Advances in the study of miRNAs in chronic kidney disease with cardiovascular complications.

Chronic kidney disease (CKD) is characterised by gradual loss of renal function and cardiovascular disease (CVD) as its principal consequence. CVD is a substantial source of morbidity and death in the CKD population and a growing global concern. Because there are no reliable early biomarkers to follow the progression of CKD and predict the risk of complications, research into such molecules continues. Many studies have demonstrated that miRNAs are potentially important variables in CKD, are very stable in blood, and may be employed as diagnostic and prognostic markers for various disorders. Vascular calcification (VC) is a cell-mediated process that necessitates genetic defects in the combined cardiovascular issues of CKD and may be modulated in part by miRNAs. Numerous miRNAs have been linked to the progression of vascular calcification. Many miRNAs have been discovered as being important in ventricular hypertrophy, including miRNA-30, miRNA-212, and miRNA-133. Endothelium miR-126, miR-92a-3p, and others are important regulators of angiogenesis, endothelium repair, and homeostasis. Several interesting non-invasive miRNA biomarkers in CKD/CVD have been found, with the potential to enhance diagnostic accuracy, predict prognosis, track disease progression, and serve as novel therapy targets. However, large-scale clinical studies are still needed to determine the therapeutic utility of miRNA.

Continuously Quantifying Oral Chemicals Based on Flexible Hybrid Electronics for Clinical Diagnosis and Pathogenetic Study.

Simultaneous monitoring of diverse salivary parameters can reveal underlying mechanisms of intraoral biological processes and offer profound insights into the evolution of oral diseases. However, conventional analytical devices with bulky volumes, rigid formats, and discrete sensing mechanisms deviate from the requirements of continuous biophysiological quantification, resulting in huge difficulty in precise clinical diagnosis and pathogenetic study. Here, we present a flexible hybrid electronic system integrated with functional nanomaterials to continuously sense Ca2+, pH, and temperature for wireless real-time oral health monitoring. The miniaturized system with an island-bridge structure that is designed specifically to fit the teeth is only 0.4 g in weight and 31.5 × 8.5 × 1.35 mm3 in dimension, allowing effective integration with customized dental braces and comfort attachment on teeth. Characterization results indicate high sensitivities of 30.3 and 60.6 mV/decade for Ca2+ and pH with low potential drifts. The system has been applied in clinical studies to conduct Ca2+ and pH mappings on carious teeth, biophysiological monitoring for up to 12 h, and outcome evaluation of dental restoration, providing quantitative data to assist in the diagnosis and understanding of oral diseases. Notably, caries risk assessment of 10 human subjects using the flexible system validates the important role of saliva buffering capacity in caries pathogenesis. The proposed flexible system may offer an open platform to carry diverse components to support both clinical diagnosis and treatment as well as fundamental research for oral diseases and induced systemic diseases.

Advances in the study of subclinical AKI biomarkers.

Acute kidney injury (AKI) is a prevalent and serious illness in all clinical departments, with a high morbidity and death rate, particularly in intensive care units, where prevention and treatment are crucial. As a result, active prevention, early detection, and timely intervention for acute kidney injury are critical. The current diagnostic criteria for acute kidney injury are an increase in serum creatinine concentration and/or a decrease in urine output, although creatinine and urine output merely reflect changes in kidney function, and AKI suggests injury or damage, but not necessarily dysfunction. The human kidney plays a crucial functional reserve role, and dysfunction is only visible when more than half of the renal mass is impaired. Tubular damage markers can be used to detect AKI before filtration function is lost, and new biomarkers have shown a new subset of AKI patients known as "subclinical AKI." Furthermore, creatinine and urine volume are only marginally effective for detecting subclinical AKI. As a result, the search for new biomarkers not only identifies deterioration of renal function but also allows for the early detection of structural kidney damage. Several biomarkers have been identified and validated. This study discusses some of the most promising novel biomarkers of AKI, including CysC, NGAL, KIM-1, lL-18, L-FABP, IGFBP7, TIMP-2, Clusterin, and Penkid. We examine their performance in the diagnosis of subclinical AKI, limitations, and future clinical practice directions.

De novo transcriptome assembly of the deep-sea hydrothermal vent, shrimp Rimicaris exoculate (Crustacea: Decapoda), from the south Mid-Atlantic Ridge.

The deep-sea hydrothermal vent is a special ecosystem, which is different from terrestrial or coastal ecosystems. Rimicaris exoculata, which adapts well to several deep-sea hydrothermal vent environments, is the ideal model for studying hydrothermal vent fauna. In the present study, we obtained R. exoculata from a newly found hydrothermal vent in the south Mid-Atlantic Ridge, and the Illumina next-generation sequencing and de novo assembly were performed by Beijing Genomics Institution. A total of 17,258 annotated Unigenes were obtained. Several Unigenes associated with sulfide metabolism, which might contribute to well adaptation to high concentration of sulfide for R. exoculata, were annotated. This study is the first report on the high-throughput sequencing of R. exoculata. Our data can allow for further studies on the ability of R. exoculata adaptation to harsh conditions and provide abundant gene resources for research and development.

