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The clinical significance of hemoglobin level and blood transfusion therapy in elderly sepsis patients remains controversial. The study investigated the relationship between mortality, hemoglobin levels, and blood transfusion in elderly sepsis patients. Elderly sepsis patients were included in the Marketplace for Medical Information in Intensive Care (MIMIC-IV) database. A multivariate regression model analyzed the relationship between the Hb level and the 28-day mortality risk. Logistic Multivariate analysis, Propensity Matching (PSM) analysis, an Inverse Probabilities Weighting (IPW) model and doubly robust estimation were applied to analyze the 28-day mortality risk between transfused and non-transfused patients in Hb at 7–8 g/dL, 8–9 g/dL, 9–10 g/dL, and 10–11 g/dL groups. 7473 elderly sepsis patients were enrolled in the study. The Hb level in the ICU and the 28-day mortality risk of patients with sepsis shared a non-linear relationship. The patients with Hb levels of <10 g/dL(p < 0.05) and > 15 g/dL(p < 0.05) within 24 h had a high mortality risk in multivariate analysis. In the Hb level 7–8 g/dL and 8–9 g/dL subgroup, the Multivariate analysis (p < 0.05), PSM (p < 0.05), IPW (p < 0.05) and doubly robust estimation (p < 0.05) suggested that blood transfusion could reduce the mortality risk. In the subgroup with a Hb level of 10–11 g/dL, IPW (p < 0.05) and doubly robust estimation (p < 0.05) suggested that blood transfusion could increase the mortality risk of elderly sepsis patients. A non-linear relationship between the Hb level and the 28-day mortality risk and Hb levels of <10 g/dL and > 15 g/dL may increase the mortality risk, and blood transfusion with a Hb level of <9 g/dL may minimize mortality risk in elderly sepsis patients. Clinical significance of hemoglobin level and blood transfusion therapy in elderly sepsis patients: a retrospective analysis. [Display omitted] [ABSTRACT FROM AUTHOR]

The ubiquitin-proteasome system (UPS) is one of the main ways of eukaryotic protein degradation and post-translational modification. It has proven as an essential process for plants to respond to abiotic stresses. Plant U-box (PUB) protein acts as a ubiquitin ligase, which recognizes and ubiquitinates the target proteins. Many PUBs have been involved in water stress in Arabidopsis and rice, but similar comprehensive studies in potato remained limited. In this study, the overexpressed and interfered transgenic potato plants of StPUB27 were obtained and their performances were evaluated under osmotic stress. The result showed that overexpression of StPUB27 accelerated the dehydration of detached leaves companied with greater stomatal conductance, while the down-regulated StPUB27 expression by RNA interference (RNAi) showed a smaller stomatal conductance and a lower rate of water loss in detached leaves, thus showing higher tolerance to osmotic stress. In addition, no significant changes in the proline content were observed between StPUB27 overexpressed and RNAi potato plants. The result demonstrated that potato E3 ubiquitin ligase PUB27 may negatively regulate drought tolerance by mediating stomatal conductance. • StPUB27 genes were cloned and sequenced from potatoes. • Overexpression of StPUB27 accelerates leaf dehydration with greater stomatal conductance. • StPUB27 was likely to participate in ubiquitination modification. • StPUB27 can negatively regulate water tolerance by mediating stomatal movement. [ABSTRACT FROM AUTHOR]

The ubiquitin/26S proteasome pathway is widely related to plant growth and metabolism and response to treatment by specifically degrading ubiquitin-modified proteins, including RING-finger-type E3 ubiquitin ligase (RING). The RING finger protein (RFP) gene family, determining the specificity of the ubiquitination process, is numerous and complex in function. In this study, we constructed a pCEGFP-StRFP2 fusion protein expression vector and transformed it into tobacco to achieve transient expression, thereby confirming that StRFP2 is localized in the cell membrane and cytoplasm. The result of qRT-PCR analysis showed that StRFP2 gene was significantly expressed in potato leaves, and the expression level of StRFP2 was significantly up-regulated under drought treatment. The transgenic plants of overexpressing StRFP2 gene were obtained with Agrobacterium tumefaciens -mediated transformation. Plant height, stem diameter, root length, fresh weight and root-shoot ratio of transgenic plants were significantly higher than those of non-transgenic plants (WT), indicating that the growth of plants was significantly promoted after overexpression of StRFP2 gene. Under PEG osmotic stress, the expressional level of StRFP2 in transgenic potato plants was significantly higher than that of WT. Furthermore, the free proline content and CAT activity in transgenic plants were higher than WT, on the contrary, MDA was lower than WT, and transgenic plants have stronger water retention capacity under simulated drought stress treatment, which indicated that StRFP2 could strengthen the tolerance of plants responding to drought stress. The above evidence strongly suggested that the StRFP2 gene is obviously up-regulated expression by drought stress, thereby enhancing the drought tolerance of the potato. • Subcellular localization of the StRFP2 protein in potato. • Tissue-specific expression analysis of potato StRFP2 gene under drought stress. • Overexpression of StRFP2 gene enhances potato plants tolerance to PEG stress. • StRFP2 gene plays a vital role in the regulation of drought stress in potato. [ABSTRACT FROM AUTHOR]

