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Yan Ji,1 Haorong Li,1 Jiguo Li,2 Guangqiang Yang,1 Wenli Zhang,1 Yan Shen,1 Bohui Xu,3 Jianping Liu,1 Jingyuan Wen,4 Wenting Song1 1Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China; 2Nanjing Miaobang Meiye Enterprise Management Co, LTD, Nanjing, People’s Republic of China; 3School of Pharmacy, Nantong University, Nantong, 226001, People’s Republic of China; 4School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New ZealandCorrespondence: Wenting Song, Department of Pharmaceutics, School of Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing, 211198, People’s Republic of China, Email songwenting908@163.com Jingyuan Wen, School of Pharmacy, Faculty of Medical and Health Sciences, the University of Auckland, Auckland, New Zealand, Email j.wen@auckland.ac.nzPurpose: Acne vulgaris is a chronic inflammatory skin disorder centered on hair follicles, making hair follicle-targeted delivery of anti-acne drugs a promising option for acne treatment. However, current researches have only focused on the delivering to healthy hair follicles, which are intrinsically different from pathologically clogged hair follicles in acne vulgaris.Patients and Methods: Azelaic acid (AZA) micro/nanocrystals with different particle sizes were prepared by wet media milling or high-pressure homogenization. An experiment on AZA micro/nanocrystals delivering to healthy hair follicles was carried out, with and without the use of physical enhancement techniques. More importantly, it innovatively designed an experiment, which could reveal the ability of AZA micro/nanocrystals to penetrate the constructed clogged hair follicles. The anti-inflammatory and antibacterial effects of AZA micro/nanocrystals were evaluated in vitro using a RAW264.7 cell model stimulated by lipopolysaccharide and a Cutibacterium acnes model. Finally, both the anti-acne e

Remote photoplethysmography (rPPG) technique extracts blood volume pulse (BVP) signals from subtle pixel changes in video frames. This study introduces rFaceNet, an advanced rPPG method that enhances the extraction of facial BVP signals with a focus on facial contours. rFaceNet integrates identity-specific facial contour information and eliminates redundant data. It efficiently extracts facial contours from temporally normalized frame inputs through a Temporal Compressor Unit (TCU) and steers the model focus to relevant facial regions by using the Cross-Task Feature Combiner (CTFC). Through elaborate training, the quality and interpretability of facial physiological signals extracted by rFaceNet are greatly improved compared to previous methods. Moreover, our novel approach demonstrates superior performance than SOTA methods in various heart rate estimation benchmarks., Comment: under-review

This study harnesses state-of-the-art AI technology for chronic disease management, specifically in detecting various mental disorders through user-generated textual content. Existing studies typically rely on fully supervised machine learning, which presents challenges such as the labor-intensive manual process of annotating extensive training data for each disease and the need to design specialized deep learning architectures for each problem. To address such challenges, we propose a novel framework that leverages advanced AI techniques, including large language models and multi-prompt engineering. Specifically, we address two key technical challenges in data-driven chronic disease management: (1) developing personalized prompts to represent each user's uniqueness and (2) incorporating medical knowledge into prompts to provide context for chronic disease detection, instruct learning objectives, and operationalize prediction goals. We evaluate our method using four mental disorders, which are prevalent chronic diseases worldwide, as research cases. On the depression detection task, our method (F1 = 0.975~0.978) significantly outperforms traditional supervised learning paradigms, including feature engineering (F1 = 0.760) and architecture engineering (F1 = 0.756). Meanwhile, our approach demonstrates success in few-shot learning, i.e., requiring only a minimal number of training examples to detect chronic diseases based on user-generated textual content (i.e., only 2, 10, or 100 subjects). Moreover, our method can be generalized to other mental disorder detection tasks, including anorexia, pathological gambling, and self-harm (F1 = 0.919~0.978).

Text-to-3D scene generation holds immense potential for the gaming, film, and architecture sectors. Despite significant progress, existing methods struggle with maintaining high quality, consistency, and editing flexibility. In this paper, we propose DreamScene, a 3D Gaussian-based novel text-to-3D scene generation framework, to tackle the aforementioned three challenges mainly via two strategies. First, DreamScene employs Formation Pattern Sampling (FPS), a multi-timestep sampling strategy guided by the formation patterns of 3D objects, to form fast, semantically rich, and high-quality representations. FPS uses 3D Gaussian filtering for optimization stability, and leverages reconstruction techniques to generate plausible textures. Second, DreamScene employs a progressive three-stage camera sampling strategy, specifically designed for both indoor and outdoor settings, to effectively ensure object-environment integration and scene-wide 3D consistency. Last, DreamScene enhances scene editing flexibility by integrating objects and environments, enabling targeted adjustments. Extensive experiments validate DreamScene's superiority over current state-of-the-art techniques, heralding its wide-ranging potential for diverse applications. Code and demos will be released at https://dreamscene-project.github.io .

Depression is a common disease worldwide. It is difficult to diagnose and continues to be underdiagnosed. Because depressed patients constantly share their symptoms, major life events, and treatments on social media, researchers are turning to user-generated digital traces on social media for depression detection. Such methods have distinct advantages in combating depression because they can facilitate innovative approaches to fight depression and alleviate its social and economic burden. However, most existing studies lack effective means to incorporate established medical domain knowledge in depression detection or suffer from feature extraction difficulties that impede greater performance. Following the design science research paradigm, we propose a Deep Knowledge-aware Depression Detection (DKDD) framework to accurately detect social media users at risk of depression and explain the critical factors that contribute to such detection. Extensive empirical studies with real-world data demonstrate that, by incorporating domain knowledge, our method outperforms existing state-of-the-art methods. Our work has significant implications for IS research in knowledge-aware machine learning, digital traces utilization, and NLP research in IS. Practically, by providing early detection and explaining the critical factors, DKDD can supplement clinical depression screening and enable large-scale evaluations of a population's mental health status., Comment: Presented at INFORMS 2022 Data Science Workshop

Virtual health has been acclaimed as a transformative force in healthcare delivery. Yet, its dropout issue is critical that leads to poor health outcomes, increased health, societal, and economic costs. Timely prediction of patient dropout enables stakeholders to take proactive steps to address patients' concerns, potentially improving retention rates. In virtual health, the information asymmetries inherent in its delivery format, between different stakeholders, and across different healthcare delivery systems hinder the performance of existing predictive methods. To resolve those information asymmetries, we propose a Multimodal Dynamic Knowledge-driven Dropout Prediction (MDKDP) framework that learns implicit and explicit knowledge from doctor-patient dialogues and the dynamic and complex networks of various stakeholders in both online and offline healthcare delivery systems. We evaluate MDKDP by partnering with one of the largest virtual health platforms in China. MDKDP improves the F1-score by 3.26 percentage points relative to the best benchmark. Comprehensive robustness analyses show that integrating stakeholder attributes, knowledge dynamics, and compact bilinear pooling significantly improves the performance. Our work provides significant implications for healthcare IT by revealing the value of mining relations and knowledge across different service modalities. Practically, MDKDP offers a novel design artifact for virtual health platforms in patient dropout management.

