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Eucommia ulmoides has lipid-lowering, antihypertensive, hypoglycemic and anti-aging effects. The main medicinal part of Eucommia ulmoides bark (EBE), but its slow growth and peeling easily lead to tree death, which limits the extensive use of Eucommia ulmoides resources and causes the lack of Eucommia ulmoides resources. It is not clear whether Eucommia ulmoides leaves (ELE), flowers (EFE) and seeds (ESE) can be used as substitutes for Eucommia ulmoides bark. In this study, UPLC-Q-Orbitrap-MS was used to analyze the active ingredients in the bark, leaves, flowers and seeds of Eucommia ulmoides. HPLC method was established for the determination of 8 common active ingredients in the bark, leaves, flowers and seeds of Eucommia ulmoides. The content of active ingredients is also based on the current research on Eucommia ulmoides, and the regulation activity of lipid metabolism was compared. The results showed that 119 compounds were identified from 12 classes of Eucommia ulmoides, and the skin and leaves of Eucommia ulmoides contained a lot of the same active ingredients. The content of turbinol diglucoside in Eucommia ulmoides bark was the highest, and the content of chlorogenic acid in Eucommia ulmoides leaves was the highest. After Eucommia intervention, all indexes of cell model were improved and lipid metabolism regulation ability was improved: EBE, ELE, EFE, ESE; EBE and ELE had similar lipid lowering effect. After Eucommia's treatment, mRNA expression of AMPK increased in a volume-dependent manner, while mRNA expression of SREBP-1c, FAS and ACC decreased in a volume-dependent manner. Therefore, Eucommia's improvement in steatosis of HepG2 cells may be related to the regulation of AMPK, SREGP-1C, FAS and ACC signaling pathways. In conclusion, it can be concluded that Eucommia ulmoides leaves can replace Eucommia ulmoides skins in the regulation of lipid metabolism and improve the comprehensive utilization of Eucommia ulmoides resources.

Eucommia ulmoides is a valuable tonic Chinese herbal medicine with a long history. It has the effects of tonifying liver and kidney, strengthening muscles and bones, regulating Chong and Ren channels, consolidating meridians and preventing miscarriage. Modern pharmacological research has demonstrated that Eucommia ulmoides has the pharmacological effects of lowering blood lipids, lowering blood pressure, lowering blood sugar, preventing aging, and inhibiting oxidation. Currently, only the bark of Eucommia ulmoides can be utilized as a therapeutic component; the plant's overall consumption is still quite limited. The growth of Eucommia ulmoides bark is extremely sluggish, typically taking more than 12 years, and the greater technical needs of Eucommia ulmoides bark can easily result in the death of the tree, which is not favorable to the sustainable use of plant resources. In order to identify raw materials that can substitute Eucommia ulmoides bark, this experiment investigated the active components of different position of Eucommia ulmoides. Through ultraperformance liquid chromatography-quadrupole tandem mass spectrometry, the chemical constituents of several Eucommia ulmoides parts were examined in this work (UPLC-Q-Orbitrap-MS). The identification of 119 compounds of twelve known and novel kinds. In this investigation, a high performance liquid chromatography (HPLC) method for analyzing the quantity of active components in various Eucommia ulmoides parts was developed. The results showed that there were some differences in the components and contents of different parts of Eucommia ulmoides. The bark of Eucommia ulmoides included higher levels of geniposidic acid, pinoresinol diglucoside, and quercetin, whereas the leaves contained higher levels of chlorogenic acid, catechin, and rutin. The bark and Eucommia ulmoides had the highest concentrations of active components, followed by the remaining sections. Therefore, Eucommia ulmoides leaves can replace Eucommia ulmoides bark for anti-oxidation, anti-inflammatory, antibacterial, and glucose and lipid metabolism regulation. This research presents a novel method for evaluating the quality of Eucommia ulmoides.

