Epitope delimitation: A new method for defining epitopes of human IgG-reactive antigenic peptides based on rabbit-recognized epitope motifs.

The use of precise epitope peptides as antigens is essential for accurate serological diagnosis of viral-infected individuals, but now it remains an unsolvable problem for mapping precise B cell epitopes (BCEs) recognized by human serum. To address this challenge, we propose a novel epitope delimitation (ED) method to uncover BCEs in the delineated human IgG-reactive (HR) antigenic peptides (APs). Specifically, the method based on the rationale of similarities in humoral immune responses between mammalian species consists of a pair of elements: experimentally delineated HR-AP and rabbit-recognized (RR) BCE motif and corresponding pair of sequence alignment analysis. As a result of using the ED approach, after decoding four RR-epitomes of human papillomavirus types 16/18-E6 and E7 proteins utilizing rabbit serum against each recombinant protein and sequence alignment analysis of HR-APs and RR-BCEs, 19 fine BCEs in 17 of 22 known HR-APs were defined based on each corresponding RR-BCE motifs, including the type-specificity of each delimited BCE in homologous proteins. The test with 22 known 16/20mer HR-APs demonstrated that the ED method is effective and efficient, indicating that it can be used as an alternative method to the conventional identification of fine BCEs using overlapping 8mer peptides.

Rapid Prediction of Adulteration Content in Atractylodis rhizoma Based on Data and Image Features Fusions from Near-Infrared Spectroscopy and Hyperspectral Imaging Techniques.

Atractylodis rhizoma (AR) is an herb and food source with great economic, medicinal, and ecological value. Atractylodes chinensis (DC.) Koidz. (AC) and Atractylodes lancea (Thunb.) DC. (AL) are its two botanical sources. The commercial fraud of AR adulterated with Atractylodes japonica Koidz. ex Kitam (AJ) frequently occurs in pursuit of higher profit. To quickly determine the content of adulteration in AC and AL powder, two spectroscopic techniques, near-infrared spectroscopy (NIRS) and hyperspectral imaging (HSI), were introduced. The partial least squares regression (PLSR) algorithm was selected for predictive modeling of AR adulteration levels. Preprocessing and feature variable extraction were used to optimize the prediction model. Then data and image feature fusions were developed to obtain the best predictive model. The results showed that if only single-spectral techniques were considered, NIRS was more suitable for both tasks than HSI techniques. In addition, by comparing the models built after the data fusion of NIRS and HSI with those built by the single spectrum, we found that the mid-level fusion strategy obtained the best models in both tasks. On this basis, combined with the color-texture features, the prediction ability of the model was further optimized. Among them, for the adulteration level prediction task of AC, the best strategy was combining MLF data (at CARS level) and color-texture features (C-TF), at which time the R2T, RMSET, R2P, and RMSEP were 99.85%, 1.25%, 98.61%, and 5.06%, respectively. For AL, the best approach was combining MLF data (at SPA level) and C-TF, with the highest R2T (99.92%) and R2P (99.00%), as well as the lowest RMSET (1.16%) and RMSEP (2.16%). Therefore, combining data and image features from NIRS and HSI is a potential strategy to predict the adulteration content quickly, non-destructively, and accurately.

Bamboo leaf: A review of traditional medicinal property, phytochemistry, pharmacology, and purification technology.

ETHNOPHARMACOLOGICAL RELEVANCE: Bamboos are perennial evergreen plants that belong to the subfamily Bambusoideae of the true grass family Poaceae, with more than thousands of species distributed around the world. They are used as a traditional medicine with demonstrated effects of anti-oxidation, free radical scavenging, anti-inflammatory, liver protection and ameliorating cognitive deficits. Bamboo leaf is mainly used for the treatment of atherosclerotic, diabetic and nervous system diseases. AIM OF THE STUDY: This review aims to provide up-to-date information on the traditional medicinal properties, phytochemistry, pharmacology, and purification technologies of bamboo leaf. MATERIALS AND METHODS: Relevant information on bamboo leaf was obtained by an online search of worldwide accepted scientific databases (Web of Science, ScienceDirect, Elsevier, SpringerLink, ACS Publications, Wiley Online Library and CNKI). RESULTS: More than 100 chemical compounds, including flavonoids and flavonoid glycosides, volatile components, phenolic acids, polysaccharide, coenzyme Q10, phenylpropanoid and amino acids have been reported to be present. These compounds were usually extracted by column chromatography and membrane separation technologies. Preparative high performance liquid chromatography (PHPLC), high-speed counter-current chromatography (HSCCC), simulated moving bed chromatography (SMB) and dynamic axial compression chromatography (DAC) were the advanced separation technologies have been used to isolate C-glycosides from bamboo leaf flavonoid, the main bioactive ingredient of bamboo leaf. Currently, bamboo leaf is mainly used for the treatment of atherosclerotic, diabetic, hepatic diseases and nervous system related symptoms, which are attributed to the presence of bioactive components of bamboo leaf. CONCLUSIONS: Phytochemical and pharmacological analyses of bamboo leaf have been revealed in recent studies. However, most of the pharmacological studies on bamboo leaf have focused on bamboo leaf flavonoids. Further studies need to pay more attention to other phytochemical components of bamboo leaf. In addition, there is lack of sufficient clinical data and toxicity studies on bamboo leaf. Therefore, more clinical and toxicity researches on this plant and constituents are recommended.

