Exendin-4 ameliorates tau hyperphosphorylation and cognitive impairment in type 2 diabetes through acting on Wnt/ß-catenin/NeuroD1 pathway.

BACKGROUND: Type 2 diabetes (T2D) is an independent risk factor for Alzheimer's disease (AD). Exendin-4 (Ex-4), a widely used glucagon-like peptide-1 receptor agonist drug in the treatment of T2D, has been demonstrated the therapeutic effects on diabetic encephalopathy (DE). Especially, the Ex-4 ameliorates the tau hyperphosphorylation and cognitive impairment in DE. And these crucial alterations are also important bridge between T2D and AD. However, its unique mechanism is unclear. METHODS: The db/db mice, high-fat-diet (HFD) / streptozotocin (STZ)-induced diabetic (HF-diabetic) mice, and high-glucose-damaged (HGD) HT-22 hippocampal cells were enrolled to examine the effects of Ex-4 on AD-like changes in T2D. The Novel object recognition test (NORT) and Morris water maze test (MWMT) were conducted to evaluate the cognitive impairment. The Dickkopf-1 (DKK1) was employed to weaken the activation of the Wnt/ß-catenin pathway to explore the mechanism of Ex-4 in protecting the brain functions. The JASPAR was based to predict the interaction between NeuroD1 and the promoter region of Ins2. Moreover, the chromatin immunoprecipitation coupled with quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter assays were performed. RESULTS: Ex-4 alleviated the tau hyperphosphorylation, increased the brain-derived insulin, and improved the PI3K/AKT/GSK3-ß signalling in db/db mice, HF-diabetic mice, and HGD HT-22 hippocampal neuronal cells. The NORT and MWMT indicated that Ex-4 alleviated the learning and memory deficits in HF-diabetic mice. The inhibitor Dickkopf-1 (DKK1) of the Wnt/ß-catenin pathway significantly blocked the protective effects of Ex-4. Regarding further molecular mechanisms, NeuroD1 was affected by Ex-4 in vivo and in vitro, and the knockdown or overexpression of NeuroD1 suggested its crucial role in promoting the brain insulin by Ex-4. Meanwhile, the ChIP‒qPCR and luciferase reporter assays confirmed the combination between NeuroD1 and the promoter region of the insulin-encoding gene Ins2. And this interaction could be promoted by Ex-4. CONCLUSIONS: Our study proposes that Ex-4 alleviates tau hyperphosphorylation and cognitive dysfunction by increasing Ins2-derived brain insulin through the Wnt/ß-catenin/NeuroD1 signaling in T2D. And its also show new lights on part of the progress and mechanism on treatment targets for the DE in T2D.

Association of normal-weight central obesity with hypertension: a cross-sectional study from the China health and nutrition survey.

BACKGROUND: Central obesity is associated with an increased risk of hypertension in the general population. However, little is known regarding the potential relationship between central obesity and the risk of hypertension among adults with a normal body mass index (BMI). Our aim was to assess the risk of hypertension among individuals with normal weight central obesity (NWCO) in a large Chinese population. METHODS: We identified 10 719 individuals aged 18 years or older from the China Health and Nutrition Survey 2015. Hypertension was defined by blood pressure measurements, physician diagnosis, or the use of antihypertensive treatment. Multivariable logistic regression was used to assess the association of obesity patterns, defined by BMI, waist circumference (WC) and waist hip ratio (WHR), with hypertension after adjusting for confounding factors. RESULTS: The patients' mean age was 53.6 ± 14.5 years, and 54.2% were women. Compared with individuals with a normal BMI but no central obesity, subjects with NWCO had a greater risk of hypertension (WC: OR, 1.49, 95% CI 1.14-1.95; WHR: OR, 1.33, 95% CI 1.08-1.65). Overweight-obese subjects with central obesity demonstrated the highest risk of hypertension after adjustment for potential confounders (WC: OR, 3.01, 95% CI 2.59-3.49; WHR: OR, 3.08, CI 2.6-3.65). Subgroup analyses showed that the combination of BMI with WC had similar findings to the overall population except for female and nonsmoking persons; when BMI was combined with WHR, a significant association of NWCO with hypertension was observed only in younger persons and nondrinkers. CONCLUSIONS: Central obesity, as defined by WC or WHR, is associated with an increased risk of hypertension in Chinese adults with normal BMI, highlighting the need to combine measures in obesity-related risk assessment.

