Folate deficiency promotes cervical squamous carcinoma SiHa cells progression by targeting miR-375/FZD4/ß-catenin signaling.

Epidemiological studies suggest an association between folate deficiency (FD) and cervical squamous cell carcinoma (SCC) progression. However, the underlying mechanism is unclear. Our study showed that FD-driven downregulation of miR-375 promoted proliferation of SCC SiHa cells and progression of xenograft tumors developed from SiHa; however, the exact mechanism of this process remained unclear. The current study aimed to elucidate the underlying mechanisms by which FD promotes the progression of SiHa cells by downregulating miR-375 expression. The results showed that miR-375 acted as a suppressor of SCC and inhibited the proliferation, migration, and invasion of SiHa cells. The FZD4 gene was identified as a target gene of miR-375, which can reverse the anti-onco effect of miR-375 and promote the proliferation and migration of SiHa cells. Furthermore, the regulatory effects of miR-375 and FZD4 on SiHa cells may be achieved by activating the ß-catenin signaling pathway. Moreover, FD may regulate the expression of miR-375 by regulating its DNA methylation level in the promoter region. In conclusion, our study reveals that FD regulates the miR-375/FZD4 axis by increasing the methylation of the miR-375 promoter, thereby activating ß-catenin signaling to promote SiHa cells progression. This study may provide new insights into the role of folic acid in the prevention and treatment of SCC.

An Arabidopsis Retention and Splicing complex regulates root and embryo development through pre-mRNA splicing.

Pre-mRNA splicing is an important step in the posttranscriptional processing of transcripts and a key regulator of development. The heterotrimeric retention and splicing (RES) complex plays vital roles in the growth and development of yeast, zebrafish, and humans by mediating pre-mRNA splicing of multiple genes. However, whether the RES complex is conserved in plants and what specific functions it has remain unknown. In this study, we identified Arabidopsis (Arabidopsis thaliana) BUD13 (AtBUD13), GROWTH, DEVELOPMENT AND SPLICING 1 (GDS1), and DAWDLE (DDL) as the counterparts of the yeast RES complex subunits Bud site selection protein 13 (Bud13), U2 snRNP component Snu17 (Snu17), and Pre-mRNA leakage protein 1, respectively. Moreover, we showed that RES is an ancient complex evolutionarily conserved in eukaryotes. GDS1 directly interacts with both AtBUD13 and DDL in nuclear speckles. The BUD13 domain of AtBUD13 and the RNA recognition motif domain of GDS1 are necessary and sufficient for AtBUD13-GDS1 interaction. Mutants of AtBUD13, GDS1, and DDL failed to properly splice multiple genes involved in cell proliferation and showed defects in early embryogenesis and root development. In addition, we found that GDS1 and DDL interact, respectively, with the U2 small nuclear ribonucleoproteins auxiliary factor AtU2AF65B and the NineTeen Complex-related splicing factor SKIP, which are essential for early steps of spliceosome assembly and recognition of splice sites. Altogether, our work reveals that the Arabidopsis RES complex is important for root and early embryo development by modulating pre-mRNA splicing.

Modeling long-term persistence after 8 years of hepatitis B booster vaccination in 5- to 15-year-old children.

Vaccination remains the most effective and cost-saving measure to protect against hepatitis B, a global health problem. It is crucial to characterize the persistence of the immune response after booster vaccination. This study aimed to quantify the persistence through mathematical modeling. Booster vaccination against hepatitis B was conducted in children 5-15 years in 2009-10 in Zhejiang Province. There were four dosage formulations of hepatitis B vaccines [Shenzhenkangtai Biotechnology Co. Ltd. Dalianhanxin Biotechnology Co. Ltd. NCPC GeneTech Biotechnology Pharmaceutical Co. Ltd. Sinovac Biotech Co. LTD. China]: 5, 10, and 20 µg hepatitis B vaccines or 5 µg hepatitis A and B (HAB) combination vaccine with a 0-1-6-month schedule. These were randomly administered to children negative for all hepatitis B markers, named as the schedule 2 group. Anti-HBs positive subjects were given one dose of booster, named as the schedule 1 group. Anti-HBs antibody was measured 1, 7, 18, 66, and 102 months after the first booster dose. A linear mixed-effects model was proposed to predict long-term persistence. One hundred two months after the booster dose, the mean anti-HBs levels were 33.8 mIU/mL, with 73.7 mIU/mL for the schedule 1 group and 20.2 mIU/mL for the schedule 2 group. The model predicted that 99.5% of subjects would remain seropositive (≥10mIU/mL) at year 20 post booster vaccination, with 100.0% and 98.8% for the schedule 1 group and the schedule 2 group, respectively, whereas at year 30, the seropositivity rates would decrease to 76.8%, with 99.4% for the schedule 1 group and 62.5% for the schedule 2 group. The immunogenicity of the booster vaccination could persist for at least 8 years. Mathematical modeling may predict even longer, up to 30 years of protection.

