211 research outputs found

    Octopus: A Secure and Anonymous DHT Lookup

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    Distributed Hash Table (DHT) lookup is a core technique in structured peer-to-peer (P2P) networks. Its decentralized nature introduces security and privacy vulnerabilities for applications built on top of them; we thus set out to design a lookup mechanism achieving both security and anonymity, heretofore an open problem. We present Octopus, a novel DHT lookup which provides strong guarantees for both security and anonymity. Octopus uses attacker identification mechanisms to discover and remove malicious nodes, severely limiting an adversary's ability to carry out active attacks, and splits lookup queries over separate anonymous paths and introduces dummy queries to achieve high levels of anonymity. We analyze the security of Octopus by developing an event-based simulator to show that the attacker discovery mechanisms can rapidly identify malicious nodes with low error rate. We calculate the anonymity of Octopus using probabilistic modeling and show that Octopus can achieve near-optimal anonymity. We evaluate Octopus's efficiency on Planetlab with 207 nodes and show that Octopus has reasonable lookup latency and manageable communication overhead

    Perioperative bilateral medial medullary infarction with “snake eyes appearance”: a case report

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    Perioperative bilateral medial medullary infarction (BMMI) cases mimicking acute motor axonal neuropathy (AMAN) under general anesthesia have not been reported. We describe a patient who suffered flaccid quadriplegia and could not wean from mechanical ventilation after emergence from general anesthesia in cardiac surgery. A diagnosis of AMAN was considered, but intravenous immunoglobulin showed little efficacy. Magnetic resonance imaging of the patient later revealed BMMI with “snake eyes appearance,” and he was found to have severe vertebral artery stenosis. Considering the association between severe coronary heart disease and cerebrovascular stenosis, we highlight the significance of preoperative evaluation and comprehensive management of the cerebrovascular system for certain patients

    Mechanism of tacrolimus in the treatment of lupus nephritis

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    Systemic lupus erythematosus (SLE) is a complex autoimmune disorder, with more than half of the patients developing lupus nephritis (LN), which significantly contributes to chronic kidney disease (CKD) and end-stage renal disease (ESRD). The treatment of lupus nephritis has always been challenging. Tacrolimus (TAC), an effective immunosuppressant, has been increasingly used in the treatment of LN in recent years. This review aims to explore the mechanisms of action of tacrolimus in treating LN. Firstly, we briefly introduce the pharmacological properties of tacrolimus, including its role as a calcineurin (CaN) inhibitor, exerting immunosuppressive effects by inhibiting T cell activation and cytokine production. Subsequently, we focus on various other immunomodulatory mechanisms of tacrolimus in LN therapy, including its effects on T cells, B cells, and immune cells in kidney. Particularly, we emphasize tacrolimus’ regulatory effect on inflammatory mediators and its importance in modulating the Th1/Th2 and Th17/Treg balance. Additionally, we review its effects on actin cytoskeleton, angiotensin II (Ang II)-specific vascular contraction, and P-glycoprotein activity, summarizing its impacts on non-immune mechanisms. Finally, we summarize the efficacy and safety of tacrolimus in clinical studies and trials. Although some studies have shown significant efficacy of tacrolimus in treating LN, its safety remains a challenge. We outline the potential adverse reactions of long-term tacrolimus use and provide suggestions on effectively monitoring and managing these adverse reactions in clinical practice. In general, tacrolimus, as a novel immunosuppressant, holds promising prospects for treating LN. Of course, further research is needed to better understand its therapeutic mechanisms and ensure its safety and efficacy in clinical practice

    Phenylboronic ester-modified polymeric nanoparticles for promoting TRP2 peptide antigen delivery in cancer immunotherapy

