Metal–Organic Framework Decorated Cuprous Oxide Nanowires for Long-lived Charges Applied in Selective Photocatalytic CO₂ Reduction to CH₄

Improving the stability of cuprous oxide (Cu2O) is imperative to its practical applications in artificial photosynthesis. In this work, Cu2O nanowires are encapsulated by metal–organic frameworks (MOFs) of Cu3(BTC)2 (BTC=1,3,5-benzene tricarboxylate) using a surfactant-free method. Such MOFs not only suppress the water vapor-induced corrosion of Cu2O but also facilitate charge separation and CO2 uptake, thus resulting in a nanocomposite representing 1.9 times improved activity and stability for selective photocatalytic CO2 reduction into CH4 under mild reaction conditions. Furthermore, direct transfer of photogenerated electrons from the conduction band of Cu2O to the LUMO level of non-excited Cu3(BTC)2 has been evidenced by time-resolved photoluminescence. This work proposes an effective strategy for CO2 conversion by a synergy of charge separation and CO2 adsorption, leading to the enhanced photocatalytic reaction when MOFs are integrated with metal oxide photocatalyst

Activation of NRG1-ERBB4 signaling potentiates mesenchymal stem cell-mediated myocardial repairs following myocardial infarction

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Potent Paracrine Effects of human induced Pluripotent Stem Cell-derived Mesenchymal Stem Cells Attenuate Doxorubicin-induced Cardiomyopathy

© 2015, Nature Publishing Group. All rights reserved.Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) can protect cardiomyocytes against anthracycline-induced cardiomyopathy (AIC) through paracrine effects. Nonetheless the paracrine effects of human induced pluripotent stem cell-derived MSCs (iPSC-MSCs) on AIC are poorly understood. In vitro studies reveal that doxorubicin (Dox)-induced reactive oxidative stress (ROS) generation and cell apoptosis in neonatal rat cardiomyocytes (NRCMs) are significantly reduced when treated with conditioned medium harvested from BM-MSCs (BM-MSCs-CdM) or iPSC-MSCs (iPSC-MSCs-CdM). Compared with BM-MSCs-CdM, NRCMs treated with iPSC-MSCs-CdM exhibit significantly less ROS and cell apoptosis in a dose-dependent manner. Transplantation of BM-MSCs-CdM or iPSC-MSCs-CdM into mice with AIC remarkably attenuated left ventricular (LV) dysfunction and dilatation. Compared with BM-MSCs-CdM, iPSC-MSCs-CdM treatment showed better alleviation of heart failure, less cardiomyocyte apoptosis and fibrosis. Analysis of common and distinct cytokines revealed that macrophage migration inhibitory factor (MIF) and growth differentiation factor-15 (GDF-15) were uniquely overpresented in iPSC-MSC-CdM. Immunodepletion of MIF and GDF-15 in iPSC-MSCs-CdM dramatically decreased cardioprotection. Injection of GDF-15/MIF cytokines could partially reverse Dox-induced heart dysfunction. We suggest that the potent paracrine effects of iPSC-MSCs provide novel "cell-free" therapeutic cardioprotection against AIC, and that MIF and GDF-15 in iPSC-MSCs-CdM are critical for these enhanced cardioprotective effects.published_or_final_versio

A Novel SALL4/OCT4 Transcriptional Feedback Network for Pluripotency of Embryonic Stem Cells

Background: SALL4 is a member of the SALL gene family that encodes a group of putative developmental transcription factors. Murine Sall4 plays a critical role in maintaining embryonic stem cell (ES cell) pluripotency and self-renewal. We have shown that Sall4 activates Oct4 and is a master regulator in murine ES cells. Other SALL gene members, especially Sall1 and Sall3 are expressed in both murine and human ES cells, and deletions of these two genes in mice lead to perinatal death due to developmental defects. To date, little is known about the molecular mechanisms controlling the regulation of expressions of SALL4 or other SALL gene family members. Methodology/Principal Findings: This report describes a novel SALL4/OCT4 regulator feedback loop in ES cells in balancing the proper expression dosage of SALL4 and OCT4 for the maintenance of ESC stem cell properties. While we have observed that a positive feedback relationship is present between SALL4 and OCT4, the strong self-repression of SALL4 seems to be the “break” for this loop. In addition, we have shown that SALL4 can repress the promoters of other SALL family members, such as SALL1 and SALL3, which competes with the activation of these two genes by OCT4. Conclusions/Significance: Our findings, when taken together, indicate that SALL4 is a master regulator that controls its own expression and the expression of OCT4. SALL4 and OCT4 work antagonistically to balance the expressions of other SALL gene family members. This novel SALL4/OCT4 transcription regulation feedback loop should provide more insight into the mechanism of governing the “stemness” of ES cells