Inorganic-Organic Hybrid Phototransistor Array with Enhanced Photogating Effect for Dynamic Near-Infrared Light Sensing and Image Preprocessing.

Narrow-band-gap organic semiconductors have emerged as appealing near-infrared (NIR) sensing materials by virtue of their unique optoelectronic properties. However, their limited carrier mobility impedes the implementation of large-area, dynamic NIR sensor arrays. In this work, high-performance inorganic-organic hybrid phototransistor arrays are achieved for NIR sensing, by taking advantage of the high electron mobility of In2O3 and the strong NIR absorption of a BTPV-4F:PTB7-Th bulk heterojunction (BHJ) with an enhanced photogating effect. As a result, the hybrid phototransistors reach a high responsivity of 1393.0 A W-1, a high specific detectivity of 4.8 × 1012 jones, and a fast response of 0.72 ms to NIR light (900 nm). Meanwhile, an integrated 16 × 16 phototransistor array with a one-transistor-one-phototransistor (1T1PT) architecture is achieved. On the basis of the enhanced photogating effect, the phototransistor array can not only achieve real-time, dynamic NIR light mapping but also implement image preprocessing, which is promising for advanced NIR image sensors.

Histological analysis for pulp mineralisation after severe intrusive luxation of immature molars in rats.

BACKGROUND/AIM: Pulp mineralisation is a survival process that may occur in the pulp of immature teeth following trauma. However, the mechanism of this process remains unclear. The aim of this study was to evaluate the histological manifestations of pulp mineralisation after intrusion in immature molars of rats. MATERIALS AND METHODS: Three-week-old male Sprague-Dawley rats were subjected to intrusive luxation of the right maxillary second molar by an impact force from a striking instrument through a metal force transfer rod. The left maxillary second molar of each rat was used as a control. The control and injured maxillae were collected at 3, 7, 10, 14, and 30 days after trauma (n = 15 per time group) and evaluated using haematoxylin and eosin staining and immunohistochemistry. Independent two-tailed Student's t-test was used for statistical comparison of the immunoreactive area. RESULTS: Pulp atrophy and mineralisation were observed in 30%-40% of the animals, and no pulp necrosis occurred. Ten days after trauma, pulp mineralisation, with osteoid tissue rather than reparative dentin, formed around the newly vascularised areas in the coronal pulp. CD90-immunoreactive cells were observed in the sub-odontoblastic multicellular layer in control molars, whereas the number of these cells was decreased in the traumatised teeth. CD105 localised in cells around the pulp osteoid tissue of the traumatised teeth, whereas in control teeth, it was only expressed in the vascular endothelial cells of capillaries in the odontoblastic or sub-odontoblastic layers. In specimens with pulp atrophy at 3-10 days after trauma, hypoxia inducible factor expression and CD11b-immunoreactive inflammatory cells increased. CONCLUSIONS: Following intrusive luxation of immature teeth without crown fractures in rats, no pulp necrosis occurred. Instead, pulp atrophy and osteogenesis around neovascularisation with activated CD105-immunoreactive cells were observed in the coronal pulp microenvironment characterised by hypoxia and inflammation.

Highly Linear and Symmetric Synaptic Memtransistors Based on Polarization Switching in Two-Dimensional Ferroelectric Semiconductors.

Brain-inspired neuromorphic computing hardware based on artificial synapses offers efficient solutions to perform computational tasks. However, the nonlinearity and asymmetry of synaptic weight updates in reported artificial synapses have impeded achieving high accuracy in neural networks. Here, this work develops a synaptic memtransistor based on polarization switching in a two-dimensional (2D) ferroelectric semiconductor (FES) of α-In2 Se3 for neuromorphic computing. The α-In2 Se3 memtransistor exhibits outstanding synaptic characteristics, including near-ideal linearity and symmetry and a large number of programmable conductance states, by taking the advantages of both memtransistor configuration and electrically configurable polarization states in the FES channel. As a result, the α-In2 Se3 memtransistor-type synapse reaches high accuracy of 97.76% for digit patterns recognition task in simulated artificial neural networks. This work opens new opportunities for using multiterminal FES memtransistors in advanced neuromorphic electronics.

Sirtuin 2 Prevents Liver Steatosis and Metabolic Disorders by Deacetylation of Hepatocyte Nuclear Factor 4α.