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    The tremendous development of peptide-based cancer vaccine has attracted incremental interest as a powerful approach in cancer management, prevention and treatment. As successful as tumor vaccine has been, major challenges associated with achieving efficient immune response against cancer are (1) drainage to and retention in lymph nodes; (2) uptake by dendritic cells (DCs); (3) activation of DCs. In order to overcome these barriers, here we construct PBE-modified TRP2 nanovaccine, which comprises TRP2 peptide tumor antigen and diblock copolymer PEG-b-PAsp grafted with phenylboronic ester (PBE). We confirmed that this TRP2 nanovaccine can be effectively trapped into lymph node, uptake by dendritic cells and induce DC maturation, relying on increased negative charge, ROS response and pH response. Consistently, this vehicle loaded with TRP2 peptide could boost the strongest T cell immune response against melanoma in vivo and potentiate antitumor efficacy both in tumor prevention and tumor treatment without any exogenous adjuvant. Furthermore, the TRP2 nanovaccine can suppress the tumor growth and prolong animal survival time, which may result from its synergistic effect of inhibiting tumor immunosuppression and increasing cytotoxic lymphocyte (CTL) response. Hence this type of PBE-modified nanovaccine would be widely used as a simple, safe and robust platform to deliver other antigen in cancer immunotherapy

    Time valid one-time signature for time-critical multicast data authentication

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    Abstract-It is challenging to provide authentication to timecritical multicast data, where low end-to-end delay is of crucial importance. Consequently, it requires not only efficient authentication algorithms to minimize computational cost, but also avoidance of buffering packets so that the data can be immediately processed once being presented. Desirable properties for a multicast authentication scheme also include small communication overhead, tolerance to packet loss, and resistance against malicious attacks. In this paper, we propose a novel signature model -Time Valid One-Time Signature (TV-OTS) -to boost the efficiency of regular one-time signature schemes. Based on the TV-OTS model, we design an efficient multicast authentication scheme "TV-HORS" to meet the above needs. TV-HORS combines one-way hash chains with TV-OTS to avoid frequent public key distribution. It provides fast signing/verification and buffering-free data processing, which make it one of the fastest multicast authentication schemes to date in terms of end-to-end computational latency (on the order of microseconds). In addition, TV-HORS has perfect tolerance to packet loss and strong robustness against malicious attacks. The communication overhead of TV-HORS is much smaller than regular OTS schemes, and even smaller than RSA signature. The only drawback of TV-HORS is a relatively large public key of size 8KB to 10KB, depending on parameters

    MiR-23a Regulates Skin Langerhans Cell Phagocytosis and Inflammation-Induced Langerhans Cell Repopulation

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    Langerhans cells (LCs) are skin-resident macrophage that act similarly to dendritic cells for controlling adaptive immunity and immune tolerance in the skin, and they are key players in the development of numerous skin diseases. While TGF-β and related downstream signaling pathways are known to control numerous aspects of LC biology, little is known about the epigenetic signals that coordinate cell signaling during LC ontogeny, maintenance, and function. Our previous studies in a total miRNA deletion mouse model showed that miRNAs are critically involved in embryonic LC development and postnatal LC homeostasis; however, the specific miRNA(s) that regulate LCs remain unknown. miR-23a is the first member of the miR-23a-27a-24-2 cluster, a direct downstream target of PU.1 and TGF-b, which regulate the determination of myeloid versus lymphoid fates. Therefore, we used a myeloid-specific miR-23a deletion mouse model to explore whether and how miR-23a affects LC ontogeny and function in the skin. We observed the indispensable role of miR-23a in LC antigen uptake and inflammation-induced LC epidermal repopulation; however, embryonic LC development and postnatal homeostasis were not affected by cells lacking miR23a. Our results suggest that miR-23a controls LC phagocytosis by targeting molecules that regulate efferocytosis and endocytosis, whereas miR-23a promotes homeostasis in bone marrow-derived LCs that repopulate the skin after inflammatory insult by targeting Fas and Bcl-2 family proapoptotic molecules. Collectively, the context-dependent regulatory role of miR-23a in LCs represents an extra-epigenetic layer that incorporates TGF-b- and PU.1-mediated regulation during steady-state and inflammation-induced repopulation
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