Herein, two orange-red emitters, 3,6-bis(9,9-dimethylacridin-10(9H)-yl)-9H-fluoren-9-one (DMAC-FO) and 3,6-di(10H-SP[acridine-9,9′-fluoren]-10-yl)-9H-fluoren-9-one (SPAC-FO), based on fluorenone have been designed and synthesized. As compared to the widely reported benzophenone acceptor, fluorenone has deeper lowest unoccupied molecular orbital (LUMO) because of its more conjugated skeleton and thus it can red-shift the emission maximum. The molecular simulation exhibits both emitters has separated highest occupied molecular orbitals (HOMOs) (@donors) and LUMOs (@acceptor), indicating they could act as thermally activated delayed fluorescence (TADF) materials which are further confirmed by the transient spectra. Consequently, external quantum efficiencies (EQEs) of 10.0% for DMAC-FO and 14.2% for SPAC-FO are achieved in the organic light-emitting diodes (OLEDs). Image 1 • Two orange-red emitters, DMAC-FO and SPAC-FO, based on fluorenone have been designed and synthesized. • TADF properties were realized in DMAC-FO and SPAC-FO due to the highly twisted structure. • High EQEs of 10.0% for DMAC-FO and 14.2% for SPAC-FO were achieved in OLEDs. [ABSTRACT FROM AUTHOR]

Background: Performance of Pooled Cohort Equations (PCEs) for atherosclerotic cardiovascular disease (ASCVD) risks varied across populations. Whether the recently developed Prediction for ASCVD Risk in China (China-PAR) model could accurately predict cardiovascular risks in real practice remains unclear.Methods: A population-based cohort study in rural Beijing in the "stroke belt" in North China was used to externally validate PCE and China-PAR models for 5-year ASCVD risk prediction. Expected 5-year prediction risk using China-PAR model was compared with PCE (white). The models were assessed for calibration, discrimination, and reclassification.Results: Among 11,169 adults aged 40 to 79 years over a median 6.44 years of follow-up, 1,921 participants developed a first ASCVD event during total 70,951 person-years. China-PAR model fairly predicted ASCVD risk in men but overestimated by 29.4% risk in women (calibration χ2 = 81.4, P < .001). Underestimations were shown by PCE as 76.2% in men and 88.2% in women with poor calibration (both P < .001). However, discrimination was similar in both models: C-statistics in men were 0.685 (95% CI 0.660-0.710) for China-PAR and 0.675 (95% CI 0.649-0.701) for PCE; C-statistics in women were 0.711 (95% CI 0.694-0.728) for China-PAR and 0.714 (95% CI 0.697-0.731) for PCE. Moreover, China-PAR did not substantially improve accuracy of reclassification compared with PCE.Conclusions: China-PAR outperformed PCE in 5-year ASCVD risk prediction in this rural Northern Chinese population at average population risk level, fairly predicted risk in men, but overestimated risk in women; however, China-PAR did not meaningfully improve the accuracy of discrimination and reclassification at individual risk level. [ABSTRACT FROM AUTHOR]

A subtle change in molecular structure of OLED material could lead to significant variation in device performance. For a better understanding of the connection between molecular structures and properties, four molecules ( 1 , 2 , 3 , and 4 ) based on different spiro-systems, namely spiro[cyclopropane-1,9′-fluorene], spiro[cyclopentane-1,9′-fluorene], 1′,3′-dihydrospiro[fluorene-9,2′-indene] and spirobifluorene, were designed and prepared. The influences of different spiro units on photophysical properties and electroluminescence performance were fully studied. The experimental results showed that photophysical properties, electrochemical behaviors, and frontier molecular orbital distributions of these different spirofluorenes are mostly identical because the π-backbones were less affected by the different cycles at the C-9 position of fluorene. However, green phosphorescent organic light-emitting diodes (PHOLEDs) based on spirobifluorene derivative 4 exhibited the highest electroluminescence performance among these four hosts. Thus, we hope this work could reveal deep understanding for the rational design of host materials based on spirofluorene blocks. [ABSTRACT FROM AUTHOR]

