A viral effector blocks the turnover of a plant NLR receptor to trigger a robust immune response.

Plant intracellular nucleotide-binding and leucine-rich repeat immune receptors (NLRs) play a key role in activating a strong pathogen defense response. Plant NLR proteins are tightly regulated and accumulate at very low levels in the absence of pathogen effectors. However, little is known about how this low level of NLR proteins is able to induce robust immune responses upon recognition of pathogen effectors. Here, we report that, in the absence of effector, the inactive form of the tomato NLR Sw-5b is targeted for ubiquitination by the E3 ligase SBP1. Interaction of SBP1 with Sw-5b via only its N-terminal domain leads to slow turnover. In contrast, in its auto-active state, Sw-5b is rapidly turned over as SBP1 is upregulated and interacts with both its N-terminal and NB-LRR domains. During infection with the tomato spotted wilt virus, the viral effector NSm interacts with Sw-5b and disrupts the interaction of Sw-5b with SBP1, thereby stabilizing the active Sw-5b and allowing it to induce a robust immune response.

Imaging the dynamics of messenger RNA with a bright and stable green fluorescent RNA.

Fluorescent RNAs (FRs) provide an attractive approach to visualizing RNAs in live cells. Although the color palette of FRs has been greatly expanded recently, a green FR with high cellular brightness and photostability is still highly desired. Here we develop a fluorogenic RNA aptamer, termed Okra, that can bind and activate the fluorophore ligand ACE to emit bright green fluorescence. Okra has an order of magnitude enhanced cellular brightness than currently available green FRs, allowing the robust imaging of messenger RNA in both live bacterial and mammalian cells. We further demonstrate the usefulness of Okra for time-resolved measurements of ACTB mRNA trafficking to stress granules, as well as live-cell dual-color superresolution imaging of RNA in combination with Pepper620, revealing nonuniform and distinct distributions of different RNAs throughout the granules. The favorable properties of Okra make it a versatile tool for the study of RNA dynamics and subcellular localization.

The influence of effort-reward imbalance and perceived organizational support on perceived stress in Chinese nurses: a cross-sectional study.

BACKGROUND: The nursing profession is characterized by high intensity and significant stress. Nurses must not only manage heavy workloads but also address diverse patient needs, engage in emotional labor, and cope with occupational exposure risks. These factors collectively contribute to substantial work-related stress for nurses. Currently, there is limited research on identifying distinct categories of nurse stress profiles and their influencing factors. OBJECTIVES: This study aimed to explore the potential categories of perceived stress among nurses using Latent profile analysis (LPA) and to analyze the influence of sociodemographic factors, effort-reward imbalance, and perceived organizational support on perceived stress categories. DESIGN: Cross-sectional study METHODS: Data were collected via electronic surveys from 696 nurses in Shanxi Province, China, from February 18 to 28, 2023. The survey parameters included sociodemographic characteristics, nurse job stressors scale, effort-reward imbalance scale, and perceived organizational support scale. Latent profile analysis (LPA) was used to classify the perceived stress levels of nurses, and disordered multi-classification logistic regression was used to identify the influencing factors. RESULTS: The most suitable model was a three-profile model, comprising the "low perceived stress" group (10.5%), "moderate perceived stress" group (66.7%), and "high perceived stress" group (22.8%). Multi-classification logistic regression analysis showed that average working hours per day (OR = 3.022, p = 0.026), extrinsic effort (C2 vs. C1, OR = 1.589, p < 0.001; C3 vs. C1, OR = 2.515, p < 0.001), and perceived organizational support (C2 vs. C1, OR = 0.853, p < 0.001; C3 vs. C1, OR = 0.753, p < 0.001) were the factors influencing the classification of nurses' perceived stress. CONCLUSIONS: Latent profile analysis revealed that nurses' perceived stress exhibits distinct characteristics. It is recommended that clinical administrators should identify these characteristics and the influencing factors of different nurse categories, and adopt targeted intervention strategies to reduce the levels of perceived stress.

Antiviral RISC mainly targets viral mRNA but not genomic RNA of tospovirus.