Plant-Specific AtS40.4 Acts as a Negative Regulator in Abscisic Acid Signaling During Seed Germination and Seedling Growth in Arabidopsis.

Abscisic acid (ABA) is an important phytohormone regulating plant growth, development and stress responses. A multitude of key factors implicated in ABA signaling have been identified; however, the regulation network of these factors needs for further information. AtS40.4, a plant-specific DUF584 domain-containing protein, was identified previously as a senescence regulator in Arabidopsis. In this study, our finding showed that AtS40.4 was negatively involved in ABA signaling during seed germination and early seedling growth. AtS40.4 was highly expressed in seeds and seedlings, and the expression level was promoted by ABA. AtS40.4 was localized both in the nucleus and the cytoplasm. Moreover, the subcellular localization pattern of AtS40.4 was affected by ABA. The knockdown mutants of AtS40.4 exhibited an increased sensitivity to ABA, whereas the overexpression of AtS40.4 decreased the ABA response during seed germination and seedling growth of Arabidopsis. Furthermore, AtS40.4 was involved in ABRE-dependent ABA signaling and influenced the expression levels of ABA INSENTIVE (ABI)1-5 and SnRK2.6. Further genetic evidence demonstrated that AtS40.4 functioned upstream of ABI4. These findings support the notion that AtS40.4 is a novel negative regulator of the ABA response network during seed germination and early seedling growth.

Disease burden of inflammatory bowel disease in China from 1990 to 2017: Findings from the global burden of diseases 2017.

BACKGROUND: A comprehensive evaluation of the burden of inflammation bowel disease (IBD) is important for identifying potential strategies to control the disease. We present results from the Global Burden of Diseases (GBD) 2017 of IBD at the national level, the trends in disease burden and its epidemiological features in China. METHODS: Using the methods and results from GBD 2017, we describe the IBD burden based on the prevalence, incidence, mortality, years of lost (YLLs), the years of life lived with disability (YLDs) and disability-adjusted life years (DALYs) in China estimated using DisMod-MR 2·1. We additionally evaluated the rate of DALYs at national locations in 2017. FINDINGS: From 1990 to 2017, the cases, deaths, YLLs, YLDs and DALYs for IBD in China were from 1,047,991 to 2,665,081, from 5701 to 5198, from 188,814 to 107,373, from 157,581 to 394,887, from 346,396 to 502,260, respectively. Increasing trends were observed in prevalence (APC: 2·9%), incidence (APC: 1·1%), DALYs (APC: 0·8%) and YLDs (APC:2·9%). There were decreasing trends in mortality (APC: -1·0%) and YLLs (APC: -2·7%). As to the age-standardized rates of DALYs, it observed a decreasing trend (APC: -0·78%). Similar trends were observed in men and women. The age-standardized APCs in incidence, mortality and rate of YLLs among women were higher than those among men. The age-standardized rate of DALYs was 27·51 per 100,000 in 2017. INTERPRETATION: Between 1990 and 2017, China experienced a decrease in the age-standardized DALYs, mortality rates and YLLs due to IBD, despite an increase in the age-standardized rate of prevalence, incidence and YLDs. China is still one of the low endemic areas. FUNDING: This work had no supporting funding.

Screening of the Repellent Activity of 12 Essential Oils Against Adult German Cockroach (Dictyoptera: Blattellidae): Preparation of a Sustained Release Repellent Agent of Binary Oil-γ-CD and its Repellency in a Small Container.

