Is 3T MR nerve-bone fusion imaging a viable alternative to MRI-CBCT to identify the relationship between the inferior alveolar nerve and mandibular third molar.

OBJECTIVES: To investigate the feasibility of MRI nerve-bone fusion imaging in assessing the relationship between inferior alveolar nerve (IAN) / mandibular canal (MC) and mandibular third molar (MTM) compared with MRI-CBCT fusion. MATERIALS AND METHODS: The MRI nerve-bone fusion and MRI-CBCT fusion imaging were performed in 20 subjects with 37 MTMs. The Hausdorff distance (HD) value and dice similarity coefficient (DSC) was calculated. The relationship between IAN/MC and MTM roots, inflammatory, and fusion patterns were compared between these two fused images. The reliability was assessed using a weighted κ statistic. RESULTS: The mean HD and DSC ranged from 0.62 ~ 1.35 and 0.83 ~ 0.88 for MRI nerve-bone fusion, 0.98 ~ 1.50 and 0.76 ~ 0.83 for MRI-CBCT fusion. MR nerve-bone fusion had considerable reproducibility compared to MRI-CBCT fusion in relation classification (MR nerve-bone fusion κ = 0.694, MRI-CBCT fusion κ = 0.644), direct contact (MR nerve-bone fusion κ = 0.729, MRI-CBCT fusion κ = 0.720), and moderate to good agreement for inflammation detection (MR nerve-bone fusion κ = 0.603, MRI-CBCT fusion κ = 0.532, average). The MR nerve-bone fusion imaging showed a lower ratio of larger pattern compared to MR-CBCT fusion (16.2% VS 27.3% in the molar region, and 2.7% VS 5.4% in the retromolar region). And the average time spent on MR nerve-bone fusion and MRI-CBCT fusion was 1 min and 3 min, respectively. CONCLUSIONS: Both MR nerve-bone fusion and MRI-CBCT fusion exhibited good consistency in evaluating the spatial relationship between IAN/MC and MTM, fusion effect, and inflammation detection. CLINICAL RELEVANCE: MR nerve-bone fusion imaging can be a preoperative one-stop radiation-free examination for patients at high risk for MTM surgery.

Grading meningiomas with diffusion metrics: a comparison between diffusion kurtosis, mean apparent propagator, neurite orientation dispersion and density, and diffusion tensor imaging.

OBJECTIVES: To compare the histogram features of multiple diffusion metrics in predicting the grade and cellular proliferation of meningiomas. METHODS: Diffusion spectrum imaging was performed in 122 meningiomas (30 males, 13-84 years), which were divided into 31 high-grade meningiomas (HGMs, grades 2 and 3) and 91 low-grade meningiomas (LGMs, grade 1). The histogram features of multiple diffusion metrics obtained from diffusion tensor imaging (DTI), diffusion kurtosis imaging (DKI), mean apparent propagator (MAP), and neurite orientation dispersion and density imaging (NODDI) in the solid tumours were analysed. All values between the two groups were compared with the Man-Whitney U test. Logistic regression analysis was applied to predict meningioma grade. The correlation between diffusion metrics and Ki-67 index was analysed. RESULTS: The DKI_AK (axial kurtosis) maximum, DKI_AK range, MAP_RTPP (return-to-plane probability) maximum, MAP_RTPP range, NODDI_ICVF (intracellular volume fraction) range, and NODDI_ICVF maximum values were lower (p < 0.0001), whilst the DTI_MD (mean diffusivity) minimum values were higher in LGMs than those in HGMs (p < 0.001). Amongst the DTI, DKI, MAP, NODDI, and combined diffusion models, no significant differences were found in areas under the receiver operating characteristic curves (AUCs) for grading meningiomas (AUCs, 0.75, 0.75, 0.80, 0.79, and 0.86, respectively; all corrected p > 0.05, Bonferroni correction). Significant but weak positive correlations were found between the Ki-67 index and DKI, MAP, and NODDI metrics (r = 0.26-0.34, all p < 0.05). CONCLUSIONS: Whole tumour histogram analyses of the multiple diffusion metrics from four diffusion models are promising methods in grading meningiomas. The DTI model has similar diagnostic performance compared with advanced diffusion models. KEY POINTS: • Whole tumour histogram analyses of multiple diffusion models are feasible for grading meningiomas. • The DKI, MAP, and NODDI metrics are weakly associated with the Ki-67 proliferation status. • DTI has similar diagnostic performance compared with DKI, MAP, and NODDI in grading meningiomas.