Antiviral RNA silencing/interference (RNAi) of negative-strand (-) RNA plant viruses (NSVs) has been studied less than for single-stranded, positive-sense (+)RNA plant viruses. From the latter, genomic and subgenomic mRNA molecules are targeted by RNAi. However, genomic RNA strands from plant NSVs are generally wrapped tightly within viral nucleocapsid (N) protein to form ribonucleoproteins (RNPs), the core unit for viral replication, transcription and movement. In this study, the targeting of the NSV tospoviral genomic RNA and mRNA molecules by antiviral RNA-induced silencing complexes (RISC) was investigated, in vitro and in planta. RISC fractions isolated from tospovirus-infected N. benthamiana plants specifically cleaved naked, purified tospoviral genomic RNAs in vitro, but not genomic RNAs complexed with viral N protein. In planta RISC complexes, activated by a tobacco rattle virus (TRV) carrying tospovirus NSs or Gn gene fragments, mainly targeted the corresponding viral mRNAs and hardly genomic (viral and viral-complementary strands) RNA assembled into RNPs. In contrast, for the (+)ssRNA cucumber mosaic virus (CMV), RISC complexes, activated by TRV carrying CMV 2a or 2b gene fragments, targeted CMV genomic RNA. Altogether, the results indicated that antiviral RNAi primarily targets tospoviral mRNAs whilst their genomic RNA is well protected in RNPs against RISC-mediated cleavage. Considering the important role of RNPs in the replication cycle of all NSVs, the findings made in this study are likely applicable to all viruses belonging to this group.

Isopolymolybdate-Based Cobalt/Nickel Coordination Polymers Constructed by V-Type N-Donor Ligands.

Four novel isopolymolybdate-based coordination polymers (CPs), constructed from 2,6-bis(1,2,4-triazol-1-yl)pyridine (btp), 1,3-bis(4H-1,2,4-triazol-4-yl)benzene (btb), and 3,5-bis(1-imidazolium)pyridine (bip), have been synthesized under a hydrothermal method: {[Co(btp)(H2O)2(ß-Mo8O26)0.5]·3H2O}n (1), [Ni(btp)(H4Mo6O22)0.5]n (2), [Co(btb)(H2O)(ß-Mo8O26)0.5]n (3), and {[Co(Hbip)2(H2O)2(γ-Mo8O26)]·6H2O}n (4). Complex 1 exhibits one 3D framework with an unexpected 3-nodal 2,4,6-c net topology containing the 1D {ß-Mo8O26}n chains, 6-connected CoII centers, and V-type coordinated btp ligands. The neighboring [Mo6O22]4- anions of complex 2 are bridged by the NiII centers to build one 2D {Ni2(Mo6O22)} network, which is arranged into the 3D framework through the weak π···π stacking interactions. In compound 3, one 3D framework is formed by the adjacent 1D {Co2(btp)2}n chains connected by {ß-Mo8O26}n units, which demonstrates a rare 4,6-c fsc topology. In complex 4, one 2D {Co(Hbip)2(γ-Mo8O26)} layer with a (4, 4) network is connected to one 3D hydrogen-bonding framework via N-H···O and O-H···O hydrogen bonds. Magnetic data indicate that complexes 1 and 4 exhibit antiferromagnetic behaviors, whereas complexes 2 and 3 reveal spin-canting magnetic behavior and metamagnetic behavior, respectively. In addition, the proton conductivity of complexes 3 and 4 was investigated, showing that compound 4 has good proton conductivity at 85 °C and a relative humidity of 98% RH.

Factors that affect the duration of wearing disposable personal protective equipment by healthcare professionals in Wuhan during treatment of COVID-19 patients: An epidemiological study.

The purpose of this study of healthcare workers who cared for COVID-19 patients was to identify factors that affected the duration of wearing personal protective equipment (PPE). The results of this study will provide initial guidance to practicing clinicians and a foundation for further research on this topic. This cross-sectional study examined 139 frontline healthcare professionals who worked at a single hospital in Wuhan, China, from March 16 to April 1, 2020. General and demographic data, physical and mental status, use of personal protective equipment, type of hospital work, and duration of wearing personal protective equipment were recorded. The mean duration of wearing personal protective equipment was 194.17 min (standard deviation: 3.71). Multiple linear regression analysis indicated that the duration of wearing personal protective equipment was significantly associated with the presence of a chronic disease, working hours when feeling discomfort, lack of patient cooperation and subsequent psychological pressure, prolonged continuous wearing of personal protective equipment, feeling anxious about physical strength, and the presence of fatigue when wearing personal protective equipment. These factors should be considered by practicing healthcare professionals and in future studies that examine the optimal duration of wearing personal protective equipment.

