DNA Matrix Operation Based on the Mechanism of the DNAzyme Binding to Auxiliary Strands to Cleave the Substrate

Numerical computation is a focus of DNA computing, and matrix operations are among the most basic and frequently used operations in numerical computation. As an important computing tool, matrix operations are often used to deal with intensive computing tasks. During calculation, the speed and accuracy of matrix operations directly affect the performance of the entire computing system. Therefore, it is important to find a way to perform matrix calculations that can ensure the speed of calculations and improve the accuracy. This paper proposes a DNA matrix operation method based on the mechanism of the DNAzyme binding to auxiliary strands to cleave the substrate. In this mechanism, the DNAzyme binding substrate requires the connection of two auxiliary strands. Without any of the two auxiliary strands, the DNAzyme does not cleave the substrate. Based on this mechanism, the multiplication operation of two matrices is realized; the two types of auxiliary strands are used as elements of the two matrices, to participate in the operation, and then are combined with the DNAzyme to cut the substrate and output the result of the matrix operation. This research provides a new method of matrix operations and provides ideas for more complex computing systems

Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in Vitro

Background/Aims: Psoralen and bakuchiol are the main active compounds found in the traditional Chinese medicine Psoralea corylifolia L., and have been used to treat osteoporosis. This study aims to investigate the anti-osteoporosis effects of these two compounds using osteoclasts precursor differentiation and bone absorption assays in vitro. Methods: Primary mouse osteoclasts precursor cells were induced by M-CSF (macrophage colony stimulating factor) plus RANKL (receptor activator of nuclear factor kappa-B ligand) in vitro. TRACP (tartrate-resistant acid phosphatase) enzyme activity and toluidine blue staining were used to observe the effects of psoralen and bakuchiol on osteoclast differentiation and bone resorption, respectively. Gelatin zymography was used to assess MMP (matrix metalloproteinase) activity, and ELISA was performed to measure cathepsin K activity. Western blotting analysis for expression of phosphorylated AKT, ERK, NF-kB, and c-jun; and immunofluorescence analysis for c-jun and p65 nuclear translocation in induced osteoclasts were then used to determine the mechanism of anti-bone resorption of psoralen and bakuchiol. Results: Mature osteoclasts were induced by M-CSF plus RANKL from primary bone marrow macrophages in vitro. Both psoralen and bakuchiol significantly inhibited TRACP enzyme activity and slightly decreased the number of TRACP+ multinuclear osteoclasts induced by M-CSF plus RANKL. Bakuchiol significantly decreased bone lacunae area and attenuated MMP-2 activity induced by M-CSF plus RANKL in osteoclasts. Both psoralen and bakuchiol significantly decreased the expression and nuclear translocation of phosphorylated c-jun stimulated by M-CSF plus RANKL, but no significant effect on p65 translocation was observed in osteoclasts. Additionally, bakuchiol significantly attenuated the increased of M-CSF plus RANKL-induced phosphorylation of AKT in osteoclasts. Conclusions: Psoralen and bakuchiol ameliorated M-CSF plus RANKL-induced osteoclast differentiation and bone resorption via inhibition of AKT and AP-1 pathways activation in vitro

A Potential Role for the Inhibition of PI3K Signaling in Glioblastoma Therapy

Glioblastoma multiforme (GBM) is the most common primary brain tumor and among the most difficult to treat malignancies per se. In almost 90% of all GBM alterations in the PI3K/Akt/mTOR have been found, making this survival cascade a promising therapeutic target, particular for combination therapy that combines an apoptosis sensitizer, such as a pharmacological inhibitor of PI3K, with an apoptosis inducer, such as radio- or chemotherapy. However, while in vitro data focusing mainly on established cell lines has appeared rather promising, this has not translated well to a clinical setting. In this study, we analyze the effects of the dual kinase inhibitor PI-103, which blocks PI3K and mTOR activity, on three matched pairs of GBM stem cells/differentiated cells. While blocking PI3K-mediated signaling has a profound effect on cellular proliferation, in contrast to data presented on two GBM cell lines (A172 and U87) PI-103 actually counteracts the effect of chemotherapy. While we found no indications for a potential role of the PI3K signaling cascade in differentiation, we saw a clear and strong contribution to cellular motility and, by extension, invasion. While blocking PI3K-mediated signaling concurrently with application of chemotherapy does not appear to be a valid treatment option, pharmacological inhibitors, such as PI-103, nevertheless have an important place in future therapeutic approaches

