Non-equilibrium Theoretical Framework and Universal Design Principles of Oscillation-Driven Catalysis

At stationary environmental conditions, a catalyst's reaction rates may be restricted by thermodynamic laws, and certain performances can never be achieved (e.g., catalysts can not change the free energy difference between reactants and products). However, it has been reported that if environments change rapidly, catalysts can be driven away from stationary states and exhibit anomalous performance. We present a general geometric non-equilibrium theory to describe and explain anomalous catalytic behaviors in rapidly oscillating environments that exceed the steady-state restrictions. It leads to a universal design principle of novel catalysts with oscillation-pumped performances. Even though a catalyst at various environmental conditions cannot be described by a single free energy landscape, we propose a novel control-conjugate landscape to encode the reaction rates over a continuous range of control parameters $\lambda$, which is inspired by the exponential form of the Arrhenius law. The control-conjugate landscape significantly simplifies the design principle and makes it applicable to large-amplitude environmental oscillations. The design principle is demonstrated by two examples, (1) inverting a spontaneous reaction to synthesize high-free-energy molecules and (2) speeding up reactions without utilizing low activation barriers. In both examples, catalysts autonomously harness energy from non-equilibrium environments to enable such functionalities

MiR-331-5p suppresses gastric cancer cell proliferation, migration, invasion, and glycolysis via targeting PFKFB3

Purpose: To examine the role of microRNAs (miRNAs), miR-331-5p, in gastric cancer (GC). Methods: The mRNA level of miR-331-5p and protein level of 6-phosphofructo-2-kinase/fructose-2,6- bisphosphatase-3 (PFKFB3) were determined using quantitative real-time reverse transcription– polymerase chain reaction (qRT–PCR) and western blotting, respectively. The cell viability and proliferation of the two GC cell lines (AGS and MKN45) were evaluated using Cell Counting Kit-8 (CCK8) and bromodeoxyuridine (BrdU)  ssays. Cell migration and invasion of AGS and MKN45 were evaluated using wound healing and invasion assays, respectively. Potential interactions between miR331-5p and PFKFB3 were assessed by luciferase activity assay, while the effects of the interactions on cell physiology and metabolism were investigated in cells  verexpressing both miR-331-5p and PFKFB3. Results: MiR-331-5p overexpression inhibited cell proliferation, suppressed migration and invasion, and inhibited glycolysis in AGS and MKN45 cells. The mRNA for the glycolytic regulatory enzyme PFKFB3 was shown to be a direct target of miR-331-5p and modulated by miR-331-5p. In rescue experiments, PFKFB3 reversed the miR-331-5p-induced inhibition of proliferation, migration, invasion, and glycolysis in AGS cells. Conclusion: This work supports a role for miR-331-5p through the modulation of PFKFB3 activity in GC in vivo, thus providing insight into novel potential therapies for the treatment of GC

Systematic Review and Meta-Analysis on the Association Between Outpatient Statins Use and Infectious Disease-Related Mortality

Background: To update and refine systematic literature review on the association between outpatient statins use and mortality in patients with infectious disease. Materials and Methods: We searched articles published before September 31, 2012, on the association between statins and infectious disease-related mortality through electronic databases. Eligible articles were analyzed in Review Manager 5.1. We conducted stratification analysis by study design, infection types, clinical outcomes and study locations. Results: The pooled odds ratio (OR) for death (statins use vs. no use) across the 41 included studies was 0.71 (95% confidence interval: 0.64, 0.78). The corresponding pooled ORs were 0.58 (0.38, 0.90), 0.66 (0.57, 0.75), 0.71 (0.57, 0.89) and 0.83 (0.67, 1.04) for the case-control study, retrospective cohort studies, prospective cohort studies and RCTs; 0.40 (0.20, 0.78), 0.61 (0.41, 0.90), 0.69 (0.62, 0.78) and 0.86 (0.68, 1.09) for bacteremia, sepsis, pneumonia and other infections; 0.62 (0.534, 0.72), 0.68 (0.53, 0.89), 0.71 (0.61, 0.83) and 0.86 (0.70, 1.07) for 30-day, 90-day, in-hospital and long-term (>1 year) mortality, respectively. Conclusions: Outpatient statins use is associated with a lower risk of death in patients with infectious disease in observational studies, but in a less extent in clinical trials. This association also varies considerably by infection types and clinical outcomes

Clinical application of CT-guided 125I seed interstitial implantation for local recurrent rectal carcinoma

<p>Abstract</p> <p>Purpose</p> <p>The present study aimed to explore the safety profile and clinical efficacy of CT-guided radioactive seed implantation in treating local recurrent rectal carcinoma.</p> <p>Materials and methods</p> <p>CT-guided ¹²⁵I seed implantation was carried out in 20 patients with locally recurrent rectal carcinoma. 14 of the 20 patient had prior adjuvant external-beam radiation therapy (EBRT). The treatment planning system (TPS) was used preoperatively to reconstruct three dimensional images of the tumor and to calculate the estimated seed number and distribution. The median matched peripheral dose (MPD) was 120 Gy (range, 100-160 Gy).</p> <p>Results</p> <p>Of the 20 patients, 12 were male, 8 were female, and ages ranged from 38 to 78, with a median age of 62. Duration of follow-up was 3-34 months. The response rate of pain relief was 85% (17/20). Repeat CT scan 2 months following the procedure revealed complete response (CR) of the tumor in 2 patients, partial response (PR) in 13 patients, stable disease (SD) in 3 patients, and progressive disease (PD) in 2 patients. 75% of patients had either CR or PR. Median survival time was 18.8 months (95% CI: 3.5-22.4 months). 1 and 2 year survival rates were 75% and 25%, respectively. 4 patients died of recurrent tumor; 4 patients died of distant metastases; 9 patients died of recurrent tumor and distant metastases. 3 patients survived after 2 year follow up. Two patients were found to have mild hematochezia, which was reversible with symptomatic management.</p> <p>Conclusion</p> <p>CT-guided ¹²⁵I seed implantation appeared to be a safe, useful and less complicated interventional treatment option for local recurrent rectal carcinoma.</p

Passive immunotherapy for influenza A H5N1 virus infection with equine hyperimmune globulin F(ab')(2 )in mice

BACKGROUND: Avian influenza virus H5N1 has demonstrated considerable pandemic potential. Currently, no effective vaccines for H5N1 infection are available, so passive immunotherapy may be an alternative strategy. To investigate the possible therapeutic effect of antibody against highly pathogenic H5N1 virus on a mammal host, we prepared specific equine anti-H5N1 IgGs from horses vaccinated with inactivated H5N1 virus, and then obtained the F(ab')(2 )fragments by pepsin digestion of IgGs. METHODS: The horses were vaccinated with inactivated H5N1 vaccine to prepare anti-H5N1 IgGs. The F(ab')(2 )fragments were purified from anti-H5N1 hyperimmune sera by a protocol for 'enhanced pepsin digestion'. The protective effect of the F(ab')(2 )fragments against H5N1 virus infection was determined in cultured MDCK cells by cytopathic effect (CPE) assay and in a BALB/c mouse model by survival rate assay. RESULTS: By the protocol for 'enhanced pepsin digestion', total 16 g F(ab')(2 )fragments were finally obtained from one liter equine antisera with the purity of over 90%. The H5N1-specific F(ab')(2 )fragments had a HI titer of 1:1024, and the neutralization titre of F(ab')(2 )reached 1: 2048. The in vivo assay showed that 100 μg of the F(ab')(2 )fragments could protect BALB/c mice infected with a lethal dose of influenza H5N1 virus. CONCLUSION: The availability of highly purified H5N1-specific F(ab')(2 )fragments may be promising for treatment of influenza H5N1 infection. Our work has provided experimental support for the application of the therapeutic equine immunoglobulin in future large primate or human trials

Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells.

MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed \u27small RNA zipper\u27. It is designed to connect miRNA molecules end to end, forming a DNA-RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30-50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes

First identification of long non-coding RNAs in fungal parasite Nosema ceranae

International audienceAbstractNosema ceranae is a unicellular fungal parasite of honey bees and causes huge losses for apiculture. Until present, no study on N. ceranae long non-coding RNAs (lncRNAs) was documented. Here, we sequenced purified spores of N. ceranae using strand-specific library construction and high-throughput RNA sequencing technologies. In total, 83 novel lncRNAs were predicted from N. ceranae spore samples, including lncRNAs, long intergenic non-coding RNAs (lincRNAs), and sense lncRNAs. Moreover, these lncRNAs share similar characteristics with those identified in mammals and plants, such as shorter length and fewer exon number and transcript isoforms than protein-coding genes. Finally, the expression of 12 lncRNAs was confirmed with RT-PCR, confirming their true existence. To our knowledge, this is the first evidence of lncRNAs produced by a microsporidia species, offering novel insights into basic biology such as regulation of gene expression of this widespread taxonomic group

Numerical simulation of scale-up effects of methanol-to-olefins fluidized bed reactors

Scale-up of fluidized bed reactors has long been regarded as a big challenge in chemical reaction engineering. While traditional scaling theories are mostly based on hydrodynamics similarity, computational fluid dynamics (CFD) aided approach allows direct coupling between hydrodynamics and reaction factors and is expected to speed up the experiment-based scale-up process with lower cost. In this study, we aim to investigate the scale-up effects through simulations of a series of methanol-to-olefins (MTO) reactors of different sizes. The two-fluid model and energy-minimization multi-scale (EMMS)-based drag models, are combined in simulations. The fluidization characteristics in terms of flow structures, velocity distribution, mass fractions of gaseous product and coke distribution are presented against available experimental data for different-sized reactors. It is found that typical hydrodynamic features can be reasonably predicted, while the prediction of reaction behavior shows growing discrepancy with increasing reactor size. Possible reasons are discussed in the last section along with future work presented for scale-up studies. (C) 2017 Elsevier Ltd. All rights reserved

High probability neurotransmitter release sites represent an energy efficient design

At most synapses, the probability of neurotransmitter release from an active zone (PAZ) is low, a design thought to confer many advantages. Yet, high PAZ can also be found at synapses. Speculating that high PAZ confers high energy efficiency, we examined energy efficiency at terminals of two Drosophila motor neurons (MNs) synapsing on the same muscle fiber, but with contrasting average PAZ. Through electrophysiological and ultrastructural measurements we calculated average PAZ for MNSNb/d-Is and MN6-Ib terminals (0.33±0.10 and 0.11±0.02 respectively). Using a miles-per-gallon analogy, we calculated efficiency as the number of glutamate molecules released for each ATP molecule that powers the release and recycling of glutamate and the removal of calcium (Ca2+) and sodium (Na+). Ca2+ and Na+ entry were calculated by microfluorimetry and morphological measurements respectively. Terminals with the highest PAZ release more glutamate but admit less Ca2+ and Na+, supporting the hypothesis that high PAZ confers greater energy efficiency than low PAZ (0.13±0.02 and 0.06±0.01 respectively). In an analytical treatment of parameters that influence efficiency we found that efficiency could be optimized in either terminal by increasing PAZ. Terminals with highest PAZ operate closest to this optimum but are less active and less able to sustain high release rates. Adopting an evolutionary biological perspective, we interpret the persistence of low PAZ release sites at more active terminals to be the result of selection pressures for sustainable neurotransmitter release dominating selection pressures for high energy efficiency