Evaluation of recanalisation treatment on posterior circulation ischemic stroke by Solitaire device—A multicenter retrospective study

Objectives Posterior circulation ischemic stroke (PCIS), accounting for approximately 20% of total ischemic stroke, is a sever disease that associated with high rate of morbidity and mortality. Though the effectiveness of endovascular mechanical thrombectomy has been well demonstrated in many types of ischemic stroke, it is still unclear what the outcome is in posterior circulation ischemic stroke. Methods and materials In current study, data was collected from 139 Chinese patients who received endovascular mechanical thrombectomy treatment with Solitaire device after acute posterior circulation ischemic stroke. We measured the mortality, symptomatic intracranial hemorrhage (SICH) and National Institutes of Health Stroke Scale (NIHSS) to evaluate the safety of endovascular mechanical thrombectomy. Meanwhile, the clinical outcome of endovascular mechanical thrombectomy was also evaluated based on recanalisation rate, HIHSS, and the modified Rankin Scale (mRS). Results Recanalisation was successful in 124 (89.3%) patients after surgery. Herniation was the second fatal stroke complication, out of the 6 patients suffered from herniation, 3 patients (50%) died during surgery and 2 (33%) died after surgery. As for other stroke complications such as pulmonary infection, 1 patient (4.3%) died during surgery and 1 patient (4.3%) died 3 days after surgery. Conclusion Our findings indicate that endovascular mechanical treatment is a safe treatment which brings clear benefit to patients suffered from posterior circulation ischemic stroke, in both the recanalisation rate and functional outcomes

Design of new drugs for medullary thyroid carcinoma

Medullary thyroid carcinoma (MTC) is one of the common malignant endocrine tumors, which seriously affects human health. Although surgical resection offers a potentially curative therapeutic option to some MTC patients, most patients do not benefit from it due to the difficulty to access the tumors and tumor metastasis. The survival rate of MTC patients has improved with the recent advances in the research, which has improved our understanding of the molecular mechanism underlying MTC and enabled the development and approval of novel targeted drugs. In this article, we reviewed the molecular mechanisms related to MTC progression and the principle for the design of molecular targeted drugs, and proposed some future directions for prospective studies exploring targeted drugs for MTC

RNAi Screen of Endoplasmic Reticulum–Associated Host Factors Reveals a Role for IRE1α in Supporting Brucella Replication

Brucella species are facultative intracellular bacterial pathogens that cause brucellosis, a global zoonosis of profound importance. Although recent studies have demonstrated that Brucella spp. replicate within an intracellular compartment that contains endoplasmic reticulum (ER) resident proteins, the molecular mechanisms by which the pathogen secures this replicative niche remain obscure. Here, we address this issue by exploiting Drosophila S2 cells and RNA interference (RNAi) technology to develop a genetically tractable system that recapitulates critical aspects of mammalian cell infection. After validating this system by demonstrating a shared requirement for phosphoinositide 3-kinase (PI3K) activities in supporting Brucella infection in both host cell systems, we performed an RNAi screen of 240 genes, including 110 ER-associated genes, for molecules that mediate bacterial interactions with the ER. We uncovered 52 evolutionarily conserved host factors that, when depleted, inhibited or increased Brucella infection. Strikingly, 29 of these factors had not been previously suggested to support bacterial infection of host cells. The most intriguing of these was inositol-requiring enzyme 1 (IRE1), a transmembrane kinase that regulates the eukaryotic unfolded protein response (UPR). We employed IRE1α(−/−) murine embryonic fibroblasts (MEFs) to demonstrate a role for this protein in supporting Brucella infection of mammalian cells, and thereby, validated the utility of the Drosophila S2 cell system for uncovering novel Brucella host factors. Finally, we propose a model in which IRE1α, and other ER-associated genes uncovered in our screen, mediate Brucella replication by promoting autophagosome biogenesis

Functional Analysis of Host Factors that Mediate the Intracellular Lifestyle of Cryptococcus neoformans