The migration of neighboring and antagonist teeth three months after implant placement in healed single tooth-missing sites

Objectives: To quantify the neighboring and antagonist teeth migration of a single posterior tooth-missing site within 3 months using digital scanning and measuring techniques. Materials and methods: Intraoral scans (IOS) were made in 40 patients presenting a single posterior tooth-missing gap and receiving implant therapy. IOS were obtained at the day of and three months after implant surgery rendering a digital baseline model (BM) and a digital follow-up model (FM). Digital models were superimposed using the implant scan body as reference. Antagonist models were processed by the best fit alignment. Dimensional change between anatomical landmarks on neighboring teeth and that of featuring points on antagonistic teeth were measured using a three-dimensional analysis software. The Mann-Whitney U test was applied to compare the tooth-moving distance between the mesial and distal neighboring teeth. The Kruskal-Wallis one-way ANOVA was used to test the difference in dimensional change in tooth-missing site among age subgroups. Results: The mean dimensional change in the tooth-missing site was -37.62 ± 106.36 μm (median: -28.33 μm, Q25 -72.65/Q75 38.97) mesial-distally and -67.91 ± 42.37 μm (median: -61.50 μm, Q25 -88.25/Q75 -36.75) occlusal-gingivally. Eighteen out of 40 mesial neighboring teeth and 24 out of 40 distal neighboring teeth showed migration towards the implants. When patients were grouped according to age, the mesial-distal reduction in the tooth-missing site was significantly larger in patients younger than 30 years compared with those older than 50 years (p < .05). Conclusions: The dimensions of posterior tooth-missing sites decreased over an observation period of 3 months. Keywords: dental implants; digital; three-dimensional; tooth migration; tooth movement

Sanger Sequencing for BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del Mutation Screen on Pap Smear Cytology Samples

Three sets of polymerase chain reaction (PCR) primers were designed for heminested PCR amplification of the target DNA fragments in the human genome which include the site of BRCA1 c.68_69del, BRCA1 c.5266dup and BRCA2 c.5946del respectively, to prepare the templates for direct Sanger sequencing screen of these three founder mutations. With a robust PCR mixture, crude proteinase K digestate of the fixed cervicovaginal cells in the liquid-based Papanicolaou (Pap) cytology specimens can be used as the sample for target DNA amplification without pre-PCR DNA extraction, purification and quantitation. The post-PCR products can be used directly as the sequencing templates without further purification or quantitation. By simplifying the frontend procedures for template preparation, the cost for screening these three founder mutations can be reduced to about US $200 per test when performed in conjunction with human papillomavirus (HPV) assays now routinely ordered for cervical cancer prevention. With this projected price structure, selective patients in a high-risk population can be tested and each provided with a set of DNA sequencing electropherograms to document the absence or presence of these founder mutations in her genome to help assess inherited susceptibility to breast and ovarian cancer in this era of precision molecular personalized medicine

Time efficiency and quality of outcomes in a model-free digital workflow using digital impression immediately after implant placement: A double-blind self-controlled clinical trial

OBJECTIVE To assess the clinical and laboratory time efficiency and quality of outcomes for posterior single implant crowns by means of a model-free digital workflow using digital impressions immediately after implant placement. METHODS Forty patients missing a single posterior tooth received implant therapy. For within-subject comparison, digital impressions were taken immediately after implant placement and conventional impressions after implant healing. Two monolithic zirconia crowns were fabricated using a laboratory-based CAD-CAM system. One crown was produced from the immediate digital impression and a model-free digital workflow (test group), and the second crown was produced from the conventional impression and a hybrid workflow (control group). Clinical and laboratory time was recorded. Quality of outcomes was evaluated double-blinded. A paired-sample t test was applied for statistical analysis. RESULTS The total mean chairside time (impression and delivery) was 23.2 min (95%CI 22.2, 24.3) in the test group and 25.7 min (95%CI 24.4, 26.9) in the control group (p = 0.013). Significantly less laboratory time was needed in the model-free digital workflow (13.6 min, 95%CI 11.5, 15.6) as compared to the model-based hybrid workflow (29.9 min, 95%CI 25.7, 34.2) (p < 0.05). At crown delivery, 4/40 (test) and 12/40 (control) had no need of chairside adjustments, and 6/40 (test) and 5/40 (control) implant crowns were in need of additional laboratory interventions. CONCLUSION The fabrication of posterior single implant crowns using digital impressions taken immediately after implant placement and a model-free, laboratory-based digital workflow was more time efficient and resulted in similar quality of outcomes as a hybrid workflow using conventional impressions

Interaction of Stellate Cells with Pancreatic Carcinoma Cells

cancer

Photosynthesis Product Allocation and Yield in Sweet Potato in Response to Different Late-Season Irrigation Levels

Soil water deficit is an important factor affecting the source–sink balance of sweet potato during its late-season growth, but water regulation during this period has not been well studied. Therefore, the aim of this study was to determine the appropriate irrigation level in late-season sweet potato, and the effect of irrigation level on accumulation and allocation of photosynthetic products. In this study, two yield-based field trials (2021–2022) were conducted in which five late-season irrigation levels set according to the crop evapotranspiration rate were tested (T0: non-irrigation, T1: 33% ETc, T2: 75% ETc, T3: 100% ETc, T4: 125% ETc). The effects of the different irrigation levels on photosynthetic physiological indexes, 13C transfer allocation, water use efficiency (WUE), water productivity (WP), and the yield and economic benefit of sweet potato were studied. The results showed that late-season irrigation significantly increased the total chlorophyll content and net photosynthetic rate of functional leaves, in addition to promoting the accumulation of above-ground-source organic biomass (p 13C allocation, maximum accumulation rate (Vmax), and average accumulation rate (Vmean) of dry matter in storage root were significantly higher under T2 irrigation than under the other treatments (p 0) and over-irrigation (T4) were not conducive to the transfer and allocation of photosynthetic products to storage roots in late-season sweet potato. However, moderate irrigation (T2) effectively promoted the source–sink balance, enhanced the source photosynthetic rate and stimulated the sink activity, such that more photosynthate was allocated to the storage sink. The results also showed that T2 irrigation treatments significantly increased yield, WUE and WP compared to T0 and T4 (p 2) can significantly promote the potential of storage root production and field productivity. There was a close relationship between economic benefit and marketable sweet potato yield, and both were highest under T2 (p 0 over the two-year study period. In conclusion, irrigation of late-season sweet potato with 75% evapotranspiration (T2) can improve both the yield and production potential. Together, these results support the use of late-season water management in the production of sweet potato

Effect of microRNA-135a on Cell Proliferation, Migration, Invasion, Apoptosis and Tumor Angiogenesis Through the IGF-1/PI3K/Akt Signaling Pathway in Non-Small Cell Lung Cancer

Objective: This study explored the ability of microRNA-135a (miR-135a) to influence cell proliferation, migration, invasion, apoptosis and tumor angiogenesis through the IGF-1/PI3K/Akt signaling pathway in non-small cell lung cancer (NSCLC). Methods: NSCLC tissues and adjacent normal tissues were collected from 138 NSCLC patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-135a and IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 mRNA; western blotting was used to determine the expression levels of IGF-1, PI3K and Akt protein; and enzyme-linked immunosorbent assay (ELISA) was used to analyze the expression levels of VEGF, bFGF and IL-8 protein. Human NSCLC cell lines (A549, H460, and H1299) and the human bronchial epithelial cell line (HBE) were selected. A549 cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, IGF-1 siRNA and miR-135a inhibitors + IGF-1 siRNA groups. The following were performed: an MTT assay to assess cell proliferation, a scratch test to detect cell migration, a Transwell assay to measure cell invasion, and a flow cytometry to analyze cell apoptosis. Results: The expression level of miR-135a was lower while those of IGF-1, PI3K and Akt mRNA were higher in NSCLC tissues than in the adjacent normal tissues. Dual-luciferase reporter assay indicated IGF-1 as a target of miR-135a. The in vitro results showed that compared with the blank group, cell proliferation, migration and invasion were suppressed, mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 were reduced, and cell apoptosis was enhanced in the miR-135a mimics and IGF-1 siRNA groups. Compared with the IGF-1 siRNA group, cells in the miR-135a inhibitors + IGF-1 siRNA group demonstrated increased cell proliferation, migration and invasion, elevated mRNA and protein levels of IGF-1, PI3K, Akt, VEGF, bFGF and IL-8 and reduced cell apoptosis. Conclusion: These findings indicated that miR-135a promotes cell apoptosis and inhibits cell proliferation, migration, invasion and tumor angiogenesis by targeting IGF-1 gene through the IGF-1/PI3K/Akt signaling pathway in NSCLC