BACKGROUND AND AIMS: Sirtuin 2 (SIRT2), an NAD+ -dependent deacetylase, is involved in various cellular processes regulating metabolic homeostasis and inflammatory responses; however, its role in hepatic steatosis and related metabolic disorders is unknown. APPROACH AND RESULTS: Integrating the published genomic data on NAFLD samples from humans and rodents available in the Gene Expression Omnibus, we found that SIRT2 was significantly down-regulated in livers from patients with advanced NAFLD and high-fat diet (HFD)-induced NAFLD mice. This study further revealed that SIRT2 was markedly decreased in obese (ob/ob) mice and in palmitate-treated HepG2 cells. Restoration of hepatic SIRT2 expression in ob/ob or HFD-fed mice largely alleviated insulin resistance, hepatic steatosis, and systematic inflammation, whereas SIRT2 liver-specific ablation exacerbated these metabolic dysfunctions in HFD-fed C57BL/6J mice. Mechanistically, SIRT2 stabilized the hepatocyte nuclear factor 4α (HNF4α) protein by binding to and deacetylating HNF4α on lysine 458. Furthermore, HNF4α was sufficient to mediate SIRT2 function, and SIRT2-HNF4α interaction was required for SIRT2 function both in vivo and in vitro. CONCLUSIONS: Collectively, the present study provided evidence that SIRT2 functions as a crucial negative regulator in NAFLD and related metabolic disorders and that targeting the SIRT2-HNF4α pathway may be a promising strategy for NAFLD treatment.

Integrated Transcriptome and Targeted Metabolite Analysis Reveal miRNA-mRNA Networks in Low-Light-Induced Lotus Flower Bud Abortion.

Most Nelumbo nucifera (lotus) flower buds were aborted during the growing season, notably in low-light environments. How lotus produces so many aborted flower buds is largely unknown. An integrated transcriptome and targeted metabolite analysis was performed to reveal the genetic regulatory networks underlying lotus flower bud abortion. A total of 233 miRNAs and 25,351 genes were identified in lotus flower buds, including 68 novel miRNAs and 1108 novel genes. Further enrichment analysis indicated that sugar signaling plays a potential central role in regulating lotus flower bud abortion. Targeted metabolite analysis showed that trehalose levels declined the most in the aborting flower buds. A potential regulatory network centered on miR156 governs lotus flower bud abortion, involving multiple miRNA-mRNA pairs related to cell integrity, cell proliferation and expansion, and DNA repair. Genetic analysis showed that miRNA156-5p-overexpressing lotus showed aggravated flower bud abortion phenotypes. Trehalose-6-P synthase 1 (TPS1), which is required for trehalose synthase, had a negative regulatory effect on miR156 expression. TPS1-overexpression lotus showed significantly decreased flower bud abortion rates both in normal-light and low-light environments. Our study establishes a possible genetic basis for how lotus produces so many aborted flower buds, facilitating genetic improvement of lotus' shade tolerance.

Association of the insulin resistance marker TyG index with the severity and mortality of COVID-19.

BACKGROUND: The triglyceride and glucose index (TyG) has been proposed as a marker of insulin resistance. This study aims to evaluate the association of the TyG index with the severity and mortality of coronavirus disease 2019 (COVID-19). METHODS: The study included a cohort of 151 patients with COVID-19 admitted in a tertiary teaching hospital in Wuhan. Regression models were used to investigate the association between TyG with severity and mortality of COVID-19. RESULTS: In this cohort, 39 (25.8%) patients had diabetes, 62 (41.1%) patients were severe cases, while 33 (22.0%) patients died in hospital. The TyG index levels were significantly higher in the severe cases and death group (mild vs. severe 8.7 ± 0.6 vs. 9.2 ± 0.6, P < 0.001; survivor vs. deceased 8.8 ± 0.6 vs. 9.3 ± 0.7, P < 0.001), respectively. The TyG index was significantly associated with an increased risk of severe case and mortality, after controlling for potential confounders (OR for severe case, 2.9, 95% CI 1.2-6.3, P = 0.007; OR for mortality, 2.9, 95% CI 1.2-6.7, P = 0.016). The associations were not statistically significant for further adjustment of inflammatory factors. CONCLUSION: TyG index was closely associated with the severity and morbidity in COVID-19 patients, thus it may be a valuable marker for identifying poor outcome of COVID-19.

CLINICAL CHARACTERISTICS OF 28 PATIENTS WITH DIABETES AND COVID-19 IN WUHAN, CHINA.