Bacillus subtilis reduces antibiotic resistance genes of animal sludge in vermicomposting by improving heat stress tolerance of Eisenia foetida and bacterial community adjustment.

Antibiotic resistance genes (ARGs) in livestock industry have been recognized as a kind of pollutant. The effect of Bacillus subtilis (B. subtilis) as an additive for the reduction of ARGs in animal sludge from livestock and poultry wastewater treatment plant during vermicomposting was investigated. We also evaluated the oxidative stress level and growth of earthworms, Eisenia foetida, bacterial community succession, and the quality of the end products. Two treatments were conducted using B. subtilis, one at 18 °C and another at 28 °C. Controls were setup without the bacteria. The results showed that inoculation of B. subtilis promoted the degradation of organics at 28 °C and increased the germination index to 236%. The increased activities of the superoxide dismutase (1.69 U/mg pr) and catalase (8.05 U/mg pr) and the decreased activity of malondialdehyde (0.02 nmol/mg pr) by B. subtilis at 28 °C showed that the earthworms were relieved of heat stress. The addition of B. subtilis reduced the abundance of 32 target ARGs, including integron (intI-1), transposase (IS613) and resistant genes, such as sulfonamide (sul2), quinolone (oprJ), macrolide-lincosamide-streptogramin group B (ermF, ermB), tetracycline (tetL-02, tetX), ß-lactama (blaOXA10-01) and aminoglycoside [strB, aac(6')-Ib(aka aacA4)-01, aac(6')-Ib(aka aacA4)-02]. Organic matter degrading Membranicola, Paludisphaera, Sphingorhabdus and uncultured bacterium belonging to the order Chitinophagales, nitrifying and nitrogen-fixing Singulisphaera and Allorhizobium-Neorhizobium-Pararhizobium-Rhizobium, soil remediating Achromobacter, and plant growth promoting Kaistia, Galbibacter and Ilumatobacter were increased significantly (P < 0.05). However, the growth of harmful bacteria such as Burkholderiaceae was inhibited in the vermicompost. In earthworm guts, the probiotic Mesorhizobium was promoted, while the pathogenic uncultured bacterium belonging to the family Enterobacteriaceae was reduced. Besides, B. subtilis enhanced the host relationships between bacteria and ARGs. These findings might be helpful in the removal of ARGs in animal wastes and in understanding the synergy between earthworms and microorganisms.

Polyamines in Ovarian Aging and Disease.

Ovarian aging and disease-related decline in fertility are challenging medical and economic issues with an increasing prevalence. Polyamines are a class of polycationic alkylamines widely distributed in mammals. They are small molecules essential for cell growth and development. Polyamines alleviate ovarian aging through various biological processes, including reproductive hormone synthesis, cell metabolism, programmed cell death, etc. However, an abnormal increase in polyamine levels can lead to ovarian damage and promote the development of ovarian disease. Therefore, polyamines have long been considered potential therapeutic targets for aging and disease, but their regulatory roles in the ovary deserve further investigation. This review discusses the mechanisms by which polyamines ameliorate human ovarian aging and disease through different biological processes, such as autophagy and oxidative stress, to develop safe and effective polyamine targeted therapy strategies for ovarian aging and the diseases.

Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins.

