Mechanisms of ssDNA aptamer binding to Cd2+ in aqueous solution: A molecular dynamics study.

ssDNA aptamers have been increasingly used to detect heavy metal ions as recognition elements due to their high affinity and specificity. However, the specific recognition and binding mechanisms between aptamers and most heavy metals were still unclear, which limits the development of aptamer-based detection methods. In this work, the interaction mechanisms of CD-2-1 aptamers with Cd2+ in aqueous solutions were investigated using molecular dynamic simulations. The most stable complex was found where Cd2+ binding at aptamer's stem-loop junction and preferred at the phosphate backbone or bases. Noteworthily, two binding modes of Cd2+ combining aptamer in aqueous solution were discovered: direct and indirect. In the former mode, Cd2+ directly coordinated O atoms of bases. For the latter, Cd2+ connected to bases with coordinated water molecules as bridges. Electrostatic interaction was found to be the main driving force, and differences of residues role between two binding modes were elucidated. Buffer molecules in aqueous solutions can stabilize aptamer-Cd2+ complex by hydrogen bonds. This study revealed the specific interaction mechanisms of aptamer with Cd2+ at an atomic level, which provided theoretical references for aptamer-based Cd2+ detection methods establishment as well as an efficient technical route of screening potential aptamers for heavy metal ions.

Effects of Dexmedetomidine Anesthesia on Early Postoperative Cognitive Dysfunction in Elderly Patients.

The stimulation of tracheal extraction and anesthesia may lead to early postoperative cognitive dysfunction (POCD) in elderly patients, especially within 72 h after surgery, due to the insufficient compensatory and regulatory effects of their cardiovascular system. This study was performed to demonstrate the effects of additional dexmedetomidine (DEX) administration on alleviating early POCD (72 h post intubation) and inflammation in elderly patients who underwent intubation. A parallel-randomized trial was performed in this study. A total of 100 patients aged 60-85 years were randomly divided into two groups (DEX, n = 50; control, n = 50). They received traditional anesthesia and additional DEX medications. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were used to assess the cognitive dysfunction of patients. The enzyme-linked immunosorbent assay (ELISA) was used to detect the stress and inflammatory response of the two groups of patients. Administration of DEX significantly improved the MMSE and MoCA scores 24 and 72 h post operation. The S100ß and neuron-specific enolase (NSE) levels in serum were downregulated by DEX 6 and 24 h post operation. The norepinephrine and cortisol levels in serum were downregulated by DEX 15 and 30 min post operation. The interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels in serum were also downregulated by DEX 15 and 30 min post operation. DEX alleviated POCD and inflammation in elderly patients who underwent intubation.

Inhibitors of IFN gene stimulators (STING) improve intestinal ischemia-reperfusion-induced acute lung injury by activating AMPK signaling.

BACKGROUND: Acute lung injury (ALI) caused by intestinal ischemia-reperfusion is a life-threatening disease. Interferon gene stimulator (STING) is a cytoplasmic DNA sensor that participates in the initiation of the inflammatory response. This study aims to establish whether C-176 (STING inhibitor) improves ALI under intestinal ischemia-reperfusion conditions. METHODS: To induce ALI, 72 male C57BL/6 mice were subjected to intestinal ischemia for 60 min and reperfusion for 3 h. Through intraperitoneal injection, C-176, a selective STING inhibitor, was injected 30 min before surgical treatment; meanwhile, compound C, an antagonist of adenosine monophosphate-activated protein kinase (AMPK), was administered 30 min after surgery. Based on immunofluorescence and Western blot assays, post-ALI assessments included lung water content (TLW), bronchoalveolar lavage fluid (BALF) protein, H&E staining, Masson staining, pulmonary pyroptosis [Gasdermin-D (GSDMD), cleaved caspase-1], and apoptosis (TUNEL, cleaved caspase-3). RESULTS: C-176 administration significantly attenuated intestinal ischemia-reperfusion-mediated ALI; this effect was reflected by exacerbated TLW and BALF protein, aggravated lung injury score, elevated degree of pulmonary fibrosis, increased TUNEL- and GSDMD-positive cells, and upregulated phospho-AMPK, cleaved caspase-1, cleaved caspase-3 and IFNß mRNA expression. Moreover, C-176 increased phospho-AMPK under ALI conditions. Nonetheless, compound C partially reversed these beneficial effects. CONCLUSION: C-176, a selective STING inhibitor, improves intestinal ischemia-reperfusion-mediated ALI, and its underlying mechanism may be associated with AMPK signal activation.

Risk factors of pulmonary embolism in the elderly patients: a retrospective study.