Objective: Previous studies on coronavirus disease 2019 (COVID-19) were based on information from the general population. We aimed to further clarify the clinical characteristics of diabetes with COVID-19. Methods: Twenty-eight patients with diabetes and COVID-19 were enrolled from January 29, 2020, to February 10, 2020, with a final follow-up on February 22, 2020. Epidemiologic, demographic, clinical, laboratory, treatment, and outcome data were analyzed. Results: The average age of the 28 patients was 68.6 ± 9.0 years. Most (75%) patients were male. Only 39.3% of the patients had a clear exposure of COVID-19. Fever (92.9%), dry cough (82.1%), and fatigue (64.3%) were the most common symptoms, followed by dyspnea (57.1%), anorexia (57.1%), diarrhea (42.9%), expectoration (25.0%), and nausea (21.4%). Fourteen patients were admitted to the intensive care unit (ICU). The hemoglobin A1c level was similar between ICU and non-ICU patients. ICU patients had a higher respiratory rate, higher levels of random blood glucose, aspartate transaminase, bilirubin, creatine, N-terminal prohormone of brain natriuretic peptide, troponin I, D-dimers, procalcitonin, C-reactive protein, ferritin, interleukin (IL)-2R, IL-6, and IL-8 than non-ICU patients. Eleven of 14 ICU patients received noninvasive ventilation and 7 patients received invasive mechanical ventilation. Twelve patients died in the ICU group and no patients died in the non-ICU group. Conclusion: ICU cases showed higher rates of organ failure and mortality than non-ICU cases. The poor outcomes of patients with diabetes and COVID-19 indicated that more supervision is required in these patients. Abbreviations: COVID-19 = coronavirus disease 2019; ICU = intensive care unit; MERS-CoV = middle East respiratory syndrome-related coronavirus; 2019- nCoV = 2019 novel coronavirus; NT-proBNP = N-terminal prohormone of brain natriuretic peptide; SARS-CoV = severe acute respiratory syndrome-related coronavirus.

Associations of iron status with apolipoproteins and lipid ratios: a cross-sectional study from the China Health and Nutrition Survey.

BACKGROUND: Iron overload has been found to be related with various cardiometabolic disorders, like dyslipidemia, metabolic syndrome, and diabetes. The disturbance of the iron status and lipid metabolism can contribute to organ damage such as atherosclerotic plaque growth and instability. An assessment on the associations of iron status with apolipoproteins and lipid ratios would be informative for maintenance of metabolic homeostasis and hinderance of disease progression. Hence, this study aims to establish the relationships of iron status with apolipoproteins and lipid ratios. METHODS: A cross-sectional study of 7540 adult participants from the China Health and Nutrition Survey 2009 was conducted. Logistic regression analyses were used to investigate the relationships between indicators of iron status and the prevalence of unfavorable apolipoprotein profiles. Multivariate linear regression models were constructed to assess the dose-response correlations between serum ferritin and lipid parameters. RESULTS: After adjustment for confounding factors, in both sexes, the subjects in the top quartile of ferritin had the highest prevalence of an elevated apolipoprotein B (men: odds ratio (OR) 1.97, 95% confidence interval (CI) 1.50-2.62; women: OR 2.13, 95% CI 1.53-2.97) and an elevated apolipoprotein B/apolipoprotein A1 ratio (men: OR 2.00, 95% CI 1.50-2.66; women: OR 1.41, 95% CI 1.04-1.92) when compared with individuals in the lowest quartile. Hemoglobin were also independently associated with unfavorable apolipoprotein B and apolipoprotein B/apolipoprotein A1 ratio both in men and women. However, transferrin (men: OR 0.74, 95% CI 0.56-0.99; women: OR 0.73, 95% CI 0.56-0.95) and soluble transferrin receptor (men: OR 0.75, 95% CI 0.57-0.99; women: OR 0.71, 95% CI 0.55-0.91) were found to be negatively associated with a decreased apolipoprotein A1. Moreover, after controlling for potential confounders, the ferritin concentrations were significantly associated with the levels of lipid ratios including TG/HDL-C, non-HDL-C/HDL-C, TC/HDL-C, apoB/apoA1, and LDL-C/HDL-C ratio in men (ß coefficient = 0.147, 0.061, 0.043, 0.038, 0.032, respectively, all P values < 0.001) and in women (ß coefficient = 0.074, 0.034, 0.025, 0.020, 0.018, respectively, all P values < 0.05). CONCLUSIONS: The indicators of iron status are significantly associated with unfavorable apolipoprotein profiles. Serum ferritin concentrations are positively correlated with the levels of lipid ratios. The management on the modifiable iron status and lipid metabolism has a clinical significance. The atherosclerotic lipid profiles of the patients with iron overload deserve special clinical concerns.