Spermidine is a naturally occurring polyamine compound that has many biological functions, such as inducing autophagy and anti-inflammatory and anti-aging effects. Spermidine can affect follicular development and thus protect ovarian function. In this study, ICR mice were fed exogenous spermidine drinking water for three months to explore the regulation of ovarian function by spermidine. The results showed that the number of atretic follicles in the ovaries of spermidine-treated mice was significantly lower than that in the control group. Antioxidant enzyme activities (SOD, CAT, T-AOC) significantly increased, and MDA levels significantly decreased. The expression of autophagy protein (Beclin 1 and microtubule-associated protein 1 light chain 3 LC3 II/I) significantly increased, and the expression of the polyubiquitin-binding protein p62/SQSTM 1 significantly decreased. Moreover, we found 424 differentially expressed proteins (DEPs) were upregulated, and 257 were downregulated using proteomic sequencing. Gene Ontology and KEGG analyses showed that these DEPs were mainly involved in lipid metabolism, oxidative metabolism and hormone production pathways. In conclusion, spermidine protects ovarian function by reducing the number of atresia follicles and regulating the level of autophagy protein, antioxidant enzyme activity, and polyamine metabolism in mice.

Lipid extract from blue mussel (Mytilus edulis) improves glycemic traits in Chinese type 2 diabetic mellitus patients: a double-blind randomized controlled trial.

BACKGROUND: Studies have shown that blue mussel lipid extract (BMLE) has strong anti-inflammatory activity in both rheumatoid arthritis patients and animal arthritis models. Chronic inflammation was closely related to type 2 diabetes mellitus (T2DM). Though the beneficial effects cannot be completely attributed to n-3 polyunsaturated fatty acids, the aim of this study was to investigate whether BMLE can improve glycemic traits of T2DM patients. METHOD: In a double-blind randomized controlled trial, 133 Chinese T2DM participants were randomized to either fish oil (FO, n = 44), BMLE (n = 44), or corn oil (CO, n = 45) groups for 60 days. The participants were asked to take the corresponding oil capsules (two capsules per day, 0.8 g per capsule), which provided 1.6 g day-1 of FO (29.9% eicosapentaenoic acid + 20.4% docosahexaenoic acid), BMLE (20.7% eicosapentaenoic acid + 26.7% docosahexaenoic acid), or CO (53.5% linoleic acid). RESULTS: The fasting serum concentration of insulin (P = 0.005) and the homeostasis model of insulin resistance (P = 0.026) were significantly decreased in the BMLE group, whereas no significant change was found in the FO or CO groups. There was no significant difference between groups on serum glycosylated hemoglobin. Tumor necrosis factor-α was significantly decreased in the BMLE group (P = 0.003), but not in the FO or CO groups. A significant decrease of interleukin-1ß was observed in the BMLE and CO groups (P = 0.004 and P = 0.011 respectively), but not in the FO group. The total cholesterol was significantly decreased in the BMLE and CO groups (P < 0.001 and P < 0.001 respectively), but not in the FO group. Triacylglycerol was significantly decreased in the BMLE group (P = 0.007), but not in the FO or CO groups. High-density lipoprotein cholesterol was significantly lower in the BMLE and CO groups than in the FO group (P = 0.003). CONCLUSION: Blue mussel lipid supplements improved glycemic traits, inflammatory cytokines, and lipids profile in Chinese T2DM patients (Chinese Clinical Trial Registration number: ChiCTR1900025617). © 2022 Society of Chemical Industry.

Farnesyl diphosphate synthase regulated endothelial proliferation and autophagy during rat pulmonary arterial hypertension induced by monocrotaline.

