHA) (0–15%) and water-cement ratio of 0.4 in this work. X-ray diffraction (XRD) method and scanning electron microscopy (SEM) were used to survey crystal composition and microstructures of specimens cured for 3 h, 1 d, 7 d and 28 d. Finally, electrical parameters (electrical resistance and AC impedance spectroscopy) of steel bars reinforced cement paste were investigated to study the effect of RHA on the corrosion resistance. Results showed that RHA could affect the cement hydration by hydration promotion and pozzolanic effect. The evaluation function for electrical resistivity and curing ages fitted well with linear increasing function. The addition of RHA higher than 5% demonstrated a decreasing role in the electrical resistivity of cement paste at earlier curing ages (3–7 d). Meanwhile, when at later curing ages (7–28 d) the result was the opposite. Moreover, RHA demonstrated positive effects on corrosion resistance of steel bars in cement paste.

High belite cement has a wide application potential due to its low energy consumption, low CO2 emission, and excellent durability performance. Due to the low hydration rate and strength development at an early age, the activation of beta-dicalcium silicate (β-C2S) crystallographic structure is essential to improve the early strength of high belite cement. In this study, the β-C2S phase is activated by dissolving Ba2+ ions into the crystal lattice to improve the hydration rate. Unlike the traditional analysis methods of thermodynamics and dynamics theory, the first principle and density functional theory were applied to study the effect of Ba2+ ions on the activation of β-C2S, especially on the crystallographic structure, lattice parameters, and electronic structure change. The crystallographic structure of β-C2S can be activated by doping Ba atom and the crystal formation energy increases and the bandgap between VBM and CBM become narrow in the activated β-C2S crystallographic structure. Comparing the Ca2+ substitution in [CaO6] or [CaO8], the lattice deformation and hydraulic reactivity is more significant in Ba2-C2S and Ba22-C2S. The first principle and density functional theory explains the change of the electronic structure of the activated crystallographic structure and provides a theoretical basis for the purposeful design of material structures.

With the depletion of fossil energy and the rise of global temperature, it is urgent to use renewable energy to solve environmental problems. By studying the heterogeneous relationship between CO2 emissions and renewable energy technology innovation in different countries, we can find out the gap and something helpful to energy development. In the empirical test, we use the negative binomial regression model with fixed effects to study the impact of CO2 emissions on renewable energy technology innovation from 1997 to 2016. The research shows that impact is positive in oil-importing countries, but this relationship is not established in oil-exporting countries. In both oil importers and oil exporters, CO2 emissions have a positive effect on the solar energy technological innovation, however, the influence on the technology innovation of solar energy in oil exporters is more significant than that of renewable energy. Whether for oil importers or oil exporters, it can be more reasonable and effective to develop renewable energy by clarifying the impact of CO2 emissions on domestic renewable energy technology innovation.

The study aims to investigate the constituents, adjuvant effects, and underlying mechanisms of purified polysaccharides from cultivated Cistanche deserticola (C. deserticola). Two macromolecules designated as CCDP-1 (26.5 kDa) and CCDP-2 (32.3 kDa) from C. deserticola were respectively identified as carbohydrate-lignin complexes with 44.1 % and 43.8 % lignin. CCDP-1 and CCDP-2 were composed of glucose, rhamnose, galactose, arabinose, and mannose respectively in the molar ratios of 7.22: 5.98:2.51:1.81:1.00 and 6.57:8.48:4.20:2.72:1.00. An in vitro experiment revealed that endotoxin-free CCDP-1 and CCDP-2 promoted splenocyte proliferation without cytotoxicity, but CCDP-2 induced dendritic cell (DC) maturation more efficiently than CCDP-1. An in vivo experiment suggested that CCDP-2 enhanced OVA-specific antibody production, antigen-specific T-cell activation, IFN-γ production, IL-4 production, and DC activation. Notably, CCDP-2 elicited a Th1-biased response. Mechanically, CCDP-2 upregulated CD40, CD80, CD86, and MHC II, facilitated allogeneic T-cell proliferation and Th1/Th2 cytokines, improved IFN-γ, IL-12, IL-6, and TNF-α production, and decreased endocytosis from DCs in vitro. Blocking assays indicated that TLR2 and TLR4 were the membrane receptor candidates of DCs. Western blot implied that CCDP-2 with the immune-enhancing activities were involved in the activation of MAPKs and NF-κB pathways in a dose-/time-related manner and could be employed as a more balanced Th1/Th2 adjuvant for vaccine exploitation.

