Exogenous methylglyoxal alleviates drought-induced 'plant diabetes' and leaf senescence in maize.

Drought-induced leaf senescence is associated with high sugar levels, which bears some resemblance to the syndrome of diabetes in humans; however, the underlying mechanisms of such 'plant diabetes' on carbon imbalance and the corresponding detoxification strategy are not well understood. Here, we investigated the regulatory mechanism of exogenous methylglyoxal (MG) on 'plant diabetes' in maize plants under drought stress applied via foliar spraying during the grain-filling stage. Exogenous MG delayed leaf senescence and promoted photoassimilation, thereby reducing the yield loss induced by drought by 14%. Transcriptome and metabolite analyses revealed that drought increased sugar accumulation in leaves through inhibition of sugar transporters that facilitate phloem loading. This led to disequilibrium of glycolysis and overaccumulation of endogenous MG. Application of exogenous MG up-regulated glycolytic flux and the glyoxalase system that catabolyses endogenous MG and glycation end-products, ultimately alleviating 'plant diabetes'. In addition, the expression of genes facilitating anabolism and catabolism of trehalose-6-phosphate was promoted and suppressed by drought, respectively, and exogenous MG reversed this effect, implying that trehalose-6-phosphate signaling in the mediation of 'plant diabetes'. Furthermore, exogenous MG activated the phenylpropanoid biosynthetic pathway, promoting the production of lignin and phenolic compounds, which are associated with drought tolerance. Overall, our findings indicate that exogenous MG activates defense-related pathways to alleviate the toxicity derived from 'plant diabetes', thereby helping to maintain leaf function and yield production under drought.

Construction of long non-coding RNA- and microRNA-mediated competing endogenous RNA networks in alcohol-related esophageal cancer.

The current study aimed to explore the lncRNA-miRNA-mRNA networks associated with alcohol-related esophageal cancer (EC). RNA-sequencing and clinical data were downloaded from The Cancer Genome Atlas and the differentially expressed genes (DEGs), long non-coding RNAs (lncRNAs, DELs), and miRNAs (DEMs) in patients with alcohol-related and non-alcohol-related EC were identified. Prognostic RNAs were identified by performing Kaplan-Meier survival analyses. Weighted gene co-expression network analysis was employed to build the gene modules. The lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed based on our in silico analyses using data from miRcode, starBase, and miRTarBase databases. Functional enrichment analysis was performed for the genes in the identified ceRNA networks. A total of 906 DEGs, 40 DELs, and 52 DEMs were identified. There were eight lncRNAs and miRNAs each, including ST7-AS2 and miR-1269, which were significantly associated with the survival rate of patients with EC. Of the seven gene modules, the blue and turquoise modules were closely related to disease progression; the genes in this module were selected to construct the ceRNA networks. SNHG12-miR-1-ST6GAL1, SNHG3-miR-1-ST6GAL1, SPAG5-AS1-miR-133a-ST6GAL1, and SNHG12-hsa-miR-33a-ST6GA interactions, associated with the N-glycan biosynthesis pathway, may have key roles in alcohol-related EC. Thus, the identified biomarkers provide a novel insight into the molecular mechanism of alcohol-related EC.

Stubby or Slender? Ear Architecture Is Related to Drought Resistance in Maize.

Ear architecture is determined by two stable heritable traits, kernel row number (KRN) and kernel number per row (KNPR), but its relationship with drought resistance is still vague. To this end, we obtained 16 and 11 hybrids with slender (less KRN but more KNPR) and stubby (more KRN but less KNPR) ears by intentionally crossbreeding, respectively. These hybrids were exposed to a seven-day water deficit (WD) since silk emergence coupled with synchronous (SP) and continuous pollination (CP) to alter the pollination time gaps on ears. The results showed that the emerged silks in CP were 9.1 and 9.0% less than in the SP treatment in the stubby and slender ears, respectively, suggesting the suppression of asynchronous pollination on silk emergence. The stubby ears performed higher silking rate and yield compared with the slender ears with or without drought stress. To eliminate the inherent difference in sink capacities, we selected four hybrids for each ear type with similar silk and kernel numbers for further analyses. Interestingly, the stubby ears were less affected in silking rate and thus performed higher yield under drought compared with the slender ears. The finding suggests that ear architecture matters in the determination of drought resistance that deserves more attention in breeding.