Predicting blood pressure from physiological index data using the SVR algorithm.

BACKGROUND: Blood pressure diseases have increasingly been identified as among the main factors threatening human health. How to accurately and conveniently measure blood pressure is the key to the implementation of effective prevention and control measures for blood pressure diseases. Traditional blood pressure measurement methods exhibit many inherent disadvantages, for example, the time needed for each measurement is difficult to determine, continuous measurement causes discomfort, and the measurement process is relatively cumbersome. Wearable devices that enable continuous measurement of blood pressure provide new opportunities and hopes. Although machine learning methods for blood pressure prediction have been studied, the accuracy of the results does not satisfy the needs of practical applications. RESULTS: This paper proposes an efficient blood pressure prediction method based on the support vector machine regression (SVR) algorithm to solve the key gap between the need for continuous measurement for prophylaxis and the lack of an effective method for continuous measurement. The results of the algorithm were compared with those obtained from two classical machine learning algorithms, i.e., linear regression (LinearR), back propagation neural network (BP), with respect to six evaluation indexes (accuracy, pass rate, mean absolute percentage error (MAPE), mean absolute error (MAE), R-squared coefficient of determination (R2) and Spearman's rank correlation coefficient). The experimental results showed that the SVR model can accurately and effectively predict blood pressure. CONCLUSION: The multi-feature joint training and predicting techniques in machine learning can potentially complement and greatly improve the accuracy of traditional blood pressure measurement, resulting in better disease classification and more accurate clinical judgements.

Annexin A8 (ANXA8) regulates proliferation of porcine endometrial cells via Akt signalling pathway.

Annexin A8 (ANXA8) gene, a member of the annexin family, encodes an anticoagulant protein involved in blood coagulation cascade and acts as an indirect inhibitor of the thromboplastin-specific complex. However, little is known about the function of ANXA8 in porcine endometrial cells so far. Here, ANXA8 mRNA was found to be abundant in porcine endometrium on days 11-13 of pregnancy. Real-time RT-PCR analysis indicated that the mRNA expression of the leukaemia inhibitory factor (LIF) and the epidermal growth factor (EGF) was upregulated by ANXA8 in porcine endometrial cells. Immunofluorescence technology and cell cycle analysis revealed that ANXA8 promoted the proliferation of endometrial cells, as evidenced by the abundant proliferating cell nuclear antigen (PCNA) expression and an increase in the S phase. Western blot analysis results indicated that ANXA8 activated the phosphorylation of the target protein kinase B (Akt) protein. Immunofluorescence technology results showed that the PCNA protein had no significant change in porcine endometrial cells with both ANXA8 overexpression and the addition of Akt inhibitor. Furthermore, the number of implantation sites was significantly reduced by injection of mus-siRNA-ANXA8 into the uterine horn of mice. Collectively, these results suggest that ANXA8 promotes the proliferation of endometrial cells through the Akt signalling pathway.

An easy-to-use wound dressing gelatin-bioactive nanoparticle gel and its preliminary in vivo study.

Beyond promoting hard tissue repairing, bioactive glasses (BGs) have also been proved to be beneficial for wound healing. Nano-scale BGs prepared by sol-gel method were found to have a better performance as they have a larger specific surface area. In this work, bioactive nanoparticles (nBPs) with mean diameter of 12 nm (BP-12) instead of conventional BGs were mixed with gelatin to form an easy-to-use hydrogel as a dressing for skin wound. It was found that the composite of BP-12 and gelatin could form a hydrogel (BP-12/Gel) under 25 °C, which showed pronounced thixotropy at a practically accessible shear rate, therefore become easy to be used for wound cover. In vitro, the composite hydrogel of BP-12 and gelatin had good biocompatibility with the fibroblast cells. In vivo, rapid cutaneous-tissue regeneration and tissue-structure formation within 7 days was observed in the wound-healing experiment performed in rats. This hydrogel is thus a promising easy-to-use wound dressing material.