It was reported that PIM (Proviral Insertion site in Moloney murine leukemia virus) proteins are family kinases (PIM1, PIM2, and PIM3), which are upregulated in several cancer types, especially PIM1 is highly expressed in hematopoietic malignancies. PIM kinase family are responsible for enhancement of cell cycle, inhibition of apoptosis, activation of transcription, and cell homing/migration. Fms-like tyrosine kinase 3 (FLT3) is part of a family of receptor tyrosine kinases (RTKs), and a molecular therapeutic target of acute myeloid leukemia (AML). There are three FTL3 inhibitors, midostaurin, gilteritinib, and quizartinib have been approved for clinical treatment of AML. We have developed a novel dual inhibitor of PIM1 and FLT3, RF-1302 and evaluated its inhibition of cell proliferation in vitro and antitumor activity in vivo. RF1302 was found to have a strong inhibitory activity against target enzymes (PIM1 IC50 at 1.0-2.3 nM and FLT3 IC50 at 0.8-2.2 nM), which were more potent than the tested positive control drugs gilteritinib, quizartinib, and midostaurin. RF-1302 showed to be highly cytotoxic to cultured human acute myeloid leukemia (AML) cells (MV4-11 and Molm-13) with IC50 at 5.7nM and 9.5 nM, respectively. The in vivo antitumor activity of RF-1302 was evaluated and compared with midostaurin and gilteritinib in the treatment of the two AML xenograft models. RF-1302 at 20 mg/kg/daily x 14, oral) significantly delayed tumor growth and resulted in a tumor growth inhibition (TGI) of 95% (p Citation Format: Weiwei Qi, Yanjun Zhang, Lei Zhao, Ailian Zhang, Chunze Zhang, Xiaoming Zhang, Lijuan Li, Huaquan Wang, Zonghong Shao, Rong Fu. RF-1302, a novel dual inhibitor of PIM1 and FLT3 in preclinical treatment of acute myeloid leukemia. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5269.

Structural derivatization of natural products has been a continuing and irreplaceable source of novel drug leads. Natural phenols are a broad category of natural products with wide pharmacological activity and have offered plenty of clinical drugs. However, the structural complexity and wide variety of natural phenols leads to the difficulty of structural derivatization. Skeleton analysis indicated most types of natural phenols can be structured by the combination and extension of three common fragments containing phenol, phenylpropanoid and benzoyl. Based on these fragments, the derivatization strategies of natural phenols were unified and comprehensively analyzed in this review. In addition to classical methods, advanced strategies with high selectivity, efficiency and practicality were emphasized. Total synthesis strategies of typical fragments such as stilbenes, chalcones and flavonoids were also covered and analyzed as the supplementary for supporting the diversity-oriented derivatization of natural phenols.

Saffron (Crocus sativus L.) is a valuable herbal plant, and is widely used as a spice, food colorant, and medicine. In this study, variations in total polysaccharides, crocin contents, and antioxidant activities (DPPH, OH, O 2 - radical-scavenging and reducing power) of saffron from seven different production areas were studied. There were significant differences (P ≤ 0.05) among populations for total polysaccharides and crocin contents. The total polysaccharides ranged from 52.65 to 67.18 mg/g, and total crocin contents varied from 80.59 to 230.36 mg/g. Fourier-transform infrared spectra (FT-IR) indicated the chemical structures of polysaccharide and ethanol extracts. High-performance liquid chromatography (HPLC) analysis showed that saffron polysaccharide extracts was composed of rhamnose, galacturonic acid, glucose, galactose, xylose and arabinose. Antioxidant assays indicated that both polysaccharide and ethanol extracts have remarkable antioxidant activities and can be used as a new potential antioxidant. Furthermore, the differences of polysaccharides, crocins and antioxidant activities in saffron from different production areas provide the basis for the cultivation and quality evaluation of saffron.

