Evaluation of different b-values in DWI and 1H MRS for pancreatic cancer and pancreatitis: a rabbit model

Pancreatic cancer is a common malignant tumor with high incidence of metastasis. Currently, there is no absolute standard for the choice of b-value for diffusion-weighted imaging (DWI) for pancreatic cancer. The b-value is rarely reported in animal model study, especially in pancreatic cancer/mass pancreatitis rabbit models. The authors\u27 aim was to determine the different b-values to differentiate the diagnosis of pancreatic cancer and mass pancreatitis in rabbit models using DWI. When comparing the effect of different b-values in diagnostic process, the pathological results could be regarded as the gold standard. In this research, 30 healthy New Zealand rabbits were selected and divided into three groups by random number table method: group 1 (pancreatic cancer), group 2 (mass pancreatitis) and the control group (healthy). After DWI (three different b-values 333, 667, 1000 s/mm2, respectively) and MRI examination, the model rabbits were then killed. Afterward, the tumor mass was removed for biopsy, and occupation anatomy and tumor histopathology were examined. Fat-suppressing sequences of T2WI, DWI, ADC, difference of ADC (DADC), and MRS were used. The present study determined that the effective differential diagnosis of pancreatic cancer and pancreatitis was determined at low b-values (333 s/mm2) when performed DWI inspection in rabbit models

Thickness dependence of the anomalous Hall effect in thin films of the topological semimetal Co2_2MnGa

Topological magnetic semimetals promise large Berry curvature through the distribution of the topological Weyl nodes or nodal lines and further novel physics with exotic transport phenomena. We present a systematic study of the structural and magnetotransport properties of Co$_2$MnGa films from thin (20 nm) to bulk like behavior (80 nm), in order to understand the underlying mechanisms and the role on the topology. The magnetron sputtered Co$_2$MnGa films are $L$$2_{\mathrm {1}}$-ordered showing very good heteroepitaxy and a strain-induced tetragonal distortion. The anomalous Hall conductivity was found to be maximum at a value of 1138 S/cm, with a corresponding anomalous Hall angle of 13 %, which is comparatively larger than topologically trivial metals. There is a good agreement between the theoretical calculations and the Hall conductivity observed for the 80 nm film, which suggest that the effect is intrinsic. Thus, the Co$_2$MnGa compound manifests as a promising material towards topologically-driven spintronic applications.Comment: 7 pages, 5 figures, 1 tabl

Attitude and Altitude Controller Design for Quad-Rotor Type MAVs

Micro air vehicles (MAVs) have a wide application such as the military reconnaissance, meteorological survey, environmental monitoring, and other aspects. In this paper, attitude and altitude control for Quad-Rotor type MAVs is discussed and analyzed. For the attitude control, a new method by using three gyroscopes and one triaxial accelerometer is proposed to estimate the attitude angle information. Then with the approximate linear model obtained by system identification, Model Reference Sliding Mode Control (MRSMC) technique is applied to enhance the robustness. In consideration of the relatively constant altitude model, a Linear Quadratic Gaussian (LQG) controller is adopted. The outdoor experimental results demonstrate the superior stability and robustness of the controllers

Constructing a dual-function surface by microcasting and nanospraying for efficient drag reduction and potential antifouling capabilities

To improve the drag-reducing and antifouling performance of marine equipment, it is indispensable to learn from structures and materials that are found in nature. This is due to their excellent properties, such as intelligence, microminiaturization, hierarchical assembly, and adaptability. Considerable interest has arisen in fabricating surfaces with various types of biomimetic structures, which exhibit promising and synergistic performances similar to living organisms. In this study, a dual bio-inspired shark-skin and lotus-structure (BSLS) surface was developed for fabrication on commercial polyurethane (PU) polymer. Firstly, the shark-skin pattern was transferred on the PU by microcasting. Secondly, hierarchical micro- and nanostructures were introduced by spraying mesoporous silica nanospheres (MSNs). The dual biomimetic substrates were characterized by scanning electron microscopy, water contact angle characterization, antifouling, self-cleaning, and water flow impacting experiments. The results revealed that the BSLS surface exhibited dual biomimetic features. The micro- and nano-lotus-like structures were localized on a replicated shark dermal denticle. A contact angle of 147° was observed on the dual-treated surface and the contact angle hysteresis was decreased by 20% compared with that of the nontreated surface. Fluid drag was determined with shear stress measurements and a drag reduction of 36.7% was found for the biomimetic surface. With continuous impacting of high-speed water for up to 10 h, the biomimetic surface stayed superhydrophobic. Material properties such as inhibition of protein adsorption, mechanical robustness, and self-cleaning performances were evaluated, and the data indicated these behaviors were significantly improved. The mechanisms of drag reduction and self-cleaning are discussed. Our results indicate that this method is a potential strategy for efficient drag reduction and antifouling capabilities