BACKGROUND: The proliferation ability and autophagy level of pulmonary artery endothelial cells (PAECs) play an important role in promoting the development of pulmonary artery hypertension (PAH), and there is still no effective treatment for PAH. Farnesyl diphosphate synthase (FDPS) is a key enzyme in the mevalonate pathway. The intermediate metabolites of this pathway are closely related to the activity of autophagy-associated small G proteins, including Ras-related C3 botulinum toxin substrate 1 (Rac1). Studies have shown that the mevalonate pathway affects the activation levels of different small G proteins, autophagy signaling pathways, vascular endothelial function, and so on. However, the exact relationship between them is still unclear in PAH. METHOD: In vitro, western blotting and mRFP-GFP-LC3 puncta formation assays were used to observe the expression of FDPS and the level of autophagy in PAECs treated with monocrotaline pyrrole (MCTP). In addition, cell proliferation and migration assays were used to assess the effect of FDPS on endothelial function, and Rac1 activity assays were used to evaluate the effect of Rac1 activation on PAEC autophagy via the PI3K/AKT/mTOR signaling pathway. In vivo, the right heart catheterization method, hematoxylin and eosin (H&E) staining and western blotting were used to determine the effect of FDPS on PAEC autophagy and monocrotaline (MCT)-induced PAH. RESULTS: We show that the expression of FDPS is increased in the PAH module in vitro and in vivo, concomitant with the induction of autophagy and the activation of Rac1. Our data demonstrate that inhibition of FDPS ameliorates endothelial function and decreases MCT-induced autophagy levels. Mechanistically, we found that FDPS promotes autophagy, Rac1 activity and endothelial disfunction through the PI3K/AKT/mTOR signaling pathway. CONCLUSION: Our study suggests that FDPS contributes to active small G protein-induced autophagy during MCT-induced PAH, which may serve as a potential therapeutic target against PAH.

Vitamin B12 status and folic acid/vitamin B12 related to the risk of gestational diabetes mellitus in pregnancy: a systematic review and meta-analysis of observational studies.

BACKGROUND: This review was conducted to investigate the association between serum vitamin B12 levels as well as folic acid/vitamin B12 during pregnancy and the risk of gestational diabetes mellitus (GDM). METHODS: A comprehensive search of electronic databases (Embase, PubMed, and Web of Science) was performed. The odds ratios (ORs) with 95% confidence intervals (CIs) of GDM risk were summarized using a random effects model. We also performed subgroup analyses to explore the source of heterogeneity. RESULTS: A total of 10 studies, including 10,595 pregnant women were assessed. Women with vitamin B12 deficiency were at higher risk for developing GDM when compared with those who were vitamin B12 sufficient (OR, 1.46; 95% CI 1.21-1.79; I2: 59.0%). Subgroup analysis indicated that this association might differ based on sample size and geographical distribution. Elevated vitamin B12 levels may decrease the risk of GDM by 23%. The role of excess folic acid and low vitamin B12 levels in the occurrence of GDM is also controversial. CONCLUSION: In summary, vitamin B12 deficiency is associated with increased risk of GDM, it is necessary to pay more attention to the balance of vitamin B12 and folic acid. However, more in-depth studies across multiple populations are needed to verify these results.

Swine wastewater treatment by combined process of iron carbon microelectrolysis-physical adsorption-microalgae cultivation.

Combined treatments were designed based on iron-carbon micro-electrolysis treatment (ICME), physical adsorption (PA) with zeolite (Z) or vermiculite (V) and microalgae cultivation (MC, Chlorella vulgaris) for removing pollutants from swine wastewater (SW): ICME + MC (IM), ICME + Z + MC (IZM) and ICME + V + MC (IVM). Results showed that the minimum total nitrogen (TN) of 43.66 mg L-1, NH4+-N of 1.33 mg-1 and total phosphorus (TP) of 0.14 mg-1 were obtained by IVM, while the minimum chemical oxygen demand (COD) was 105 mg-1 via IM. During the process of combined treatments, ICME contributed most to the removal of TN (84.52% by IZM), TP (97.78% by IVM and IZM) and COD (62.44% by IVM), and maximum NH4+-N removal (55.64%) was obtained by MC procedure in IM process. Vermiculite performed better than zeolite during all the combined treatments. Besides, the maximum cell dry weight (CDW, 0.74 g-1) of C. vulgaris was obtained by IM on day 13. The results provide an efficient integrated method for swine wastewater treatment.

Comparison of synchronization between left bundle branch and his bundle pacing in atrial fibrillation patients: An intra-patient-controlled study.