Cockroaches are important sanitary pests and very difficult to control worldwide. With public concern about traditional insecticides, cockroach control agents should be environmentally friendly, highly efficient, and economical. In this article, 12 essential oils were screened to test their repellent effect against Blattella germanica. To develop essential oils as repellent agents, the oils were further examined in binary synergistic combinations. Ilex chinensis Sims (Sapindales: Aquifoliaceae) oil, Lavandula spp (Tubiflorae: Labiatae) oil, and Elsholtzia ciliata (Thunb.) Hyland (Tubiflorae: Labiatae) oil showed excellent repellent activities with lower RD50 (repellency dose for 50% of treated adults) values of 218.634, 154.590, and 223.989 µg/cm2, respectively, compared to those of other oils and the positive control. The I. chinensis oil and E. ciliata oil (weight ratio of 1:1.41) combination also displayed a remarkable synergistic effect against B. germanica. Their cotoxicity coefficient was 214.4. The major chemical constituents in E. ciliata and I. chinensis oils were respectively 3,7-dimethyl-1, 6-octadien-3-ol and methyl salicylate. The binary oil mixtures were formulated as a sustained release agent with γ-CD. The optimal preparation should be an 8:1 ratio of γ-CD to oils, with a 1 h stirring time, 50°C stirring temperature, and 1:12 ratio of γ-CD to ddH2O. The results of this study suggest that sustained release of binary oil-γ-CD exhibited a prolonged repellent activity (10 h) against B. germanica. This sustained-release agent could be further investigated and developed as a novel repellent preparation.

Effects of Horseradish Oil and Eight Isothiocyanates Vapour Treatment on Postharvest Disease Control and Their Efficacy as Preservatives of Mature Green Tomato.

This study evaluated the potential of horseradish (Armoracia rusticana) oil (ARO) and eight isothiocyanates (propyl ITC [ProITC], isopropyl ITC [IsoproITC], n-butyl ITC [n-BuITC], 3-butenyl ITC [3-BeITC], phenyl ITC [PhITC], benzyl ITC [BzITC], 2-phenylethyl ITC [PhEITC], and allyl ITC [AITC]) as preservatives and antifungal agents for postharvest tomato disease control. Results showed that ARO and eight ITCs demonstrated antifungal activities against Botrytis cinerea, Alternaria alternata, Rhizopus stolonifer, and Geotrichum candidum, which can cause the decay of mature green tomato during storage. Allyl-ITC (AITC) had the lowest EC50 values of mycelia growth suppression, with 0.18, 0.44, 0.29, and 0.43 µg/ml air for B. cinerea, A. alternata, R. stolonifer, and G. candidum, respectively. ARO, 2-PhEITC, BzITC, and AITC exhibited better efficacy as preservatives of mature green tomato than other ITCs on the basis of some parameters, such as low decay rate, slow reduction in weight loss, slight change in hardness, slow decrease in acidity, and total soluble solid content of treated tomatoes. GC-MS revealed that 2-PhEITC (77.78%) and AITC (15.87%) were the major components of ARO. These results can be used as a basis to develop preservative products composed of ITCs.

Strategies for hepatitis B booster vaccination among children: an 8-year prospective cohort study.

Debate continues regarding the need for a booster vaccination in children who received a universal infant hepatitis B virus (HBV) vaccination. The aim was to explore the need and the strategies for the booster HBV vaccination. 8-year prospective cohort study was conducted among children aged 5-15 years in 2009-2010 in Zhejiang Province. The participants were divided into groups A (<0.1 mIU/mL), B (0.1 to < 1 mIU/mL) and C (1 to <10 mIU/mL) according to the pre-booster anti-HBs antibody levels. 5 µg (group I), 10 µg (group II), 20 µg hepatitis B vaccines (group III) or 5 µg hepatitis A and B (HAB) vaccines (group IV) with 0-1-6-month schedule were randomly administered to children negative for all markers. Blood samples were collected at baseline HBV marker testing, 1 month after the first dose, 1 month, 1 year, 5 years and 8 years after the third dose. Among 4170 children, 2326 (55.8%) were negative for all HBV markers. Group II showed the highest seropositive rates of 92.8%, 99.7%, 97.6%, 90.3% and 83.4% with GMTs of 4194.5 mIU/ml, 4163.9 mIU/ml, 466.9 mIU/ml, 190.6 mIU/ml, 122.6 mIU/ml from 1 month after dose 1 to 8 years after dose 3, respectively (P < .01). Participants in group C showed seropositive rates of 98.9%, 99.9%, 99.5%, 95.5%, 92.8% after the revaccination with GMTs of 6519.6 mIU/ml, 5267.4 mIU/ml, 547.1 mIU/ml, 249.5 mIU/ml, 155.3 mIU/ml, respectively, higher than group A and B (P < .001), except 1 month after the third dose. The 10 µg of HBV vaccine with a 0-1-6-month booster regimen may elicit robust responses and persist for 8 years or longer. Additionally, 1-dose revaccination maybe suitable for children with 1 to < 10 mIU/ml anti-HBs titers.