HIV-1 can infect northern pig-tailed macaques (Macaca leonina) and form viral reservoirs in vivo

Viral reservoirs of HIV-1 are a major obstacle for curing AIDS. The novel animal models that can be directly infected with HIV-1 will contribute to develop effective strategies for eradicating infections. Here, we inoculated 4 northern pig-tailed macaques (NPM) with the HIV-1 strain HIV-1NL4.3 and monitored the infection for approximately 3 years (150 weeks). The HIV-1-infected NPMs showed transient viremia for about 10 weeks after infection. However, cell-associated proviral DNA and viral RNA persisted in the peripheral blood and lymphoid organs for about 3 years. Moreover, replication-competent HIV-1 could be successfully recovered from peripheral blood mononuclear cells (PBMCs) during long-term infection. The numbers of resting CD4+ T cells in HIV-1 infected NPMs harboring proviruses fell within a range of 2- to 3-log10 per million cells, and these proviruses could be reactivated both ex vivo and in vivo in response to co-stimulation with the latency-reversing agents JQ1 and prostratin. Our results suggested that NPMs can be infected with HIV-1 and a long-term viral reservoir was formed in NPMs, which might serve as a potential model for HIV-1 reservoir research

A physical and regulatory map of host-influenza interactions reveals pathways in H1N1 infection

available in PMC 2010 June 28.During the course of a viral infection, viral proteins interact with an array of host proteins and pathways. Here, we present a systematic strategy to elucidate the dynamic interactions between H1N1 influenza and its human host. A combination of yeast two-hybrid analysis and genome-wide expression profiling implicated hundreds of human factors in mediating viral-host interactions. These factors were then examined functionally through depletion analyses in primary lung cells. The resulting data point to potential roles for some unanticipated host and viral proteins in viral infection and the host response, including a network of RNA-binding proteins, components of WNT signaling, and viral polymerase subunits. This multilayered approach provides a comprehensive and unbiased physical and regulatory model of influenza-host interactions and demonstrates a general strategy for uncovering complex host-pathogen relationships.National Institutes of Health (U.S.) (grant U01 AI074575)National Institutes of Health (U.S.) (grant U54 AI057159)National Institutes of Health (U.S.) (NIH New Innovator Award)Ford Foundation (Predoctoral Fellowship)Ellison Medical FoundationNational Institutes of Health (U.S.) (NIH grant R01 HG001715)National Institutes of Health (U.S.) (grant P50 HG004233)National Institutes of Health (U.S.) (PIONEER award)Howard Hughes Medical InstituteBurroughs Wellcome Fund (Career Award at the Scientific Interface)Alfred P. Sloan Foundatio

SCARB2/LIMP-2 Regulates IFN Production of Plasmacytoid Dendritic Cells by Mediating Endosomal Translocation of TLR9 and Nuclear Translocation of IRF7

Scavenger receptor class B, member 2 (SCARB2) is essential for endosome biogenesis and reorganization and serves as a receptor for both β-glucocerebrosidase and enterovirus 71. However, little is known about its function in innate immune cells. In this study, we show that, among human peripheral blood cells, SCARB2 is most highly expressed in plasmacytoid dendritic cells (pDCs), and its expression is further upregulated by CpG oligodeoxynucleotide stimulation. Knockdown of SCARB2 in pDC cell line GEN2.2 dramatically reduces CpG-induced type I IFN production. Detailed studies reveal that SCARB2 localizes in late endosome/lysosome of pDCs, and knockdown of SCARB2 does not affect CpG oligodeoxynucleotide uptake but results in the retention of TLR9 in the endoplasmic reticulum and an impaired nuclear translocation of IFN regulatory factor 7. The IFN-I production by TLR7 ligand stimulation is also impaired by SCARB2 knockdown. However, SCARB2 is not essential for influenza virus or HSV-induced IFN-I production. These findings suggest that SCARB2 regulates TLR9-dependent IFN-I production of pDCs by mediating endosomal translocation of TLR9 and nuclear translocation of IFN regulatory factor 7

High-frequency rTMS over bilateral primary motor cortex improves freezing of gait and emotion regulation in patients with Parkinson’s disease: a randomized controlled trial

