Abstract
MicroRNAs (miRNAs) are small non-coding RNAs (typically consisting of 18–25 nucleotides) that negatively control expression of target genes at the post-transcriptional level. Owing to the ...biological significance of miRNAs, miRTarBase was developed to provide comprehensive information on experimentally validated miRNA–target interactions (MTIs). To date, the database has accumulated >13,404 validated MTIs from 11,021 articles from manual curations. In this update, a text-mining system was incorporated to enhance the recognition of MTI-related articles by adopting a scoring system. In addition, a variety of biological databases were integrated to provide information on the regulatory network of miRNAs and its expression in blood. Not only targets of miRNAs but also regulators of miRNAs are provided to users for investigating the up- and downstream regulations of miRNAs. Moreover, the number of MTIs with high-throughput experimental evidence increased remarkably (validated by CLIP-seq technology). In conclusion, these improvements promote the miRTarBase as one of the most comprehensively annotated and experimentally validated miRNA–target interaction databases. The updated version of miRTarBase is now available at http://miRTarBase.cuhk.edu.cn/.
Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and ...impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global
knockout (
) mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α (TNF-α), we determined that recombinant omentin-1 reduces the production of pro-inflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the pro-inflammatory cytokines.
Background
Diagnostic criteria for sarcopenia have not been established in Chinese. This study established criteria based on the L3‐skeletal muscle index (L3‐SMI) and assessed its value for outcomes ...predicting in cirrhotic Chinese patients.
Methods
Totally 911 subjects who underwent a CT scan at two centres were enrolled in Cohort 1 (394 male and 417 female subjects, aged 20–80 years). The data of those subjects younger than 60 years (365 male and 296 female subjects) were used to determine the reference intervals of the L3‐SMI and its influencing factors. Cohort 2 consisted of 480 patients (286 male and 184 female patients) from three centres, and their data were used to investigate the prevalence of sarcopenia and evaluate the value of L3‐SMI for predicting the prognosis and complications of cirrhosis.
Results
Age and sex had the greatest effects on the L3‐SMI (P < 0.001). The L3‐SMI scores were clearly higher in male patients than in female patients (52.94 ± 8.41 vs. 38.91 ± 5.65 cm2/m2, P < 0.001) and sharply declined in subjects aged ≥ 60 years. Based on the mean −1.28 × SD among adults aged < 60 years, the L3‐SMI cut‐off value for sarcopenia was 44.77 cm2/m2 in male patients and 32.50 cm2/m2 in female patients. Using these values, 22.5% of the cirrhotic patients (28.7% of male patients and 11.9% of female patients) were diagnosed with sarcopenia. Compared with non‐sarcopenia individuals, sarcopenia patients had lower body mass index (21.28 ± 3.01 vs. 24.09 ± 3.39 kg/m2, P < 0.001) and serum albumin levels (31.54 ± 5.93 vs. 32.93 ± 5.95 g/L, P = 0.032), longer prothrombin times (16.39 ± 3.05 vs. 15.71 ± 3.20 s, P = 0.049), higher total bilirubin concentrations (41.33 ± 57.38 vs. 32.52 ± 31.48 μmol/L, P = 0.039), worse liver function (Child–Pugh score, 8.05 ± 2.11 vs. 7.32 ± 2.05, P = 0.001), higher prevalence of cirrhosis‐related complications (81.82% vs. 62.24%, P < 0.001) and mortality (30.68% vs. 11.22%, P < 0.001). Overall survival was significantly lower in the sarcopenia group risk ratio (RR) = 2.643, 95% confidence interval (CI) 1.646–4.244, P < 0.001, accompanied with an increased cumulative incidence of ascites (RR = 1.827, 95% CI 1.259–2.651, P = 0.002), spontaneous bacterial peritonitis (RR = 3.331, 95% CI 1.404–7.903, P = 0.006), hepatic encephalopathy (RR = 1.962, 95% CI 1.070–3.600, P = 0.029), and upper gastrointestinal varices (RR = 2.138, 95% CI 1.319–3.466, P = 0.002). Subgroup analysis showed sarcopenia shortened the survival of the patients with Model For End‐Stage Liver Disease score > 14 (RR = 4.310, 95% CI 2.091–8.882, P < 0.001) or Child–Pugh C (RR = 3.081, 95% CI 1.516–6.260, P = 0.002).