MicroRNA-144 represses gliomas progression and elevates susceptibility to Temozolomide by targeting CAV2 and FGF7.

Malignant gliomas are the most common tumor in central nervous system with poor prognosis. Due to the limitation of histological classification in earlier diagnosis and individualized medicine, it is necessary to combine the molecular signatures and the pathological characteristics of gliomas. Lots of microRNAs presented abnormal expression in gliomas and modulated gliomas development. Exploration the miRNAs profile is helpful for the diagnosis, therapy and prognosis of gliomas. It has been demonstrated that miR-144 plays important roles in solid tumors. However, the detail mechanisms remained unrevealed. In this study, we have demonstrated the level of miR-144 decreased in glioma tissues from patients, especially in gliomas with higher grades. MiR-144 was also validated have lower expression in glioma cell lines compared with cortical neuron cell by using qRT-PCR. The in vitro functional experiment indicated miR-144 improved gliomas progression through repressing proliferation, sensitizing to chemotherapeutics and inhibiting metastasis. We further identified fibroblast growth factor 7 (FGF7) and Caveolin 2 (CAV2) were target genes of miR-144 by luciferase reporter assay and western blotting. The mechanisms study suggested forced FGF7 expression elevated Akt activation and decreased reactive oxygen species (ROS) generation. The MTT and cell cycle assay indicated miR-144 suppressed glioma cells proliferation through modulating FGF mediated Akt signaling pathway. Meanwhile, miR-144 promoted Temozolomide (TMZ) induced apoptosis in glioma cells via increasing ROS production by using FACS. On the other hand, CAV2, as another target of miR-144, accelerated glioma cells migration and invasion via promoting glioma cells EMT progress. Retrieved expression of FGF7 or CAV2 rescued the proliferation and migration function mediated by miR-144. Furthermore, the in vivo experiments in PDX models displayed the anti-tumor function of miR-144, which could be retrieved by overexpression of FGF7 and CAV2. Taken together, these findings indicated miR-144 acted as a potential target against gliomas progression and uncovered a novel regulatory mechanism, which may provide a new therapeutic strategy and prognostic indicator for gliomas.

The Cannabinoid WIN 55,212-2 Reduces Delayed Neurologic Sequelae After Carbon Monoxide Poisoning by Promoting Microglial M2 Polarization Through ST2 Signaling.

Delayed neurologic sequelae (DNS) are among the most serious complications of carbon monoxide (CO) poisoning caused partly by elevated neuroinflammation. WIN 55,212-2, a non-selective agonist of cannabinoid receptors, has been demonstrated to have anti-inflammatory properties in various brain disorders. The anti-inflammatory action of WIN 55,212-2 is potentially associated with driving microglial M2 polarization. ST2 signaling is important in regulating inflammatory responses and microglial polarization. Therefore, we aimed to investigate the neuroprotective effect of WIN 55,212-2 on DNS after CO poisoning and elucidate its relationship with ST2-mediated microglial M2 polarization. The behavioral tests showed that treatment with WIN 55,212-2 significantly ameliorates the cognitive impairment induced by CO poisoning. This behavioral improvement was accompanied by reduced neuron loss, decreased production of pro-inflammatory cytokines, and a limited number of microglia in the hippocampus. Moreover, WIN 55,212-2 elevated the protein expression of IL-33 (the ligand of ST2) and ST2, increased the ratio of CD206-positive (M2 phenotype) and ST2-positive microglia, and augmented production of M2 microglia-associated cytokines in the hippocampus of CO-exposed rats. Furthermore, we observed that the WIN 55,212-2-mediated increases in ST2 protein expression, CD206-positive and ST2-positive microglia, and microglia-associated cytokines were blocked by the cannabinoid receptor 2 (CB2R) antagonist AM630 but not by the cannabinoid receptor 1 (CB1R) antagonist AM251. In contrast, the WIN 55,212-2-induced upregulation of the IL-33 protein expression was inhibited by AM251 but not by AM630. Altogether, these findings reveal cannabinoid receptors as promising therapeutic agents for CO poisoning and identify ST2 signaling-related microglial M2 polarization as a new mechanism of cannabinoid-induced neuroprotection.