Impact of Rumination, and Dyadic Coping on Parenting Sense of Competence Among Puerperal Women in China: A Cross-sectional Study.

PURPOSE: This study aimed to explore the potential categories of parenting sense of competence and to analyze the influence of rumination and dyadic coping on the potential categories of parenting sense of competence. METHODS: A total of 199 postpartum women who met the criteria were surveyed from a tertiary grade-A hospital in Shanxi (China) from May 2023 to August 2023. The instruments included the general demographic characteristics, Chinese version of parenting sense of competence scale, Chinese event related rumination inventory, and Chinese version of dyadic coping inventory. Latent profile analysis (LPA) was used to classify the parenting sense of competence in postpartum women, and logistic regression analysis was used to identify the influencing factors. RESULTS: The characteristics of parenting sense of competence in postpartum women can be divided into two potential categories, namely, easy-to-satisfy group (39.3%) and strict-demand group (60.7%). Logistic regression analysis showed that years of marriage, place of residence, deliberate rumination, and dyadic coping were the influencing factors of the potential categories of parenting sense of competence in postpartum women (p < .05). CONCLUSIONS: Through Latent profile analysis (LPA) analysis, it was found that postpartum women's parenting sense of competence exhibits different characteristics. Clinical workers should identify the characteristics and influencing factors of different categories of women and adopt targeted intervention strategies to promote the level of parenting sense of competence.

Effect of auricular acupressure on sleep quality in breast cancer patients: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND PURPOSE: Sleep disturbance is a very common problem among breast cancer patients, and auricular acupressure is a non-pharmacologic intervention to improve the sleep quality. This study aimed to investigate the effectiveness and safety of auricular acupressure to improve sleep quality in breast cancer patients. METHODS: Overall, 8 electronic databases in English and Chinese were systematically searched from inception to August 12, 2023 to identify eligible randomized controlled trials (RCTs). The risk of bias was assessed by version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2.0). RESULTS: A total of 16 studies with 1199 participants were included. The synthesized results showed that compared with the control group, auricular acupressure had a significant effect on improving the effective rate of sleep quality improvement in patients with breast cancer (risk ratio [RR] 1.56, 95 % confidence interval [CI] 1.14 to 2.14; P < 0.001), and that significantly reduced the Pittsburgh Sleep Quality Index (PSQI) global score (mean difference [MD] -3.47, 95 % CI -4.37 to -2.58; P < 0.001). Subgroup analysis of effective rate and PSQI score showed similar significant effects. Additionally, the improvement of sleep quality was better when auricular acupressure was performed by nurses using Vaccaria seeds. Furthermore, the optimal intervention program was performed 1-2 times a day, 3-5 min each time, and lasted for 2-4 weeks. CONCLUSION: Auricular acupressure may effectively improve the sleep quality of patients with breast cancer. However, more rigorously designed, large-sample, multi-center RCTs are required to further validate the results.

Design and Synthesis of Dual-Targeting Inhibitors of sEH and HDAC6 for the Treatment of Neuropathic Pain and Lipopolysaccharide-Induced Mortality.

Epoxyeicosatrienoic acids with anti-inflammatory effects are inactivated by soluble epoxide hydrolase (sEH). Both sEH and histone deacetylase 6 (HDAC6) inhibitors are being developed as neuropathic pain relieving agents. Based on the structural similarity, we designed a new group of compounds with inhibition of both HDAC6 and sEH and obtained compound M9. M9 exhibits selective inhibition of HDAC6 over class I HDACs in cells. M9 shows good microsomal stability, moderate plasma protein binding rate, and oral bioavailability. M9 exhibited a strong analgesic effect in vivo, and its analgesic tolerance was better than gabapentin. M9 improved the survival time of mice treated with lipopolysaccharide (LPS) and reversed the levels of inflammatory factors induced by LPS in mouse plasma. M9 represents the first sEH/HDAC6 dual inhibitors with in vivo antineuropathic pain and anti-inflammation.