Effectively representing medical concepts and patients is important for healthcare analytical applications. Representing medical concepts for healthcare analytical tasks requires incorporating medical domain knowledge and prior information from patient description data. Current methods, such as feature engineering and mapping medical concepts to standardized terminologies, have limitations in capturing the dynamic patterns from patient description data. Other embedding-based methods have difficulties in incorporating important medical domain knowledge and often require a large amount of training data, which may not be feasible for most healthcare systems. Our proposed framework, MD-Manifold, introduces a novel approach to medical concept and patient representation. It includes a new data augmentation approach, concept distance metric, and patient-patient network to incorporate crucial medical domain knowledge and prior data information. It then adapts manifold learning methods to generate medical concept-level representations that accurately reflect medical knowledge and patient-level representations that clearly identify heterogeneous patient cohorts. MD-Manifold also outperforms other state-of-the-art techniques in various downstream healthcare analytical tasks. Our work has significant implications in information systems research in representation learning, knowledge-driven machine learning, and using design science as middle-ground frameworks for downstream explorative and predictive analyses. Practically, MD-Manifold has the potential to create effective and generalizable representations of medical concepts and patients by incorporating medical domain knowledge and prior data information. It enables deeper insights into medical data and facilitates the development of new analytical applications for better healthcare outcomes., Comment: The initial version was presented at the 54th Hawaii International Conference on System Sciences. http://hdl.handle.net/10125/71209

Ni Fang,1,2,* Jia Liu,1,* Jingxin Hou,1,2 Yixin Zhong,1,2 Ying Luo,1,2 Liu Hu,1,2 Wenli Zhang,1,2 Junrui Wang,1,2 Jie Xu,1 Jun Zhou,1 Yu Zhang,1 Haitao Ran,2 Dajing Guo1 1Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dajing Guo, Email guodaj@163.comBackground: Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability.Materials and Methods: In the bionic system, gelatin was chosen as a carrier, and Fe3O4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide.Results: In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in viv

Carcinomas are characterized by a widespread upregulation of intercellular junctions that create a barrier to immune response and drug therapy. Desmoglein 2 (DSG2) represents such a junction protein and serves as one adenovirus receptor. Importantly, the interaction between human adenovirus type 3 (Ad3) and DSG2 leads to the shedding of the binding domain followed by a decrease in the junction protein expression and transient tight junction opening. Junction opener 4 (JO-4), a small recombinant protein derived from the Ad3 fiber knob, was previously developed with a higher affinity to DSG2. JO-4 protein has been proven to enhance the effects of antibody therapy and chemotherapy and is now considered for clinical trials. However, the effect of the JO4 mutation in the context of a virus remains insufficiently studied. Therefore, we introduced the JO4 mutation to various adenoviral vectors to explore their infection properties. In the current experimental settings and investigated cell lines, the JO4-containing vectors showed no enhanced transduction compared with their parental vectors in DSG2-high cell lines. Moreover, in DSG2-low cell lines, the JO4 vectors presented a rather weakened effect. Interestingly, DSG2-negative cell line MIA PaCa-2 even showed resistance to JO4 vector infection, possibly due to the negative effect of JO4 mutation on the usage of another Ad3 receptor: CD46. Together, our observations suggest that the JO4 vectors may have an advantage to prevent CD46-mediated sequestration, thereby achieving DSG2-specific transduction.

To develop adenoviral cell- or tissue-specific gene delivery, understanding of the infection mechanisms of adenoviruses is crucial. Several adenoviral attachment proteins such as CD46, CAR and sialic acid have been identified and studied. However, most receptor studies were performed on non-human cells. Combining our reporter gene-tagged adenovirus library with an in vitro human gene knockout model, we performed a systematic analysis of receptor usage comparing different adenoviruses side-by-side. The CRISPR/Cas9 system was used to knockout CD46 and CAR in the human lung epithelial carcinoma cell line A549. Knockout cells were infected with 22 luciferase-expressing adenoviruses derived from adenovirus species B, C, D and E. HAdV-B16, -B21 and -B50 from species B1 as well as HAdV-B34 and -B35 were found to be CD46-dependent. HAdV-C5 and HAdV-E4 from species E were found to be CAR-dependent. Regarding cell entry of HAdV-B3 and -B14 and all species D viruses, both CAR and CD46 play a role, and here, other receptors or attachment structures may also be important since transductions were reduced but not completely inhibited. The established human knockout cell model enables the identification of the most applicable adenovirus types for gene therapy and to further understand adenovirus infection biology.

Emerging and future applications rely heavily upon systems consisting of Internet of Things (IoT), edges, data centers, and humans-in-the-loop. Significantly different from warehouse-scale computers that serve independent concurrent user requests, this new class of computer systems directly interacts with the physical world, considering humans an essential part and performing safety-critical and mission-critical operations; their computations have intertwined dependencies between not only adjacent execution loops but also actions or decisions triggered by IoTs, edge, datacenters, or humans-in-the-loop; the systems must first satisfy the accuracy metric in predicting, interpreting, or taking action before meeting the performance goal under different cases. This article argues we need a paradigm shift to reconstruct the IoTs, edges, data centers, and humans-in-the-loop as a computer rather than a distributed system. We coin a new term, high fusion computers (HFCs), to describe this class of systems. The fusion in the term has two implications: fusing IoTs, edges, data centers, and humans-in-the-loop as a computer, fusing the physical and digital worlds through HFC systems. HFC is a pivotal case of the open-source computer systems initiative. We laid out the challenges, plan, and call for uniting our community's wisdom and actions to address the HFC challenges. Everything, including the source code, will be publicly available from the project homepage: https://www.computercouncil.org/HFC/., Comment: This paper has been published in BenchCouncil Transactions on Benchmarks, Standards and Evaluations (TBench). Link: https://www.sciencedirect.com/science/article/pii/S277248592200062X

Novel Ni-PSF@PAO40 microcapsules (NPPMS) with high stability were prepared by using a combined processing method of electroless nickel plating and solvent volatilization. The results indicate that Ni is completely assembled on the surfaces of PSF/PAO40 microcapsules with the encapsulation capacity of NPPMS achieved at 50%. Organic solvents immersion shows that NPPMS have an excellent chemical stability. Macro thermal stability tests reveal that the softening temperature of NPPMS is increased up to over 400 °C while it becomes lower than 200 °C for PSF/PAO40 microcapsules. Furthermore, NPPMS were embedded into polyamide 6 (PA6) to prepare PA6/NPPMS composites. The cross-sectional morphology shows that NPPMS are intact in PA6 matrices. The microhardness of PA6 is effectively improved with the incorporation of NPPMS. As compared with neat PA6, the coefficient of friction (COF) for PA6/NPPMS composites with 10% NPPMS could be reduced by 87.7% (from 0.49 to 0.06) and the wear rate could be decreased by 96.8% (from 1.29×10−⁵ to 4.15×10−⁷ mm³/(N·m)). Further studies confirmed that increasing test loads and test temperatures was beneficial to improve the lubrication performance of NPPMS despite the opposite trend occurred when increasing the sliding speeds. It has been demonstrated that synergistic effects between PAO40 and Ni layer play an important role in improving the tribological properties of PA6. Therefore, NPPMS significantly improve the ability of microcapsules to resist a harsh environment, which has important scientific significance for expanding the use of microcapsules more practically in self-lubricating composites.