AtU2AF65b functions in abscisic acid mediated flowering via regulating the precursor messenger RNA splicing of ABI5 and FLC in Arabidopsis.

In mammalians and yeast, the splicing factor U2AF65/Mud2p functions in precursor messenger RNA (pre-mRNA) processing. Arabidopsis AtU2AF65b encodes a putative U2AF65 but its specific functions in plants are unknown. This paper examines the function of AtU2AF65b as a negative regulator of flowering time in Arabidopsis. We investigated the expression and function of AtU2AF65b in abscisic acid (ABA)-regulated flowering as well as the transcript abundance and pre-mRNA splicing of flowering-related genes in the knock-out mutants of AtU2AF65b. The atu2af65b mutants show early-flowering phenotype under both long-day and short-day conditions. The transcript accumulation of the flowering repressor gene FLOWERING LOCUS C (FLC) is reduced in the shoot apex of atu2af65b, due to both increased intron retention and reduced transcription activation. Reduced transcription of FLC results, at least partially, from the abnormal splicing and reduced transcript abundance of ABSCISIC ACID-INSENSITIVE 5 (ABI5), which encodes an activator of FLC in ABA-regulated flowering signaling. Additionally, the expression of AtU2AF65b is promoted by ABA. Transition to flowering and splicing of FLC and ABI5 in the atu2af65b mutants are compromised during ABA-induced flowering. ABA-responsive AtU2AF65b functions in the pre-mRNA splicing of FLC and ABI5 in shoot apex, whereby AtU2AF65b is involved in ABA-mediated flowering transition in Arabidopsis.

Trichoderma harzianum Improves Defense Against Fusarium oxysporum by Regulating ROS and RNS Metabolism, Redox Balance, and Energy Flow in Cucumber Roots.

Plant survival in the terrestrial ecosystem is influenced by both beneficial and harmful microbes. Trichoderma spp. are a group of filamentous fungi that promote plant growth and resistance to harmful microbes. Previously, we showed that the genus Trichoderma could effectively suppress Fusarium wilt in cucumber. However, the mechanisms that underlie the effects of the genus Trichoderma on plant defense have not been fully substantiated. Two essential metabolic pathways, such as the ascorbate (AsA)-glutathione (GSH) cycle and the oxidative pentose phosphate pathway (OPPP), have been shown to participate in plant tolerance to biotic stressors; nevertheless, the involvement of these pathways in Trichoderma-induced enhanced defense remains elusive. Here, we show that Trichoderma harzianum could alleviate oxidative and nitrostative stress by minimizing reactive oxygen species (ROS; hydrogen peroxide and superoxide) and reactive nitrogen species (nitric oxide [NO]) accumulation, respectively, under Fusarium oxysporum infection in cucumber roots. The genus Trichoderma enhanced antioxidant potential to counterbalance the overproduced ROS and attenuated the transcript and activity of NO synthase and nitrate reductase. The genus Trichoderma also stimulated S-nitrosylated glutathione reductase activity and reduced S-nitrosothiol and S-nitrosylated glutathione content. Furthermore, the genus Trichoderma enhanced AsA and GSH concentrations and activated their biosynthetic enzymes, γ-GCS and l-galactono-1,4-lactone dehydrogenase. Interestingly, the genus Trichoderma alleviated Fusarium-inhibited activity of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, enzymes involved in the OPPP. Such positive regulation of the key enzymes indicates the adequate maintenance of the AsA-GSH pathway and the OPPP, which potentially contributed to improve redox balance, energy flow, and defense response. Our study advances the current knowledge of Trichoderma-induced enhanced defense against F. oxysporum in cucumber.