EZH2/G9a interact to mediate drug resistance in non-small-cell lung cancer by regulating the SMAD4/ERK/c-Myc signaling axis.

Drug resistance is the leading problem in non-small-cell lung cancer (NSCLC) therapy. The contribution of histone methylation in mediating malignant phenotypes of NSCLC is well known. However, the role of histone methylation in NSCLC drug-resistance mechanisms remains unclear. Here, our data show that EZH2 and G9a, two histone methyltransferases, are involved in the drug resistance of NSCLC. Gene manipulation results indicate that the combination of EZH2 and G9a promotes tumor growth and mediates drug resistance in a complementary manner. Importantly, clinical study demonstrates that co-expression of both enzymes predicts a poor outcome in patients with NSCLC. Mechanistically, G9a and EZH2 interact and promote the silencing of the tumor-suppressor gene SMAD4, activating the ERK/c-Myc signaling pathway. Finally, SU08, a compound targeting both EZH2 and G9a, is demonstrated to sensitize resistant cells to therapeutic drugs by regulating the SMAD4/ERK/c-Myc signaling axis. These findings uncover the resistance mechanism and a strategy for reversing NSCLC drug resistance.

Impact of treatments before allogeneic hematopoietic stem cell transplantation in patients with higher-risk myelodysplastic syndrome.

OBJECTIVE: The study aimed to evaluate pre-allogeneic hematopoietic stem cell transplantation (allo-HSCT) treatment, compare the endpoints related to disease management between pre-HSCT cytoreduction patients and upfront transplantation patients with higher-risk myelodysplastic syndrome (MDS). METHODS: A total of 90 higher-risk MDS patients administered allo-HSCT in the Hematology Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed, which included 28 patients with upfront transplantation and 62 patients with pre-transplant cytoreduction, including 30 patients received hypomethylating agents (HMA) and 32 patients received hypomethylating agents and induction chemotherapy (HMA+IC). Difference between the two groups regarding hematopoietic reconstruction, graft-versus-host disease (GVHD), relapse rate, non-relapse death (NRM), overall survival (OS) and relapse-free survival (RFS) was compared. RESULTS: No significant differences in OS, DFS and NRM were found between the upfront transplantation and pre-transplant cytoreduction groups, and cumulative cGVHD occurrence and relapse rates were 35.7 % and 14.5 % (P = 0.029), and 10.7 % and 12.9 % (p = 0.535), respectively. Survival rates were significantly higher in the upfront transplantation and HMA+IC groups compared with the HMA group (3-year OS: 67.9 %, 68.8 %, 43.3 %, P = 0.039; 3-year RFS: 64.3 %, 62.5 %, 43.3 %, P = 0.107; 3-year NRM: 25.0 %, 21.9 %, 50.0 %, P = 0.025). Compared with the upfront transplantation group, overall response to cytoreductive therapy (OR) and non-response to cytoreductive therapy (NR), 3-year OS were 67.9 %, 73.0 % and 32.0 % (P < 0.001), 3-year RFS were 64.3 %, 73.0 % and 24.0 % (P < 0.001) and 3-year NRM were 25.0 %, 21.6 %, and 56.0 %, respectively (P < 0.001). Upfront transplantation (n = 11) had better OS and RFS compared with the cytoreductive group (n = 10) in patients with ≥ 10 % bone marrow blast cells before transplantation (3-year OS: 63.64 %, 22.22 %, p = 0.010; 3-year DFS: 63.64 %, 20.00 %, p = 0.012, respectively). CONCLUSION: The pre-transplant treatment regimen was an independent prognostic factor of OS and NRM. If the donor is suitable, upfront transplantation may provide longer survival in higher-risk MDS patients, which, however, may also increase the incidence of cGVHD. Even in patients with bone marrow blast cells ≥ 10 % before transplantation, upfront transplantation was not worse than transplantation after cytoreductive therapy. While waiting for a transplant, HMA+IC therapy may be a good pre-transplant treatment option.

