Plasminogen activator inhibitor 1: mechanisms of its synergistic regulation by growth factors

As the major physiological inhibitor of plasminogen activator (PA), the type I plasminogen activator inhibitor (PAI-1) is important for controlling blood clotting and tissue remodeling events such as those that involve cell migration. The changing needs for protease activity under various physiological conditions necessitates a tight cellular control of gene expression to enable rapid changes in the levels of PAI-1 and PA activity. Cooperation between epidermal growth factor (EGF) and transforming growth factor-β (TGF-β) dramatically increase PAI-1 protein level. In this study, we found activators of tyrosine kinase (EGF, FGF, IGF-I and TNF α) or an activator of PKC (PMA) synergize with TGF- β in stimulation of PAI-1. The mechanism by which EGF and TGFyβ synergistically increase PAI-1 expression was explored. TGF-β increases the sensitivity of the cells to EGF, thereby recruiting EGF at suboptimal concentrations to contribute to the synergistic activation of PAI-1. The contribution of EGF to the regulation of PAI involves the MAPK pathway and the synergistic interface with the TGF-β pathway is downstream of MEK and neither involves phosphorylation of Erk1/2 nor Smad2/3. EGF and TGF-β synergistically increase PAI-1 transcription that involves cooperation between transcription factors Smad and AP-1. This increase of PAI-1 mRNA is further amplified by a decrease in the rate of mRNA degradation, the latter being regulated only by EGF. This work demonstrates the existence of a multidimensional cellular mechan€ism by which EGF and TGF-β are able to promote large and rapid changes in PAI-1 expression. Identification of regions on mRNAs that are accessible for hybridization in the living cell is required for antisense and RNAi technologies and for accurate prediction of authentic targets of microRNAs. Although the sequence of an mRNA holds some useful information, the secondary and tertiary RNA structure determines access for hybridization. Because in vivo assays are very time consuming and expensive, computational and cell culture analysis have been utilized with varying success for identifying effective oligonucleotide inhibitors. With the advent of microarray spotters and readers as standard equipment in many research facilities, this approach to analyze RNA for accessible regions is worthy of investigation for its application to identify antisense and RNAi targets. We have utilized a tiled microarray format to investigate the accessible regions in two mRNAs (Bcl2 and Lcn2) and compared this with cell culture and computational approaches for predicting accessible targets for antisense oligodeoxynucleotides (ODNs) and siRNAs. Our results suggest that a tiled microarray is an effective means of identifying the mRNA regions that are accessible to antisense ODNs and RNAi

Community-based Message Opportunistic Transmission

Mobile Social Networks (MSNs) is a kind of opportunistic networks, which is composed of a large number of mobile nodes with social characteristic. Up to now, the prevalent communitybased routing algorithms mostly select the most optimal social characteristic node to forward messages. But they almost don\u27t consider the effect of community distribution on mobile nodes and the time-varying characteristic of network. These algorithms usually result in high consumption of network resources and low successful delivery ratio if they are used directly in mobile social networks. We build a time-varying community-based network model, and propose a community-aware message opportunistic transmission algorithm (CMOT) in this paper. For inter-community messages transmission, the CMOT chooses an optimal community path by comparing the community transmission probability. For intra-community in local community, messages are forwarded according to the encounter probability between nodes. The simulation results show that the CMOT improves the message successful delivery ratio and reduces network overhead obviously, compared with classical routing algorithms, such as PRoPHET, MaxProp, Spray and Wait, and CMTS

Effects of OMMT on the aging behaviors of halogen-antimony flame-retarded LGFPA6 composites: Flammability and thermal degradation kinetics

After a long-term thermo-oxidative exposure, compared to the long-glass-fiber reinforced polyamide 6 composite containing halogen-antimony flame retardants (FR/LGFPA6), substitution of a certain content of flame retardants with organo-modified montmorillonite (OMMT) was found to positively affect the FR/LGFPA6 composite in some cases (i.e. flammability and thermal degradation kinetics). The aged OMMT/FR/LGFPA6 composite not only was less flammable but also behaved better in the formation of char residues. All the calculated apparent activation energy obtained by the methods of Friedman, Flynn-Wall-Ozawa and Coats- Redfern in a dynamic measurement showed an obvious increase for the OMMT/FR/LGFPA6 composite after aging, a theoretical evidence for its improved flame retardancy

Morphology-Enhanced CAM-Guided SAM for weakly supervised Breast Lesion Segmentation