Nicotinamide mononucleotide ameliorates DNFB-induced atopic dermatitis-like symptoms in mice by blocking activation of ROS-mediated JAK2/STAT5 signaling pathway.

BACKGROUND AND PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disease, characterized by pruritus and impaired skin barrier function. The pathology of AD involves in immune dysfunction and epidermal barrier disruption. Reactive oxygen species (ROS) are found to be associated with AD, and play a role in the immunological abnormalities and dysfunctional skin barrier. Nicotinamide mononucleotide (NMN) plays an important role in oxidative stress related diseases, but its role in AD is unclear. METHODS: KM mice were treated with DNFB to induce AD-like lesion and typical applied with NMN for two weeks. The dermatitis score, the degree of itching and TEWL were evaluated during modeling. Epidermal thickness of skin lesions and histopathological changes were detected. Further, inflammatory factors, epidermal differentiation-related genes, oxidative stress indicators and JAK2/STAT5 signaling pathway were evaluated. NHEK cells were stimulated by TNF-α/IFN-γ after pre-treatment with NMN, then ROS levels, inflammatory factors and JAK2/STAT5 signaling pathway were detected. RESULTS: NMN exhibited potent anti-atopic activities, shown by alleviated AD-like symptoms, inhibited the increased expression of inflammatory cytokines and restored proteins and mRNA level of skin barrier genes. In addition, NMN inhibited TNF-α/IFN-γ-stimulated elevation of inflammatory chemokines, which was associated with blocking the activation of ROS-mediated JAK2/STAT5 pathway. CONCLUSION: NMN may have a positive effect on relieving symptoms of AD.

Methylome and transcriptome analyses of soybean response to bean pyralid larvae.

BACKGROUND: Bean pyralid is one of the major leaf-feeding insects that affect soybean crops. DNA methylation can control the networks of gene expressions, and it plays an important role in responses to biotic stress. However, at present the genome-wide DNA methylation profile of the soybean resistance to bean pyralid has not been reported so far. RESULTS: Using whole-genome bisulfite sequencing (WGBS) and RNA-sequencing (RNA-seq), we analyzed the highly resistant material (Gantai-2-2, HRK) and highly susceptible material (Wan82-178, HSK), under bean pyralid larvae feeding 0 h and 48 h, to clarify the molecular mechanism of the soybean resistance and explore its insect-resistant genes. We identified 2194, 6872, 39,704 and 40,018 differentially methylated regions (DMRs), as well as 497, 1594, 9596 and 9554 differentially methylated genes (DMGs) in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48 comparisons, respectively. Through the analysis of global methylation and transcription, 265 differentially expressed genes (DEGs) were negatively correlated with DMGs, there were 34, 49, 141 and 116 negatively correlated genes in the HRK0/HRK48, HSK0/HSK48, HSK0/HRK0 and HSK48/HRK48, respectively. The MapMan cluster analysis showed that 114 negatively correlated genes were clustered in 24 pathways, such as protein biosynthesis and modification; primary metabolism; secondary metabolism; cell cycle, cell structure and component; RNA biosynthesis and processing, and so on. Moreover, CRK40; CRK62; STK; MAPK9; L-type lectin-domain containing receptor kinase VIII.2; CesA; CSI1; fimbrin-1; KIN-14B; KIN-14 N; KIN-4A; cytochrome P450 81E8; BEE1; ERF; bHLH25; bHLH79; GATA26, were likely regulatory genes involved in the soybean responses to bean pyralid larvae. Finally, 5 DMRs were further validated that the genome-wide DNA data were reliable through PS-PCR and 5 DEGs were confirmed the relationship between DNA methylation and gene expression by qRT-PCR. The results showed an excellent agreement with deep sequencing. CONCLUSIONS: Genome-wide DNA methylation profile of soybean response to bean pyralid was obtained for the first time. Several specific DMGs which participated in protein kinase, cell and organelle, flavonoid biosynthesis and transcription factor were further identified to be likely associated with soybean response to bean pyralid. Our data will provide better understanding of DNA methylation alteration and their potential role in soybean insect resistance.