BACKGROUND: His bundle pacing (HBP) is a physiological pacing strategy to preserve the electrical synchrony of ventricular conduction and left ventricular (LV) function. Left bundle branch pacing (LBBP) has emerged as an alternative physiological pacing technique. OBJECTIVE: To evaluate cardiac electrical and mechanical synchrony comparing LBBP and HBP in patients with permanent atrial fibrillation (AF). METHODS: Consecutive patients with symptomatic bradycardia and AF were enrolled from January to June of 2019. The cardiac electrical and mechanical synchrony in different pacing mode were evaluated at baseline and after implantation. RESULTS: Both HBP and LBBP were performed in 20 patients. LBBP significantly widened the QRS duration compared with the intrinsic conduction (113.2 ± 14.5  vs. 96.5 ± 16.2 ms; p = .01), while HBP did not (104.5 ± 22.3  vs. 96.5 ± 16.2 ms; p = .12). Both LBBP and HBP patients had similar LV myocardial strain measurements for the mechanical synchrony evaluation without significant change compared with baseline. There was no significant difference in right ventricular synchrony measurement between LBBP and HBP. Compared to HBP, LBBP had less interventricular synchrony (IMVD, 14.7 ± 9.2  vs. 3.1 ± 12.7 ms, p < .01; Ts-LV-RV, 37.9 ± 10.7  vs. 18.5 ± 10.8 ms, p < .001). CONCLUSIONS: Although LBBP's a physiological pacing mode can achieve a similar cardiac electrical and mechanical synchronization when compared to HBP, LBBP results in modest delay in RV activation, and the clinical implication remains to be studied.

Profiling and Functional Analysis of Long Noncoding RNAs and mRNAs during Porcine Skeletal Muscle Development.

Gene transcripts or mRNAs and long noncoding RNAs (lncRNAs) are differentially expressed during porcine skeletal muscle development. However, only a few studies have been conducted on skeletal muscle transcriptome in pigs based on timepoints according to the growth curve for porcine. Here, we investigated gene expression in Qingyu pigs at three different growth stages: the inflection point with the maximum growth rate (MGI), the inflection point of the gradually increasing stage to the rapidly increasing stage (GRI), and the inflection point of the rapidly increasing stage to the slowly increasing stage (RSI). Subsequently, we explored gene expression profiles during muscle development at the MGI, GRI and RSI stages by Ribo-Zero RNA sequencing. Qingyu pigs reached the MGI, GRI and RSI stages at 156.40, 23.82 and 288.97 days of age with 51.73, 3.14 and 107.03 kg body weight, respectively. A total of 14,530 mRNAs and 11,970 lncRNAs were identified at the three stages, and 645, 323 differentially expressed genes (DEGs) and 696, 760 differentially expressed lncRNAs (DELs) were identified in the GRI vs. MGI, and RSI vs. MGI, comparisons. Functional enrichment analysis revealed that genes involved in immune system development and energy metabolism (mainly relate to amino acid, carbohydrate and lipid) were enriched at the GRI and MGI stages, respectively, whereas genes involved in lipid metabolism were enriched at the RSI stage. We further characterized G1430, an abundant lncRNA. The full-length sequence (316 nt) of lncRNA G1430 was determined by rapid amplification of cDNA ends (RACE). Subcellular distribution analysis by quantitative real-time PCR (qRT-PCR) revealed that G1430 is a cytoplasmic lncRNA. Binding site prediction and dual luciferase assay showed that lncRNA G1430 directly binds to microRNA 133a (miR-133a). Our findings provide the basis for further investigation of the regulatory mechanisms and molecular genetics of muscle development in pigs.

Natural occurrence of Alternaria mycotoxins in wheat and potential of reducing associated risks using magnolol.

