Screening of functional antidotes of RNA aptamers against bovine thrombin

AbstractA specific RNA aptamer (T705) against bovine thrombin had been obtained after seven rounds of SELEX (systematic evolution of ligands by exponential enrichment) selection from a random RNA library previously. In order to further investigate the relationship between the structure and function of this aptamer, three truncated RNA aptamers, T705a, T705b and T705c, were designed according to the secondary structure of T705 RNA. Our results showed that T705c keeping the precise stem–loop structure but lacking most of the stem region sequence of T705 could inhibit clot formation in vitro in the same way as its parental form. We also report here that single-stranded DNA (ssDNA) antisense oligonucleotides, c′ and c′-22, which were complementary to different portions of T705c could act as efficient antidotes reversing the inhibitory activity of T705. It is demonstrated for the first time that ssDNA antisense oligonucleotides are potential antidotes of RNA aptamers and this may be an effective, rapid strategy to find antidotes of RNA aptamers which would be of important usefulness in basic research and drug screening

Pre- and Post-surgical Prevalence of Hyperglycemia in Patients with Subclinical Cushing's Syndrome Secondary to Adrenal Incidentaloma

Background Subclinical Cushing's syndrome (SCS) is a common subtype of adrenal incidentaloma. There are few reports on the correlation between hyperglycemia and hypercortisone secretion and its postoperative change in SCS patients. Objective To assess the pre- and post-surgical prevalence of hyperglycemia in patients with SCS secondary to adrenal incidentaloma. Methods The data of 202 patients who consulted in respiratory department of endocrinology, renhe hospital affiliated to shanghai university (shanghai baoshan district renhe hospital). Participants included 36 SCS patients, 41 patients with Cushing's syndrome due to adrenal tumor (CSA), 47 with nonfunctional adrenal tumor (NAT), and 53 controls. OGTT was performed in all of them, and based on the results, HOMA-IR, the area under the curve of blood glucose (AUCGlu) and insulin (AUCIns) were calculated, and plasma cortisol and urinary free cortisol and plasma ACTH were measured, then the values of the parameters were compared between controls and patients. Surgical treatment was given to SCS and CSA patients. The association of hormone and glucose metabolism parameters was assessed using Pearson correlation analysis. Results The prevalence of hyperglycemia in SCS, CSA and NAT patients before surgery and in controls was 41.7%, 51.2%, 25.5%, and 24.5%, respectively. The HbA1c, 2-hour post-load insulin (2 hPIN), AUCGlu and AUCIns in SCS patients were higher than those of controls (P<0.05). CSA patients had higher fasting insulin, AUCIns and HOMA-IR than SCS patients, NAT patients and controls (P<0.05). CSA patients had higher HbA1c, fasting plasma glucose (FPG), 2-hour post-load plasma glucose (2 hPPG), 2 hPIN and AUCGlu than NAT patients and controls (P<0.05). After controlling for sex and age, in SCS patients, HbA1c was positively associated with cortisol measured at 8: 00 and 16: 00 on the day after admission, and 24-hour urinary free cortisol (r=0.68, 0.657, 0.522, P<0.05), and so was 2 hPPG (r=0.569, 0.544, 0.369, P<0.05) ; FPG was positively associated with cortisol measured at 8: 00 on the day after admission (r=0.434, P<0.05) ; AUCGlu was positively associated with cortisol measured at 8: 00 and 16: 00 on the day after admission (r=0.397, 0.409, P<0.05). In CSA group, HbA1c was positively associated with cortisol measured at 8: 00 on the day after admission (r=0.748, P<0.05), and so was FPG, 2 hPPG, AUCGlu, and 2 hPIN (r=0.631, 0.669, 0.602, 0.319, P<0.05). HbA1c was also positively associated with cortisol measured at 16: 00 on the day after admission (r=0.674, P<0.05), and so was FPG, 2 hPPG, AUCGlu, (r=0.655, 0.640, 0.624, P<0.05). Plasma cortisol and 24-hour urinary free cortisol decreased in SCS and CSA patients after surgery (P<0.05). 2 hPIN and AUCIns decreased in SCS patients after surgery (P<0.05). FIN, 2 hPIN, AUCGlu, AUCIns and HOMA-IR decreased in CSA patients after surgery (P<0.05). The postsurgical prevalence of hyperglycemia SCS and CSA patients was 33.3% and 39.0%, respectively. Conclusion The high prevalence of hyperglycemia may be related to high secretion of glucocorticoid in SCS patients, and the hyperglycemic condition was improved after surgical treatment

Structure Connectivity and Substructure Connectivity of Hypercubes

The connectivity of a network - the minimum number of nodes whose removal will disconnect the network - is directly related to its reliability and fault tolerability, hence an important indicator of the network\u27s robustness. In this paper, we extend the notion of connectivity by introducing two new kinds of connectivity, called structure connectivity and substructure connectivity, respectively. Let H be a certain particular connected subgraph of G. The H-structure connectivity of graph G, denoted κ(G;H), is the cardinality of a minimal set of subgraphs F={H1\u27,H2\u27,. . .,Hm\u27} in G, such that every Hi\u27∈F is isomorphic to H, and F\u27s removal will disconnect G. The H-substructure connectivity of graph G, denoted κs(G;H), is the cardinality of a minimal set of subgraphs F={J1, J2, . . ., Jm}, such that every Ji∈F is a connected subgraph of H, and F\u27s removal will disconnect G. In this paper, we will establish both κ(Qn;H) and κs(Qn;H) for the hypercube Qn and H∈{K1, K1,1, K1,2, K1,3, C4}