Breast cancer diagnosis challenges both patients and clinicians, with early detection being crucial for effective treatment. Ultrasound imaging plays a key role in this, but its utility is hampered by the need for precise lesion segmentation-a task that is both time-consuming and labor-intensive. To address these challenges, we propose a new framework: a morphology-enhanced, Class Activation Map (CAM)-guided model, which is optimized using a computer vision foundation model known as SAM. This innovative framework is specifically designed for weakly supervised lesion segmentation in early-stage breast ultrasound images. Our approach uniquely leverages image-level annotations, which removes the requirement for detailed pixel-level annotation. Initially, we perform a preliminary segmentation using breast lesion morphology knowledge. Following this, we accurately localize lesions by extracting semantic information through a CAM-based heatmap. These two elements are then fused together, serving as a prompt to guide the SAM in performing refined segmentation. Subsequently, post-processing techniques are employed to rectify topological errors made by the SAM. Our method not only simplifies the segmentation process but also attains accuracy comparable to supervised learning methods that rely on pixel-level annotation. Our framework achieves a Dice score of 74.39% on the test set, demonstrating compareable performance with supervised learning methods. Additionally, it outperforms a supervised learning model, in terms of the Hausdorff distance, scoring 24.27 compared to Deeplabv3+'s 32.22. These experimental results showcase its feasibility and superior performance in integrating weakly supervised learning with SAM. The code is made available at: https://github.com/YueXin18/MorSeg-CAM-SAM

Activated Protein C Induces Endoplasmic Reticulum Stress and Attenuates Lipopolysaccharide-Induced Apoptosis Mediated by Glycogen Synthase Kinase-3β

This study investigated the relationship between antiapoptotic activities induced by activated protein C and endoplasmic reticulum stress. In this study, it was observed that activated protein C elicited a rise in glucose-regulated protein 78 and glycogen synthase kinase-3β and inhibited apoptosis in human umbilical vein endothelial cells induced by lipopolysaccharide. Calcium inhibition did not alter the antiapoptotic effect of activated protein C. The antiapoptotic efficiency of activated protein C was reduced in human umbilical vein endothelial cells following treatment with glycogen synthase kinase-3β-siRNA. In summary, activated protein C induced endoplasmic reticulum stress and attenuated lipopolysaccharide-induced human umbilical vein endothelial cell apoptosis mediated by glycogen synthase kinase-3β

A single-step preparation of carbohydrate functionalized monoliths for separation and trapping of polar compounds

A single-step copolymerization strategy was developed for the preparation of carbohydrate (glucose and maltose) functionalized monoliths using click reaction. Firstly, novel carbohydrate-functionalized methacrylate monomers were synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition (alkyne-azide reaction) of terminal alkyne with azide of carbohydrate derivatives. The corresponding carbohydrate functionalized monolithic columns were then prepared through a single-step in-situ copolymerization. The physicochemical properties and performance of the fabricated monolithic columns were evaluated using scanning electron microscopy, Fourier-transform infrared spectroscopy, and nano-liquid chromatography. For the optimized monolithic column, satisfactory column permeability and good separation performance were demonstrated for polar compounds including nucleoside, phenolic compounds and benzoic acid derivatives. The monolithic column is also highly useful for selective and efficient enrichment of glycopeptides from human IgG tryptic digests. This study not only provided a novel hydrophilic column for separation and selective trapping of polar compounds, but also proposed a facile and efficient approach for preparing carbohydrate functionalized monoliths

Cytoplasmic-genetic male sterility gene provides direct evidence for some hybrid rice recently evolving into weedy rice

Weedy rice infests paddy fields worldwide at an alarmingly increasing rate. There is substantial evidence indicating that many weedy rice forms originated from or are closely related to cultivated rice. There is suspicion that the outbreak of weedy rice in China may be related to widely grown hybrid rice due to its heterosis and the diversity of its progeny, but this notion remains unsupported by direct evidence. We screened weedy rice accessions by both genetic and molecular marker tests for the cytoplasmic male sterility (CMS) genes (Wild abortive, WA, and Boro type, BT) most widely used in the production of indica and japonica three-line hybrid rice as a diagnostic trait of direct parenthood. Sixteen weedy rice accessions of the 358 tested (4.5%) contained the CMS-WA gene; none contained the CMS-BT gene. These 16 accessions represent weedy rices recently evolved from maternal hybrid rice derivatives, given the primarily maternal inheritance of this trait. Our results provide key direct evidence that hybrid rice can be involved in the evolution of some weedy rice accessions, but is not a primary factor in the recent outbreak of weedy rice in China