AtBUD13 affects pre-mRNA splicing and is essential for embryo development in Arabidopsis.

Pre-mRNA splicing is an important step for gene expression regulation. Yeast Bud13p (bud-site selection protein 13) regulates the budding pattern and pre-mRNA splicing in yeast cells; however, no Bud13p homologs have been identified in plants. Here, we isolated two mutants that carry T-DNA insertions at the At1g31870 locus and shows early embryo lethality and seed abortion. At1g31870 encodes an Arabidopsis homolog of yeast Bud13p, AtBUD13. Although AtBUD13 homologs are widely distributed in eukaryotic organisms, phylogenetic analysis revealed that their protein domain organization is more complex in multicellular species. AtBUD13 is expressed throughout plant development including embryogenesis and AtBUD13 proteins is localized in the nucleus in Arabidopsis. RNA-seq analysis revealed that AtBUD13 mutation predominantly results in the intron retention, especially for shorter introns (≤100 bases). Within this group of genes, we identified 52 genes involved in embryogenesis, out of which 22 are involved in nucleic acid metabolism. Our results demonstrate that AtBUD13 plays critical roles in early embryo development by effecting pre-mRNA splicing.

Suitable hepatitis B vaccine for adult immunization in China: a systematic review and meta-analysis.

Hepatitis B virus (HBV) infection remains an important public health problem in China, and adults need to be vaccinated. This systematic review and meta-analysis assessed the appropriate immunization of adults in China. Only randomized controlled trials (RCTs) were eligible, and seroprotection was defined as anti-HBs≥ 10 mIU/ml; 18,308 participants in 27 studies were included. Relative risk (RR) and random effects models were used. Twenty micrograms of HBV vaccine resulted in a better response than 10 µg (RR: 1.05, 95% confidence interval (CI): 1.02 to 1.08), and the 0-, 1-, and 6-month schedule was more effective than the 0-, 1-, and 2 - or 3-month schedule (RR: 0.98, 95% CI: 0.96 to 1.00). No significant differences were observed between 10 µg and 5 µg (RR: 1.05, 95% CI: 0.88 to 1.01); (yeast-derived hepatitis B vaccines) YDV and recombinant Chinese hamster ovary cell (CHO) hepatitis B vaccine (RR: 1.01, 95% CI: 0.98 to 1.04); domestic and imported (RR: 1.02, 95% CI: 0.99 to 1.05); or 0-, 1-, and 6-month and 0-, 1-, and 12-month schedules (RR: 1.02, 95% CI: 0.89 to 1.08). In conclusion, 20 µg of vaccine is recommended for adults in China, and the 0-, 1-, and 12-month immunization program schedule is also worth choosing when it is not possible to complete the 0-, 1-, and 6-month schedule.

miR-183-96-182 clusters alleviated ox-LDL-induced vascular endothelial cell apoptosis in vitro by targeting FOXO1.

OBJECTIVE: To investigate the role of FOXO1 and miR-183-96-182 clusters in ox-LDL induced endothelial cell apoptosis. METHODS: FOXO1 overexpression (OE) and knockdown (KD) as well as AKT1 OE in human umbilical vein endothelial cells (HUVECs) and human aortic endothelial cells (HAECs) were achieved by lentiviral transduction. Upregulation of miR-183-5p, miR-182-5p or miR-96-5p was mimicked by agomir treatment. FOXO1 gene transcription was monitored by FOXO1 promotor reporter assay. Cell apoptosis in culture was monitored by TiterTACS in situ detection. Regulation of FOXO1 gene expression by an miRNA targeting mechanism was monitored by AGO2-RNA immunoprecipitation assay. RESULTS: FOXO1 mRNA and protein expression levels in ox-LDL treated HUVECs or HAECs were significantly upregulated due to transcriptional and miRNA targeting mechanisms. MiR-183-5p, miR-182-5p and miR-96-5p expression levels in HUVECs or HAECs were significantly reduced by ox-LDL treatment, the overexpression of which by agomir treatment partially reduced the FOXO1 mRNA/protein expression levels and cell apoptosis which was upregulated by ox-LDL treatment. FOXO1 overexpression antagonized the effect of the agomir treatment indicated above. MiR-183-5p, miR-182-5p and miR-96-5p agomir treatment partially rescued the FOXO1 pSer256/total FOXO1 protein ratio and the AKT1 pSer473 level that were reduced by ox-LDL treatment in the HUVECs or HAECs. AKT1 overexpression significantly reduced FOXO1 protein expression, increased miR-182-5p and miR-183-5p expression, and partially alleviated ox-LDL induced HUVEC or HAEC apoptosis in an miR-183-5p and miR-182-5p-dependent manner. CONCLUSION: miR-183-96-182 clusters could partially alleviate ox-LDL-induced apoptosis in HUVECs or HAECs by targeting FOXO1.