Effects of slight shading in summer on the leaf senescence and endogenous hormone and polyamine contents in herbaceous peony.

Herbaceous peony is a perennial root plant that likes light and is cold-resistant. During summer, high temperature and strong light intensity advance its entry into the leaf wilting stage, which limits the accumulation of nutrients and formation of strong buds and severely affects its growth and development the following year. In this study, the wild herbaceous peony species and two main cultivars, 'Zifengyu' and 'Hongfengyu', were subjected to slight shading and strong light environments in summer, and their effects on leaf senescence and endogenous hormone and polyamine contents were explored. Slight shading treatment significantly delayed withering, increased the leaf net photosynthetic rate, and increased the chlorophyll, soluble sugar, indole-3-acetic acid, zeatin, gibberellin, spermine, spermidine, putrescine, and polyamine contents. Additionally, slight shading significantly reduced the proline and abscisic acid contents. Slight shading during summer prolonged the green period and delayed leaf senescence. The tolerance of tested materials to strong light intensity in summer was ranked as follows: 'Zifengyu' > 'Hongfengyu' > wild species. In conclusion, this study revealed that summer leaf senescence is delayed in herbaceous peony through shading and growth regulators. Additional varieties should be evaluated to provide reference for high-efficiency, high-quality, and high-yield cultivation of herbaceous peony.

Structure-Directed Discovery of Potent Soluble Epoxide Hydrolase Inhibitors for the Treatment of Inflammatory Diseases.

Soluble epoxide hydrolase (sEH) has been identified as an attractive target for anti-inflammatory drug design in recent years. Picomolar level compound G1 against sEH was obtained by introducing the hydrophilic group homopiperazine and hydrophobic fragment propionyl onto the structure of lead compound A. G1 showed good microsomal stability, a moderate plasma protein binding rate, and good oral bioavailability and was well tolerated in rats. G1 has significant analgesic effects on CFA-induced AIA mice, ameliorated the pancreatic injury in acute pancreatitis induced by l-arginine, reversed pancreatic injury, edema, and neutrophil infiltration, and increased the survival time of C57BL/6 mice in a lipopolysaccharide (LPS)-induced sepsis model. Moreover the expression levels of sEH, COX-2, NOS-2, vascular cell adhesion molecule (VCAM), IL-6, MCP-5, and tumor necrosis factor α (TNF-α) were measured by Western blot or enzyme-linked immunosorbent assay (ELISA), with varying degrees of decrease. These results suggested that G1 is a drug candidate worthy of further evaluation for the treatment of inflammation-induced diseases such as arthritis, acute pancreatitis, and sepsis.

Discovery of Dual Lysine Methyltransferase G9a and EZH2 Inhibitors with In Vivo Efficacy against Malignant Rhabdoid Tumor.

In recent years, it has been proposed that G9a/EZH2 dual inhibition is a promising cancer treatment strategy. Herein, we present the discovery of G9a/EZH2 dual inhibitors that merge the pharmacophores of G9a and EZH2 inhibitors. Among them, the most promising compound 15h displayed potent inhibitory activities against G9a (IC50 = 2.90 ± 0.05 nM) and EZH2 (IC50 = 4.35 ± 0.02 nM), superior antiproliferative profiles against RD (CC50 = 19.63 ± 0.18 µM) and SW982 (CC50 = 19.91 ± 0.50 µM) cell lines. In vivo, 15h achieved significant antitumor efficacy in a xenograft mouse model of human rhabdoid tumor with a tumor growth inhibitory rate of 86.6% without causing observable toxic effects. The on-target activity assays illustrated that compound 15h can inhibit tumor growth by specifically inhibiting EZH2 and G9a. Therefore, 15h is a potential anticancer drug candidate for the treatment of malignant rhabdoid tumor.

Structure of Industrial Sacrificial Fragile Cementitious Foams.