BACKGROUND: Wheat is one of three major food crops in China. Alternaria species can cause spoilage of wheat with consequent mycotoxin accumulation. Alternariol (AOH), alternariol monomethyl ether (AME), and tenuazonic acid (TeA) are the most common and frequently studied mycotoxins. There are limited regulations placed on Alternaria mycotoxin concentrations worldwide due to the lack of toxicity data available. More data on the levels of mycotoxin contamination are also needed. It is also important to reduce the risks of Alternaria mycotoxins. RESULTS: One hundred and thirty-two wheat samples were collected from Hebei Province, China, and analyzed for AOH, AME, and TeA. Tenuazonic acid was found to be the predominant Alternaria mycotoxin, especially in flour samples. Studying Alternaria species that cause black-point disease of wheat indicated that Alternaria alternata and Alternaria tenuissima were the dominant species. Most of the Alternaria strains studied produced more than one mycotoxin and TeA was produced at the highest concentration, which may have resulted in the high level of TeA contamination in the wheat samples. Furthermore, magnolol displayed obvious antifungal and antimycotoxigenic activity against Alternaria. This is the first report on the antimycotoxigenic activity of magnolol against Alternaria species. CONCLUSION: The Alternaria mycotoxin contamination levels in wheat and wheat products from Hebei Province, China, were correlated with the toxigenic capacity of the Alternaria strains colonizing the wheat. Considering its safety, magnolol could be developed as a natural fungicide in wheat, or as a natural alternative food preservative based on its strong antifungal and antimycotoxigenic activity against Alternaria strains. © 2020 Society of Chemical Industry.

miR-10b-5p Regulates C2C12 Myoblasts Proliferation and Differentiation.

The development of skeletal muscle is a complex process including myoblasts proliferation and differentiation. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression at post-transcriptional level. Increasing evidences indicate that miRNAs are important regulators in myogenic processes. Here, we reported that the expression of miR-10b-5p steadily decreased during myoblasts proliferation, but significantly increased during myoblasts differentiation. The over-expression of miR-10b-5p promoted myoblasts proliferation and blunted myofiber formation in C2C12 cells, while miR-10b-5p down-regulation showed an opposite result. At the same time, we observed that the down-regulation of nuclear factor of activated T-cells 5 (NFAT5) repressed the differentiation of C2C12 cells, and interestingly, miR-10b-5p could suppress NFAT5 expression. Luciferase activity assays confirmed that miR-10b-5p directly target the 3'-untranslated region (3'-UTR) of NFAT5. Overall, we proposed here a novel insight that miR-10b-5p regulates the proliferation and differentiation of C2C12 myoblasts, and the impact on myogenic differentiation is partly through targeting NFAT5. Abbreviations: NFAT5: nuclear factor of activated T-cells 5; Cyclin B: cycle protein B; Cyclin D1: cycle protein D1; Cyclin E: cycle protein E; CDK4: cyclin-dependent kinase 4; MyoD: myogenic differentiation antigen; MyoG: myogenin; Myf5: myogenic factor 5; MRF4: myogenic regulatory factor 4; MyHC: myosin heavy chain; AQP5: aquaporin-5; CACNA1C: calcium voltage-gated channel subunit alpha1 C; SRF: serum response factor; Pax7: paired box 7; KLF4: Kruppel-like factor 4; 3'-UTR: 3'-untranslated region; GM: growth medium; DM: differentiation medium.

MicroRNA-451 and Genistein Ameliorate Nonalcoholic Steatohepatitis in Mice.

Effective, targeted therapy for chronic liver disease nonalcoholic steatohepatitis (NASH) is imminent. MicroRNAs (miRNAs) are a potential therapeutic target, and natural products that regulate miRNA expression may be a safe and effective treatment strategy for liver disease. Here, we investigated the functional role of miR-451 and the therapeutic effects of genistein in the NASH mouse model. MiR-451 was downregulated in various types of liver inflammation, and subsequent experiments showed that miR-451 regulates liver inflammation via IL1ß. Genistein is a phytoestrogen with anti-inflammatory and anti-oxidant effects. Interestingly, we found that the anti-inflammatory effects of genistein were related to miR-451 and was partially antagonized by the miR-451 inhibitor. MiR-451 overexpression or genistein treatment inhibited IL1ß expression and inflammation. Taken together, this study shows that miR-451 has a protective effect on hepatic inflammation, and genistein can be used as a natural promoter of miR-451 to ameliorate NASH.

Modulation of GSK-3ß/ß-Catenin Signaling Contributes to Learning and Memory Impairment in a Rat Model of Depression.