Actin filaments regulate the adhesion between the plasma membrane and the cell wall of tobacco guard cells.

During the opening and closing of stomata, guard cells undergo rapid and reversible changes in their volume and shape, which affects the adhesion of the plasma membrane (PM) to the cell wall (CW). The dynamics of actin filaments in guard cells are involved in stomatal movement by regulating structural changes and intracellular signaling. However, it is unclear whether actin dynamics regulate the adhesion of the PM to the CW. In this study, we investigated the relationship between actin dynamics and PM-CW adhesion by the hyperosmotic-induced plasmolysis of tobacco guard cells. We found that actin filaments in guard cells were depolymerized during mannitol-induced plasmolysis. The inhibition of actin dynamics by treatment with latrunculin B or jasplakinolide and the disruption of the adhesion between the PM and the CW by treatment with RGDS peptide (Arg-Gly-Asp-Ser) enhanced guard cell plasmolysis. However, treatment with latrunculin B alleviated the RGDS peptide-induced plasmolysis and endocytosis. Our results reveal that the actin depolymerization is involved in the regulation of the PW-CW adhesion during hyperosmotic-induced plasmolysis in tobacco guard cells.

Motivations and Training Needs of General Practitioner Preceptors.

BACKGROUND: General practitioner (GP) preceptors play an important role in the cultivation of GPs. Many problems exist in the training of GP preceptors. This study aimed to explore the willingness and training needs of GP preceptors and compare the differences between preceptors from general practice and other specialties. METHODS: A total of 375 questionnaire forms were sent to 375 GP preceptors from 11 different provinces, and 344 completed forms were returned. The main outcome included general information, teaching motivations, and training needs of GP preceptors. RESULTS: The study showed that about 89.2% of GP preceptors were willing to be teachers. The majority of respondents strongly agreed that the motivation for becoming a GP supervisor was to learn from teaching. The most important capability they should master was clinical teaching (92.2%), followed by lecture (83.1%) and doctor-patient communication (83.1%). The top three preferred methods of GP preceptors training were case discussion (78.8%), workshop (57.6%), and classroom teaching (56.4%). The domains in which most GP preceptors wanted to acquire knowledge and skill were mental health (59.3%), rehabilitation (47.1%), pediatrics (41.0%), and obstetrics (37.5%). No significant differences were found in the willingness to train GPs (χ2 = 3.34, P > 0.05) and whether they would become or continue to become a GP supervisor after the training (χ2 = 1.106, P > 0.05). CONCLUSIONS: Although most preceptors were under on-the-job training, they were glad to train GPs. To be qualified, preceptors should be trained according to the actual needs of GP preceptors.

A Shared Decision-Making System for Diabetes Medication Choice Utilizing Electronic Health Record Data.