Cultivated Artemisia rupestris L. polysaccharide CARP2 as an adjuvant for influenza vaccines to prolong immune responses.

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.

Allergic diseases aggravate the symptoms of SARS-CoV-2 infection in China.

Background: The relationship between allergic diseases and the adverse outcomes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a subject of controversy. This study aimed to investigate the association between allergic diseases and the incidence and severity of symptoms in SARS-CoV-2 infection. Methods: Clinical data of individuals, including children and their parents, infected with SARS-CoV-2 from December 2022 to January 2023 in China were retrospectively analyzed. The data were collected through questionnaires. Statistical analysis, including chi-squared tests, nonparametric analysis, one-way ANOVA, and logistic regression analysis, was used to examine the relationship between allergic diseases, prior medication, and the symptoms of SARS-CoV-2 infection. Results: There were 3,517 adults and 3,372 children with SARS-CoV-2 infection included in the study. Fever was found to occur at similar rates in children (86.5%) and adults (86.8%). However, other symptoms related to respiratory issues (such as cough and sore throat), neurological symptoms (headache, loss of smell, and loss of taste), and systemic symptoms (muscle soreness and weakness) were observed more frequently in adults (P < 0.001). Additionally, adults exhibited higher overall symptom scores, indicating greater severity. Allergic diseases were found to be associated with the incidence of certain SARS-CoV-2 infection symptoms in both children and adults. Specifically, children with allergic rhinitis (AR) were observed to be more susceptible to upper respiratory symptoms (OR: 1.320, 95% CI: 1.081-1.611, P = 0.006), while asthma patients were found to be more susceptible to severe respiratory symptoms (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). Similar patterns were identified in adults. Furthermore, AR was also suggested to be a risk factor for symptom severity in both children (OR: 1.704, 95% CI: 1.314-2.209, P < 0.001) and adults (OR: 1.736, 95% CI: 1.250-2.411, P = 0.001). However, prior medication for allergic diseases did not exhibit a preventive effect on SARS-CoV-2 infection symptoms. Conclusions: Both children and adults with allergic diseases were found to be more prone to experiencing symptoms of SARS-CoV-2 infection, and these symptoms tended to be more severe.

Chemical composition and adjuvant properties of the macromolecules from cultivated Cistanche deserticola Y. C. Ma as an immunopotentiator.

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.

In silico screening of off-line comprehensive two-dimensional counter-current chromatography with liquid chromatography for four saponins isolation.

Being restrained by the limited peak capacity, one-dimensional chromatography usually leads to an unsatisfactory separation with low purity of compounds in a complex mixture. To obtain more highly pure targets for standard reference and to discover new substances for structural elucidation, two-dimensional chromatography is more and more prevalent in many fields. As few metrics on assessment of the preparative capability of two-dimensional chromatographic separations are reported, a methodology of in silico screening of various two-dimensional chromatographic separations with a minimal number of experiments was demonstrated in this work, which was based on three descriptors including the occupation rate of peaks and system homogeneity of a two-dimensional separation space, and the minimal distance of all nearest-neighbor distances of peaks. Combining the advantages of counter-current chromatography and liquid chromatography, we elaborated the methodology by employing off-line comprehensive two-dimensional counter-current chromatography with liquid chromatography to be in silico screened for separation of four saponins from Panax notoginseng at an analytical scale to simulate the case of preparative scale transfer. The predictive results were presented by two-dimensional contour plots and verified by experiments. The result showed that the experimental results were in general accord with the predictive results.