Rui Ni,1– 3 Lele Huang,3 Zhen Li,4 Wenli Zhang,4 Yajie Wang,4 Yan Shen,4 Jianxin Wang,1 Weigen Lu2 1School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 2China State Institute of Pharmaceutical Industry, Shanghai, People’s Republic of China; 3National Advanced Medical Engineering Research Center, Shanghai, People’s Republic of China; 4Department of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of ChinaCorrespondence: Jianxin Wang, School of Pharmacy, Fudan University, Shanghai, 201203, People’s Republic of China, Email jxwang@shmu.edu.cn Weigen Lu, China State Institute of Pharmaceutical Industry, Shanghai, 201203, People’s Republic of China, Email sipiluwg@163.comPurpose: To enhance tumor penetration by formulation design and tumor microenvironment (TME) modulation, herein a novel reactive oxygen species (ROS)-responsive size/shape transformable lipid-polymer hybrid nanoparticle (LPN) has been fabricated for the co-delivery of an anticancer and collagen-inhibition drug.Methods: A ROS-responsive poly(D, L-lactide)-thioketal-polyethylene glycol (PLA-TK-PEG) co-polymer was synthesized. LPNs were then fabricated by encapsulation of losartan (LST)-loaded micelles as the core to support paclitaxel (PTX)-loaded liposomes. The PEG content in the lipid shell of LPNs was then adjusted to obtain the size-/shape-transformable LPNs (M/LST-Lip/PTX-PEG5%). The ROS-responsiveness was observed in vitro by transmission electron microscopy and the tumor-penetration of the LPNs was evaluated in 3D tumor spheroids by confocal laser scanning microscopy. Tumor-targeting, tumor-penetrating, and antitumor efficacies of the NPs in 4T1 tumor-bearing mice were determined by in vivo imaging.Results: ROS-responsive micellar core degradation and the transformation of spherical LPNs (120nm) to smaller 40 mm discoid nanoparticles (NP) were observed. The transformable LPNs exhibited enhanced capacity of penetration in contrast to the

Liu Hu1,2 *, Jie Xu1 *, Wenli Zhang,1,2 Junrui Wang,1,2 Ni Fang,1,2 Ying Luo,1,2 Lian Xu,1,2 Jia Liu,1 Yu Zhang,1 Haitao Ran,3 Dajing Guo,1 Jun Zhou1 1Department of Radiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Ultrasound, Institute of Ultrasound Imaging, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jun Zhou, Tel +86 23 6288 7295, Email zhoujun@hospital.cqmu.edu.cnBackground and Objective: Thrombosis is a common disease that poses a great threat to life and health. Most thrombolytic effects of traditional treatments or nanomedicine are not efficient or safe enough. Therefore, we designed a nanoparticle (NP) with a combination of a phase transition material and thrombolytic drugs for efficient and safe thrombolysis.Methods: A thrombus fibrin-targeted and phase transition NP was designed and contained perfluorohexane (PFH) and the thrombolytic drug rtPA core, with CREKA polypeptides attached to the shell of the PLGA NPs. Characterization of the phase transition and ultrasound imaging of the NPs was carried out under low-intensity focused ultrasound (LIFU). LIFU-responsive drug release in vitro was also explored. Under the synergistic effect of PFH and rtPA, the efficient thrombolysis ability of the NPs was studied in vitro and in vivo. In vivo monitoring of thrombosis and biosafety were also verified.Results: The PPrC NPs had good ultrasound imaging ability under LIFU irradiation and were related to the phase transition characteristics of the NPs. CREKA polypeptides can effectively increase the aggregation of the NPs on thrombi. Under static and dynam

Ni Fang,1,2,* Jia Liu,1,* Jingxin Hou,1,2 Yixin Zhong,1,2 Ying Luo,1,2 Liu Hu,1,2 Wenli Zhang,1,2 Junrui Wang,1,2 Jie Xu,1 Jun Zhou,1 Yu Zhang,1 Haitao Ran,2 Dajing Guo1 1Department of Radiology, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Chongqing Key Laboratory of Ultrasound Molecular Imaging & Department of Ultrasound, Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dajing Guo, Email guodaj@163.comBackground: Arterial thrombosis is a serious threat to human health. Recently, many thrombus-targeted nanoparticles (NPs) have been constructed for detecting thrombi or monitoring thrombolysis, but their thrombus-targeting performance is limited. Considering this drawback, we designed a specific bionic system with enhanced thrombus-targeting ability.Materials and Methods: In the bionic system, gelatin was chosen as a carrier, and Fe3O4 served as a magnetic navigation medium and a magnetic resonance (MR) imaging agent. The CREKA peptide, which targets fibrin, was conjugated to the surface of gelatin to prepare targeted NPs (TNPs), which were then engulfed by macrophages to construct the bionic system. At the targeted site, the bionic system released its interior TNPs under low-intensity focused ultrasound (LIFU) irradiation. Moreover, the targeting performance was further improved by the conjugated CREKA peptide.Results: In this study, we successfully constructed a bionic system and demonstrated its targeting ability in vitro and in vivo. The results indicated that most TNPs were released from macrophages under LIFU irradiation at 2 W/cm2 for 10 min in vitro. Additionally, the enhanced thrombus-targeting ability, based on the natural tropism of macrophages toward inflammatory thrombi, magnetic navigation and the CREKA peptide, was verified ex vivo and in viv

Cheng Zhang,1,2,* Wenli Zhang,1,2,* Ying Huang,1,2 Jianxiang Qiu,3 Zhi-Xin Huang1,2,4,5 1Department of Neurology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 2The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 3Medical Research Center, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of China; 4Jinan University Faculty of Medical Science, Guangzhou, Guangdong, People’s Republic of China; 5University of South China, Hengyang, Hunan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jianxiang Qiu, Medical Research Center, Guangdong Second Provincial General Hospital, No. 466 xingang Middle Road, Guangzhou, Guangdong, 510000, People’s Republic of China, Tel +86-02089168114, Email qiujx@gd2h.org.cn Zhi-Xin Huang, Department of Neurology, Guangdong Second Provincial General Hospital, No. 466 xingang Middle Road, Guangzhou, Guangdong, 510000, People’s Republic of China, Tel +86-02089168080, Email hzxd6@163.comPurpose: Despite receiving standard-of-care treatments, a significant proportion of patients with acute ischemic stroke (AIS) are left with long-term functional impairment. Therefore, an easy-to-use tool for predicting of unfavorable outcome following AIS plays an important role in clinical practice. This study was aimed to develop a dynamic nomogram to predict the 3-month unfavorable outcome for AIS patients.Methods: This was a prospective observational study conducted in consecutive patients with AIS admitted to our stroke center between September 2019 and June 2020. Baseline demographic, clinical, and laboratory information were obtained. The primary outcome was evaluated with modified Rankin Scale (mRS) scores at 3 months. Least absolute shrinkage and selection operator regression was used to select the optimal predictive factors. Mu

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.