Corosolic acid and its structural analogs: A systematic review of their biological activities and underlying mechanism of action.

BACKGROUND: The corosolic acid (CA), also known as plant insulin, is a pentacyclic triterpenoid extracted from plants such as Lagerstroemia speciosa. It has been shown to have anti-diabetic, anti-inflammatory and anti-tumor effects. Its structural analogs ursolic acid (UA), oleanolic acid (OA), maslinic acid (MA), asiatic acid (AA) and betulinic acid (BA) display similar individual pharmacological activities to those of CA. However, there is no systematic review documenting pharmacological activities of CA and its structural analogues. This study aims to fill this gap in literature. PURPOSE: This systematic review aims to summarize the medical applications of CA and its analogues. METHODS: A systematic review summarizes and compares the extraction techniques, pharmacokinetic parameters, and pharmacological effects of CA and its structural analogs. Hypoglycemic effect is one of the key inclusion criteria for searching Web of Science, PubMed, Embase and Cochrane databases up to October 2020 without language restrictions. 'corosolic acid', 'ursolic acid', 'oleanolic acid', 'maslinic acid', 'asiatic acid', 'betulinic acid', 'extraction', 'pharmacokinetic', 'pharmacological' were used to extract relevant literature. The PRISMA guidelines were followed. RESULTS: At the end of the searching process, 140 articles were selected for the systematic review. Information of CA and five of its structural analogs including UA, OA, MA, AA and BA were included in this review. CA and its structural analogs are pentacyclic triterpenes extracted from plants and they have low solubilities in water due to their rigid scaffold and hydrophobic properties. The introduction of water-soluble groups such as sugar or amino groups could increase the solubility of CA and its structural analogs. Their biological activities and underlying mechanism of action are reviewed and compared. CONCLUSION: CA and its structural analogs UA, OA, MA, AA and BA are demonstrated to show activities in lowering blood sugar, anti-inflammation and anti-tumor. Their oral absorption and bioavailability can be improved through structural modification and formulation design. CA and its structural analogs are promising natural product-based lead compounds for further development and mechanistic studies.

Preventive and Control Measures for the Coronavirus Pandemic in Clinical Dentistry.

A severe public health crisis has been declared worldwide since coronavirus disease 2019 (COVID-19) was classified as a pandemic of acute respiratory infectious disease by the World Health Organisation (WHO). China has taken strict measures to curb the spread of the disease to save lives, and has managed to control the outbreak. COVID-19 is mainly transmitted through respiratory droplets and close physical contact, so it is challenging to prevent nosocomial infection and possible spread during dental treatment. Since the initial phase of the COVID-19 outbreak, a disease prevention and control strategy based on the new concept of population risk classification and rational use of personal protective equipment has been implemented by the Peking University Hospital of Stomatology. Nosocomial infection prevention and control concepts and measures relating to dental diagnosis and treatment are critically checked in the hospital. Our experiences in handling this situation are shared here and may have wide-ranging implications for infection prevention and control (IPC) for COVID-19 in dental practices worldwide.

Effects of RNA interference-mediated E-selectin gene silencing on cell adhesion molecule expression and cell-cell adhesion in vascular endothelial cells in mice with immunologic contact urticaria.

