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A H2O2-responsive and plaque-penetrating S2P–CeO2–ASOs nanoplatform was developed for the effective silencing of mTOR and treatment of atherosclerosis., The mammalian target of rapamycin (mTOR) that controls autophagy and lipid metabolism is pivotal for atherosclerosis initiation and progression. Although blocking the mTOR function with rapamycin and its analogs may stimulate autophagy and consequently attenuate lipid storage and atherosclerotic lesions, only limited success has been achieved in clinical applications due to the unsatisfactory efficacy and safety profiles. In this study, we engineered a cerium oxide nanowire (CeO2 NW)-based RNA interference (RNAi) oligonucleotide delivery nanoplatform for the effective silencing of mTOR and treatment of atherosclerosis. This nanoplatform is composed of the following three key components: (i) a stabilin-2-specific peptide ligand (S2P) to improve plaque targeting and penetration; (ii) polyethylene glycosylation (PEGylation) to extend in vivo circulation time; and (iii) a high aspect ratio CeO2 core to facilitate endosome escape and ensure “on-demand” release of the RNAi payloads through competitive coordination of cytosolic hydrogen peroxide (H2O2). Systemic administration of the nanoplatforms efficiently targeted stabilin-2-expressing plaque and suppressed mTOR expression, which significantly rescued the impaired autophagy and inhibited the atherosclerotic lesion progression in apolipoprotein E-deficient (ApoE–/–) mice fed with a high-fat diet. These results demonstrated that this H2O2-responsive and plaque-penetrating nanoplatform can be a potent and safe tool for gene therapy of atherosclerosis.

We have developed a new fluorescent and photoacoustic dual-mode probe, ER-P, for the detection of ER polarity of liver tissues in normal and diabetic mice., As one of the complications of diabetes, liver injury results in significant hazards. Therefore, accurately diagnosing diabetes-induced liver injury beforehand is crucial for the warning and treatment of hepatic diseases. Diabetes-induced liver injury can cause changes in the microstructure and morphology of liver tissue, leading to changes in the hydrophilic and hydrophobic domains in the endoplasmic reticulum (ER), which is closely associated with changes in cellular ER polarity. So, differences in the ER polarity can indicate the degree of diabetes-induced liver injury. Herein, we develop a new fluorescent and photoacoustic dual-mode probe, ER-P, for detection of the ER polarity of liver tissue in normal and diabetic mice. Upon excitation with a 633 nm laser, ER-P showed increasing fluorescence intensity at 800 nm accompanying a decline in the polarity. Due to its polarity-sensitivity, ER-P was utilized for confocal fluorescence imaging in live cells, and the results demonstrate that ER-P can exclusively accumulate in the ER and indicate an increase in the polarity during ER stress. Importantly, ER-P displayed different absorbance intensities at 700 nm and 800 nm in different polarity environments because of intramolecular charge transfer. The photoacoustic intensity ratios between 700 nm and 800 nm will enable quantification of polarity to be achieved. The ratiometric photoacoustic imaging data demonstrate that the polarity of the liver tissue of diabetic mice is higher than that of the liver tissue of normal mice. Meanwhile, after treatment with the antidiabetic drug metformin, diabetic mice exhibit a reduced polarity environment in their liver tissue. The proposed study may serve as a new approach for the early diagnosis and therapeutic evaluation of diabetes-induced liver injury.

Here, a non-destructive amplification strategy is developed to image miRNAs in living cells, utilizing the enzyme-free hybridization chain reaction (HCR) with graphene oxide (GO) as a carrier. This provides a new tool for highly sensitive and simultaneous imaging of multiple low-level biomarkers, improving the accuracy of early disease diagnosis., In situ imaging of miRNA in living cells could facilitate the monitoring of the dynamic expression and distribution of miRNA and research on miRNA-related cellular processes and diseases. Given the low expression levels and even down-regulation of cellular miRNA that is associated with some diseases, amplification strategies are imperative for intracellular miRNA imaging. The present paper proposes a non-destructive amplification strategy for use in living cells. This amplification strategy utilizes the enzyme-free hybridization chain reaction (HCR) with graphene oxide (GO) as a carrier to image cellular miRNA. The resulting signal amplification provides excellent recognition and signal enhancement of specific miRNAs in living cells. As the fluorescence quencher and probe carrier, GO enables activation of the signal switch and effective intracellular delivery of amplification reagents. This new imaging method realizes simple, sensitive and non-destructive signal amplification of miRNA in living cells and has an ability to simultaneously image two types of miRNA in the same cell. This method supplies accurate information regarding cellular miRNA-related biological events and provides a new tool for highly sensitive and simultaneous imaging of multiple low-level biomarkers, thereby improving the accuracy of early disease diagnosis.