Human adenoviruses (HAdVs) are a major cause for disease in children, in particular after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, effective therapies for HAdV infections in immunocompromised hosts are lacking. To decipher immune recognition of HAdV infection and determine new targets for immune-mediated control, we used an HAdV infection 3D organoid system, based on primary human intestinal epithelial cells. HLA-F, the functional ligand for the activating NK cell receptor KIR3DS1, was strongly up-regulated and enabled enhanced killing of HAdV5-infected cells in organoids by KIR3DS1(+) NK cells. In contrast, HLA-A and HLA-B were significantly down-regulated in HAdV5-infected organoids in response to adenoviral E3/glycoprotein 19K, consistent with evasion from CD8(+) T cells. Immunogenetic analyses in a pediatric allo-HSCT cohort showed a reduced risk to develop severe HAdV disease and faster clearance of HAdV viremia in children receiving KIR3DS1(+)/HLA-Bw4(+) donor cells compared with children receiving non-KIR3DS1(+)/HLA-Bw4(+) cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease.

Wenli Zhang,1,* Enshi Hu,1,* Yajie Wang,1,* Si Miao,1 Yanyan Liu,1 Yumin Hu III,1 Ji Liu,1 Bohui Xu,2 Daquan Chen,3 Yan Shen1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 2School of Pharmacy, Nantong University, Nantong, 226001, People’s Republic of China; 3School of Pharmacy, Yantai University, State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, 264005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Shen; Daquan Chen Tel +86-25-83271305; +86-535-6706021Email shenyan@cpu.edu.cn; cdq1981@126.comAbstract: At present, some bacteria have developed significant resistance to almost all available antibiotics. One of the reasons that cannot be ignored is long-term exposure of bacteria to the sub-minimum inhibitory concentration (MIC) of antibiotics. Therefore, it is necessary to develop a targeted antibiotic delivery system to improve drug delivery behavior, in order to delay the generation of bacterial drug resistance. In recent years, with the continuous development of nanotechnology, various types of nanocarriers that respond to the infection microenvironment, targeting specific bacterial targets, and targeting infected cells, and so on, are gradually being used in the delivery of antibacterial agents to increase the concentration of drugs at the site of infection and reduce the side effects of drugs in normal tissues. Here, this article describes in detail the latest research progress on nanocarriers for antimicrobial, and commonly used targeted antimicrobial strategies. The advantages of the combination of nanotechnology and targeting strategies in combating bacterial infections are highlighted in this review, and the upcoming opportunities and remaining challenges in this field are rationally prospected.Keywords: nanocarriers, antimicrobial, drug delivery, targeting strategies

Curiosity about the mysteries of outer space has driven humans to organize space exploration. Space missions and polar-region expeditions require the use of new energy storage technologies with excellent tolerance to extremely low temperatures and the capability to operate efficiently for extended periods of time. In this context, there is an urgent need to explore new approaches and concepts that address the critical related challenges, gaining a mechanistic understanding of new electrochemical reactions and phenomena in diverse scenarios. This paper presents an overview of how electrode and electrolyte materials in supercapacitor (SC) cells operate at extremely low temperatures. The critical challenges related to engineering such SCs and the major breakthroughs that have overcome these problems are presented. In addition, the effects of different electrolytes (e.g., aqueous, organic, and ionic liquid (IL) examples) on ion accessibility, interfacial charge transfer, and transport kinetics in SC cells under cold conditions are discussed. This review is expected to contribute to the development of high-performance SC cells that can function at extreme temperatures via providing insight into key challenges and guidelines that could facilitate future work.

Previous studies reported on the broad-spectrum antiviral function of heparin. Here we investigated the antiviral function of magnesium-modified heparin and found that modified heparin displayed a significantly enhanced antiviral function against human adenovirus (HAdV) in immortalized and primary cells. Nuclear magnetic resonance analyses revealed a conformational change of heparin when complexed with magnesium. To broadly explore this discovery, we tested the antiviral function of modified heparin against herpes simplex virus type 1 (HSV-1) and found that the replication of HSV-1 was even further decreased compared to aciclovir. Moreover, we investigated the antiviral effect against the new severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and measured a 55-fold decreased viral load in the supernatant of infected cells associated with a 38-fold decrease in virus growth. The advantage of our modified heparin is an increased antiviral effect compared to regular heparin.

Wenli Zhang,1,* Enshi Hu,1,* Yajie Wang,1,* Si Miao,1 Yanyan Liu,1 Yumin Hu III,1 Ji Liu,1 Bohui Xu,2 Daquan Chen,3 Yan Shen1 1Department of Pharmaceutics, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China; 2School of Pharmacy, Nantong University, Nantong, 226001, People’s Republic of China; 3School of Pharmacy, Yantai University, State Key Laboratory of Long-acting and Targeting Drug Delivery System, Yantai, 264005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yan Shen; Daquan Chen Tel +86-25-83271305; +86-535-6706021Email shenyan@cpu.edu.cn; cdq1981@126.comAbstract: At present, some bacteria have developed significant resistance to almost all available antibiotics. One of the reasons that cannot be ignored is long-term exposure of bacteria to the sub-minimum inhibitory concentration (MIC) of antibiotics. Therefore, it is necessary to develop a targeted antibiotic delivery system to improve drug delivery behavior, in order to delay the generation of bacterial drug resistance. In recent years, with the continuous development of nanotechnology, various types of nanocarriers that respond to the infection microenvironment, targeting specific bacterial targets, and targeting infected cells, and so on, are gradually being used in the delivery of antibacterial agents to increase the concentration of drugs at the site of infection and reduce the side effects of drugs in normal tissues. Here, this article describes in detail the latest research progress on nanocarriers for antimicrobial, and commonly used targeted antimicrobial strategies. The advantages of the combination of nanotechnology and targeting strategies in combating bacterial infections are highlighted in this review, and the upcoming opportunities and remaining challenges in this field are rationally prospected.Keywords: nanocarriers, antimicrobial, drug delivery, targeting strategies

Human adenoviruses (HAdVs) are a major cause for disease in children, in particular after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Currently, effective therapies for HAdV infections in immunocompromised hosts are lacking. To decipher immune recognition of HAdV infection and determine new targets for immune-mediated control, we used an HAdV infection 3D organoid system, based on primary human intestinal epithelial cells. HLA-F, the functional ligand for the activating NK cell receptor KIR3DS1, was strongly up-regulated and enabled enhanced killing of HAdV5-infected cells in organoids by KIR3DS1(+) NK cells. In contrast, HLA-A and HLA-B were significantly down-regulated in HAdV5-infected organoids in response to adenoviral E3/glycoprotein 19K, consistent with evasion from CD8(+) T cells. Immunogenetic analyses in a pediatric allo-HSCT cohort showed a reduced risk to develop severe HAdV disease and faster clearance of HAdV viremia in children receiving KIR3DS1(+)/HLA-Bw4(+) donor cells compared with children receiving non-KIR3DS1(+)/HLA-Bw4(+) cells. These findings identify the KIR3DS1/HLA-F axis as a new target for immunotherapeutic strategies against severe HAdV disease.

