One of the basic questions in the aging field is whether there is a fundamental difference between the aging of lower invertebrates and mammals. A major difference between the lower invertebrates and mammals is the abundancy of noncoding RNAs, most of which are not conserved. We have previously identified a noncoding RNA Terc-53 that is derived from the RNA component of telomerase Terc. To study its physiological functions, we generated two transgenic mouse models overexpressing the RNA in wild-type and early-aging Terc-/- backgrounds. Terc-53 mice showed age-related cognition decline and shortened life span, even though no developmental defects or physiological abnormality at an early age was observed, indicating its involvement in normal aging of mammals. Subsequent mechanistic study identified hyaluronan-mediated motility receptor (Hmmr) as the main effector of Terc-53. Terc-53 mediates the degradation of Hmmr, leading to an increase of inflammation in the affected tissues, accelerating organismal aging. adeno-associated virus delivered supplementation of Hmmr in the hippocampus reversed the cognition decline in Terc-53 transgenic mice. Neither Terc-53 nor Hmmr has homologs in C. elegans. Neither do arthropods express hyaluronan. These findings demonstrate the complexity of aging in mammals and open new paths for exploring noncoding RNA and Hmmr as means of treating age-related physical debilities and improving healthspan.
Animals ; Mice ; RNA, Untranslated/metabolism* ; Aging/genetics* ; Mice, Transgenic ; Telomerase/metabolism* ; RNA/genetics* ; Hippocampus/metabolism* ; Humans ; Mice, Inbred C57BL

BACKGROUND: Islet transplantation is currently considered the most promising method for treating insulin-dependent diabetes. The two most-studied artificial islets are alginate-encapsulated b cells or b cell spheroids. As three-dimensional (3D) models, both artificial islets have better insulin secretory functions and transplantation efficiencies than cells in twodimensional (2D) monolayer culture. However, the effects of these two methods have not been compared yet. Therefore, in this study, cells from the mouse islet b cell line Min6 were constructed as scaffold-free spheroids or alginate-encapsulated dispersed cells. METHODS: MIN6 cell spheroids were prepared by using Agarose-base microwell arrays. The insulin secretion level was determined by mouse insulin ELISA kit, and the gene and protein expression status of the MIN6 were performed by Quantitative polymerase chain reaction and immunoblot, respectively. RESULTS: Both 3D cultures effectively promoted the proliferation and glucose-stimulated insulin release (GSIS) of MIN6 cells compared to 2D adherent cells. Furthermore, 1% alginate-encapsulated MIN6 cells demonstrated more significant effects than the spheroids. In general, three pancreatic genes were expressed at higher levels in response to the 3D culture than to the 2D culture, and pancreatic/duodenal homeobox-1 (PDX1) expression was higher in the cells encapsulated in 1% alginate than that in the spheroids. A western blot analysis showed that 1% alginate-encapsulated MIN6 cells activated the phosphoinositide 3-kinase (PI3K)/serine/threonine protein kinase (AKT)/forkhead transcription factor FKHR (FoxO1) pathway more than the spheroids, 0.5% alginate-, or 2% alginate-encapsulated cells did. The 3D MIN6 culture, therefore, showed improved effects compared to the 2D culture, and the 1% alginate-encapsulated MIN6 cells exhibited better effects than the spheroids. The upregulation of PDX1 expression through the activation of the PI3K/AKT/FoxO1 pathway may mediate the improved cell proliferation and GSIS in 1% alginate-encapsulated MIN6 cells. CONCLUSION This study may contribute to the construction of in vitro culture systems for pancreatic islets to meet clinical requirements.

Protein nitration and nitrosylation are essential post-translational modifications (PTMs) involved in many fundamental cellular processes. Recent studies have revealed that excessive levels of nitration and nitrosylation in some critical proteins are linked to numerous chronic diseases. Therefore, the identification of substrates that undergo such modifications in a site-specific manner is an important research topic in the community and will provide candidates for targeted therapy. In this study, we aimed to develop a computational tool for predicting nitration and nitrosylation sites in proteins. We first constructed four types of encoding features, including positional amino acid distributions, sequence contextual dependencies, physicochemical properties, and position-specific scoring features, to represent the modified residues. Based on these encoding features, we established a predictor called DeepNitro using deep learning methods for predicting protein nitration and nitrosylation. Using n-fold cross-validation, our evaluation shows great AUC values for DeepNitro, 0.65 for tyrosine nitration, 0.80 for tryptophan nitration, and 0.70 for cysteine nitrosylation, respectively, demonstrating the robustness and reliability of our tool. Also, when tested in the independent dataset, DeepNitro is substantially superior to other similar tools with a 7%-42% improvement in the prediction performance. Taken together, the application of deep learning method and novel encoding schemes, especially the position-specific scoring feature, greatly improves the accuracy of nitration and nitrosylation site prediction and may facilitate the prediction of other PTM sites. DeepNitro is implemented in JAVA and PHP and is freely available for academic research at http://deepnitro.renlab.org.
Amino Acid Sequence ; Amino Acids ; metabolism ; Deep Learning ; Humans ; Internet ; Neural Networks (Computer) ; Nitrosation ; Proteins ; chemistry ; metabolism ; Reproducibility of Results ; Software