Several methods have been developed to improve the efficacy of foot-and-mouth disease virus (FMDV) vaccine. The study aims to determine whether aqueous extracts of Artemisia rupestris L. (AEAR) as an immunoactivator in combination with inactivated FMDV vaccine can promote immune responses in mice. Intramuscular co-immunization in ICR mice with different doses of AEAR plus FMDV vaccine could substantially improve the FMDV-specific antibody production (IgG, IgG1, and IgG2a) and lead to significant lymphocyte proliferative responses. Th1-type immune responses were also observed, including proliferative responses of CD8+, CD4+, CD4+CD44+, and CD8+CD44+ T cells and the killing efficacy of cytotoxic T lymphocyte (CTL) responses. AEAR also elicited the higher levels of IL-4 and IFN-γ in CD4+ T cells as well as the higher level of IFN-γ in CD8+ T cells. The medium dose of AEAR induced the significant adjuvant activity. Further tests in mice indicated that AEAR could activate DCs maturation by increasing the expression levels of co-stimulatory molecules (CD40, CD86, CD80, and MHC-II) on dendritic cells (DCs) from splenocytes and reduce the activity of regulatory T cells (Treg). Abnormal behaviors, side effects or death were not observed in immunized mice. AEAR could boost humoral and cell-mediated immunity elicited by FMDV vaccine, especially Th1-type immune responses.

To improve fiber orientation in ultra-high performance concrete (UHPC), one L-shape device was developed to control the flow of fresh mixture. A smoothed particle hydrodynamics (SPH) method was used to analyze and simulate the motion of steel fibers in UHPC with flow through this L-shape apparatus. SPH simulation indicated that steel fibers tended to rotate to be parallel with local streamlines and most fibers were aligned in the horizontal channel of this L-shape device, inducing an improvement of fiber orientation in hardened specimens. This modification effect of fiber orientation can be a little strengthened with the decreasing height of the horizontal channel. On the other hand, a colorless, transparent and viscous concentrated suspension was obtained by adding super absorbent polymer (SAP) into water for representing fresh UHPC matrix and the visualization of fiber motion was achieved. This visualization approach, coupled with image analysis of steel fibers in hardened UHPC specimens, well verified the SPH numerical simulation results. Therefore, this type of L-shape apparatus provides a potential method to manually improve the steel fiber orientation in UHPC for better mechanical properties.

Two components (CARP-1 and CARP-2) were fractionated from cultivated Artemisia rupestris L. and then characterized by HPGPC and HPLC. CARP-1 with a molecular weight of 2.72 × 10

The electrical resistance and polarization effect of cement paste containing reinforcement were tested to research the anti-corrosion properties of steel bars in cement paste. Moreover, the microstructure and composition of passivation film and rust on the steel bars were studied. The water–cement ratio of the cement paste in this study was 0.3, with 0.5% NaCl, 1% NaNO2, and 1% Benzotriazole, and an assembly unit of 0.5% NaNO2 + 0.5% Benzotriazole by mass of cement was added to the cement to provide a chloride environment. X-ray photoelectron spectroscopy (XPS) and scanning electron microscope (SEM) were applied to research the composition of the passivation film and the microstructure of the cement paste, respectively. The results indicated that the samples with the assembly unit of 0.5% NaNO2 + 0.5% Benzotriazole showed the highest electrical resistance and polarization electrical resistance, while the specimens with 1.0% Benzotriazole showed the lowest electrical resistance and polarization electrical resistance. Moreover, the passivation film of steel bars weakened with increasing distance from the surface of the steel bars. Therefore, the corrosion of steel bars becomes more serious with increasing distance. Finally, the influence of the rust inhibitor on the corrosion resistance of steel bars in the specimens decreased in the following order: 0.5% NaNO2 + 0.5% Benzotriazole &gt, 1.0% NaNO2&gt, 1.0% Benzotriazole.