Drought has become a serious problem that threatens global food security. Foxtail millet (Setaria italica) can be used as a model crop for drought-resistant research because of its excellent performance in drought tolerance. In this study, the typical drought-tolerant foxtail millet landrace ‘Huangjinmiao’ was grown in a field under control and drought stress conditions to investigate its response to drought stress. The proteins in the harvested grains were analysed through two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization-tandem time-of-flight (MALDI-TOF/TOF) analysis to characterize the response of foxtail millet under drought stress at a proteomic level. A total of 104 differentially abundant protein spots (DAPs) were identified; among them, 57 were up-regulated and 47 were down-regulated under drought treatment. The identified proteins were involved in an extensive range of biological processes, including storage proteins, protein folding, starch and sucrose metabolism, glycolysis/gluconeogenesis, biosynthesis of amino acids, detoxification and defense, protein degradation, tricarboxylic acid (TCA) cycle, protein synthesis, energy metabolism, transporter, pentose phosphate pathway, and signal transduction. Post-translational protein modifications might also occur. Moreover, the albumin content greatly decreased under drought stress, whereas the gliadin content considerably increased (p<0.01). In conclusion, this study provides new information on the proteomic changes in foxtail millet under drought stress and a framework for further studies on the function of these identified proteins.

Drought has become a serious problem that threatens global food security. Foxtail millet (Setaria italica) can be used as a model crop for drought-resistant research because of its excellent performance in drought tolerance. In this study, the typical drought-tolerant foxtail millet landrace ‘Huangjinmiao’ was grown in a field under control and drought stress conditions to investigate its response to drought stress. The proteins in the harvested grains were analysed through two-dimensional electrophoresis (2-DE) coupled with matrix-assisted laser desorption/ionization-tandem time-of-flight (MALDI-TOF/TOF) analysis to characterize the response of foxtail millet under drought stress at a proteomic level. A total of 104 differentially abundant protein spots (DAPs) were identified; among them, 57 were up-regulated and 47 were down-regulated under drought treatment. The identified proteins were involved in an extensive range of biological processes, including storage proteins, protein folding, starch and sucrose metabolism, glycolysis/gluconeogenesis, biosynthesis of amino acids, detoxification and defense, protein degradation, tricarboxylic acid (TCA) cycle, protein synthesis, energy metabolism, transporter, pentose phosphate pathway, and signal transduction. Post-translational protein modifications might also occur. Moreover, the albumin content greatly decreased under drought stress, whereas the gliadin content considerably increased (p<0.01). In conclusion, this study provides new information on the proteomic changes in foxtail millet under drought stress and a framework for further studies on the function of these identified proteins.

Jingren Shi,1 Wenli Zhang,2 Lu He,2 Fanhong Kong,2 Meichen Pan,1 Jingjing Guo,1 Xinmin Xu,1 Jie Guo,1 Huizhu Wang,1 Yajie Wang11Department of Clinical Laboratory, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, People’s Republic of China; 2Department of Clinical Laboratory, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, People’s Republic of ChinaAim: To investigate the anticancer effects of Jinlong capsule (JLC) against human glioblastoma cells and the possible underlying mechanism.Methods: Cell Counting Kit-8 and colony formation assay were adopted for the analysis of cell viability. Cell invasion and migration were evaluated by transwell and wound healing assays. Then, the expression level of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), S6 and phosphorylated S6 (p-S6) were determined by western blotting.Results: The results showed that JLC significantly inhibited human glioblastoma cell proliferation, invasion and migration in a dose-dependent manner. The expressions of p-mTOR and p-S6 were dramatically suppressed by JLC. Furtherly, inhibition of mTOR reduced the cell migration and invasion, while the mTOR agonist (MHY1485) could partially reverse the anti-migration and anti-invasion activity of JLC.Conclusion: The above results suggested that JLC would be a potential candidate for the treatment of glioblastoma.Keywords: Jinlong capsule, invasion, migration, glioblastoma, mTOR, S6 &nbsp

More than 70 human adenoviruses with type-dependent pathogenicity have been identified but biological information about the majority of these virus types is scarce. Here we employed multiple sequence alignments and structural information to predict receptor usage for the development of an adenoviral vector with novel biological features. We report the generation of a cloned adenovirus based on human adenovirus type 17 (HAdV17) with high sequence homology to the well characterized human adenovirus type 37 (HAdV37) that causes epidemic keratoconjunctivitis (EKC). Our study revealed that human CD46 (CD46) is involved in cell entry of HAdV17. Moreover, we found that HAdV17 infects endothelial cells (EC) in vitro including primary cells at higher efficiencies compared to the commonly used human adenovirus type 5 (HAdV5). Using a human CD46 transgenic mouse model, we observed that HAdV17 displays a broad tropism in vivo after systemic injection and that it transduces ECs in this mouse model. We conclude that the HAdV17-based vector may provide a novel platform for gene therapy.

Chronic diseases are the leading causes of decreasing quality of life, hospitalization, disability and death in the United States (US) and all over the world. For a long time, researchers have been seeking ways that promote management and prevention of chronic conditions, (i) to save time, money and energy, (ii) to support evidence-based health care decisions and (iii) to customize individual patients’ disease management plans. Healthcare related Big Data Analytical tools have the potential to leverage data from large-scale longitudinal sources for population-level chronic disease prevention, as well as to capture trends and propose models for individual-level proactive self-management. Nonetheless, the exact role of Big Data Analytical tools in the area of chronic disease management has not been fully studied. To take full advantage of Big Data, there is an urgent need to enrich our understanding of Big Data and use it to provide insights for researchers, patients, and health providers. By choosing asthma, one of the most serious chronic diseases in the US, as a research case, this dissertation addresses three research questions: (I) How can we use Big Data for asthma surveillance to enable health providers to respond promptly? (II) How can we apply Big Data for asthma risk factors analysis and enhance chronic disease self-management and population-level interventions? (III) By identifying smoking as one of the highest population-attributable risk factors, can we use Big Data in evaluating possible substitutes like e-cigarettes? The dissertation comprises of four essays. The first essay seeks to provide an efficient framework to extract signals from social media and make social media data available to answer these questions. The second essay focuses on building robust Big Data based population-level surveillance models that enable health providers to respond to chronic conditions, like asthma, in real time. In the third essay, a framework for comprehensive asthma r

Xiang Fang,1 Hongyuan Liu,1 Yan Xiong,1 Wenli Zhang,1 Yi Luo,1 Fan Wu,2 Yong Zhou,1 Liuhong Song,3 Zeping Yu,1 Chongqi Tu,1 Hong Duan1 1Department of Orthopedics, West China School of Medicine/West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 2Department of Orthopedics, Fourth People’s Hospital of ZiGong, ZiGong, Sichuan, People’s Republic of China; 3Department of Orthopedics, People’s Hospital of Pengzhou, Pengzhou, Sichuan, People’s Republic of China Purpose: Arthrodesis is one of the most widely accepted surgical recommended methods for tumors of the talus, but it may be associated with poor limb functions. The aim of this study was to present a novel reconstruction with ankle function preserved after en bloc talus tumor resection.Patient and method: A 43-year-old female with mesenchymal sarcoma of the talus was admitted in West China Hospital. Total talar replacement with three-dimensional (3D) printed modular prosthesis was prepared for reconstruction. The 3D printed modular prosthesis was designed exactly as the mirror image of the contralateral talus with complete filling of the sinus tarsi and subtalar joint space. The upper modular component of prosthesis was made of ultra high molecular weight polyethylene, and the lower component, titanium alloy. Pre-drilled holes in three directions were prepared for screw fixation of the subtalar joint.Results: The patient underwent en bloc talus resection through anterior approach, followed by reconstruction with the 3D printed prosthesis. The whole procedure took 2 hours, and intra-operative blood loss was 50 mL. At the last follow-up, our patient was disease free and she could walk almost normally without any aid or pain. The Musculoskeletal Tumor Society score was 26/30. The American Orthopedic Foot and Ankle Society score was 91/100. The range of motion for dorsiflexion and plantar flexion was 40°. And no abnormalities we