Background: It is widely accepted that cognitive processes, such as learning and memory, are affected in depression, but the molecular mechanisms underlying the interactions of these 2 disorders are not clearly understood. Recently, glycogen synthase kinase-3 beta (GSK-3ß)/ß-catenin signaling was shown to play an important role in the regulation of learning and memory. Methods: The present study used a rat model of depression, chronic unpredictable stress, to determine whether hippocampal GSK-3ß/ß-catenin signaling was involved in learning and memory alterations. Results: Our results demonstrated that chronic unpredictable stress had a dramatic influence on spatial cognitive performance in the Morris water maze task and reduced the phosphorylation of Ser9 of GSK-3ß as well as the total and nuclear levels of ß-catenin in the hippocampus. Inhibition of GSK3ß by SB216763 significantly ameliorated the cognitive deficits induced by chronic unpredictable stress, while overexpression of GSK3ß by AAV-mediated gene transfer significantly decreased cognitive performance in adult rats. In addition, chronic unpredictable stress exposure increased the expression of the canonical Wnt antagonist Dkk-1. Furthermore, chronic administration of corticosterone significantly increased Dkk-1 expression, decreased the phosphorylation of Ser9 of GSK-3ß, and resulted in the impairment of hippocampal learning and memory. Conclusions: Our results indicate that impairment of learning and memory in response to chronic unpredictable stress may be attributed to the dysfunction of GSK-3ß/ß-catenin signaling mediated by increased glucocorticoid signaling via Dkk-1.

Rationale and Design of the Evaluation of Oral Anticoagulation for Reduction of Thrombo-embolism in Chinese Patients with Device-Detected Subclinical Atrial Fibrillation (ART-CAF) Trial: an Open-Label Registry-Based Clinical Trial.

PURPOSE: Subclinical atrial fibrillation (AF) was found in a large number of pacemaker patients. It is not certain whether there is a similar risk/benefit ratio for oral anticoagulation in patients with subclinical AF compared to patients with similar risk profiles and clinically diagnosed AF. Given the weakness of clinical evidence for oral anticoagulation in patients with device-detected subclinical AF, specific recommendations in most guidelines for this population are scarce and rarely similar. METHODS: ART-CAF trial was primarily designed to evaluate the efficacy and safety of oral anticoagulant agent use in patients with device-detected subclinical AF at the approved dosage to prevent stroke and systemic arterial embolism. It is an open-label, registry-based, prospective, multicenter, cohort study, recruiting patients with subclinical AF first detected by a pacemaker, implantable cardioverter-defibrillator, or insertable cardiac monitor after device implantation for more than 3 months. The primary outcome is a composite of ischemic stroke and systemic arterial embolism. The primary safety outcome is the occurrence of clinically overt major bleeding. Approximately 750 patients will be needed to be enrolled to the two treatment groups in a 1:1 ratio until 66 primary efficacy outcomes are observed. The anticipated follow-up period is approximately 70 months from the enrollment of the first patient. CONCLUSIONS: ART-CAF evaluates the feasibility of selecting high-risk patients suitable for anticoagulation by AF burden combined with CHA2DS2-VASc score after pacemaker implantation and aims to select patients who could benefit from anticoagulation. TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx ChiCTR1800016221.

Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency in Sichuan, China.

BACKGROUND: Our goals were to screen newborns and characterize the occurrence of glucose-6-phosphate dehydrogenase (G6PD) deficiency in southwestern China. Meanwhile, we would like to analyze the factors that might affect the results of neonatal dried blood spots for glucose-6-phosphate dehydrogenase screening test, to improve the clinical quality control level, effectively reduce the external factors in the process of detection. METHODS: This study involved an evaluation of G6PD data for 20,644 newborns from a universal newborn screening program. Heel prick blood specimens were collected around 72 hours after birth and were dried on filter papers. For G6PD deficiency the fluorescent spot test was employed. We studied the association between incidence of G6PD deficiency and influence factors. RESULTS: This study involved an evaluation of G6PD data for 20,644 neonatal heel prick blood samples from 10,984 males and 9,660 females. There were 503 positive results for G6PD deficiency (299 males and 204 females), and the G6PD deficiency-positive rate was estimated to be around 2.4%. The gender-specific prevalence for males was 2.7%, and for females 2.1%. Multiple factors may influence the result of the G6PD test, such as season, temperature, and specimen of indwelling time. CONCLUSIONS: This study analyzed the prevalence of G6PD deficiency in Sichuan, China. Accelerating the speed of sample delivery and ensuring availability of screening results can aid the screening and diagnosis.