The use of a shared decision-making (SDM) process in antihyperglycemic medication strategy decisions is necessary due to the complexity of the conditions of diabetes patients. Knowledge of guidelines is used as decision aids in clinical situations, and during this process, no patient health conditions are considered. In this paper, we propose an SDM system framework for type-2 diabetes mellitus (T2DM) patients that not only contains knowledge abstracted from guidelines but also employs a multilabel classification model that uses class-imbalanced electronic health record (EHR) data and that aims to provide a recommended list of available antihyperglycemic medications to help physicians and patients have an SDM conversation. The use of EHR data to serve as a decision-support component in decision aids helps physicians and patients to reach a more intuitive understanding of current health conditions and allows the tailoring of the available knowledge to each patient, leading to a more effective SDM. Real-world data from 2542 T2DM inpatient EHRs were substituted by 77 features and eight output labels, i.e., eight antihyperglycemic medications, and these data were utilized to build and validate the recommendation model. The multilabel recommendation model exhibited stable performance in every single-label classification and showed the ability to predict minority positive cases in which the average recall value of the eight classes was 0.9898. As a whole multilabel classifier, the recommendation model demonstrated outstanding performance, with scores of 0.0941 for Hamming Loss, 0.7611 for Accuracyexam, 0.9664 for Recallexam, and 0.8269 for Fexam.

Associations between serum HBX quasispecies and their integration in hepatocellular carcinoma.

HBV quasispecies are closely related to the course and outcome of liver disease. However, whether the complexity and diversity of HBX quasispecies affects its integration in the liver cell and thereby enhances the resultant carcinogenesis is still not clear. 15 HCC patients were recruited; genomic DNA and HBV DNA were extracted from liver cancer tissue and serum respectively. The integrated HBX fragment in liver cancer tissue was amplified by Alu repeat sequence-polymerase chain reaction (Alu-PCR) and sequenced. The serum HBX gene was amplified by nested PCR and sequenced. Quasispecies complexity and diversity, phylogenetic characteristics, lymphocyte count and survival time between HBX-integrated and HBX-unintegrated patients were evaluated. Results showed that the integrated HBX fragment was detected in the tumor tissue of nine patients, and the integration rate was 60.00% (9/15). Compared with the HBX-unintegrated patients, the HBX-integrated patients had a higher quasispecies complexity (P=0.028 and 0.004, at the nucleotide and amino acid levels, respectively). The HBX-integrated patients had a tendency of higher quasispecies diversity, lower lymphocyte count and the survival time. A total of 12 mutation sites were revealed in the HBX-integrated fragment after alignment with the reference sequence. In these, the HBX-integrated groups had significantly higher mutation frequencies at C1497T, A1630G, G1721A, A1762T/G1764A and A1774G. This study revealed influence factors of HBX integration both in virus and the host. The increased complexity and diversity of HBX quasispecies might destroy the host immune balance, and lead to HBX integration ultimately.

Suitable hepatitis B vaccine for adult immunization in China.

The aim of this study was to evaluate, in adults, the immunogenicity of six hepatitis B vaccines with different doses or different manufacturers in the Chinese market and to provide evidence to support adult hepatitis B vaccination. Participants were randomly divided into six groups (I-VI). Six vaccines (4 at 10 µg/dose and 2 at 20 µg/dose) were administered intramuscularly to healthy adults at 0, 1 and 6 month intervals. All participants (16-50 years) who were negative for any hepatitis B virus serological markers were vaccinated. Anti-HBs levels were assessed 1 month and 1 year after the third vaccination. The anti-HBs seroconversion rate (anti-HBs >10 mIU/ml) was 99.4 % (99.9 % for 10 µg dose groups and 97.9 % for 20 µg dose groups) 1 month after the third vaccination, and the anti-HBs seroreversion rate was 77.0 % (75.3 and 82.6 %) 1 year after the third vaccination (n = 1036). One month after completing the vaccinations, the seroconversion rates were not significantly different (100.0, 100.0, 99.6, 100.0 %) for the four 10 µg dose and two 20 µg dose groups (99.1, 96.9 %). One year after the third vaccination, the group II positive rate was significantly higher than the other three 10 µg dose groups, and the group VI positive rate was significantly higher than the other 20 µg dose group. Groups II and VI showed a significantly higher positive rate and anti-HBs geometric mean titer (GMT) than the other groups. The anti-HBs level declined with increasing age, and the seroreversion rate and GMT decreased over time. All six vaccines had high anti-HBs seroconversion rates and good immunization effects. The 10 µg dose vaccine (Dalian High-Tech) and the 20 µg dose vaccine (GlaxoSmithKline) are recommended for adults.