Sacrificial fragile cementitious foams (SFCFs) act as a core material of the engineered material arresting system (EMAS) installed in airports to enhance the safe take-offs and landings of aircrafts. The foam structures and foaming mechanisms that greatly impact the collapse strength, specific energy, and arresting efficiency of SFCFs, however, have not been fully addressed. Herein, the engineering properties, chemical characteristics, and pore-skeleton structures of three batches of industrial SFCFs were experimentally investigated. Penetration tests showed significant differences in collapse strength and specific energy among the SFCFs with a similar density. Three-dimensional (3D) pore-skeleton structures were resolved by microfocused X-ray computed tomography. The pore-skeleton anisotropy was investigated to uncover the stages of differences in the SFCFs' engineering properties. The results demonstrate that the pore anisotropy rather than the porosity dominates the collapse of cementitious foams. Viscosity-associated nucleation and growth mechanisms were proposed to account for the featured pore-skeleton structures of the SFCFs. The findings would contribute to better pore structure controls of SFCFs toward the improved quality of EMAS.

Effects of multidisciplinary exercise management on patients after percutaneous coronary intervention: A randomized controlled study.

Objectives: To explore the effectiveness of the mobile app-based multidisciplinary exercise management on patients who receive percutaneous coronary intervention (PCI). Methods: From January to October 2020, 54 patients after PCI were randomly assigned to the intervention group (n = 27) and the control group (n = 27). The intervention group received the mobile app-based multidisciplinary exercise management, whereas the control group received routine care. The patients after PCI began to take intervention one month after the operation, and the intervention lasted for two months. Before and after the intervention, 6-Minute Walking Distance was used to evaluate the patient's exercise tolerance, and the patient's exercise compliance was evaluated according to the patient's exercise status recorded by the mobile app. The cognitive questionnaire on knowledge about PCI treatment for Coronary Heart Disease, the Self-efficacy for Chronic Disease Scale and the Perceived Social Support Scale were used to evaluate patients' disease-related cognition, self-efficacy and perception of social support. This study was registered on Clinical Trials.gov with registration number ChiCTR2000028930. Results: Totally 51 patients after PCI who completed this study (25 patients in the intervention group and 26 patients in the control group) were included in the analysis. After 2 months of intervention, the exercise compliance of patients in the intervention group was better than that in the control group. And 6-Minute Walking Distance (469.36 ± 57.48 vs. 432.81 ± 67.09), and the scores of knowledge of PCI treatment for coronary heart disease (52.64 ± 9.82 vs. 42.42 ± 8.54), Self-efficacy for Chronic Disease Scale (42.40 ± 8.04 vs. 36.88 ± 7.73) and Perceived Social Support Scale (74.04 ± 5.73 vs. 66.69 ± 6.86) in the intervention group were higher than those in the control group with statistical significance (P < 0.05). Conclusions: The multidisciplinary exercise management based on the mobile app can effectively improve exercise tolerance, exercise compliance, disease-related cognition, self-efficacy, and perception of social support during exercise training for patients after PCI.

Family care and subjective well-being of coronary heart disease patients after percutaneous coronary intervention: Mediating effects of coping strategies.

OBJECTIVES: To analyze the correlations between family care, coping strategies and the subject well-being (SWB) of patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI). METHODS: From November 2019 to October 2020, 264 CHD patients who had undergone PCI were enrolled in this questionnaire survey. The research tools applied included General Information Questionnaire, the Adaptation, Partnership, Growth, Affection and Resolve, Medical Coping Modes Questionnaire, and the General Well-being Schedule. SPSS 24.0 and Amos 23.0 software packages were used for statistical analysis. RESULTS: The mean scores for family care, confrontation, avoidance, acceptance-resignation and SWB, were 7.59 ± 2.24, 20.03 ± 3.78, 16.49 ± 2.70, 10.42 ± 2.01, and 73.31 ± 11.63, respectively. Subgroup analysis showed that the path coefficient between family care and subjective well-being was higher in males than females. Family care was directly related to coping strategies. The coping strategies were directly related to SWB, while family care showed an indirect association with SWB via coping strategies. CONCLUSIONS: Family care can improve CHD patients' SWB post-PCI, and coping strategies are important for the link between family care and SWB. Also, men received more family care than women. Based on a patient's characteristics, healthcare providers can promote patients' positive coping strategies, increase their perceived family care, and improve the patient's SWB.

Structure-guided discovery of potent and oral soluble epoxide hydrolase inhibitors for the treatment of neuropathic pain.