Structured Background Modeling for Hyperspectral Anomaly Detection.

Background modeling has been proven to be a promising method of hyperspectral anomaly detection. However, due to the cluttered imaging scene, modeling the background of an hyperspectral image (HSI) is often challenging. To mitigate this problem, we propose a novel structured background modeling-based hyperspectral anomaly detection method, which clearly improves the detection accuracy through exploiting the block-diagonal structure of the background. Specifically, to conveniently model the multi-mode characteristics of background, we divide the full-band patches in an HSI into different background clusters according to their spatial-spectral features. A spatial-spectral background dictionary is then learned for each cluster with a principal component analysis (PCA) learning scheme. When being represented onto those dictionaries, the background often exhibits a block-diagonal structure, while the anomalous target shows a sparse structure. In light of such an observation, we develop a low-rank representation based anomaly detection framework that can appropriately separate the sparse anomaly from the block-diagonal background. To optimize this framework effectively, we adopt the standard alternating direction method of multipliers (ADMM) algorithm. With extensive experiments on both synthetic and real-world datasets, the proposed method achieves an obvious improvement in detection accuracy, compared with several state-of-the-art hyperspectral anomaly detection methods.

MicroRNA-125a-5p Mediates 3T3-L1 Preadipocyte Proliferation and Differentiation.

Excessive accumulation of adipose tissue is a main cause of obesity or overweight, which is significantly involved in increasing the risk of diseases. Recently, numerous studies have proved that microRNAs (miRNAs) play important roles in adipogenesis by negatively regulating gene expression at posttranscriptional levels. In this study, we showed that miR-125a-5p was expressed at lower levels in the adipose tissues of high-fat diet (HFD)-fed mice than the normal chow (NCW)-fed mice. MiR-125a-5p expression were strongly up-regulated by nearly five-fold, when 3T3-L1 preadipocyte were induced and differentiated into mature adipocytes. Functional analysis indicated that overexpression of miR-125a-5p promoted 3T3-L1 preadipocyte proliferation and inhibited its differentiation. By contrast, inhibition of miR-125a-5p repressed 3T3-L1 preadipocyte proliferation and accelerated its differentiation. Furthermore, a dual-luciferase reporter assay demonstrated that signal transducer and activator of transcription 3 (STAT3) is a direct target gene of miR-125a-5p during 3T3-L1 preadipocyte differentiation. Further analysis confirmed that the process of miR-125a-5p inhibiting 3T3-L1 preadipocyte differentiation might be associated with the regulation of fatty acid metabolism related genes. Taken together, our results indicated that miR-125a-5p might promote 3T3-L1 preadipocyte proliferation, whereas inhibiting 3T3-L1 preadipocyte differentiation by negatively regulating STAT3.

Functional analysis of a viroid RNA motif mediating cell-to-cell movement in Nicotiana benthamiana.

Cell-to-cell trafficking through different cellular layers is a key process for various RNAs including those of plant viruses and viroids, but the regulatory mechanisms involved are still not fully elucidated and good model systems are important. Here, we analyse the function of a simple RNA motif (termed 'loop19') in potato spindle tuber viroid (PSTVd) which is required for trafficking in Nicotiana benthamiana leaves. Northern blotting, reverse transcriptase PCR (RT-PCR) and in situ hybridization analyses demonstrated that unlike wild-type PSTVd, which was present in the nuclei in all cell types, the trafficking-defective loop19 mutants were visible only in the nuclei of upper epidermal and palisade mesophyll cells, which shows that PSTVd loop19 plays a role in mediating RNA trafficking from palisade to spongy mesophyll cells in N.benthamiana leaves. Our findings and approaches have broad implications for studying the RNA motifs mediating trafficking of RNAs across specific cellular boundaries in other biological systems.