Cryptococcus neoformans (Cn), the major causative agent of human fungal meningoencephalitis, replicates within phagolysosomes of infected host cells. Despite more than a half-century of investigation into host-Cn interactions, host factors that mediate infection by this fungal pathogen remain obscure. Here, we describe the development of a system that employs Drosophila S2 cells and RNA interference (RNAi) to define and characterize Cn host factors. The system recapitulated salient aspects of fungal interactions with mammalian cells, including phagocytosis, intracellular trafficking, replication, cell-to-cell spread and escape of the pathogen from host cells. Fifty-seven evolutionarily conserved host factors were identified using this system, including 29 factors that had not been previously implicated in mediating fungal pathogenesis. Subsequent analysis indicated that Cn exploits host actin cytoskeletal elements, cell surface signaling molecules, and vesicle-mediated transport proteins to establish a replicative niche. Several host molecules known to be associated with autophagy (Atg), including Atg2, Atg5, Atg9 and Pi3K59F (a class III PI3-kinase) were also uncovered in our screen. Small interfering RNA (siRNA) mediated depletion of these autophagy proteins in murine RAW264.7 macrophages demonstrated their requirement during Cn infection, thereby validating findings obtained using the Drosophila S2 cell system. Immunofluorescence confocal microscopy analyses demonstrated that Atg5, LC3, Atg9a were recruited to the vicinity of Cn containing vacuoles (CnCvs) in the early stages of Cn infection. Pharmacological inhibition of autophagy and/or PI3-kinase activity further demonstrated a requirement for autophagy associated host proteins in supporting infection of mammalian cells by Cn. Finally, systematic trafficking studies indicated that CnCVs associated with Atg proteins, including Atg5, Atg9a and LC3, during trafficking to a terminal intracellular compartment that was decorated with the lysosomal markers LAMP-1 and cathepsin D. Our findings validate the utility of the Drosophila S2 cell system as a functional genomic platform for identifying and characterizing host factors that mediate fungal intracellular replication. Our results also support a model in which host Atg proteins mediate Cn intracellular trafficking and replication

A Latency-Aware Offloading Strategy over Fiber-Wireless (FiWi) Infrastructures for Tactile Internet Services

With the emergence of the tactile internet, low-latency, even, real-time data transmission is indispensable for human-agent–robot teamwork. Offloading is considered a feasible approach. Determining the offloading solution according to the dynamic network circumstance is attractive. In this paper, we investigate the resource management issue in a three-tier, heterogeneous, fiber-wireless (FiWi) network with offloading. Based on the model of the wireless link, the fiber link, the data rate, and the offloading, a mixed-integer, non-linear problem is formulated to obtain the minimum total latency for tactile internet services. Through constraint relaxation, MINLP is converted to a linear problem (LP). A Lagrange multiplier method with Karush–Kuhn–Tucker (KKT) conditions is used to solve LP. Using the numerical simulation, the superiority of our work is evaluated and compared with the previous work

A Design of Differential-Low Earth Orbit Opportunistically Enhanced GNSS (D-LoeGNSS) Navigation Framework

Considering the problem of GNSS service interruption caused by the insufficient number of available satellites in complex environments, Low Earth Orbit (LEO) satellites can supplement GNSS effectively. To eliminate the unknown satellite clock error and the atmospheric delay error with spatial correlation in LEO observations, a Differential-Low Earth Orbit opportunistically enhancing GNSS (D-LoeGNSS) navigation framework is proposed. Firstly, because of the uncertainty of the LEO orbit, we derive the effect of the LEO orbit error on the differential measurement model. Secondly, aiming at the noise amplification and correlation in double-difference (DD), we propose a Householder-Based D-LoeGNSS (HB-DLG) algorithm, which suppresses noise by introducing an orthogonal matrix. Thirdly, in D-LoeGNSS, the typical measurement of LEO is Doppler, which is heterogeneous with the GNSS pseudorange, rendering the Dilution of Precision (DOP) evaluation method unsuitable. Given the unbiasedness of differential measurements, the Cramer Rao Lower Bound (CRLB) is derived as a metric to characterize the positioning accuracy and satellite spatial distribution. Finally, a field experiment using Orbcomm (ORB) and GPS is conducted. The experimental results show that the performance of the HB-DLG algorithm is superior to DD. Especially when the number of satellites is insufficient or the measurement redundancy is poor; the D-LoeGNSS framework has advantages of rapid convergence and high accuracy compared with a single constellation

A Latency-Aware Offloading Strategy over Fiber-Wireless (FiWi) Infrastructures for Tactile Internet Services

With the emergence of the tactile internet, low-latency, even, real-time data transmission is indispensable for human-agent–robot teamwork. Offloading is considered a feasible approach. Determining the offloading solution according to the dynamic network circumstance is attractive. In this paper, we investigate the resource management issue in a three-tier, heterogeneous, fiber-wireless (FiWi) network with offloading. Based on the model of the wireless link, the fiber link, the data rate, and the offloading, a mixed-integer, non-linear problem is formulated to obtain the minimum total latency for tactile internet services. Through constraint relaxation, MINLP is converted to a linear problem (LP). A Lagrange multiplier method with Karush–Kuhn–Tucker (KKT) conditions is used to solve LP. Using the numerical simulation, the superiority of our work is evaluated and compared with the previous work