Two-dimensional chromatography in screening of bioactive components from natural products.

INTRODUCTION: 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. OBJECTIVE: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSION: 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.

Isolation, Characterization of Bamboo Leaf Flavonoids by Size Exclusion Chromatography and Their Antioxidant Properties.

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.

Immunoregulatory properties of the cultivated Artemisia rupestris L. polysaccharide as a potential adjuvant.

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 × 104 Da and CARP-2 with a molecular weight of 2.08 × 104 Da were mainly composed of galactose, arabinose, glucose and rhamnose. Polysaccharides were the active components as confirmed by the increased CD40, CD86, TNF-α, and IL-6, allogeneic T-cell activation, and reduced endocytosis in vitro assays. CARP-1 and CARP-2 at 10 to 3200 µg/mL was not cytotoxic to the splenocytes of mice. After immunization, CARP-1 and CARP-2 combined with OVA elicited mixed Th1/Th2 responses, especially polarized Th1 response. Furthermore, TLR4 inhibitor decreased CARP-1- and CARP-2-induced DC activation. Western blot revealed that CARP-1 and CARP-2 stimulated the phosphorylation changes of target proteins in NF-κB and MAPK pathways in a dose- or time-related manner. Overall, CARP-1 and CARP-2 could be exploited as an effective and safe adjuvant for vaccines.

Improving adjuvanticity of crude polysaccharides from cultivated Artemisia rupestris L. for influenza vaccine by promoting long-term immunity and TH1/TH2 response with dose-sparing effect.

ETHNOPHARMACOLOGICAL RELEVANCE: Influenza virus vaccines (IVV) with balanced TH1/TH2 responses are critical for controlling seasonal influenza. Emerging evidences suggest that herbal polysaccharides can induce potent TH1 or mixed TH1/TH2 responses. AIM OF STUDY: The study aims to determine the efficacy and safety of crude polysaccharides from cultivated Artemisia rupestris L. (CPCAR) as an adjuvant for IVV. MATERIALS AND METHODS: CPCAR was prepared with hot extraction and ethanol precipitation method and primary physico-chemical characters were tested. Mice were vaccinated by subcutaneous route with IVV formulated with different dose of CPCAR to detecting the elicited TH1/TH2 responses and long-term immune responses with dose-sparing sparing effect. RESULTS: IVV formulated with CPCAR without LPS contamination could augment balanced TH1/TH2 responses, as indicated by early IgG response, hemagglutination inhibition (HAI) antibodies, effector T-cells, and cytotoxic T lymphocytes (CTL). Moreover, CPCAR elicited long-term IgG, HAI antibodies, memory T cells, and balanced CD4/CD8 responses within 168 days after vaccination. Compared with IVV alone, a low or high dose of IVV formulated with CPCAR improved the levels of IgG, IgG1, and IgG2a and enhanced memory T cells and balanced CD4/CD8 responses, displaying a 10-fold dose-sparing effect. As determined by IgE response and monitoring results of weekly body weight and daily symptoms after vaccination, anaphylaxis or adverse effect was not observed. CONCLUSIONS: Collectively, the study demonstrated the potential of CPCAR as an aqueous polysaccharide adjuvant for IVV to induce rapid and balanced TH1/TH2 responses and long-lasting immunity with dose-sparing effect.

Structural derivatization strategies of natural phenols by semi-synthesis and total-synthesis.

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.

Restoring VTA DA neurons excitability accelerates emergence from sevoflurane general anesthesia of anxiety state.

Preoperative anxiety is common and often comes with a higher probability of worse recovery. However, the neurological mechanism of the effect of preoperative anxiety on general anesthesia and subsequent awakening remains unknown. In this study, we report an anxious state results in delayed awakening in anxiety model mice from sevoflurane general anesthesia. More profound inhibition of DA neurons in the VTA contributes to delayed awakening. Optogenetic stimulation of VTA DA neurons can reverse the delay. The results indicate that VTA DA neurons may be involved in the delay in awakening from general anesthesia caused by anxiety.

Aqueous extracts from cultivated Cistanche deserticola Y.C. Ma as polysaccharide adjuvant promote immune responses via facilitating dendritic cell activation.

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.

Enhancing immune responses to inactivated foot-and-mouth virus vaccine by a polysaccharide adjuvant of aqueous extracts from Artemisia rupestris L.