Ethnopharmacological relevance Herbal polysaccharides have exhibited great immune-enhancing potential. Adjuvants are a key tool for developing efficacious vaccines. In our previous study, a water-soluble polysaccharide extracted from wild Cistanche deserticola Y.C. Ma showed potent immunostimulatory activity. Aim of study In this study, the immune profiles and efficacy of aqueous extracts of cultivated Cistanche deserticola Y.C. Ma (AECCD) on ICR mice against ovalbumin (OVA) were investigated. In vitro experiments, the possible DC activation mechanism by AECCD was evaluated. Materials and methods AECCD were extracted using hot water after which the crude polysaccharides were precipitated by ethanol. Mice were firstly immunized subcutaneously with OVA (10 μg per mouse) alone or OVA (10 μg per mouse) respectively containing different dose of AECCD (200, 400 and 800 μg per mouse) on Days 1 and 14 and the magnitude and kinetics of antibodies and cell-mediated responses were then assessed. Results AECCD elicited vigorous and long-term IgG responses with mixed Th1/Th2 responses and up-regulated levels of Th-associated cytokines (CD4+IL-4, CD4+IFN-γ and CD8+IFN-γ). Moreover, AECCD induced the strong cellular immune response characterized by increased splenocyte proliferation as well as the activated T cell response. Notably, AECCD significantly enhanced the maturation of dendritic cells (DCs) and inhibited Tregs. In vitro experiments, Preliminary tests indicated that AECCD induced DC activation by promoting phenotypic maturation, cytokine section and allostimulatory activity. Toll-like receptor 4 (TLR4) was an essential receptor for DCs to directly bind AECCD. The inhibitors of NF-κB decreased the expression levels of CD40, CD80, CD86 and MHC-II and the production of IFN-γ, TNF-α and IL-6 through DCs. Conclusions Finally, these findings suggested that AECCD could elicit potent and durable antigen specific immune responses through DC activation, which was involved in the regulation of maturation markers and cytokine expression via TLR4-related NF-κB pathway. The study indicates that AECCD is a potential immunomodulator.

Objective: To explore potential predictors of RMPP in early stage.Study design: The prospective study, multicenter study was conducted in Zhejiang, China from May 1st, 2019 to January 31st, 2020. Children aged 29 days to 14 years old, with fever time during 48 to 120 hours were included. A total of 1428 children completed the study. A questionnaire was designed to collect patients’ information. Pharyngeal swab samples were collected. M. pneumoniae DNA in pharyngeal swab specimens were detected. Whether the patients develop to RMPP were assessed. Logistic regression analyses were used to examine associations between clinical data and RMPP.Results: The ages of the patients ranged from 34 days to 13.9 years with a median 4.3 years. The positive rate of M. pneumoniae -DNA was 37.4% (534/1428), and 446 cases were Mycoplasma pneumoniae pneumonia (MPP). In MPP patients, 55 cases were RMPP (12.3%), others were general MPP (GMPP) patients (n=391, 87.7%). Only the peak body temperature before the first visit and LDH level in RMPP patients were higher than that in GMPP [39.6 (39.1-40.0) °C vs. 39.2 (38.9-39.7) °C, p=0.003, and 332.5 (278.8-392.1) U/L vs. 310.5 (259.0-358.8) U/L, p=0.024]. Logistic regression also only included the above two parameters in the prediction probability. The area under ROC curve of the prediction probability π of RMPP was 0.682 (95% CI, 0.593-0.771), PConclusions: AND RELEVANCE A prediction probability, calculating from the peak body temperature before the first visit and LDH level for early identifying RMPP from other MPP within 2-5 days of fever duration, with a cut-off value of 0.12 may be helpful in clinical practice.