Soluble epoxide hydrolase (sEH) is related to arachidonic acid cascade and is over-expressed in a variety of diseases, making sEH an attractive target for the treatment of pain as well as inflammatory-related diseases. A new series of memantyl urea derivatives as potent sEH inhibitors was obtained using our previous reported compound 4 as lead compound. A preferential modification of piperidinyl to 3-carbamoyl piperidinyl was identified for this series via structure-based rational drug design. Compound A20 exhibited moderate percentage plasma protein binding (88.6%) and better metabolic stability in vitro. After oral administration, the bioavailability of A20 was 28.6%. Acute toxicity test showed that A20 was well tolerated and there was no adverse event encountered at dose of 6.0 g/kg. Inhibitor A20 also displayed robust analgesic effect in vivo and dose-dependently attenuated neuropathic pain in rat model induced by spared nerve injury, which was better than gabapentin and sEH inhibitor (±)-EC-5026. In one word, the oral administration of A20 significantly alleviated pain and improved the health status of the rats, demonstrating that A20 was a promising candidate to be further evaluated for the treatment of neuropathic pain.

Andrographolide Inhibition of Th17-Regulated Cytokines and JAK1/STAT3 Signaling in OVA-Stimulated Asthma in Mice.

Asthma has long been considered a disease of airway inflammation. The excessive or prolonged production of inflammatory mediators can result in airway remodeling and severe clinical syndromes such as dyspnea or even apnea. Therefore, pharmaceutical intervention is required to restrain the excessive release of such inflammatory mediators in control of asthma. Novel therapeutics and mechanistic insight are sought for the management of this chronic inflammatory disease. Andrographolide (AG) is a type of diterpenoid ester compound and is reported to demonstrate multiple properties such as antioxidation and anti-inflammation. However, the anti-inflammatory capacity of AG by regulating immunologic function in airway of asthma has not been fully studied to date. Therefore, this study investigates whether AG is capable of suppressing the inflammatory response of asthma in OVA-stimulated mice and the mechanism by which this is achieved. Animals were randomly divided into 4 groups: control group, OVA model group, OVA + AG (0.1 mg/ml) group, and OVA + dimethylsulfoxide (DMSO) group. The serum, BALF, and lung tissue of the mice were collected separately for the administration of ELISA, rt-PCR, western blot and pathological section and staining. We found that AG attenuated the OVA-induced production of IL-6, IL-17A, IL-17F, and RORγt; inhibited the OVA-mediated phosphorylation of JAK 1 and STAT3; and alleviated airway remodeling and the neutrophil infiltration of lung tissue. We conclude that AG inhibits the inflammatory response of asthma in OVA-stimulated mice by blocking the activation of Th17-regulated cytokines and the JAK1/STAT3 signaling pathway.

[Effect of premolars scissor bite on the sagittal position of mandible].

PURPOSE: To study the effect of adolescent premolar scissor bite on the sagittal position of mandible and provide proper reference for correct orthodontic diagnosis and right time to treatment. METHODS： One hundred adolescents (54 females, 46 males) with scissor bite of premolars(70 were unilateral,30 were bilateral) were selected as experimental group between 2004 to 2017 from the Department of Orthodontics, Stomatological Hospital of China Medical University. Among them, 54 females served as female group, 46 males served as male group; 30 were bilateral and 70 were unilateral. Lateral cephalograms were recorded before treatment. 16 sagittal hard tissue variables on maxilla and mandible were measured cephalometrically by Winceph 9.0 software, and the cephalometric data were analyzed statistically by using SPSS 21.0 software package. RESULTS: Compared with normal occlusion, Beta angle, SNB, SND, ANB, AB-Plane angle, APDI, convexity angle, facial angle, Wits, Co-Po showed statistically significant difference in both unilateral group and bilateral group (P<0.05). In addition, Go-Pog showed statistically significant difference between normal occlusion and unilateral group(P<0.05). CONCLUSIONS: Adolescents with premolar scissor bite restricts the sagittal position of mandible and tend to have skeletal Ⅱ sagittal jaw relationship. Scissor bite affects the growth of mandible and makes mandibular body length and mandibular length less than normal. More attention should be paid to scissor bite as early as possible to decrease the harmful effects on growth of mandible and sagittal jaw relationship.