Table S1. The expression levels of the 153 targeted genes in brain. Table S2. The quality assurance (QA) /quality control (QC) of targeted sequencing. Table S3. The frequencies of different mutation locations in SCN1A gene and their corresponding phenotypes in Dravet syndrome patients. Table S4. The frequencies of different mutation types in SCN1A gene and their corresponding phenotypes in Dravet syndrome patients. (DOCX 98 kb)

Predicting the dynamic response of a floating and submerged structure subjected to underwater explosion is greatly complicated by the explosion of a high explosive, propagation of shock wave, bubble-pulse and complex fluid–structure interaction (FSI) phenomena. A numerical simulation has been carried out to examine the behavior of optimized composite elliptical submersible pressure hull to non-contact underwater explosion (UNDEX) and take the effect of bubble-pulse. Various explosive weights and explosion distances were explored to determine the critical weights and safe distance. The optimization process is performed using ANSYS parametric design language (APDL). After that the finite element package ABAQUS was used to model the UNDEX and the FSI phenomena. Time histories of the wet-surface displacement, velocity and Tsai–Hill failure index are presented for different composite plies. All of these results can be a valuable reference for designing underwater vehicles to resist UNDEX.

The design of laminated composite structures is very susceptible to changes in angle of fiber orientation and ply thickness. In the present work, different lay-up sequences for laminates including, cross-ply [0m/90n]s, [90m/0n]s and angle-ply [0m/±αn]s, [90m/±αn]s, [±α]ns, are analyzed. The lay-up sequence, orientation and ply number are optimized using three composite materials T700/epoxy composites, T300/Graphite/Epoxy and B(4)/5505 Boron/Epoxy. Minimize the buoyancy factor of the submersible pressure hull is considered as the objective function. The constraints based on the failure strength and the buckling strength of the pressure hull, incorporating both the Tsai–Wu and the maximum stress failure criteria. The finite element analysis and the optimization process are performed using ANSYS. Additionally, a sensitivity analysis is performed to study the influence of the design variables on the optimal structural strength design.

Multi-surface environments (MSEs) combine several of surfaces in a variety of physical arrangements to form a seamless information space. The large surfaces, such as tabletops and wall-displays are often used as a shared space to coordinate efforts, and handheld devices, such as tablets and smartphones are regarded as personal space supporting individual tasks. MSEs have shown benefits for supporting co-located activities, especially the ones involving rich data exploration, such as complex collaborative problem-solving and decision-making activities. However, the diversity of MSE also raises questions and challenges, as different configuration and devices factors of MSE can be suited for different kinds of activities, and developing collaborative activities in MSE remains complex. This dissertation studies how MSE can support users' collaboration in general, and collaborative learning specifically. It provides insights on how the configuration and form factors of devices in MSE shape users' collaborative behaviors, and offers implications on designing collaborative activities in MSE. It also contributes with a rapid prototyping tool, which can be easily used by non-experts, such as teachers, to create collaborative decision-making activities in MSE.; Les environnements multi-surfaces (MSE) combinent plusieurs surfaces dans une variété d'arrangements physiques pour former un espace d'information continu. Les grandes surfaces, telles que les tables et les écrans muraux, sont souvent utilisées comme espace partagé pour coordonner les efforts, et les périphériques portables, tels que les tablettes et les smartphones sont considérés comme des espaces personnels prenant en charge les tâches individuelles. Les MSE ont montré des avantages pour soutenir les activités co-implémentées, en particulier celles impliquant une exploration de données riches, telles que des activités collaboratives complexes de résolution de problèmes et de prise de décision. Cependant, la diversité des MSE soulève également des questions et des défis, car différents facteurs de configuration et dispositifs de MSE peuvent être adaptés à différents types d'activités, et le développement d'activités de collaboration dans les MSE reste complexe. Cette dissertation étudie comment les MSE peuvent soutenir la collaboration des utilisateurs en général et l'apprentissage collaboratif en particulier. Elle fournit des informations sur la façon dont la configuration et les facteurs de forme des périphériques des MSE façonnent les comportements collaboratifs des utilisateurs et propose des implications pour la conception d'activités collaboratives dans des MSE. Elle offre également un outil de prototypage rapide, qui peut être facilement utilisé par des non-experts, tels que des enseignants, afin de créer des activités de prise de décision collaboratives dans des MSE.