Epstein-Barr virus (EBV) primary infection is usually asymptomatic, but it sometimes progresses to infectious mononucleosis (IM). Occasionally, some people develop chronic active EBV infection (CAEBV) with underlying immunodeficiency, which belongs to a continuous spectrum of EBV-associated lymphoproliferative disorders (EBV+ LPD) with heterogeneous clinical presentations and high mortality. It has been well established that T cell-mediated immune response plays a critical role in the disease evolution of EBV infection. Recently, high-throughput sequencing of the hypervariable complementarity-determining region 3 (CDR3) segments of the T cell receptor (T cell receptor β (TCRβ)) has emerged as a sensitive approach to assess the T cell repertoire. In this study, we fully characterized the diversity of peripheral blood TCRβ repertoire in IM (n = 6) and CAEBV patients (n = 5) and EBV-seropositive controls (n = 5). Compared with the healthy EBV-seropositive controls, both IM and CAEBV patients demonstrate a significant decrease in peripheral blood TCRβ repertoire diversity, basically, including narrowed repertoire breadth, highly expanded clones, and skewed CDR3 length distribution. However, there is no significant difference between IM and CAEBV patients. Furthermore, we observed some disease-related preferences in TRBV/TRBJ usage and combinations, as well as lots of T cell clones shared by different groups (unique or overlapped) involved in public T cell responses, which provide more detailed insights into the divergent disease evolution. © 2017, Springer-Verlag Berlin Heidelberg.

A low profile power converter structure is provide wherein volume is reduced and power density is increased to approach 1 KW/in3 by at least one of forming an inductor as a body of magnetic material embedded in a substrate formed by a plurality of printed circuit board (PCB) lamina and forming inductor windings of PCB cladding and vias which may be of any desired number of turns and may include inversely coupled windings and which provide a lateral flux path, forming the body of magnetic material from high aspect ratio flakes of magnetic material which are aligned with the inductor magnetic field in an insulating organic binder and hot-pressed and providing a four-layer architecture comprising two layers of PCB lamina including the embedded body of magnetic material, a shield layer and an additional layer of PCB lamina, including cladding for supporting and connecting a switching circuit, a capacitor and the inductor.

Mengyuan Zhang, Jianhua He, Cuiping Jiang, Wenli Zhang, Yun Yang, Zhiyu Wang, Jianping LiuDepartment of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of ChinaAbstract: Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiology of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-density lipoprotein (rHDL) for iMΦ and its limited cholesterol efflux ability, we designed a hyaluronan (HA)-anchored core–shell rHDL. This nanoparticle achieved efficient iMΦ-targeted drug delivery via a multistage-targeting approach, and excellent cellular cholesterol removal. It contained a biodegradable poly (lactic-co-glycolic acid) (PLGA) core within a lipid bilayer, and apolipoprotein A-I (apoA-I) absorbing on the lipid bilayer was covalently decorated with HA. The covalent HA coating with superior stability and greater shielding was favorable for not only minimizing the liver uptake but also facilitating the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors in atherosclerotic plaques. The ultimate iMΦ homing was achieved via apoA-I after HA coating degraded by hyaluronidase (HAase) (abundant in atherosclerotic plaque). The multistage-targeting mechanism was revealed on the established injured endothelium–macrophage co-culture dynamic system. Upon treatment with HAase in vitro, the nanoparticle HA-(C)-PLGA-rHDL exhibited a greater cholesterol efflux capacity compared with conventional rHDL (2.43-fold). Better targeting efficiency toward iMΦ and attenuated liver accumulation were further proved by results from ex vivo imaging and iMΦ-specific fluorescence localization. Ultimately, HA-(C)-PLGA-rHDL loaded with simvastatin realized the most potent anti-atherogenic effic

Mengyuan Zhang, Jianhua He, Cuiping Jiang, Wenli Zhang, Yun Yang, Zhiyu Wang, Jianping LiuDepartment of Pharmaceutics, China Pharmaceutical University, Nanjing, People’s Republic of ChinaAbstract: Increasing evidence has highlighted the pivotal role that intimal macrophage (iMΦ) plays in the pathophysiology of atherosclerotic plaques, which represents an attractive target for atherosclerosis treatment. In this work, to address the insufficient specificity of conventional reconstituted high-density lipoprotein (rHDL) for iMΦ and its limited cholesterol efflux ability, we designed a hyaluronan (HA)-anchored core–shell rHDL. This nanoparticle achieved efficient iMΦ-targeted drug delivery via a multistage-targeting approach, and excellent cellular cholesterol removal. It contained a biodegradable poly (lactic-co-glycolic acid) (PLGA) core within a lipid bilayer, and apolipoprotein A-I (apoA-I) absorbing on the lipid bilayer was covalently decorated with HA. The covalent HA coating with superior stability and greater shielding was favorable for not only minimizing the liver uptake but also facilitating the accumulation of nanoparticles at leaky endothelium overexpressing CD44 receptors in atherosclerotic plaques. The ultimate iMΦ homing was achieved via apoA-I after HA coating degraded by hyaluronidase (HAase) (abundant in atherosclerotic plaque). The multistage-targeting mechanism was revealed on the established injured endothelium–macrophage co-culture dynamic system. Upon treatment with HAase in vitro, the nanoparticle HA-(C)-PLGA-rHDL exhibited a greater cholesterol efflux capacity compared with conventional rHDL (2.43-fold). Better targeting efficiency toward iMΦ and attenuated liver accumulation were further proved by results from ex vivo imaging and iMΦ-specific fluorescence localization. Ultimately, HA-(C)-PLGA-rHDL loaded with simvastatin realized the most potent anti-atherogenic effic

A low profile power converter structure is provide wherein volume is reduced and power density is increased to approach 1 KW/in3 by at least one of forming an inductor as a body of magnetic material embedded in a substrate formed by a plurality of printed circuit board (PCB) lamina and forming inductor windings of PCB cladding and vias which may be of any desired number of turns and may include inversely coupled windings and which provide a lateral flux path, forming the body of magnetic material from high aspect ratio flakes of magnetic material which are aligned with the inductor magnetic field in an insulating organic binder and hot-pressed and providing a four-layer architecture comprising two layers of PCB lamina including the embedded body of magnetic material, a shield layer and an additional layer of PCB lamina, including cladding for supporting and connecting a switching circuit, a capacitor and the inductor.

A low profile power converter structure is provide wherein volume is reduced and power density is increased to approach 1 KW/in3 by at least one of forming an inductor as a body of magnetic material embedded in a substrate formed by a plurality of printed circuit board (PCB) lamina and forming inductor windings of PCB cladding and vias which may be of any desired number of turns and may include inversely coupled windings and which provide a lateral flux path, forming the body of magnetic material from high aspect ratio flakes of magnetic material which are aligned with the inductor magnetic field in an insulating organic binder and hot-pressed and providing a four-layer architecture comprising two layers of PCB lamina including the embedded body of magnetic material, a shield layer and an additional layer of PCB lamina, including cladding for supporting and connecting a switching circuit, a capacitor and the inductor.

Fan Tang, Yong Zhou, Li Min, Wenli Zhang, Rui Shi, Yi Luo, Hong Duan, Chongqi TuDepartment of Orthopedics, West China Hospital, Sichuan University, Chengdu, People’s Republic of ChinaObjective: To evaluate the medium-term outcome of limb-salvage surgery using all-polyethylene tibial endoprosthetic replacement following en-block resection for distal femoral tumors.Methods: Forty-nine patients with distal femoral tumor were treated between June 2006 and June 2012. The follow-up period was 6–110 months (average 53.4 months). The prosthetic survival was analyzed using the Kaplan–Meier method. The classification of failure of limb salvage after reconstructive surgery for bone tumors was adapted. Limb function was evaluated with the scoring system of the Musculoskeletal Tumor Society (MSTS).Results: Complications were observed in six cases (12.2%). Four suffered infection around the prosthesis, of which two cases were treated with debridement, drainage, and antibiotics without removal of the prosthesis, and the other two cases underwent amputation. Two cases were identified as radiographically loose at 7 year follow-up and did not require revision surgery. One patient underwent amputation due to local recurrence. Failure of limb salvage occurred in nine cases (18.4%), of which two cases were of type 1A, two cases of type 2B, three cases of type 4A, one case of type 4B, and one case of type 5A. The mean MSTS score was 84.3%. Twelve cases died due to distant metastases (24.5%), and the average survival time for these patients was 13.5 months. Thirty-seven patients survived (75.5%), for whom the average follow-up time was 66.3 months and the 5-year prosthetic survival rate was 88.2%.Conclusion: The outcome of medium-term and long-term clinical follow-up was satisfactory. All-polyethylene tibial endoprosthetic replacement following en-block resection can be an alternative method of limb salvage for distal femoral tumors.Keywords: limb salvage, en

Yan Xiong,1 Cheng Ren,1 Bin Zhang,1 Hongsheng Yang,1 Yun Lang,1 Li Min,1 Wenli Zhang,1 Fuxing Pei,1 Yonggang Yan,2 Hong Li,2 Anchun Mo,3 Chongqi Tu,1 Hong Duan11Department of Orthopedics, West China Hospital, 2School of Physical Science and Technology, 3Department of Oral Implant, West China College of Stomatology, Sichuan University, Chengdu, People's Republic of ChinaAbstract: The aim of this study was to analyze the behavior of the porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite grafted for bone defect repair through a series of biological safety experiments, animal experiments, and a more than 5-year long clinical follow-up. The biological safety experiments, carried out in accordance with the Chinese Guo Biao and Tolerancing (GB/T)16886 and GB/T16175, revealed that porous n-HA/PA66 composite had no cytotoxicity, no sensitization effect, no pyrogenic reaction, and that its hemolysis rate was 0.59% (less than 5%). Rabbit models of tibia defects with grafted porous n-HA/PA66 composite were established. After 2 weeks, the experiment showed that osteogenesis was detected in the porous n-HA/PA66 composite; the density of new bone formation was similar to the surrounding host bone at 12 weeks. After 26 weeks, the artificial bone rebuilt to lamellar bone completely. In the clinical study, a retrospective review was carried out for 21 patients who underwent serial radiographic assessment after treatment with porous n-HA/PA66 composite grafts following bone tumor resection. All wounds healed to grade A. No postoperative infections, delayed deep infection, nonspecific inflammation, rejection, or fractures were encountered. At a mean follow-up of 5.3 years, the mean Musculoskeletal Tumor Society's (MSTS) 93 score was 29.3 points (range: 28–30 points) and mean radiopaque density ratio was 0.77±0.10. The radiologic analysis showed that porous n-HA/PA66 composite had been completely incorporated with the host bone about 1.5 y

Yan Xiong,1 Cheng Ren,1 Bin Zhang,1 Hongsheng Yang,1 Yun Lang,1 Li Min,1 Wenli Zhang,1 Fuxing Pei,1 Yonggang Yan,2 Hong Li,2 Anchun Mo,3 Chongqi Tu,1 Hong Duan11Department of Orthopedics, West China Hospital, 2School of Physical Science and Technology, 3Department of Oral Implant, West China College of Stomatology, Sichuan University, Chengdu, People's Republic of ChinaAbstract: The aim of this study was to analyze the behavior of the porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66) composite grafted for bone defect repair through a series of biological safety experiments, animal experiments, and a more than 5-year long clinical follow-up. The biological safety experiments, carried out in accordance with the Chinese Guo Biao and Tolerancing (GB/T)16886 and GB/T16175, revealed that porous n-HA/PA66 composite had no cytotoxicity, no sensitization effect, no pyrogenic reaction, and that its hemolysis rate was 0.59% (less than 5%). Rabbit models of tibia defects with grafted porous n-HA/PA66 composite were established. After 2 weeks, the experiment showed that osteogenesis was detected in the porous n-HA/PA66 composite; the density of new bone formation was similar to the surrounding host bone at 12 weeks. After 26 weeks, the artificial bone rebuilt to lamellar bone completely. In the clinical study, a retrospective review was carried out for 21 patients who underwent serial radiographic assessment after treatment with porous n-HA/PA66 composite grafts following bone tumor resection. All wounds healed to grade A. No postoperative infections, delayed deep infection, nonspecific inflammation, rejection, or fractures were encountered. At a mean follow-up of 5.3 years, the mean Musculoskeletal Tumor Society's (MSTS) 93 score was 29.3 points (range: 28–30 points) and mean radiopaque density ratio was 0.77±0.10. The radiologic analysis showed that porous n-HA/PA66 composite had been completely incorporated with the host bone about 1.5 y

Hong Duan,1 Hongsheng Yang,1 Yan Xiong,1 Bin Zhang,1 Cheng Ren,1 Li Min,1 Wenli Zhang,1 Yonggang Yan,2 Hong Li,2 Fuxing Pei,1 Chongqi Tu11Department of Orthopedics, 2School of Physical Science and Technology, Sichuan University, Chengdu, People's Republic of ChinaBackground and methods: Guided bone regeneration (GBR) is a new treatment for bone defects, and the property of membrane is critical to the success of GBR. This study focuses on a novel membrane tube for GBR, which was prepared by a nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer (n-CDHA-MAC) composite. The biomechanical strength and degradability of this membrane tube under mechanical loading after immersion in phosphate-buffered solution were investigated to evaluate the effects of mechanical loading on the membrane tube. The membrane-tube group with no mechanical loading and femora bone were used as controls.Results: The compressive strength and bending strength of n-CDHA-MAC membrane tubes were 66.4 ± 10.2 MPa and 840.7 ± 12.1 MPa, which were lower than those of the goats’ femoral bones (69.0 ± 5.5 MPa and 900.2 ± 17.3 MPa), but there were no significant (P > 0.05) differences. In the in vitro degradability experiment, all membrane tubes were degradable and showed a surface-erosion degradation model. The PH of solution fluctuated from 7.2 to 7.5. The weight and mechanical strength of loaded tubes decreased more quickly than nonloaded ones, with significant differences (P < 0.05). However, the strength of the loaded group after degradation achieved 20.4 ± 1.2 MPa, which was greater than the maximum mechanical strength of 4.338 MPa based on goat femoral middle stationary state by three-dimensional finite-element analysis.Conclusions: n-CDHA-MAC membrane tubes have good biomechanical strength during degradation under mechanical loading. Therefore, this membrane tube is an ideal GBR membrane for