Contact urticaria is recognized as the wheal and flare reaction at a site from direct contact with a chemical or protein agent. Ongoing studies have proposed that gene silencing may have a promising future in finding optimal treatment of a variety of disease; hence, the aim of the study was to investigate the effect of RNA interference-mediated E-selectin ( SELE) gene silencing on cell adhesion molecule expression and on cell-cell adhesion in vascular endothelial cells (VECs) in a mouse model of immunologic contact urticaria (ICU). Following the successful establishment of mouse models of ICU induced by antidinitrophenol immunoglobulin E (IgE) combining 2,4-dinitrofluorobenzene challenge, enzyme-linked immunosorbent assay and immunohistochemistry were used to measure the levels of IgE, interleukin 4 (IL-4), interferon-γ (IFN-γ), and histamine as well as the positive expression rate of SELE, respectively. The siRNA- SELE vector was constructed and transfection efficiency was estimated prior to performing quantitative reverse-transcription polymerase chain reaction and Western blot assay to determine the relative expression of SELE, eosinophil cationic protein (ECP), intercellular adhesion molecule 1 (ICAM-1), L-selectin (CD62L), and the alpha chain of leukocyte function-associated antigen-1 (CD11a). Adhesion assay was then performed to assess the cell adhesion ability in VECs. Elevated levels of IgE, IL-4, IFN-γ, and histamine and increased positive expression rate of SELE were indicative of successful establishment of mouse models of ICU. Furthermore, the relative expression levels of SELE, ECP, ICAM-1, CD62L, and CD11a were highest in the OE- SELE group. Besides, cell adhesion ability of VECs was notably promoted. Collectively, the current study define the potential role of SELE silencing as an inhibitor to ICU development by inhibiting cell adhesion ability of VECs.

Three-dimensional reconstruction of pelvic CT in guiding iliac nail implantation / 中国组织工程研究

BACKGROUND: Iliac screw implantation has no unified standard. Because of the large individual differences, preoperative pelvic three-dimensional (3D) CT reconstruction can measure the diameter, depth and angle of the screws, which increases the placement accuracy. OBJECTIVE: To measure the screw placement-related data by pelvic 3D CT reconstruction, so as to guide the screw placement and improve its accuracy. METHODS: Fifty patients with pelvic lesions or fractures admitted in Shandong Provincial Third Hospital from January 2013 to December 2016 were selected, and the pelvis was scanned with CT and then was reconstructed. The point A (the intersection of S1posterior sacral posterior wall and posterior superior iliac spine) was as the screw placement point, and three paths were measured on the point: posterior superior iliac spine path (AD path); anterior inferior iliac spine path (AC path); top of greater sciatic notch to the acetabular roof (AB path). On the plane of these three pathes, the section was made on the iliac bone, respectively; in each section, the channel for iliac nail was designed. RESULTS AND CONCLUSION: (1) In the same path, there was no significant difference in the path length of the screw between male and female patients (P > 0.05). Paired t test showed that the diameter and length depth and angle of the screws were significantly different between AD and AC paths, AC and AD (P < 0.05). (2) There was no significant difference in the inclination angle of the spiral channel between male and female patients (P > 0.05). The inclination angle of the spiral channel and lateral angle at different paths showed significant difference between male and female patients (P < 0.05). (3) To conclude, 3D reconstruction of pelvis CT can be used to measure the length, diameter and angle of the iliac screw, and to guide the surgical treatment.

Suppression of IFN-induced transcription underlies IFN defects generated by activated Ras/MEK in human cancer cells.

Certain oncolytic viruses exploit activated Ras signaling in order to replicate in cancer cells. Constitutive activation of the Ras/MEK pathway is known to suppress the effectiveness of the interferon (IFN) antiviral response, which may contribute to Ras-dependent viral oncolysis. Here, we identified 10 human cancer cell lines (out of 16) with increased sensitivity to the anti-viral effects of IFN-α after treatment with the MEK inhibitor U0126, suggesting that the Ras/MEK pathway underlies their reduced sensitivity to IFN. To determine how Ras/MEK suppresses the IFN response in these cells, we used DNA microarrays to compare IFN-induced transcription in IFN-sensitive SKOV3 cells, moderately resistant HT1080 cells, and HT1080 cells treated with U0126. We found that 267 genes were induced by IFN in SKOV3 cells, while only 98 genes were induced in HT1080 cells at the same time point. Furthermore, the expression of a distinct subset of IFN inducible genes, that included RIGI, GBP2, IFIT2, BTN3A3, MAP2, MMP7 and STAT2, was restored or increased in HT1080 cells when the cells were co-treated with U0126 and IFN. Bioinformatic analysis of the biological processes represented by these genes revealed increased representation of genes involved in the anti-viral response, regulation of apoptosis, cell differentiation and metabolism. Furthermore, introduction of constitutively active Ras into IFN sensitive SKOV3 cells reduced their IFN sensitivity and ability to activate IFN-induced transcription. This work demonstrates for the first time that activated Ras/MEK in human cancer cells induces downregulation of a specific subset of IFN-inducible genes.