Multi-surface environments (MSEs) combine several of surfaces in a variety of physical arrangements to form a seamless information space. The large surfaces, such as tabletops and wall-displays are often used as a shared space to coordinate efforts, and handheld devices, such as tablets and smartphones are regarded as personal space supporting individual tasks. MSEs have shown benefits for supporting co-located activities, especially the ones involving rich data exploration, such as complex collaborative problem-solving and decision-making activities. However, the diversity of MSE also raises questions and challenges, as different configuration and devices factors of MSE can be suited for different kinds of activities, and developing collaborative activities in MSE remains complex. This dissertation studies how MSE can support users' collaboration in general, and collaborative learning specifically. It provides insights on how the configuration and form factors of devices in MSE shape users' collaborative behaviors, and offers implications on designing collaborative activities in MSE. It also contributes with a rapid prototyping tool, which can be easily used by non-experts, such as teachers, to create collaborative decision-making activities in MSE.; Les environnements multi-surfaces (MSE) combinent plusieurs surfaces dans une variété d'arrangements physiques pour former un espace d'information continu. Les grandes surfaces, telles que les tables et les écrans muraux, sont souvent utilisées comme espace partagé pour coordonner les efforts, et les périphériques portables, tels que les tablettes et les smartphones sont considérés comme des espaces personnels prenant en charge les tâches individuelles. Les MSE ont montré des avantages pour soutenir les activités co-implémentées, en particulier celles impliquant une exploration de données riches, telles que des activités collaboratives complexes de résolution de problèmes et de prise de décision. Cependant, la diversité des MSE soulève également des questions et des défis, car différents facteurs de configuration et dispositifs de MSE peuvent être adaptés à différents types d'activités, et le développement d'activités de collaboration dans les MSE reste complexe. Cette dissertation étudie comment les MSE peuvent soutenir la collaboration des utilisateurs en général et l'apprentissage collaboratif en particulier. Elle fournit des informations sur la façon dont la configuration et les facteurs de forme des périphériques des MSE façonnent les comportements collaboratifs des utilisateurs et propose des implications pour la conception d'activités collaboratives dans des MSE. Elle offre également un outil de prototypage rapide, qui peut être facilement utilisé par des non-experts, tels que des enseignants, afin de créer des activités de prise de décision collaboratives dans des MSE.

Aiming at discovering target customers, this article establishes the value assessment system for government & corporate customers according to the level, stability and accessibility of customer value. With 137 customers as samples, it builds the government & corporate customer value assessment system through analytic hierarchy process (AHP) and identifies target government & corpora te customers by indicator optimization, model fitting and cluster analysis. All these achievements help accurate identification of high-value government and corporate customers and optimization of resource allocation for customer service.

A numerical simulation has been carried out to examine the response of steel plates with different arrangement of stiffeners and subjected to noncontact underwater explosion (UNDEX) with different shock loads. Numerical analysis of the underwater explosion phenomena is implemented in the nonlinear finite element code ABAQUS/Explicit. The aim of this work is to enhance the dynamic response to resist UNDEX. Special emphasis is focused on the evolution of mid-point displacements. Further investigations have been performed to study the effects of including material damping and the rate-dependant material properties at different shock loads. The results indicate that stiffeners configurations and shock loads affect greatly the overall performance of steel plates and sensitive to the materials data. Also, the numerical results can be used to obtain design guidelines of floating structures to enhance resistance of underwater shock damage, since explosive tests are costly and dangerous.

National audience; Multi-surface environments (MSEs) are becoming increasingly common. They combine numerous surfaces in a variety of physical arrangements to support a wide range of tasks and interactions. In this context, my PhD research focuses on applying collaborative learning activities in MSEs, which includes exploring appropriate design of interactions and collaboration in MSEs, and providing a framework to rapidly develop collaborative learning activities in MSEs.