Conclusions
Sarcopenia is a common comorbidity of cirrhosis and can be used to predict cirrhosis‐related complications and the prognosis.
A new binuclear complex {Cd(phen)2(H2O) ⋅ (TMA)2−}2 has been synthesized through the reaction of o‐phenanthroline (phen), 3‐thiophenemalonic acid (H2TMA), and cadmium acetate in a 1 : 2 (v/v) ...EtOH‐H2O mixture at room temperature. This complex can undergo single‐crystal‐to‐single‐crystal (SCSC) transformation to a new mononuclear complex Cd(phen)3 ⋅ 2(HTMA)− ⋅ H2TMA} by a simple in‐situ solvent evaporation method at room temperature without changing the reaction system. In the whole SCSC process, with the solvent water molecules decreasing and the concentration of ligands increasing, the phen ligands replace the coordination water and coordinate with cadmium ions, finally resulting in the crystal structure transformation in the solid state.
As a major component of the LAMOST Galactic surveys, the LAMOST Spectroscopic Survey of the Galactic Anticentre (LSS-GAC) aims to survey a significant volume of the Galactic thin/thick discs and halo ...for a contiguous sky area of over 3400 deg2 centred on the Galactic anticentre (|b| ≤ 30°, 150 ≤ l ≤ 210°), and obtain λλ3700–9000 low-resolution (R ∼ 1800) spectra for a statistically complete sample of ∼3 M stars of all colours down to a limiting magnitude of r ∼ 17.8 mag (to 18.5 mag for limited fields). Together with Gaia, the LSS-GAC will yield a unique data set to advance our understanding of the structure and assemblage history of the Galaxy, in particular its disc(s). In addition to the main survey, the LSS-GAC will also target hundreds of thousands objects in the vicinity fields of M 31 and M 33 and survey a significant fraction (over a million) of randomly selected very bright stars (r ≤ 14 mag) in the Northern hemisphere. During the Pilot and the first year Regular Surveys of LAMOST, a total of 1042 586 750 867 spectra of a signal-to-noise ratio S/N(7450 Å) ≥ 10 S/N(4650 Å) ≥ 10 have been collected. In this paper, we present a detailed description of the target selection algorithm, survey design, observations and the first data release of value-added catalogues (including radial velocities, effective temperatures, surface gravities, metallicities, values of interstellar extinction, distances, proper motions and orbital parameters) of the LSS-GAC.
In elderly people particularly in postmenopausal women, inadequate bone formation by osteoblasts originating from bone marrow mesenchymal stem cells (BMSCs) for compensation of bone resorption by ...osteoclasts is a major reason for osteoporosis. Enhancing osteoblastic differentiation of BMSCs is a feasible therapeutic strategy for osteoporosis. Here, bone marrow stromal cell (ST)-derived exosomes (STExos) are found to remarkably enhance osteoblastic differentiation of BMSCs in vitro. However, intravenous injection of STExos is inefficient in ameliorating osteoporotic phenotypes in an ovariectomy (OVX)-induced postmenopausal osteoporosis mouse model, which may be because STExos are predominantly accumulated in the liver and lungs, but not in bone. Hereby, the STExo surface is conjugated with a BMSC-specific aptamer, which delivers STExos into BMSCs within bone marrow. Intravenous injection of the STExo-Aptamer complex enhances bone mass in OVX mice and accelerates bone healing in a femur fracture mouse model. These results demonstrate the efficiency of BMSC-specific aptamer-functionalized STExos in targeting bone to promote bone regeneration, providing a novel promising approach for the treatment of osteoporosis and fracture.
Like classical block codes, a locally repairable code also obeys the Singleton-type bound (we call a locally repairable code optimal if it achieves the Singleton-type bound). In the breakthrough work ...of Tamo and Barg, several classes of optimal locally repairable codes were constructed via subcodes of Reed-Solomon codes. Thus, the lengths of the codes given by Tamo and Barg are upper bounded by the code alphabet size q. Recently, it was proved through the extension of construction by Tamo and Barg that the length of q-ary optimal locally repairable codes can be q +1 by Jin et al. Surprisingly, Barg et al. presented a few examples of q-ary optimal locally repairable codes of small distance and locality with code length achieving roughly q 2 . Very recently, it was further shown in the work of Li et al. that there exist q-ary optimal locally repairable codes with the length bigger than q+1 and the distance proportional to n. Thus, it becomes an interesting and challenging problem to construct new families of q-ary optimal locally repairable codes of length bigger than q+1. In this paper, we construct a class of optimal locally repairable codes of distances 3 and 4 with unbounded length (i.e., length of the codes is independent of the code alphabet size). Our technique is through cyclic codes with particular generator and parity-check polynomials that are carefully chosen.