Turning agricultural waste into effective remediation materials is a highly promising approach for reducing in-field crop burning and promoting affordable wastewater treatment. This comparative study aims to identify active adsorption sites for methylene blue (MB), crystal violet (CV), and cadmium (Cd) as model pollutants on wheat straw materials modified by a thermal partial-oxidation process. The optimal modification temperature was found to be 160-180 °C for MB and CV adsorption, which is much lower than that of Cd(II) at 220-240 °C. A strong linear correlation exits between total surface group concentrations and Cd(II) uptake, indicating that both acidic and basic functional groups are favourable adsorption sites of Cd(II). By contrast, basic groups generated at higher modification temperatures might have adverse effects on MB and CV adsorption. These results provided mechanistic insights and predictive approach into reuse of agricultural waste for environmental remediation.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by insulin deficiency due to pancreatic β-cell damage and leads to hyperglycemia. The precise molecular mechanisms of the etiology of T1DM are not completely understood. Oxidative stress and the antioxidant status of pancreatic β-cells play a vital role in the pathogenesis and progression of T1DM. The Keap1/Nrf2 signaling pathway plays a critical role in cellular resistance to oxidative stress. This study is aimed at investigating the role of the Keap1/Nrf2 signaling pathway in the progression of T1DM. An alloxan- (ALX-) stimulated T1DM animal model in wild-type (WT) and Nrf2 knockout (Nrf2-/-) C57BL/6J mice and a mouse pancreatic β-cell line (MIN6) were established. Compared with the tolerant (ALX exposure, nondiabetic) WT mice, the sensitive (ALX exposure, diabetic) WT mice exhibited higher blood glucose levels and lower plasma insulin levels. The Keap1/Nrf2 signaling pathway was significantly inhibited in the sensitive WT mice, which was reflected by overexpression of Keap1 and low expression of Nrf2, accompanied by a marked decrease in the expression of the antioxidative enzymes. Compared with WT mice, the Nrf2-/- mice had an increased incidence of T1DM and exhibited more severe pancreatic β-cell damage. The results of in vitro experiments showed that ALX significantly inhibited the viability and proliferation and promoted the apoptosis of MIN6 cells. ALX also markedly increased intracellular ROS production and caused DNA damage in MIN6 cells. In addition, the Keap1/Nrf2 signaling pathway was significantly inhibited in the damaged MIN6 cells. Moreover, Nrf2 silencing by transfection with Nrf2 siRNA markedly exacerbated ALX-induced MIN6 cell injury. Conclusively, this study demonstrates that inhibition of the Keap1/Nrf2 signaling pathway could significantly promote the incidence of T1DM. This study indicates that activation of Keap1/Nrf2 signaling in pancreatic β-cells may be a useful pharmacological strategy for the clinical prevention and treatment of T1DM.

Cellular vehicle-to-everything (C-V2X) communications is regarded as a promising and feasible solution for 5G-enabled vehicular communications and networking. In this paper, we investigate the pilot design and channel estimation problem in MIMO-OFDM-based C-V2X systems with severe co-channel interference due to spectrum reusing among different V2X communication links. By using zero-correlation zone (ZCZ) sequences, we provide an interference-free pilot design scheme and a corresponding time-domain (TD) correlation-based channel estimation (TD-CCE) method. We employ the ZCZ sequences from the same family set to be designed as the TD pilot symbols and guarantee the pilot sequeneces for neighboring V2X communication links are code-division multiplexing (CDM). The co-channel pilot interference of the deisgned pilot symbols can be effectively eliminated by exploiting the provided TD-CCE method. Simulation results indicate that the accuracy of channel estimation can be effectively improved by the proposed scheme, whose performance is close to that of the non-interference situation.