Characteristics of predictor sets found using differential prioritization

<p>Abstract</p> <p>Background</p> <p>Feature selection plays an undeniably important role in classification problems involving high dimensional datasets such as microarray datasets. For filter-based feature selection, two well-known criteria used in forming predictor sets are relevance and redundancy. However, there is a third criterion which is at least as important as the other two in affecting the efficacy of the resulting predictor sets. This criterion is the degree of differential prioritization (DDP), which varies the emphases on relevance and redundancy depending on the value of the DDP. Previous empirical works on publicly available microarray datasets have confirmed the effectiveness of the DDP in molecular classification. We now propose to establish the fundamental strengths and merits of the DDP-based feature selection technique. This is to be done through a simulation study which involves vigorous analyses of the characteristics of predictor sets found using different values of the DDP from toy datasets designed to mimic real-life microarray datasets.</p> <p>Results</p> <p>A simulation study employing analytical measures such as the distance between classes before and after transformation using principal component analysis is implemented on toy datasets. From these analyses, the necessity of adjusting the differential prioritization based on the dataset of interest is established. This conclusion is supported by comparisons against both simplistic rank-based selection and state-of-the-art equal-priorities scoring methods, which demonstrates the superiority of the DDP-based feature selection technique. Reapplying similar analyses to real-life multiclass microarray datasets provides further confirmation of our findings and of the significance of the DDP for practical applications.</p> <p>Conclusion</p> <p>The findings have been achieved based on analytical evaluations, not empirical evaluation involving classifiers, thus providing further basis for the usefulness of the DDP and validating the need for unequal priorities on relevance and redundancy during feature selection for microarray datasets, especially highly multiclass datasets.</p

Cryptosporidium Priming Is More Effective than Vaccine for Protection against Cryptosporidiosis in a Murine Protein Malnutrition Model

Cryptosporidium is a major cause of severe diarrhea, especially in malnourished children. Using a murine model of C. parvum oocyst challenge that recapitulates clinical features of severe cryptosporidiosis during malnutrition, we interrogated the effect of protein malnutrition (PM) on primary and secondary responses to C. parvum challenge, and tested the differential ability of mucosal priming strategies to overcome the PM-induced susceptibility. We determined that while PM fundamentally alters systemic and mucosal primary immune responses to Cryptosporidium, priming with C. parvum (106 oocysts) provides robust protective immunity against re-challenge despite ongoing PM. C. parvum priming restores mucosal Th1-type effectors (CD3+CD8+CD103+ T-cells) and cytokines (IFNγ, and IL12p40) that otherwise decrease with ongoing PM. Vaccination strategies with Cryptosporidium antigens expressed in the S. Typhi vector 908htr, however, do not enhance Th1-type responses to C. parvum challenge during PM, even though vaccination strongly boosts immunity in challenged fully nourished hosts. Remote non-specific exposures to the attenuated S. Typhi vector alone or the TLR9 agonist CpG ODN-1668 can partially attenuate C. parvum severity during PM, but neither as effectively as viable C. parvum priming. We conclude that although PM interferes with basal and vaccine-boosted immune responses to C. parvum, sustained reductions in disease severity are possible through mucosal activators of host defenses, and specifically C. parvum priming can elicit impressively robust Th1-type protective immunity despite ongoing protein malnutrition. These findings add insight into potential correlates of Cryptosporidium immunity and future vaccine strategies in malnourished children

Strengthening of short splices in RC beams using Post-Tensioned Metal Straps

This paper investigates the effectiveness of a novel and cost-effective strengthening technique using Post-Tensioned Metal Straps (PTMS) at enhancing the bond behaviour of short lap spliced steel bars in reinforced concrete (RC) beams. Twelve RC beams with a short lap splice length of 10d b (d b = bar diameter) at the midspan zone were tested in flexure to examine the bond splitting failure. The effect of confinement (no confinement, internal steel stirrups or external PTMS), bar diameter and concrete cover were examined. The results show that, whilst unconfined control beams failed prematurely due to cover splitting, the use of PTMS confinement enhanced the bond strength of the spliced bars by up to 58 % and resulted in a less brittle behaviour. Based on the test results, a new analytical model is proposed to predict the additional bond strength provided by PTMS confinement. The model should prove useful in the strengthening design of substandard lap spliced RC elements

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort

BACKGROUND: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. METHODS: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. FINDINGS: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. INTERPRETATION: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. FUNDING: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore