Causal linkage between type 2 diabetes mellitus and inflammatory bowel disease: an integrated Mendelian randomization study and bioinformatics analysis

BackgroundObservational studies have indicated associations between type 2 diabetes mellitus (T2DM) and both colorectal cancer (CRC) and inflammatory bowel disease (IBD). However, the underlying causality and biological mechanisms between these associations remains unclear.MethodsWe conducted a bidirectional Mendelian randomization (MR) analysis employing summary statistics from genome-wide association studies involving European individuals. The inverse variance weighting (IVW) method was the primary method used to assess causality. Additionally, we applied MR Egger, Weighted median, Simple mode, and Weighted mode to evaluate the robustness of the results. Outliers were identified and eliminated using the MR-PRESSO, while the MR-Egger intercept was used to assess the horizontal pleiotropic effects of single nucleotide polymorphisms (SNPs). The heterogeneity was evaluated using the Cochrane Q test, and sensitivity analysis was performed using leave-one-out method. The F statistic was calculated to evaluate weak instrumental variable bias. Finally, a pilot bioinformatics analysis was conducted to explore the underlying biological mechanisms between T2DM and IBD/UC.ResultsThe IVW results demonstrated that T2DM significantly reduced risks of IBD (OR=0.885, 95% CI: 0.818–0.958, P=0.002) and ulcerative colitis (UC) (OR=0.887, 95% CI: 0.812–0.968, P=0.007). Although the 95% CIs of MR Egger, Weighted median, Simple mode, and Weighted mode were broad, the majority of their estimates were consistent with the direction of IVW. Despite significant heterogeneity among SNPs, no horizontal pleiotropy was observed. The leave-one-out analysis showed that the causality remained consistent after each SNP was removed, underscoring the reliability of the results. Reverse MR analysis indicated that genetic susceptibility to both CRC and IBD had no significant effect on the relative risk of T2DM. Ten hub genes were identified, which mainly enriched in pathways including maturity onset diabetes of the young, thyroid cancer, gastric acid secretion, longevity regulating pathway, melanogenesis, and pancreatic secretion.ConclusionThe presence of T2DM does not increase the risk of CRC or IBD. Moreover, T2DM might reduce risk of IBD, including UC. Conversely, the occurrence of CRC or IBD does not influence the risk of T2DM. The association between T2DM and IBD/UC may be related to the changes in multiple metabolic pathways and CTLA-4-mediated immune response

Varanoid Tooth Eruption and Implantation Modes in a Late Cretaceous Mosasaur

Erupting teeth are some of the oldest witnesses of developmental processes in the vertebrate fossil record and provide an important resource for vertebrate cladistics. Here we have examined a mosasaur jaw fragment from central Texas using ultrathin ground section histology and 3D tomographic imaging to assess features critical for the cladistic placement of mosasaurs among varanoids versus snakes: (i) the orientation of replacement teeth compared to the major tooth axis, (ii) the occurrence of resorption pits, and (iii) the mode of tooth implantation/attachment to the tooth bearing element. The replacement tooth studied here developed in an inclined position slightly distal of the deciduous parent tooth, similar to another varanoid squamate, the Gila monster Heloderma suspectum. Ground sections and tomographs also demonstrated that the replacement tooth attachment apparatus was entirely intact and that there was no evidence of mechanical deformation. Sections and tomographs further illustrated that the replacement tooth was located within a bony crypt and the inclination of the crypt matched the inclination of the replacement tooth. These preparations also revealed the presence of a resorption pit within the boundaries of the deciduous tooth that surrounded the developing replacement tooth. This finding suggests that developing mosasaur teeth developed within the walls of resorption pits similar to varanoid tooth germs and unlike developing snake teeth which are surrounded by fibrous connective tissue integuments. Finally, mosasaurs featured pseudo-thecodont tooth implantation with teeth anchored within a socket of mineralized tissue by means of a mineralized periodontal ligament. Together, these data indicate that the moderate inclination of the erupting mosasaur tooth studied here is neither a result of postmortem displacement nor a character representative of snakes, but rather a shared character between Mosasaurs and other varanoids such as Heloderma. In conjunction with the presence of resorption pits and the evidence for pseudothecodont tooth implantation, the tooth eruption and implantation characters described in the present study either place mosasaurs among the varanoids or suggest convergent evolution mechanisms between both clades, with mosasaurs evolving somewhat independently from a common varanoid ancestor

The Synthetic Biology Knowledge System

The Synthetic Biology Knowledge System (SBKS) is an instance of the SynBioHub repository that includes text and data information that has been mined from papers published in ACS Synthetic Biology. This paper describes the SBKS curation framework that is being developed to construct the knowledge stored in this repository. The text mining pipeline performs automatic annotation of the articles using natural language processing techniques to identify salient content such as key terms, relationships between terms, and main topics. The data mining pipeline performs automatic annotation of the sequences extracted from the supplemental documents with the genetic parts used in them. Together these two pipelines link genetic parts to papers describing the context in which they are used. Ultimately, SBKS will reduce the time necessary for synthetic biologists to find the information necessary to complete their designs. &nbsp;</p

Characterization of Biomimetically Enhanced Anorganic Graft Material for Bone Regenerative Applications

Clefts of the lip and palate are the most prevalent congenital craniofacial birth defects. Several surgeries are usually required to correct these defects and they involve extensive bone grafting procedures. From an orthodontic perspective, the aim of bone grafting at the alveolar cleft is to provide continuity and stabilization of the maxillary arch and to permit tooth eruption and orthodontic tooth movement. Although autologous bone graft is the gold standard, it requires a secondary surgical site and the risks of pain, morbidity, infection and scarring at donor site. Tissue engineering approaches that are aimed at improving the functionality of existing clinical materials may provide clinicians with new alternatives. Recently, biomimetic strategies that incorporate the native osteogenic extracellular matrix (ECM) within collagen-based materials have been developed to improve the osteoinductive nature of the biomaterials. This application will focus on utilizing this biomimetic strategy to integrate the osteoinductivity to a frequently used bone graft material Bio-Oss. For decade, Bio-Oss, the porous bone mineral substitute, has been widely and safely applied to dental bone grafting procedure. It is osteoconductive and functions primarily as a space maintainer. However, the clinical Bio-Oss® does not support cell attachment and is not osteoinductive. We hypothesize that: the biomimetically enhanced anorganic bone graft material will impart osteoinductivity by improving stem cell attachment, proliferation and osteogenic differentiation and, ultimately, facilitating new bone formation and remodeling. The goal of this research project was to establish a stable 3D pro-osteogenic ECM coating on Bio-Oss®, and investigate the improved osteoinductive capacity of the biomimetically enhanced Bio-Oss (BE Bio-Oss)by a series of in vitro and in vivo tests. Upon the SEM comparison, the particle size and surface morphologies of BE Bio-Oss demonstrated no difference compared to control but exhibited ECM fibers deposition. However, the HMSC proliferation and the expression of osteogenic marker genes, such as Runx2, Bmp2, colI, and OCN were increased significantly on BE-Bio-Oss. Applied the BE Bio-Oss and control Bio-Oss in the rat critical-sized calvarial bone defects, comparing the bone healing during 4-, 8- and 12-week periods, the µ-CT analysis showed that the bony content (BV/TV), bone structures and bone mineral density were different in BE-Bio-Oss group compare to the control. Under the histological analysis, the BE Bio-Oss demonstrated increased osteogenic cell infiltration and attachment on particle surface as well as enhanced particle remodeling and collagen deposition. Osteogenic markers proteins, DMP1, fibronectin, BMP2, TGFβ and osteocalcin, were strongly expressed in the experimental group compared to Bio-Oss controls. Together, our data indicate existing anorganic bone graft material, Bio-Oss, possess poor osteoinductive properites. The biomimetically enhanced Bio-Oss could promote better cell attachment, proliferation and osteogenic differentiation in vitro, and facilitate stem cell attachments, differentiation and mineralized tissue remodeling in vivo. Our results show a methodology to enhance existing anorganic clinical bone graft materials for improved osteoinductive ability

Ameloblastin Functions in Enamel, Periodontium and Long Bone

Though first introduced from developing enamel matrix, there is increasing evidence that ameloblastin (AMBN), first known as an adhesion molecule, is localized in other tissues such as bone, where it plays significant roles associated with mineral metabolism. To study the effect of AMBN in enamel formation, we overexpressed AMBN using a keratin 14 promoter and removed amelogenin (AMELX) by crossbreeding with AMELX null (amelx-/-) mice. Enamel coverings of amelx-/- mice and of the squamate Iguana were used for comparison. SEM analysis documented that AMBN transgenic (AMBN TG) × amelx-/- mouse molars were covered by a thin 'enameloid' layer resembling that the Iguana squamate. TEM revealed that the enamel of developing AMBN TG × amelx-/- mouse molars contained short and randomly oriented crystals. These studies illustrate that Ameloblastin-rich enamel matrix favors short and randomly oriented apatite crystals. To investigate AMBN function in the periodontium, we characterized the phenotype of the mandibular bone of AMBN overexpressor. Transgenic mice suffered from root cementum resorption. In an in vitro model of osteoclastogenesis, AMBN modulated osteoclast differentiation from bone marrow derived monocytes (BMMCs), demonstrated by dramatically increased osteoclast numbers and resorption pits, doubled BMMCs adhesion, accelerated cell spreading, and promoted actin ring formation. These effects were associated with elevated ERK1/2 phosphorylation as well as higher expression of osteoclast activation related genes. Blocking integrin α2β1 and ERK 1/2 pathways alleviated the effects of AMBN on osteoclast differentiation. These data indicate that Ameloblastin modulates osteoclastogenesis through the integrin/ERK pathway. Third part of our studies, we employed an AMBN-deficient mouse model (AMBNΔ5-6) to investigate AMBN function in long bone. AMBN mutants were delayed femur growth during the first 6. µ-CT documented decreases in bone mass which corresponded to the changes in femur biomechanical. Histological studies showed that AMBN mutation resulted in a shortened growth plate with less proliferating chondrocytes. In vitro studies indicated that bone marrow stromal cells (BMSCs) isolated from AMBN mutant had defects in cell proliferation and differentiation potential. PCR array and qRT-PCR analyses demonstrated down-regulation of several osteogensis-related growth factors in AMBN-deficient BMSCs. Together, our data indicate that AMBN is not only involved in tooth amelogenesis, but also functions outside of enamel in periodontal tissue homeostasis and long bone development and fracture healing

QRS Detection Based on Improved Adaptive Threshold

Cardiovascular disease is the first cause of death around the world. In accomplishing quick and accurate diagnosis, automatic electrocardiogram (ECG) analysis algorithm plays an important role, whose first step is QRS detection. The threshold algorithm of QRS complex detection is known for its high-speed computation and minimized memory storage. In this mobile era, threshold algorithm can be easily transported into portable, wearable, and wireless ECG systems. However, the detection rate of the threshold algorithm still calls for improvement. An improved adaptive threshold algorithm for QRS detection is reported in this paper. The main steps of this algorithm are preprocessing, peak finding, and adaptive threshold QRS detecting. The detection rate is 99.41%, the sensitivity (Se) is 99.72%, and the specificity (Sp) is 99.69% on the MIT-BIH Arrhythmia database. A comparison is also made with two other algorithms, to prove our superiority. The suspicious abnormal area is shown at the end of the algorithm and RR-Lorenz plot drawn for doctors and cardiologists to use as aid for diagnosis

Overcoming nitrite oxidizing bacteria adaptation through alternating sludge treatment with free nitrous acid and free ammonia