Hong Duan,1 Hongsheng Yang,1 Yan Xiong,1 Bin Zhang,1 Cheng Ren,1 Li Min,1 Wenli Zhang,1 Yonggang Yan,2 Hong Li,2 Fuxing Pei,1 Chongqi Tu11Department of Orthopedics, 2School of Physical Science and Technology, Sichuan University, Chengdu, People's Republic of ChinaBackground and methods: Guided bone regeneration (GBR) is a new treatment for bone defects, and the property of membrane is critical to the success of GBR. This study focuses on a novel membrane tube for GBR, which was prepared by a nanocalcium-deficient hydroxyapatite–multi(amino acid) copolymer (n-CDHA-MAC) composite. The biomechanical strength and degradability of this membrane tube under mechanical loading after immersion in phosphate-buffered solution were investigated to evaluate the effects of mechanical loading on the membrane tube. The membrane-tube group with no mechanical loading and femora bone were used as controls.Results: The compressive strength and bending strength of n-CDHA-MAC membrane tubes were 66.4 ± 10.2 MPa and 840.7 ± 12.1 MPa, which were lower than those of the goats’ femoral bones (69.0 ± 5.5 MPa and 900.2 ± 17.3 MPa), but there were no significant (P > 0.05) differences. In the in vitro degradability experiment, all membrane tubes were degradable and showed a surface-erosion degradation model. The PH of solution fluctuated from 7.2 to 7.5. The weight and mechanical strength of loaded tubes decreased more quickly than nonloaded ones, with significant differences (P < 0.05). However, the strength of the loaded group after degradation achieved 20.4 ± 1.2 MPa, which was greater than the maximum mechanical strength of 4.338 MPa based on goat femoral middle stationary state by three-dimensional finite-element analysis.Conclusions: n-CDHA-MAC membrane tubes have good biomechanical strength during degradation under mechanical loading. Therefore, this membrane tube is an ideal GBR membrane for

Fault tolerance overhead of high performance computing (HPC) applications is becoming critical to the efficient utilization of HPC systems at large scale. HPC applications typically tolerate fail-stop failures by checkpointing. Another promising method is in the algorithm level, called algorithmic recovery. These two methods can achieve high efficiency when the system scale is not very large, but will both lose their effectiveness when systems approach the scale of Exaflops, where the number of processors including in system is expected to achieve one million. This paper develops a new and efficient algorithm-based fault tolerance scheme for HPC applications. When failure occurs during the execution, we do not stop to wait for the recovery of corrupted data, but replace them with the corresponding redundant data and continue the execution. A background accelerated recovery method is also proposed to rebuild redundancy to tolerate multiple times of failures during the execution. To demonstrate the feasibility of our new scheme, we have incorporated it to the High Performance Linpack. Theoretical analysis demonstrates that our new fault tolerance scheme can still be effective even when the system scale achieves the Exaflops. Experiment using SiCortex SC5832 verifies the feasibility of the scheme, and indicates that the advantage of our scheme can be observable even in a small scale., Comment: 11 pages, 8 figures, 1 table, submitted to conference SC 2011

Fixed beds of cylindrical particles are important in chemical engineering applications, but their packing structures are not as well understood or as well characterized as sphere packings. In this work, X-ray microtomography is used to obtain 3D images of 1.8 mm diameter equilateral cylinders in a 23 mm cylindrical container over a range of bulk porosities. A novel algorithm is used to computationally reconstruct the packings, resulting in data sets that give the location and orientation of each cylinder in the imaged packings. Extensive analysis has been performed, including bulk and local porosities, radial distribution functions, and parameters describing local and global ordering. The major factors affecting packing structure are the overall packing density and the proximity to the wall. At the highest overall packing densities, near-wall porosity becomes nearly equal to interior porosity, and significant global ordering occurs near the wall. For a vertical container, global ordering is characterized by the alignment of the particles with an orthogonal coordinate system that has one axis coincident with r (as defined by the container) and the other two axes in the z-theta plane, but rotated 45 degrees with the horizontal. The observed structures are relevant in the context of flow maldistribution and heat transfer in fixed beds., The original document contains color images. All DTIC reproductions will be in black and white. Sponsored in part by the Naval Research Lab and NSF, 0140175 and EEC-0139656. Published in Chemical Engineering Science, v61 p8060-8074, 2006.

Packing of granular media is an extremely important determinant in reservoir rock evolution, sound speed propagation, fluid flow and sediment compressibility. X-ray microfocus computed tomography (XMCT) images with high-resolution were evaluated using a grain-based algorithm that quantifies discrete components and bulk properties of sedimentary systems at different states of compaction or at approximately minimum and maximum packing densities. Angularity of these sands ranges from rounded to subrounded to subangular. Network permeability compares reasonably well to measured values; grain aspect ratios and coordination number are reasonable for sands. The grain-based algorithm provides a robust and efficient capability., Presented at the International Workshop on X-Ray CT for Geomaterials (GeoX 2006) (2nd), held in Grenoble and Aussois, France, on 4-7 Oct 2006. Published in the Proceedings of GeoX 2006, p264-268, 2006. Prepared in collaboration with Louisiana State University, Baton Rouge, LA. The original document contains color images.

Purpose: To develop a simple method to extract the whole apolipoproteins (apo) including apoA-I in native high density lipoproteins (HDLs) and prepare discoidal Tanshinone IIA-loaded reconstituted HDL (TA-rHDLs) as a dual functional drug delivery system with plaque-site target and therapeutic promises in atherosclerotic lesions. Methods: A method based on isoelectric precipitation coupled with organic solvent precipitation was developed to isolate the whole apolipoproteins (apos). TA-rHDLs were prepared by incubating the resultant apos with liposomes and the incubation conditions were optimized using fluorescence quenching experiment. TA-rHDLs were characterized in terms of size, zeta potential, morphology, interaction between lipid and apos, safety, and bionic function. Results: The extraction results showed that the yield of the HDL apos was 82.4%, with 59% being apoA-I type, similar ratio of apoA-I in the native apos. TA-rHDL prepared were disc-like with an average diameter of 157.6 ± 4.8 nm, zeta potential of -20.90 ± 0.15 mV, and entrapment efficiency of (90.13 ± 1.4) %. The interaction between the lipids and apos was electrostatic and hydrophobic force and was associated with amino acid sequence. Haemolysis and cytotoxicity assays showed good biocompatibility of TA-rHDL. Sterol efflux assay from macrophages mediated by TA-rHDLs and structure remodeling behavior from discs to spheres proved that TA-rHDL could resemble the biological activity of native nascent HDL irrespective of the size. Conclusions: The simple approach to isolate apos may provide a convenient and economical resource to support the development of rHDL as a potential targeting nanocarrier for lipophilic cardiovascular drugs. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.