Activated Ras/MEK inhibits the antiviral response of alpha interferon by reducing STAT2 levels.

The ability of interferon (IFN) to induce the expression of antiviral genes, and therefore suppress viral infection, is dependent on the activity of cellular suppressors. The Ras/MEK pathway is one of these cellular suppressors, since the activation of Ras/MEK permits viral replication in the presence of alpha IFN (IFN-alpha). Here, we have investigated the mechanism by which activated Ras/MEK inhibits the IFN-alpha response. We found that the induction of antiviral proteins in response to IFN-alpha was impaired in Ras-transformed NIH 3T3 (RasV12) cells. The inhibition of the Ras/MEK pathway restored the IFN-mediated induction of antiviral genes, indicating that activated Ras interrupts the IFN pathway upstream of antiviral gene transcription. Indeed, the IFN-induced phosphorylation of signal transducer and activator of transcription 1 (STAT1) and STAT2 was inhibited in RasV12 cells compared to that of vector control cells. In addition, we found that the total amount of STAT2 was reduced in RasV12 cells. To determine if the impaired IFN-alpha response can be rescued by restoring the overall level of STAT2, we overexpressed STAT2 in RasV12 cells. The IFN-alpha-induced phosphorylation of STAT1 and STAT2, as well as the expression of antiviral protein, were restored, and IFN-induced antiviral protection was partially restored. Moreover, we demonstrated that the downregulation of STAT2 levels by Ras/MEK was mediated at the transcriptional level. Thus, the activation of the Ras/MEK pathway reduces the amount of STAT2 available for propagating the IFN signal, resulting in the impairment of the IFN-alpha-induced antiviral response.

Synthesis and iron(III)-chelating properties of novel 3-hydroxypyridin-4-one hexadentate ligand-containing copolymers.

Iron overload is a critical clinical problem that can be prevented by the use of iron-specific chelating agents. An alternative method of relieving iron overload is to reduce the efficiency of iron absorption from the intestine by administering iron chelators, which can bind iron irreversibly to form nontoxic, kinetically inert complexes that are not absorbed and are therefore excreted in the feces. A series of polymeric chelators with various iron binding capacities were therefore prepared as nonabsorbable iron-selective additives. A novel 3-hydroxypyridin-4-one hexadentate ligand CP254 has been synthesized and incorporated into polymers by copolymerisation with N, N-dimethylacrylamide (DMAA), and N, N'-ethylene-bis-acrylamide (EBAA) using (NH4)2S2O8 as the initiator. The physicochemical properties of CP254 were determined, namely, log K = 33.2 and pFe(3+) = 27.24. The chelating capacity of the CP254-DMAA copolymers was determined at physiological pH. The iron(III) chelation was found to achieve 80% capacity after 1 h and was virtually complete after 5 h, which is much quicker than that of the commercially available chelating resin Chelex100. The chelating copolymers were found to be readily regenerated and reusable. The copolymers possess a high selectivity for iron(III). The conditional affinity (log K') for iron(III) at pH 7.46 was determined to be 26.55, which is not significantly different to that of the hexadentate ligand CP254 (log K' = 26.47). In vitro perfusion studies indicate that the polymeric chelators described in this study can reduce iron absorption from the intestine.

MALDI mass spectrometric determination of dendritic iron chelation stoichiometries and conditional affinity constants.