Stable suppression of nitrite oxidizing bacteria (NOB) is one of the major bottlenecks for achieving mainstream nitrite shunt or partial nitritation/anammox (PN/A). It is increasingly experienced that NOB could develop resistance to suppressions over an extended time, leading to failure of nitrite shunt or PN/A. This study reports and demonstrates the first effective strategy to overcome NOB adaptation through alternating sludge treatment with free nitrous acid (FNA) and free ammonia (FA). During over 650 days of reactor operation, NOB adaptation to both FNA and FA was observed, but the adaptation was successfully overcome by deploying the alternate treatment strategy. Microbial community analysis showed Nitrospira and Nitrobacter, the key NOB populations in the reactor, have the ability to adapt to FNA and FA, respectively, but do not adapt to the alternation. Stable nitrite shunt with nitrite accumulation ratio over 95% and excellent nitrogen removal were maintained for the last 10 months with only one alternation applied. NO emission increased initially as the attainment of nitrite shunt but exhibited a declining trend during the study. By using on-site-produced nitrite and ammonium, the proposed strategy is feasible and sustainable. This study brings the mainstream nitrite shunt and PN/A one step closer to wide applications

Infrared and Visible Image Fusion Based on Autoencoder Composed of CNN-Transformer

Image fusion model based on autoencoder network gets more attention because it does not need to design fusion rules manually. However, most autoencoder-based fusion networks use two-stream CNNs with the same structure as the encoder, which are unable to extract global features due to the local receptive field of convolutional operations and lack the ability to extract unique features from infrared and visible images. A novel autoencoder-based image fusion network which consist of encoder module, fusion module and decoder module is constructed in this paper. For the encoder module, the CNN and Transformer are combined to capture the local and global feature of the source images simultaneously. In addition, novel contrast and gradient enhancement feature extraction blocks are designed respectively for infrared and visible images to maintain the information specific to each source images. The feature images obtained from encoder module are concatenated by the fusion module and input to the decoder module to obtain the fused image. Experimental results on three datasets show that the proposed network can better preserve both the clear target and detailed information of infrared and visible images respectively, and outperforms some state-of-the-art methods in both subjective and objective evaluation. At the same time, the fused image obtained by our proposed network can acquire the highest mean average precision in the target detection which proves that image fusion is beneficial for downstream tasks

Influence of a Landslide on a Tunnel in Loess-Bedrock Ground

By combining model testing and numerical simulation, this paper focuses on the influence of landslides on tunnels in loess-bedrock strata by using the perfect landslide&ndash;tunnel system (LTS). A mechanical test and simulation (MTS) system was used to provide thrust for loading and unloading the trailing edge of the slope. A Particle Image Velocimetry (PIV) and 32 cluster strain gauges were adopted to monitor the deformation of the tunnel structure and landslide soil, and the sliding surface, respectively. By means of a numerical simulation, the deformation characteristics of a tunnel crossing loess-bedrock strata are comprehensively described. The influence of a cyclic load on the mechanical behavior and displacement of the tunnel and sliding surface is discussed in detail. The experimental results show that the thrust required for the first landslide is the largest, during multiple loading and unloading. With the increase in loading and unloading time, the sliding thrust gradually decreases and eventually remains stable. The landslide presents a progressive failure mode. There is a stress concentration in the upper part of the tunnel, which causes the secondary sliding phenomenon. The deformation of the sliding surface mainly occurs in the upper soil of the tunnel. The deformation direction of the tunnel is consistent with the sliding direction, and the deformation of the sliding surface mainly occurs in the soil above the tunnel. When disturbed by an external force, the tunnel deforms downward, and, when unloaded, the tunnel has a small rebound deformation. However, with the increase in loading&ndash;unloading times, the rebound deformation of the tunnel gradually decreases, and the permanent deformation gradually accumulates until the tunnel fails. The research results can provide reference for the construction and protection of tunnel engineering in loess regions, and have reference value for the control of tunnels crossing landslides