Effects of Cerium Oxide Nanoparticles on the Proliferation, Osteogenic Differentiation and Adipogenic Differentiation of Primary Mouse Bone Marrow Stromal Cells In Vitro.

The effects of cerium oxide nanoparticles (nanoceria) on the proliferation, osteogenic and adipogenic differentiation of primary mouse bone marrow stromal cells (BMSCs) were studied by employing 3-(4,5-dimethylthiazol-2-yl)-2,5-dipheny tetrazolium bromide (MTT), alkaline phosphatase (ALP) activity, collagen production, alizarin red-S (ARS) and oil red o stain assays. The results indicated that nanoceria increased the viability of BMSCs at all tested concentrations with evident dose dependence for 24 and 72 h. On day 14, nanoceria inhibited the osteogenic differentiation of BMSCs at all tested concentrations. On day 19 and 24, nanoceria inhibited the formation of mineralized matrix nodules of BMSCs at all tested concentrations. On day 17, nanoceria inhibited the adipogenic differentiation of BMSCs at all tested concentrations. This suggests that the effects of nanoceria on the proliferation, osteogenic differentiation and adipogenic differentiation of BMSCs are very complicated. Both the concentration and culture time have significant influence on the proliferation, osteogenic differentiation and adipogenic differentiation of BMSCs. These results will be helpful for rational applications of nanoceria in the future.

Microbacterium hydrothermale sp. nov., an actinobacterium isolated from hydrothermal sediment.

A Gram-stain-positive, aerobic, non-motile, rod-shaped bacterium, strain 0704C9-2(T), was isolated from hydrothermal sediment of the Indian Ocean. The organism grew with 0-5% (w/v) NaCl and at 10-37 °C, with optimal growth occurring with 1% NaCl and at 28-30 °C. Comparative 16S rRNA gene sequence analysis revealed that strain 0704C9-2(T) belonged to the genus Microbacterium. It exhibited highest 16S rRNA gene sequence similarity with Microbacterium testaceum DSM 20166(T) (98.4%). Levels of similarity with the type strains of all other recognized species of the genus Microbacterium were less than 98.0%. DNA-DNA hybridization experiments with strain 0704C9-2(T) and its closest relative, M. testaceum DSM 20166(T), revealed a low reassociation value of 42.9%. The DNA G+C content of strain 0704C9-2(T) was 73.3 mol%. The cell-wall peptidoglycan contained ornithine and the acyl type was glycolyl. The major whole-cell sugars were mannose, galactose, rhamnose and glucose. The major cellular fatty acids were anteiso-C15:0, anteiso-C17:0, iso-C16:0 and iso-C15:0. The predominant menaquinones were MK-11, MK-10 and MK-12. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unknown glycolipids and an unknown phospholipid. On the basis of phenotypic, phylogenetic and genotypic data, strain 0704C9-2(T) represents a novel species within the genus Microbacterium, for which the name Microbacterium hydrothermale sp. nov. is proposed. The type strain is 0704C9-2(T) ( = LMG 27542(T) = CGMCC 1.12512(T)).

Janibacter indicus sp. nov., isolated from hydrothermal sediment of the Indian Ocean.

A Gram-staining-positive, aerobic and non-motile strain, 0704P10-1(T), was isolated from hydrothermal sediment of the Indian Ocean. Phylogenetic, phenotypic and chemotaxonomic data for the organism supported that it belonged to the genus Janibacter. Strain 0704P10-1(T) showed 97.2-98.7% 16S rRNA gene sequence similarities to the type strains of recognized members of the genus Janibacter. It contained meso-diaminopimelic acid as the diagnostic diamino acid in the cell wall. MK-8(H4) was the only menaquinone detected. The major fatty acids were iso-C16 : 0, C17 : 1ω8c and 10-methyl C17 : 0. Meanwhile, the results of DNA-DNA hybridization studies and other physiological and biochemical tests allowed the genotypic and phenotypic differentiation of strain 0704P10-1(T) from closely related species. Thus, strain 0704P10-1(T) represents a novel species of the genus Janibacter, for which the name Janibacter indicus sp. nov. is proposed. The type strain is 0704P10-1(T) ( = LMG 27493(T) = CGMCC 1.12511(T)).

Sporosarcina siberiensis sp. nov., isolated from the East Siberian Sea.