Characterization of a novel extracellular CuZn superoxide dismutase from Rimicaris exoculata living around deep-sea hydrothermal vent.

Superoxide dismutase (SOD, EC 1.15.1.1) is a member of metalloenzyme that plays a key role in protecting organisms from oxidative damage. A novel extracellular CuZn superoxide dismutase RESOD was identified from Rimicaris exoculata, a dominant species that lives in close proximity to the deep-sea hydrothermal vents. It encoded a protein consisting of 227 amino acids with a signal peptide of 22 amino acids. Sequence analysis revealed that it had the characteristics of CuZn superoxide dismutase, and had low homology with the known SODs. Then the recombinant RESOD was expressed successfully, and high-purity RESOD was obtained. The recombinant RESOD exhibited maximal activity and stability with a temperature range of 0 °C to 10 °C. And the optimal pH for the activity and stability was about 10. However, RESOD was sensitive to some metal ions, particularly calcium. Furthermore, the biological function of RESOD was investigated in HeLa cells. It was found that RESOD could reduce the level of oxidation, and decrease the apoptosis resulted from excessive oxidant challenge. In conclusion, a novel alkali-tolerant cold-active extracellular CuZn SOD was characterized. The characteristics make RESOD a good candidate in a wide range of applications.

Diastereoselective Construction of 2-Aminoindanones via an In(OTf)3-Catalyzed Domino Reaction.

An In(OTf)3-catalyzed domino reaction involving sequential oxidative ring opening of aziridines by using the solvent dimethyl sulfoxide and intramolecular Michael addition has been developed for the modular synthesis of 2-aminoindanone compounds by the formation of one new C═O bond and one new C-C bond. The notable feature of this strategy includes broad substrate scope, excellent trans-diastereoselectivities, highly functionalized products, and mild conditions. The catalyst In(OTf)3 plays an important role in the formation of the indanone ring.

[Association of dietary energy intake and energy density with gestational weight gain in Chengdu City].

OBJECTIVE: To determine the association of dietary energy intake and energy density( ED) with gestational weight gain among pregnant women in Chengdu. METHODS: A total of 503 pregnant women who took the prenatal examination in West China Second University Hospital were selected in the prospective study in 2015. ED, computed as the ratio of energy intake( kcal) per weight( g) of foods( kcal/g), was calculated using three methods as follows:( 1) ED1 included foods only, excluding all beverages;( 2) ED2 included foods and milk;( 3) ED3 included foods and beverages. Energy intake were calculated using dietary data respectively collected in the first, second and third trimester of pregnancy by validated 24-hour recalls, in which ED was calculated based on three calculation method. Data on gestational weight gain was calculated by using pre-pregnancy weight and prenatal weight. Excessive gestational weight gain was determined by the 2009 Institute of Medicine( IOM) recommendations for gestational weight gain. Logistic regression analyses were performed to explore the association of energy intake and ED with excessive gestational weight gain. RESULTS: The risk of excessive gestational weight gain was higher among pregnant women whose dietary energy intake during the third trimester of pregnancy was higher( OR = 1. 94, 95% CI 1. 18-3. 23). After adjusting for covariates, ED based on foods and milk during the third trimester of pregnancy was identified as a protect factor of excessive gestational weight gain( OR = 0. 56, 95% CI 0. 34-0. 93). Dietary energy intake and ED in the first and second trimester of pregnancy were not associated with excessive gestational weight gain after adjustment of all covariates. CONCLUSION: Dietary energy intake in the third trimester of pregnancy might be the risk factor of excessive gestational weight gain, while moderate ED may be the protect factor.

Combined Inoculation with Multiple Arbuscular Mycorrhizal Fungi Improves Growth, Nutrient Uptake and Photosynthesis in Cucumber Seedlings.