Mycobacterium bovis (M. bovis) is a zoonotic pathogen that causes bovine and human tuberculosis. Dendritic cells play a critical role in initiating and regulating immune responses by promoting antigen-specific T-cell activation. Prostaglandin E2 (PGE2)-COX signaling is an important mediator of inflammation and immunity and might be involved in the pathogenesis of M. bovis infection. Therefore, this study aimed to reveal the character of PGE2 in the differentiation of na&iuml, ve CD4+ T cells induced by infected dendritic cells (DCs). Murine bone marrow-derived DCs were pre-infected with M. bovis and its attenuated strain M. bovis bacillus Calmette-Gu&eacute, rin (BCG). Then, the infected DCs were co-cultured with na&iuml, ve CD4+ T cells with or without the cyclooxygenase (COX) inhibitor indomethacin. Quantitative RT-PCR analysis and protein detection showed that PGE2/COX-2 signaling was activated, shown by the upregulation of PGE2 production as well as COX-2 and microsomal PGE2 synthase (mPGES1) transcription in DCs specifically induced by M. bovis and BCG infection. The further co-culture of infected DCs with na&iuml, ve CD4+ T cells enhanced the generation of inflammatory cytokines IL-17 and IL-23, while indomethacin suppressed their production. Following this, the differentiation of regulatory T cells (Treg) and Th17 cell subsets was significantly induced by the infected DCs rather than uninfected DCs. Meanwhile, M. bovis infection stimulated significantly higher levels of IL-17 and IL-23 and the differentiation of Treg and Th17 cell subsets, while BCG infection led to higher levels of TNF-&alpha, and IL-12, but lower proportions of Treg and Th17 cells. In mice, M. bovis infection generated more bacterial load and severe abnormalities in spleens and lungs, as well as higher levels of COX-2, mPGE2 expression, Treg and Th17 cell subsets than BCG infection. In conclusion, PGE2/COX-2 signaling was activated in DCs by M. bovis infection and regulated differentiation of Treg and Th17 cell subsets through the crosstalk between DCs and naive T cells under the cytokine atmosphere of IL-17 and IL-23, which might contribute to M. bovis pathogenesis in mice.

Pancreatic stem/progenitor cells convert from a proliferative to a differentiated fate passing through proliferation cease to a resting state. However, the molecular mechanisms of cell cycle arrest are poorly understood. In this study, we demonstrated that the microRNA-124a (miR-124a) inhibited the proliferation of pancreatic progenitor cells both in vitro and ex vivo and promoted a quiescent state. The miR-124a directly targeted SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1), IQ motif-containing GTPase-activating protein 1 (IQGAP1), signal transducer and activator of transcription 3 (STAT3), and cyclin D2 (CCND2), thereby inactivating epidermal growth factor receptor (EGFR) downstream signaling pathways including mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK/ERK), phosphatidylinositol 3-kinase-protein kinase B (PI3K/AKT) and Janus kinase (JAK)/STAT3. miR-124a blocked cell proliferation mainly through targeting STAT3 to inhibit PI3K/AKT and JAK/STAT3 signaling. Moreover, miR-124a expression was negatively regulated by EGFR downstream PI3K/AKT signaling. These results indicated that miR-124a and EGFR signaling mutually interact to form a regulating circuit that determines the proliferation of pancreatic progenitor cells.

Activation of endogenous stem/progenitor cells to repair injured tissues is an ideal option for disease treatment. However, adult pancreatic progenitor cells remain in a quiescent state in vivo. Thus, it is difficult to stimulate proliferation and differentiation in these progenitor cells, and the cause remains elusive. miR-17-92 cluster miRNAs are highly conserved in mammals and are expressed in multiple tissue stem/progenitor cells, but their role in pancreatic progenitor cells are less well known. In the present study, we demonstrate that miR-18a, but not the other members of the miR-17-92 gene cluster, inhibits the proliferation of pancreatic progenitor cells in vitro and ex vivo. miR-18a inhibits proliferation of adult pancreatic progenitor cells through arresting the cell cycle at G1 stage, indicating that miR-18a plays a role in keeping the adult pancreatic progenitor cells in quiescence. miR-18a inhibits pancreatic progenitor proliferation by targeting the gene expressions of connective tissue growth factor (CTGF), neural precursor cell expressed, developmentally down-regulated 9 (Nedd9), and cyclin dependent kinase 19 (CDK19), as well as by suppressing activation of the proliferation-related signaling pathways phosphatidylinositol 3-kinase–protein kinase B (PI3K/AKT) and extracellular signal-regulated kinase (ERK).

The Notch signaling pathway plays a significant role in embryonic cell fate determination and adult tissue homeostasis. Various studies have demonstrated the deep involvement of Notch signaling in the development of the pancreas and the lateral inhibition of Notch signaling in pancreatic progenitor differentiation and maintenance. The targeted inactivation of the Notch pathway components promotes premature differentiation of the endocrine pancreas. However, there is still the contrary opinion that Notch signaling specifies the endocrine lineage. Here, we review the current knowledge of the Notch signaling pathway in pancreatic development and its crosstalk with the Wingless and INT-1 (Wnt) and fibroblast growth factor (FGF) pathways.

In this paper work, four naked nanocrystals (size range 80–700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold.