Effect of rs1344706 in the ZNF804A gene on the brain network.

ZNF804A rs1344706 (A/C) was the first SNP that reached genome-wide significance for schizophrenia. Recent studies have linked rs1344706 to functional connectivity among specific brain regions. However, no study thus far has examined the role of this SNP in the entire functional connectome. In this study, we used degree centrality to test the role of rs1344706 in the whole-brain voxel-wise functional connectome during the resting state. 52 schizophrenia patients and 128 healthy controls were included in the final analysis. In our whole-brain analysis, we found a significant interaction effect of genotype × diagnosis at the precuneus (PCU) (cluster size = 52 voxels, peak voxel MNI coordinates: x = 9, y = - 69, z = 63, F = 32.57, FWE corrected P < 0.001). When we subdivided the degree centrality network according to anatomical distance, the whole-brain analysis also found a significant interaction effect of genotype × diagnosis at the PCU with the same peak in the short-range degree centrality network (cluster size = 72 voxels, F = 37.29, FWE corrected P < 0.001). No significant result was found in the long-range degree centrality network. Our results elucidated the contribution of rs1344706 to functional connectivity within the brain network, and may have important implications for our understanding of this risk gene's role in functional dysconnectivity in schizophrenia

Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment

<p>Abstract</p> <p>Background -</p> <p>Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906.</p> <p>Methods -</p> <p>Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of CPT-11 (CPT-11) by PHY906 in a well-characterized pre-clinical model; the administration of PHY906 and CPT-11 to female BDF-1 mice bearing subcutaneous Colon 38 tumors.</p> <p>Results -</p> <p>We observed that 1) individually PHY906 and CPT-11 induce distinct alterations in tumor, liver and spleen; 2) PHY906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of CPT-11, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection.</p> <p>Conclusions -</p> <p>PHY906 together with CPT-11 triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response.</p

Giant polarization in super-tetragonal ferroelectric thin films through interphase strain

Strain engineering has emerged as a powerful tool to enhance the performance of known functional materials. Here we demonstrate a general and practical method to obtain super-tetragonality and giant polarization using interphase strain. We use this method to create an out-of-plane–to–in-plane lattice parameter ratio of 1.238 in epitaxial composite thin films of tetragonal lead titanate (PbTiO3), compared to 1.065 in bulk. These thin films with super-tetragonal structure possess a giant remanent polarization, 236.3 microcoulombs per square centimeter, which is almost twice the value of known ferroelectrics. The super-tetragonal phase is stable up to 725°C, compared to the bulk transition temperature of 490°C. The interphase-strain approach could enhance the physical properties of other functional materials.PostprintPeer reviewe

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke

BackgroundDual antiplatelet treatment has been shown to reduce recurrence of stroke compared to aspirin alone when initiated early after an acute stroke. The effect of clopidogrel and aspirin versus aspirin alone within 72 hours of acute cerebral ischemia from atherosclerosis has not been well studied.MethodsWe conducted a randomized, double-blind, placebo-controlled, 2-by-2 factorial trial in patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause, not receiving thrombolysis or thrombectomy in 222 hospitals in China. Patients were randomly assigned within 72 hours after symptom onset in a 1:1 ratio, to receive clopidogrel (300mg on day 1, 75mg daily on days 2-90) and aspirin (100-300mg on day1, 100mg daily on days 2-21), or clopidogrel placebo and aspirin (100-300mg on day1, 100mg daily on days 2-90). There was no interaction between this component of the factorial trial design trial and a second part that tested immediate vs delayed stain treatment and is reported separately. The primary efficacy outcome was a new stroke, and the primary safety outcome was moderate-to-severe bleeding, both within 90 days.ResultsA total of 6100 patients were enrolled, 3050 assigned to each trial group. The qualifying event for enrollment was TIA in 13%. Approximately 13% of patients were assigned to a treatment group within 24 hours and 87% were assigned between 24 and 72 hours of onset of stroke. A new stroke occurred in 222 (7.3%) in the clopidogrel-aspirin group, and 279 (9.2%) in the aspirin group (hazard ratio, 0.79; 95% confidence interval [CI], 0.66-0.94; P=0.008). Moderate-to-severe bleeding occurred in 27 (0.9%) and 13 patients (0.4%), respectively (hazard ratio, 2.08; 95% CI, 1.07-4.04, P=0.03).ConclusionsAmong patients with mild ischemic stroke or high-risk TIA of presumed atherosclerotic cause, combined clopidogrel-aspirin initiated within 72 hours of onset was superior to aspirin alone in reducing the risk of new stroke at 90 days but was associated with a low but increased risk of moderate-to-severe bleeding

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.

Survey on research and development of on-orbit active debris removal methods

Space debris is growing dramatically with the rapid pace of human exploration of space, which seriously threatens the safety of artificial spacecraft in orbit. Therefore, the active debris removal (ADR) is important. This review aims to review the ADR methods and to advance related research in the future. The current research and development status are clearly demonstrated by mapping knowledge domain and charts. In this paper, the latest research results are classified and summarized in detail from two aspects of space debris capture and removal. The scheme comparison and evaluation of all ADR methods are performed, and the applicable scopes of various methods are summarized. Each ADR method is scored using a cobweb evaluation model based on six indicators. Future development of ADR is discussed to promote further research interest

How Proactive Environmental Strategy Facilitates Environmental Reputation: Roles of Green Human Resource Management and Discretionary Slack

Based on natural resource-based theory, we examined how firms&rsquo; environmental strategies and environmental reputation depended on their green human resource management and discretionary slack. From the perspective of human resource management, we hypothesized that proactive environmental strategy predicted firms&rsquo; environmental reputation through the mediation of green human resource management. We further proposed that slack resources, which can be used discretely by managers for environmental management, enhanced the hypothesized relationships. Using data from firms in environmentally sensitive industries in eastern China, we provided empirical support for our hypotheses. The findings highlight the vital roles played by managers and green human resource management in implementing firms&rsquo; environmental strategies and promoting firms&rsquo; environmental reputation