Objective To investigate the advantages of glucocorticoid combined with traditional meth-ods and to explore glucocorticoid use in appropriate time in the whole course of the disease and the appropriate dose.Methods With reference to Kawasaki disease(KD)diagnostic criteria,363 cases of patients with KD were enrolled,and divided into conventional treatment group and combined hormone group randomly. Combined hormone group according to clinical manifestations can be divided into sub groups as typical KD and atypical KD group. We analyzed respectively before and after 1 week treatment in two groups of children with the onset of age,gender,heating duration after treatment, IVIG treatment time, hospitalization days and total hospitalization expenses,tips and course of acute stage,recovery period the relevant indexes to the test,and coronary artery le-sion( CAL) in one month. Results Thermal process after treatment,hospitalization duration and hospitalization expenses decreased significantly in combined hormone group compared with conventional treatment group. The difference between the two,in the clinical laboratory indexes and CAL have no obvious difference. In different types of KD, the thermal process after treatment, hospitalization days and hospitalization expenses, have de-creased significantly in typical KD sub group when treating with combined hormone therapy comparing with hor-mone therapy atypical sub group. Other clinical laboratory indexes and CAL have no obvious differences in com-pared between the sub groups. Conclusion Combined hormone therapy for KD patients,plays an important role in shortening the thermal process after treatment and reducing the hospitalization expense.

OBJECTIVETo explore the value of electronic data capture (EDC) system in large-sample size studies on Kawasaki disease (KD).

METHODThe clinical data of 602 KD cases from 2007 to 2012 admitted to Shanghai Children's Hospital with EDC system connected with hospital information system (HIS) were retrospectively analyzed. Age, gender, acute symptoms, laboratory results, echocardiography, therapy were collected. The differences in parameters were compared between KD with and without coronary artery lesion (CAL). Furthermore, the difference between intravenous immunoglobulin (IVIG) resistant group and sensitive group were compared. Multi-factor logistic regression analyses were used to analyze the risk factors. The sensitivity and specificity of IVIG resistance parameters were detected with receiver operating characteristic curve (ROC) analysis.

RESULTThe male to female ratio of KD cases was 1.85: 1. The median age of KD cases was 2.0 years (one month to 11.7 years old); 20.1% cases (121/602) exhibited CAL. Compared with KD without CAL (n = 481), the incidence of bright red cracked lips (71.1% vs. 88.6%, P = 0.001), peeling of the skin of the toes (28.1% vs. 41.6%, P = 0.021) and perianal skin peeling (29.8% vs. 38.9%, P = 0.031) were statistically lower in KD with CAL (n = 121). The incidence of CAL in KD IVIG resistant group was significantly higher than KD IVIG sensitive group (34.6% (9/26) vs.21.3% (112/525), P = 0.05 ). Male ratio (80.8% vs. 63.4%, P = 0.05), time of IVIG ( (6 ± 2) vs. (8 ± 5) d, P = 0.009), erythrocyte sedimentation rate(ESR) ( (81 ± 2) vs. (66 ± 30) mm/1 h, P = 0.014), C-reactive protein ((107 ± 51) vs. (87 ± 52) mg/L, P = 0.017), blood platelet ( (599 ± 178) vs. (489 ± 182) ×10(9)/L, P = 0.003), hemoglobin ( (96 ± 13) vs. (102 ± 19) g/L, P = 0.032) and albumin ((34 ± 6) vs. (37 ± 6) g/L, P = 0.020) were significantly different between IVIG resistant group and sensitive group. Logistic regression analysis showed that alanine aminotransferase (ALT) ≥ 80 U/L was the independent risk factor of IVIG resistance (P = 0.012). C-reactive protein = 104 mg/L (sensitivity 61.5%, specificity 62.7%), ESR = 106 mm/1 h (sensitivity 26.9%, specificity 93.6%) and blood platelet = 187×10(9)/L (sensitivity 76.9%, specificity 53.1%) of KD in acute phase were predictive for IVIG resistance with receiver operate characteristic curve analysis.

CONCLUSIONEDC system can acquire KD clinical data quickly and accurately. It is helpful for multicenter retrospective analysis of KD.