The iron chelation stoichiometries of a dendritic iron(III) chelator with N(1), N(3), N(5)-trimethylbenzene-1,3,5-tricarboxamide at its core, and containing 3 identical hexadentate tris-hydroxypyridinone branches D was studied by MALDI mass spectrometry. At pH 7.2, the speciation of the system included FeD, Fe(2)D and Fe(3)D species with the respective conditional stability constants of 26.74, 26.03 and 25.36. The differences in the stepwise affinity constants arise from the statistical distribution of iron(III), and there was no evidence for cooperativity between the iron-binding sites.

Iron binding dendrimers: a novel approach for the treatment of haemochromatosis.

A range of iron binding dendrimers terminated with hexadentate ligands formed from hydroxypyridinone, hydroxypyranone, and catechol moieties have been synthesized in order to investigate their potential as clinically useful iron(III)-selective chelators capable of removing dietary iron from the gastrointestinal tract and preventing the development of iron overload typical of haemochromatosis and thalassaemia intermedia. The iron chelating abilities of these molecules have been characterized by MALDI-TOF mass spectrometry and UV spectrometry. Hydroxypyridinone-terminated dendrimers were found to possess a high affinity and selectivity for iron(III). A hydroxypyridinone-based dendrimer was demonstrated to be highly efficient at reducing the absorption of iron(III) in rat intestine. This family of dendrimers may find an application in the treatment of iron overload.

Negative regulation of the alpha interferon-induced antiviral response by the Ras/Raf/MEK pathway.

Interferon (IFN) is one of the molecules released by virus-infected cells, resulting in the establishment of an antiviral state within infected and neighboring cells. IFN-induced antiviral response may be subject to modulation by the cellular signaling environment of host cells which impact the effectiveness of viral replication. Here, we show that cells with an activated Ras/Raf/MEK signaling cascade allow propagation of viruses in the presence of IFN. Ras-transformed (RasV12) and vector control NIH 3T3 cells were infected with vesicular stomatitis virus (VSV) or an IFN-sensitive vaccinia virus (delE3L) in the presence of alpha interferon. While IFN protected vector control cells from infection by both viruses, RasV12 cells were susceptible to viral infection regardless of the presence of IFN. IFN sensitivity was restored in RasV12 cells upon RNA interference (RNAi) knockdown of Ras. We further investigated which elements downstream of Ras are responsible for counteracting IFN-induced antiviral responses. A Ras effector domain mutant that can only stimulate the Raf kinase family of effectors was able to suppress the IFN response and allow VSV replication. IFN-induced antiviral mechanisms were also restored in RasV12 cells by treatment with a MEK inhibitor (U0126 or PD98059). Moreover, by using RNAi to MEK1 and MEK2, we determined that MEK2, rather than MEK1, is responsible for suppression of the IFN response. In conclusion, our results suggest that activation of the Ras/Raf/MEK pathway downregulates IFN-induced antiviral response.

High affinity iron(III) scavenging by a novel hexadentate 3-hydroxypyridin-4-one-based dendrimer: synthesis and characterization.

The synthesis of a novel iron(III)-selective hydroxypyridinone hexadentate-terminated dendritic chelator based on a benzene tricarbonyl core polyamine dendrimer is described. The iron-chelating ability of the dendritic chelator was demonstrated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and UV-vis spectroscopy. The physicochemical properties of the isolated hexadentate unit were also investigated. The dendrimer was found to possess an extremely high affinity for iron(III), namely logK=34.8, pFe3+=30.6.

[Cloning, expression and bio-activity assay of chimeric fusion protein sTNFRII-IgG Fc].

Tumor necrosis factor (TNF) is a key cytokine in immunology system and is related to many human diseases. In order to inhibit the activity of TNF, cDNA coding for soluble TNF receptor II (sTNFRII) and human IgG Fc were linked using a flexible hinge. This gene was expressed in E. coli as a chimeric protein and purified by metal chelate chromatography. The results show that the fusion protein exists in the physiological form as a dimer, has the ability to bind with TNF and inhibits the cytotoxicity of TNF on L929 cells. Contrasting to monomer sTNFRII, the chimeric protein has an improved bioactivity, and displays potential prospects for research and application.