A Gram-stain positive, non-motile, rod-shaped bacterium, designated strain 1111S-42(T), was isolated from the East Siberian Sea. The organism was found to grow at 4-30 °C, pH 7.0-8.5 and in 0-8 % (w/v) NaCl, with optimal growth occurring at 28 °C, pH 7.5 and in 1 % NaCl. Based on 16S rRNA gene sequence similarity studies, strain 1111S-42(T) was found to belong to the genus Sporosarcina and to be most closely related to Sporosarcina contaminans CCUG53915(T) (97.3 %) and Sporosarcina soli I80(T) (97.2 %). The main polar lipids were found to include diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The predominant menaquinone was identified as MK-7. The major cellular fatty acids were identified as anteiso-C15:0 (34.4 %), iso-C15:0 (29.8 %) and anteiso-C17:0 (22.4 %). The DNA G+C content of strain 1111S-42(T) was determined to be 39 mol %. The values of DNA-DNA relatedness between the strain 1111S-42(T) and related type strains of the genus Sporosarcina were less than 30 %. Based on the phylogenetic analysis, along with extensive physiological and chemotaxonomic testing, we conclude that the bacterium represents a novel species of the genus Sporosarcina, for which the name Sporosarcina siberiensis sp. nov. is proposed. The type strain is strain 1111S-42(T) (=CGMCC 1.12516(T) = LMG 27494(T)).

NOTUM plays a bidirectionally modulatory role in the odontoblastic differentiation of human stem cells from the apical papilla through the WNT/ß-catenin signaling pathway.

OBJECTIVE: Notum is a secreted deacylase, which is crucial for tooth dentin development in mice. This study aimed to investigate the effect of NOTUM on the odontoblastic differentiation of human stem cells from the apical papilla (hSCAPs), to reveal the potential value of NOTUM in pulp-dentin complex regeneration. DESIGN: The expression pattern of NOTUM in human tooth germs and during in vitro odontoblastic differentiation of hSCAPs was evaluated by immunohistochemical staining, and quantitative polymerase chain reaction, respectively. To manipulate the extracellular NOTUM level, ABC99 or small interfering RNA was used to down-regulate it, while recombinant NOTUM protein was added to up-regulate it. The effects of changing NOTUM level on the odontoblastic differentiation of hSCAPs and its interaction with the WNT/ß-catenin signaling pathway were studied using alkaline phosphatase staining, alizarin red staining, quantitative polymerase chain reaction, and western blot. RESULTS: NOTUM was observed in the apical papilla of human tooth germs. During in vitro odontoblastic differentiation of hSCAPs, NOTUM expression initially increased, while the WNT/ß-catenin pathway was activated. Downregulation of NOTUM hindered odontoblastic differentiation. Recombinant NOTUM protein had varying effects on odontoblastic differentiation depending on exposure duration. Continuous addition of the protein inhibited both odontoblastic differentiation and the WNT/ß-catenin pathway. However, applying the protein solely in the first 3 days enhanced odontoblastic differentiation and up-regulated the WNT/ß-catenin pathway. CONCLUSION: NOTUM demonstrated a bidirectional impact on in vitro odontoblastic differentiation of hSCAPs, potentially mediated by the WNT/ß-catenin pathway. These findings suggest its promising potential for pulp-dentin complex regeneration.

TRIB2-Mediated Modulation of AMPK Promotes Hepatic Insulin Resistance.

Insulin resistance and its linked health complications are increasing in prevalence. Recent work has caused the role of Tribbles2 (TRIB2) in metabolism and cellular signaling to be increasingly appreciated, but its role in the progression of insulin resistance has not been elucidated. Here, we explore the functions of TRIB2 in modulating insulin resistance and the mechanism involved in insulin-resistant mice and palmitic acid-treated HepG2 cells. We demonstrate that whole-body knockout and hepatic-specific TRIB2 deficiency protect against diet-induced insulin resistance, inflammation, and endoplasmic reticulum stress. Accordingly, upregulation of TRIB2 in the liver aggravates these metabolic disturbances in high-fat diet-induced mice and ob/ob mice. Mechanistically, TRIB2 directly binds to the αγ-SBS domain of PRKAB through its pseudokinase domain, subsequently inhibiting the formation and activity of the AMPK complex. Moreover, the results of intervention against AMPK suggest that the effects of TRIB2 depend on AMPK. Our findings reveal that TRIB2 is a novel target for the treatment of insulin resistance and its associated metabolic complications and clarify the function of TRIB2 as a regulatory component of AMPK activity.