Blood Platelets ; Blood Sedimentation ; C-Reactive Protein ; Child ; Child, Preschool ; China ; Coronary Artery Disease ; Echocardiography ; Electronic Health Records ; Female ; Hemoglobins ; Humans ; Immunoglobulins, Intravenous ; Male ; Mucocutaneous Lymph Node Syndrome ; Retrospective Studies ; Risk Factors

OBJECTIVETo provide scientific proofs for the exploitation, utilization, and normalized cultivation of Houttuynia cordata.

METHODThe underground parts of 17 wild H. cordata populations from different valleys and altitudes of mountain. Emei were transplanted to the same growth conditions. After one year's cultivation, volatile oil was obtained by steam distillation from the aerial part of the materials. The chemical constituents were separated and identified by GC-MS, and the relative content of each constituent was determined by area normalization.

RESULTTotally, 31 chemical components were identified, 19 components could be detected in all materials. The t-test results indicated that the contents of alpha-pinene and D-limonene were extremely significantly higher than that in the wild populations, and the contents of camphene and 2-undecanone were also significantly higher than that in the wild populations. And the reverse was found in the content of trans-beta-ocimene. All these 31 components could be divided into 9 chemical compositions, and 7 chemical compositions could be detected in the wild and cultivated. RSD values of 5 chemical compositions in wild populations were higher than that in the cultivated, except for the contents of diterpenyl alcohols and diterpenyl aldehydes. These five chemical compositions accounted for 84.05% and 90.12% of the whole volatile oils in the wild and cultivated conditions, respectively.

CONCLUSIONThe components and contents of the volatile oils between wild and cultivated were different. The volatile oils polymorphism decrease distinctively as all the wild populations of H. cordata were transplanted to the uniform environmental conditions.

Houttuynia ; chemistry ; growth & development ; Oils, Volatile ; analysis ; chemistry ; Organic Chemicals ; analysis

Objective To explore the origin of fluoride in the coal-combustion endemic fluorosis areas in the middle part of Hunan Province and to provide basic data for making preventive measure in the regions. Methods In November, 2006, the prevalence rate of dental fluorosis of children aged 10-12 years were examined, the villages were divided into three groups based on the prevalence rate of dental fluorosis. The fluoride content in the drinking water, coal, briquettes, briquette ash, clay and indoor air was determined by fluoride ion selective electrode. The quantity of fluoride release was calculated. Results There was no significant difference in the concentration of fluoride in water among the three groups, and it was below 1.0 mg/L in fluorosis and non-fluorosis areas. The fluoride levels in the coal, briquette ash and indoor air showed no statistical difference among groups. The fluoride levels of briquettes, clay and the quantity of fluorine release showed significant difference (P

plant height.Multiple regression analysis showed that branch height from base(X_2),number of primary branches(X_4),number of effective cones per plant(X_6),number of ineffective cones per plant(X_7),number of grains per cone(X_9),and diameter of primary head(X_(10)) were the main factors affecting flower yield(Y) per plant.Multiple regression equation of flower yield per plant and six characters was Y=-3.037 0+(0.002 7) X_2+0.045 9 X_4+0.074 5 X_6+0.043 2 X_7+0.023 0 X_9+1.148 2 X_(10)(F=21.84~()).The direct effect of number of effective cones per plant was the strongest,followed by diameter of primary head.There were significant differences within the flower yield per plant and the safflor yellow A content of different species.The correlation between the safflor yellow A content and the flower yield per plant was insignificant.Conclusion High-yield and high-quality are compatible in breeding of safflower which is used as herbal medicine.Number of effective cones per plant and diameter of primary head are focused on the high yield breeding and cultivation of safflower species.The plant type of higher flower yield safflower species should have more effective cone numbers,more number of cones,number of branches,number of primary branches,bigger diameter of primary head,moderate plant height,branch height from base,and ineffective cones per plant.Of all accessions,PI 239226,PI 253540,PI 367833,and Jianyang Honghua are outstanding and optimal for cultivating in Sichuan Province.

Objective To explore the adverse effect of endemic fluorosis caused by fluoride from coal burning on the intelligence of children. Methods Four primary schools were selected respectively from slight, moderate, severe endemic fluorosis areas and the control area in Xinhua county of Hu'nan Province, and twenty children of grade 5 were randomly chosen in each school. The seriousness of dental fluorosis was examined by Dean's method and intelligence level was evaluated by CRT-RC. The morning urine was collected and the fluoride content in urine was measured by fluoride ion selection electrode method. Results The dental fluorosis was positively related to the fluoride content in urine (P0.05), but the difference was significant in the abilities of comparative inference, serial relationship and abstract inference (P