Mycorrhizal inoculation stimulates growth, photosynthesis and nutrient uptake in a wide range of host plants. However, the ultimate effects of arbuscular mycorrhyzal (AM) symbiosis vary with the plants and fungal species involved in the association. Therefore, identification of the appropriate combinations of AM fungi (AMF) that interact synergistically to improve their benefits is of high significance. Here, three AM fungal compositions namely VT (Claroideoglomus sp., Funneliformis sp., Diversispora sp., Glomus sp., and Rhizophagus sp.) and BF (Glomus intraradices, G. microageregatum BEG and G. Claroideum BEG 210), and Funneliformis mosseae (Fm) were investigated with respect to the growth, gas exchange parameters, enzymes activities in Calvin cycles and related gene expression in cucumber seedlings. The results showed that VT, BF and Fm could successfully colonize cucumber root to a different degree with the colonization rates 82.38, 74.65, and 70.32% at 46 days post inoculation, respectively. The plant height, stem diameter, dry weight, root to shoot ratio of cucumber seedlings inoculated with AMF increased significantly compared with the non-inoculated control. Moreover, AMF colonization greatly increased the root activity, chlorophyll content, net photosynthetic rate, light saturated rate of the CO2 assimilation (Asat), maximum carboxylation rate (Vcmax) and maximum ribulose-1,5-bis-phosphate (RuBP) regeneration rate (Jmax), which were increased by 52.81, 30.75, 58.76, 47.00, 69.15, and 65.53% when inoculated with VT, respectively. The activities of some key enzymes such RuBP carboxylase/oxygenase (RuBisCO), D-fructose-1,6-bisphosphatase (FBPase), D-fructose-6-phosphatase (F6P) and ribulose-5-phosphate kinase (Ru5PK), and related gene expression involved in the Calvin cycle including RCA, FBPase, FBPA, SBPase, rbcS and rbcL were upregulated by AMF colonization. AMF inoculation also improved macro- and micro nutrient contents such as N, P, K, S, Ca, Cu, Fe, Mn, Mg, and Zn in roots. Further analysis revealed that inoculation with VT had relatively better effect on growth of cucumber seedling followed by BF and Fm, indicating that AMF composition consisting of distant AMF species may have a better effect than a single or closely related AMF spp. This study advances the understanding of plant responses to different AM fungi toward development of strategies on AMF-promoted vegetable production.

Carbon-Dot and Quantum-Dot-Coated Dual-Emission Core-Satellite Silica Nanoparticles for Ratiometric Intracellular Cu(2+) Imaging.

Copper (Cu(2+)) is physiologically essential, but excessive Cu(2+) may cause potential risk to plants and animals due to the bioaccumulative properties. Hence, sensitive recognition is crucial to avoid overintake of Cu(2+), and visual recognition is more favored for practical application. In this work, a dual-emission ratiometric fluorescent nanoprobe was developed possessing the required intensity ratio, which can facilitate the sensitive identification of Cu(2+) by the naked eye. The probe hybridizes two fluorescence nanodots (quantum dots (QDs) and carbon dots (CDs)). Although both of them can be viable fluorescence probes for metal ion detection, rarely research has coupled this two different kinds of fluorescence material in one nanosensor to fabricate a selectively ratiometric fluorescence probe for intracellular imaging. The red emitting CdTe/CdS QDs were capped around the silica microsphere to serve as the response signal label, and the blue-emitting CDs, which is insensitive to the analyte, were covalently attached to the QDs surface to act as the reference signal. This core-satellite hybrid sphere not only improves the stability and brightness of QDs significantly but also decreases the cytotoxicity toward HeLa cells tremendously. Moreover, the Cu(2+) could quench the QDs emission effectively but have no ability for reduction of the CDs emission. Accordingly, a simple, efficient, and precise method for tracing Cu(2+) was proposed. The increase of Cu(2+) concentration in the series of 0-3 × 10(-6) M was in accordance with linearly decrease of the F650/F425 ratio. As for practical application, this nanosensor was utilized to the ratiometric fluorescence imaging of copper ions in HeLa cells.

HSA: integrating multi-track Hi-C data for genome-scale reconstruction of 3D chromatin structure.

Genome-wide 3C technologies (Hi-C) are being increasingly employed to study three-dimensional (3D) genome conformations. Existing computational approaches are unable to integrate accumulating data to facilitate studying 3D chromatin structure and function. We present HSA ( http://ouyanglab.jax.org/hsa/ ), a flexible tool that jointly analyzes multiple contact maps to infer 3D chromatin structure at the genome scale. HSA globally searches the latent structure underlying different cleavage footprints. Its robustness and accuracy outperform or rival existing tools on extensive simulations and orthogonal experiment validations. Applying HSA to recent in situ Hi-C data, we found the 3D chromatin structures are highly conserved across various human cell types.

Joint modeling of RNase footprint sequencing profiles for genome-wide inference of RNA structure.

Recent studies have revealed significant roles of RNA structure in almost every step of RNA processing, including transcription, splicing, transport and translation. RNase footprint sequencing (RNase-seq) has emerged to dissect RNA structures at the genome scale. However, it remains challenging to analyze RNase-seq data because of the issues of signal sparsity, variability and correlations among various RNases. We present a probabilistic framework, joint Poisson-gamma mixture (JPGM), for integrative modeling of multiple RNase-seq profiles. Combining JPGM with hidden Markov model allows genome-wide inference of RNA structures. We apply the joint modeling approach for inferring base pairing states on simulated data sets and RNase-seq profiles of the double-strand specific RNase V1 and single-strand specific RNase S1 in yeast. We demonstrate that joint analysis of V1 and S1 profiles outputs interpretable RNA structure states, while approaches that analyze each profile separately do not. The joint modeling approach predicts the structure states of all nucleotides in 3196 transcripts of yeast without compromising accuracy, while the simple thresholding approach misses 43% of the nucleotides. Furthermore, the posterior probabilities outputted by our model are able to resolve the structural ambiguity of ≈300 000 nucleotides with overlapping V1 and S1 cleavage sites. Our model also generates RNA accessibilities, which are associated with three-dimensional conformations.