Uncertain Random Spectra: A New Metric for Assessing the Survivability of Mobile Wireless Sensor Networks

In this paper, a soft computing method, a probability theory, and a graph theoretic approach are utilized to describe this phenomenon. Uncertain random spectra, namely, natural tenacity, are established in this paper for assessing the survivability of MWSNs. We propose an elaborate mathematical formulation that relates the survivability to the natural tenacity. In addition, then the probability of link connectivity is proposed in order to connect the natural tenacity to the connectivity of the network, which reflects the most important indicators of network survivability. The natural tenacity of MWSNs is explored by both analytical and numerical ways. Moreover, we also compare it with other survivability measures. Under the smooth Gauss–semi-Markov mobility model, the effectiveness of the measure is verified through numerical analysis. The result indicates that the natural tenacity has a strong analytical ability to measure the survivability of MWSNs objectively

The Minimal Exposure Path in Mobile Wireless Sensor Network

Target traversing is an important research topic in wireless sensor networks. Most works in this area consider the coverage issues of the target\u27s moving paths. The minimal exposure path problem is to find a path among sensors so that the target\u27s total exposure to the sensors is minimized. Most existing traversal algorithms ensure the target to stay as far as possible from static sensors. In this paper, we take into account the situation where there are moving sensors as well. We propose an effective algorithm based on tangent to not only stay as far as possible from static sensors, but also avoid mobile sensors. Simulations show that the proposed algorithms can solve the traversal path with mobile sensors\u27 patrolling in wireless sensor networks

A promising natural killer cell-based model and a nomogram for the prognostic prediction of clear-cell renal cell carcinoma

Abstract Background Clear-cell renal cell carcinoma (ccRCC) is one of prevalent kidney malignancies with an unfavorable prognosis. There is a need for a robust model to predict ccRCC patient survival and guide treatment decisions. Methods RNA-seq data and clinical information of ccRCC were obtained from the TCGA and ICGC databases. Expression profiles of genes related to natural killer (NK) cells were collected from the Immunology Database and Analysis Portal database. Key NK cell-related genes were identified using consensus clustering algorithms to classify patients into distinct clusters. A NK cell-related risk model was then developed using Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression to predict ccRCC patient prognosis. The relationship between the NK cell-related risk score and overall survival, clinical features, tumor immune characteristics, as well as response to commonly used immunotherapies and chemotherapy, was explored. Finally, the NK cell-related risk score was validated using decision tree and nomogram analyses. Results ccRCC patients were stratified into 3 molecular clusters based on expression of NK cell-related genes. Significant differences were observed among the clusters in terms of prognosis, clinical characteristics, immune infiltration, and therapeutic response. Furthermore, six NK cell-related genes (DPYSL3, SLPI, SLC44A4, ZNF521, LIMCH1, and AHR) were identified to construct a prognostic model for ccRCC prediction. The high-risk group exhibited poor survival outcomes, lower immune cell infiltration, and decreased sensitivity to conventional chemotherapies and immunotherapies. Importantly, the quantitative real-time polymerase chain reaction (qRT-PCR) confirmed significantly high DPYSL3 expression and low SLC44A4 expression in ACHN cells. Finally, the decision tree and nomogram consistently show the dramatic prediction performance of the risk score on the survival outcome of the ccRCC patients. Conclusions The six-gene model based on NK cell-related gene expression was validated and found to accurately mirror immune microenvironment and predict clinical outcomes, contributing to enhanced risk stratification and therapy response for ccRCC patients

Optimization of Physical Refining Process of Camellia Oil for Reduction of 3-Monochloropropane-1,2-Diol (3-MCPD) Ester Formation Using Response Surface Methodology on a Laboratory Scale

Refined and deodorized camellia oil has been reported to contain a high amount of 3-monochloropropane-1,2-diol esters (3-MCPDE) due to the high-temperature deodorization step. To reduce 3-MCPDE in camellia oil, the physical refining process of camellia oil was simulated on a laboratory scale. Response surface methodology (RSM) was designed to modify and optimize the refining process with five processing parameters (water degumming dosage, degumming temperature, activated clay dosage, deodorization temperature and deodorization time). The optimized new refining approach achieved a 76.9% reduction in 3-MCPDE contents, in which the degumming moisture was 2.97%, the degumming temperature was 50.5 °C, the activated clay dosage was 2.69%, the deodorizing temperature was 230 °C, and the deodorizing time was 90 min. A significance test and analysis of variance results demonstrated that the deodorization temperature and deodorization time contributed significantly to the reduction of 3-MCPD ester. The joint interaction effects of activated clay dosage and deodorization temperature were significant for 3-MCPD ester formation

Approximate Algorithms for Vertex Cover Problems in WSN Topology Design

The Vertex Cover (VC) problem is a classical optimization problem that can be applied in topology design in Wireless Sensor Networks (WSNs). In this paper, we first propose two polynomial time approximation schemes (PTASs) for the Minimum Vertex Cover (MVC) problem and the Minimum Weighted Vertex Cover (MWVC) problem in growth-bounded graphs. We then propose an approximation algorithm, with a performance guarantee of (1 +2ε/(1 -ε)) for sufficiently small ε\u3e0, for the Minimum Connected Vertex Cover (MCVC) problem. In contrast to previously proposed schemes for VC problems, our approach does not assume geometric representation of vertices in growth-bounded graphs. We also prove that the running times of the proposed algorithms are bounded by a polynomial in terms of the graph size and the input ε. We evaluate the performance of our algorithms through simulation