BACKGROUND: New-generation adjuvants for foot-and-mouth disease virus (FMDV) vaccines can improve the efficacy of existing vaccines. Chinese medicinal herb polysaccharide possesses better promoting effects. OBJECTIVES: In this study, the aqueous extract from Artemisia rupestris L. (AEAR), an immunoregulatory crude polysaccharide, was utilized as the adjuvant of inactivated FMDV vaccine to explore their immune regulation roles. METHODS: The mice in each group were subcutaneously injected with different vaccine formulations containing inactivated FMDV antigen adjuvanted with three doses (low, medium, and high) of AEAR or AEAR with ISA-206 adjuvant for 2 times respectively in 1 and 14 days. The variations of antibody level, lymphocyte count, and cytokine secretion in 14 to 42 days after first vaccination were monitored. Then cytotoxic T lymphocyte (CTL) response and antibody duration were measured after the second vaccination. RESULTS: AEAR significantly induced FMDV-specific antibody titers and lymphocyte activation. AEAR at a medium dose stimulated Th1/Th2-type response through interleukin-4 and interferon-γ secreted by CD4⁺ T cells. Effective T lymphocyte counts were significantly elevated by AEAR. Importantly, the efficient CTL response was remarkably provoked by AEAR. Furthermore, AEAR at a low dose and ISA-206 adjuvant also synergistically promoted immune responses more significantly in immunized mice than those injected with only ISA-206 adjuvant and the stable antibody duration without body weight loss was 6 months. CONCLUSIONS: These findings suggested that AEAR had potential utility as a polysaccharide adjuvant for FMDV vaccines.

Nanostructured RuO2-Co3O4@RuCo-EO with low Ru loading as a high-efficiency electrochemical oxygen evolution catalyst.

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.

Immune-Enhancing Activity of Aqueous Extracts from Artemisia rupestris L. via MAPK and NF-kB Pathways of TLR4/TLR2 Downstream in Dendritic Cells.

Artemisia rupestris L. has long been used as a traditional herbal medicine owing to its immunomodulatory activity. Aqueous extracts of Artemisia rupestris L. (AEAR) contain the main functional component and can activate the maturation of dendritic cells (DCs) and enhance the adaptive immunity as the adjuvant against infections. To explore the underlying mechanism of immunomodulatory activities of AEAR, DCs were produced from bone-marrow cells of mice and the effects of AEAR on cell viability were assessed by the Cell Counting Kit 8 (CCK8) method and annexin V/propidium iodide staining assays. Then, the effects of AEAR on the morphology, maturation, and function of DCs were detected using a microscope, flow cytometry-based surface receptor characterization, and endocytosis assays. The secretion levels of cytokines were then analyzed with enzyme-linked immunosorbent assay (ELISA). The activation state of DCs was evaluated by the mixed lymphocyte reaction (MLR). The activity of MAPKs and NF-κB pathways, which were involved in the regulation of AEAR on DCs, was further detected by Western blot. AEAR did not have a cytotoxic effect on DCs or mouse splenocytes. AEAR remarkably enhanced the phenotypic maturation of DCs and promoted the expression of costimulatory molecules and the secretion of cytokines in DCs. AEAR also significantly decreased the phagocytic ability of DCs and augmented the abilities of DCs to present antigens and stimulate allogeneic T-cell proliferation. Simultaneously, AEAR potently activated toll-like receptor (TLR)4-/TLR2-related MAPKs and induced the degradation of IκB and the translocation of NF-κB. In short, AEAR can profoundly enhance the immune-modulating activities of DCs via TLR4-/TLR2-mediated activation of MAPKs and NF-κB signaling pathways and is a promising candidate immunopotentiator for vaccines.

"Smart Process" of Medical Innovation: The Synergism Based on Network and Physical Space.

Medical innovation has a profound impact on public health, and it is always of social concern to encourage innovation and enhance the value in health care delivery. Based on a sample of China's listed firms in the medical industry from 2007 to 2018, this paper highlights the independent and mixed roles of informatization and high-speed rail in public medical innovation. The results show that informatization at network space and high-speed rail at physical space effectively promote the innovation of medical enterprises. In addition, "online" information technology and "offline" high-speed rail technology have a synergistic effect on medical innovation, especially in areas with a low level of innovation. The conclusion supports the positive significance of technology in the application of public health and proposes that the construction of smart society is very important to public health.