BackgroundFreezing of gait (FOG) is a common and disabling phenomenon in patients with Parkinson’s disease (PD), but effective treatment approach remains inconclusive. Dysfunctional emotional factors play a key role in FOG. Since primary motor cortex (M1) connects with prefrontal areas via the frontal longitudinal system, where are responsible for emotional regulation, we hypothesized M1 may be a potential neuromodulation target for FOG therapy. The purpose of this study is to explore whether high-frequency rTMS over bilateral M1 could relieve FOG and emotional dysregulation in patients with PD.MethodsThis study is a single-center, randomized double-blind clinical trial. Forty-eight patients with PD and FOG from the Affiliated Hospital of Xuzhou Medical University were randomly assigned to receive 10 sessions of either active (N = 24) or sham (N = 24) 10 Hz rTMS over the bilateral M1. Patients were evaluated at baseline (T0), after the last session of treatment (T1) and 30 days after the last session (T2). The primary outcomes were Freezing of Gait Questionnaire (FOGQ) scores, with Timed Up and Go Test (TUG) time, Standing-Start 180° Turn (SS-180) time, SS-180 steps, United Parkinson Disease Rating Scales (UPDRS) III, Hamilton Depression scale (HAMD)-24 and Hamilton Anxiety scale (HAMA)-14 as secondary outcomes.ResultsTwo patients in each group dropped out at T2 and no serious adverse events were reported by any subject. Two-way repeated ANOVAs revealed significant group × time interactions in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14. Post-hoc analyses showed that compared to T0, the active group exhibited remarkable improvements in FOGQ, TUG, SS-180 turn time, SS-180 turning steps, UPDRS III, HAMD-24 and HAMA-14 at T1 and T2. No significant improvement was found in the sham group. The Spearman correlation analysis revealed a significantly positive association between the changes in HAMD-24 and HAMA-14 scores and FOGQ scores at T1.ConclusionHigh-frequency rTMS over bilateral M1 can improve FOG and reduce depression and anxiety in patients with PD

Forebrain NR2B Overexpression Facilitating the Prefrontal Cortex Long-Term Potentiation and Enhancing Working Memory Function in Mice

Prefrontal cortex plays an important role in working memory, attention regulation and behavioral inhibition. Its functions are associated with NMDA receptors. However, there is little information regarding the roles of NMDA receptor NR2B subunit in prefrontal cortical synaptic plasticity and prefrontal cortex-related working memory. Whether the up-regulation of NR2B subunit influences prefrontal cortical synaptic plasticity and working memory is not yet clear. In the present study, we measured prefrontal cortical synaptic plasticity and working memory function in NR2B overexpressing transgenic mice. In vitro electrophysiological data showed that overexpression of NR2B specifically in the forebrain region resulted in enhancement of prefrontal cortical long-term potentiation (LTP) but did not alter long-term depression (LTD). The enhanced LTP was completely abolished by a NR2B subunit selective antagonist, Ro25-6981, indicating that overexpression of NR2B subunit is responsible for enhanced LTP. In addition, NR2B transgenic mice exhibited better performance in a set of working memory paradigms including delay no-match-to-place T-maze, working memory version of water maze and odor span task. Our study provides evidence that NR2B subunit of NMDA receptor in prefrontal cortex is critical for prefrontal cortex LTP and prefrontal cortex-related working memory

Ticagrelor vs Clopidogrel in CYP2C19 loss-of-function carriers with Stroke or TIA

BACKGROUNDComparisons between ticagrelor- aspirin and clopidogrel-aspirin in CYP2C19 loss-of-function carriers have not been well studied for secondary stroke prevention.METHODSWe conducted a randomized, double-blind, placebo-controlled trial of 6,412 patients with a minor ischemic stroke or TIA who carried CYP2C19 LOF alleles determined by point-of-care testing. Patients were randomly assigned within 24 hours after symptom onset, in a 1:1 ratio to receive ticagrelor (180 mg loading dose on day 1 followed by 90 mg twice daily for days 2 through 90) or clopidogrel (300 mg loading dose on day 1 followed by 75 mg per day for days 2 through 90), plus aspirin (75-300 mg loading dose followed by 75 mg daily for 21 days). The primary efficacy outcome was stroke and the primary safety outcome was severe or moderate bleeding, both within 90 days. RESULTSStroke occurred within 90 days in 191 (6.0%) versus 243 (7.6%), respectively (hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.94; P=0.008). Moderate or severe bleeding occurred in 9 patients (0.3%) in the ticagrelor-aspirin group and in 11 patients (0.3%) in the clopidogrel-aspirin group; any bleeding event occurred in 170 patients (5.3%) vs 80 (2.5%), respectively. CONCLUSIONSAmong Chinese patients with minor ischemic stroke or TIA within 24 hours after symptoms onset who were carriers of CYP2C19 loss-of-function alleles, ticagrelor- aspirin was modestly better than clopidogrel-aspirin for reducing the risk of stroke but was associated with more total bleeding events at 90 days. (CHANCE-2 ClinicalTrials.gov number, NCT04078737.