AIM: We aimed to summarize the clinical feature and risk factors of patients suffering from pulmonary embolism (PE) in the elderly patients, and explore the change in D-dimer after anti-coagulant therapy. METHODS: A total of 426 patients with PE admitted from August 2012 to January 2019 in the Cangzhou Central Hospital were analyzed in this retrospective study. A comparison of clinical features and risk factors was conducted between the elderly group and non-elderly groups. Blood levels of D-dimer, C-reactive protein (CRP), tumor necrosis factor-α and interferon-γ were measured before and 3 days after anti-coagulant therapy in two groups. RESULTS: The most important risk factor for the elderly patients was stroke, while for non-elderly patients was deep vein thrombosis (DVT). After anti-coagulant therapy, the decreasing level of D-dimer and CRP showed statistically significant differences between the two groups. Between the elderly and non-elderly groups, the main clinical manifestations were similar. The risk factors of elderly patients were chronic obstructive pulmonary disease, malignant tumor, DVT and stroke. After anti-coagulant therapy, the content of D-dimer was lower than 3 days ago. CONCLUSION: Blood levels of D-dimer and CRP may be potent screening markers for PE especially among elderly patients.

LncRNA promoted inflammatory response in ischemic heart failure through regulation of miR-455-3p/TRAF6 axis.

OBJECTIVES: Ischemic heart failure (IHF) is the most common cause of death globally. Growing evidence shows abnormal expression of long non-coding RNAs in heart failure patients. This study aims to investigate the effect of sex-determining region Y-box 2 (SOX2) overlapping transcript (SOX2-OT) on the regulation of the inflammatory response in ischemic heart failure. METHODS: IHF rat and oxygen and glucose deprivation (OGD) cell models were established. qRT-PCR was employed to investigate the expression of SOX2-OT. ELISA, western blot and cell viability/apoptosis assays were performed to assess the effects of SOX2-OT. Online software program was used to identify miRNAs that target SOX2-OT, followed by validation using RNA pull-down. Potential targets of miRNAs were searched, and examined by immunoblotting, qRT-PCR and luciferase reporter assay. RESULTS: SOX2-OT was up-regulated in IHF and OGD. Knockdown of SOX2-OT promoted cell proliferation, decreased apoptosis rate and cell oxidative damage, and ameliorated inflammatory response. SOX2-OT contains binding sites for miR-455-3p, miR-5586-3p and miR-1252-5p. RNA pull-down confirmed the binding ability between SOX2-OT and miR-455-3p. TRAF6 is a direct target of miR-455-3p. Moreover, the regulatory activity of SOX2-OT on inflammatory response was partially through its negative regulation of miR-455-3p, which directly regulates TRAF6. Down-regulation of SOX2-OT improved myocardial dysfunction in IHF rat. CONCLUSIONS: Our results reveal that SOX2-OT may be a driver of IHF through repression of miR-455-3p, and miR-455-3p alleviates IHF by targeting TRAF6. Therefore, SOX2-OT/miR-455-3p/TRAF6 may be a potential target for advanced therapeutic strategy for IHF.

Effect of Particle Size Ratios on the Physical and Chemical Properties of Surgical-Grade Calcium Sulfate Hemihydrate.

OBJECTIVES: To analyze the optimum particle size or formula ratio of surgical-grade calcium sulfate (CS) for appropriate compressive strength, setting time, and vitro degradation rate. METHODS: Three types of calcium sulfate hemihydrate (CSH) particles with diameters of 0-37.5 µm, 37.5-75 µm, and >75 µm were screened. Based on formulation ratio of different particles, this topic is divided into 10 groups by the unconstrained third-order simplex lattice mixing design scheme in formula design experiment. The optimum formulation ratio of particle diameter for compressive strength, solidification time, and degradation rate in vitro was analyzed. RESULTS: When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm and >75 µm are 55.0%, 17.4%, and 27.6% respectively, the compressive strength of the test sample is the highest, which is 14.16 MPa. When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm, and >75 µm are 0.00%, 0.00%, and 100.00% respectively, the initial setting time of the sample is the longest, which is 410.0 s. When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm, and >75 µm are 0.00%, 0.00%, and 100.00% respectively, the final setting time of the sample is the largest, and the final setting time of the sample is 460.00 s. When the percentage of the particle diameter of CS with 0-37.5 µm, 37.5-75 µm, and >75 µm are 0.00%, 0.00%, and 100.00% respectively, the degradation rate of the sample in vitro is the slowest, which is 18.8%. CONCLUSION: The morphological structure of surgical-grade CS can affect compressive strength, setting time, and in vitro degradation rate. Surgical CS should be prepared based on different uses.

Effects of daily energy expenditure on academic performance of elementary students in Taiwan.

AIM: The objective of the study was to investigate the potential effects of daily energy expenditure on the academic performance (AP) of elementary schoolchildren, the results of which will be used as the basis of planning physical activity (PA) for children in the future. METHODS: Participants were collected from 4th to 6th grade children at an elementary school in southern Taiwan. The effective sample data size was 1065 (79.8%; 528 boys and 537 girls). Daily mean energy expenditure was obtained using the 3 Day Physical Activity Recall (3-DPAR), and the intensive activities degrees of physical activity were categorized into lowest PA, middle PA, and highest PA group, and academic performance assessed with weighted academic score. RESULTS: The significant effect on the academic performance of schoolchildren was only in energy expenditure but not for sexes and tutorials attended. All students in the middle PA group performed better academically than those in the highest PA group. After controlling sexes, male students in the middle PA group performed better than other groups; female students in the lowest PA group performed better than other groups. CONCLUSION: These results may be consulted by schools, academic faculties, and parents in setting up exercise plans for children.