This study aimed to establish an effective prognostic nomogram with or without plasma Epstein-Barr virus DNA (EBV DNA) for nondisseminated nasopharyngeal carcinoma (NPC).
The nomogram was based on a ...retrospective study of 4630 patients who underwent radiotherapy with or without chemotherapy at Sun Yat-sen University Cancer Center from 2007 to 2009. The predictive accuracy and discriminative ability of the nomogram were determined by a concordance index (C-index) and calibration curve and were compared with EBV DNA and the current staging system. The results were validated using bootstrap resampling and a prospective cohort study on 1819 patients consecutively enrolled from 2011 to 2012 at the same institution. All statistical tests were two-sided.
Independent factors derived from multivariable analysis of the primary cohort to predict recurrence were age, sex, body mass index (BMI), T stage, N stage, plasma EBV DNA, pretreatment high sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), and hemoglobin level (HGB), which were all assembled into the nomogram with (nomogram B) or without EBV DNA (nomogram A). The calibration curve for the probability of recurrence showed that the nomogram-based predictions were in good agreement with actual observations. The C-index of nomogram B for predicting recurrence was 0.728 (P < .001), which was statistically higher than the C-index values for nomogram A (0.690), EBV DNA (0.680), and the current staging system (0.609). The C-index of nomogram B (0.730) and nomogram A (0.681) remained higher for predicting recurrence among patients treated with intensity-modulated radiotherapy (P < .001). The results were confirmed in the validation cohort.
The proposed nomogram with or without plasma EBV DNA resulted in more accurate prognostic prediction for NPC patients.
•TAMs are involved in tumor progression via multiple mechanisms.•TAMs serve as angiogenesis promoting cells in cancer.•TAMs play vital roles in tumor metastasis.•TAMs are the promising candidate in ...cancer therapy.
Tumor associated macrophages (TAMs) are the most frequent immune cells within tumor microenvironment (TME). There is growing evidence that TAMs are involved in tumor progression via multiple mechanisms. TAMs create an immunosuppressive TME by producing growth factors, chemokines, and cytokines which modulate recruitment of immune cells and inhibit anti-tumor responses. They also serve as angiogenesis promoting cells by production of pro-angiogenic factors and matrix metalloproteinases (MMPs) and vascular constructing which guarantee supplying oxygen and nutrients to solid tumor cells. Furthermore, TAMs play important functions in tumor metastasis through contributing to invasion, extravasation, survival, intravasation, and colonization of tumor cells. In this review, we summarized macrophage classification, TAMs polarization, and mechanisms underlying TAM-promoting angiogenesis and metastasis.
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•RNN-LSTM for classifying three different types of relations from clinical notes.•Two different representations (sentence vs segment) for encoding the relations.•Comparable LSTM ...performance to state-of-the-art, with minimal feature engineering.•Word embeddings from clinical text more useful to the task than from general text.
We proposed the first models based on recurrent neural networks (more specifically Long Short-Term Memory - LSTM) for classifying relations from clinical notes. We tested our models on the i2b2/VA relation classification challenge dataset. We showed that our segment LSTM model, with only word embedding feature and no manual feature engineering, achieved a micro-averaged f-measure of 0.661 for classifying medical problem-treatment relations, 0.800 for medical problem-test relations, and 0.683 for medical problem-medical problem relations. These results are comparable to those of the state-of-the-art systems on the i2b2/VA relation classification challenge. We compared the segment LSTM model with the sentence LSTM model, and demonstrated the benefits of exploring the difference between concept text and context text, and between different contextual parts in the sentence. We also evaluated the impact of word embedding on the performance of LSTM models and showed that medical domain word embedding help improve the relation classification. These results support the use of LSTM models for classifying relations between medical concepts, as they show comparable performance to previously published systems while requiring no manual feature engineering.
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