Ordered colloidal crystals possess unique photonic properties for a wide range of applications in engineering, material science, communications, and medicine. However, ordered structures are hard to achieve even in small systems, due to the formation of defects during the process. In this paper, we focus on the control of a micron-sized SiO 2 colloidal self-assembly process for defect-free crystal in an externally applied electric field batch system. Five control strategies including time-constant and time-varying, heuristic and model-based open-loop and closed-loop policies are investigated, to understand their control mechanisms. The model-based policies are designed using a reduced-order Markov state model, built with samples from Brownian dynamics simulations, and are calculated with dynamic programming. The performance of all the five strategies are evaluated on both the Brownian dynamics simulation and the experiments. Time-varying control strategies can improve the yield of grain-boundary-free crystals over that of their time-constant counterparts. Moreover, using feedback as “endpoint detection” to terminate the process can also shorten the process time, compared to open-loop strategies. [ABSTRACT FROM AUTHOR]

A series of highly luminescent [Pt(NˆCˆCˆN)] emitters (ZPt1, ZPt2 and ZPt3) based on pyrazolo[1,5- f ]phenanthridine-containing ligands were designed and synthesized. These Pt(II) complexes demonstrated extremely high thermal stabilities with the 5% weight-reduction temperatures over 450 °C due to the incorporation of the rigid pyrazolo[1,5- f ]phenanthridine motif and the robustness of the tetradentate coordination framework. These Pt(II) complexes have the same coordination set (pyridineˆbenzeneˆbenzeneˆpyrazole) but with slightly different linkage between coordination groups. Within ZPt1 and ZPt2, pyridine and the neighboring benzene groups are separated by oxygen and aniline, respectively. In ZPt3, pyridine group is rigidly grafted on the carbazole unit. The effect of the different linkages on the frontier orbital energies, the photophysical and electroluminescent properties of ZPt1-ZPt3 was investigated systematically. Organic light emitting diodes (OLEDs) based on these Pt(II) complexes were fabricated with typical device structure. The Pt(II) complexes displayed intense electroluminescence in the blue to yellowish green spectral region. Among the three Pt(II) complexes, the 3-(pyridin-2-yloxy)phenoxy-based ZPt1 compound showed the highest electroluminescence performance with the maximum CE, PE, and EQE of 58.0 cd A −1 , 51.6 lm W −1 , and 16.4%, respectively. [ABSTRACT FROM AUTHOR]

One polycyclic aromatic hydrocarbon compound, 3,6,11,14-tetraphenyldibenzo[ g,p ]chrysene ( TPDBC ), was designed, synthesized, and fabricated in a red phosphorescent organic light-emitting diode (PHOLED) with a maximum external quantum efficiency (EQE) of 14.4%, which represented the first report of a dibenzo[ g,p ]chrysene motif as the building block for host materials. It was conjectured that dibenzo[ g,p ]chrysene may serve as a next generation molecular platform which is readily functionalizable for the preparation of electroactive materials for applications in the emerging areas of molecular electronics. [ABSTRACT FROM AUTHOR]

Objective To understand the relationships between CDH13 (T-cadherin) genetic polymorphisms, adiponectin levels and ischemic stroke, and possible interactions between CDH13 polymorphisms and other risk factors. Methods We recruited 342 Chinese ischemic stroke sib pairs. We genotyped rs4783244 and rs7193788 on CDH13 using time-of-flight mass spectrometry genotyping technology and measured total and high-molecular weight (HMW) adiponectin levels. We investigated associations between SNPs and ischemic stroke, and interactions between SNPs and other risk factors using multi-level mixed-effects regression model. Results In individuals without ischemic stroke, CDH13 rs4783244 was associated with total adiponectin levels (per T: Coef = −0.257, P = 0.001). CDH13 rs7193788 was associated with total adiponectin levels (per A: Coef = −0.221, P = 0.001) and HMW adiponectin levels (per A: Coef = −0.163, P = 0.003). rs7193788 was significantly associated with ischemic stroke (GA/AA vs. GG: OR = 1.55, 95% CI : 1.07 to 2.24, P = 0.020) after Bonferroni correction (α = 0.025). There was an interaction between rs7193788 and diabetes ( P = 0.036). Compared to diabetes-free individuals with rs7193788 GG genotype, diabetes patients with rs7193788 GA/AA genotypes had higher risks for ischemic stroke ( OR = 2.64, 95% CI : 1.58-4.40, P < 0.001). Conclusion CDH13 genetic polymorphisms are associated with adiponectin levels and ischemic stroke. An interaction is found between CDH13 SNP and diabetes for ischemic stroke. [ABSTRACT FROM AUTHOR]

An organic molecule, hexaazatriphenylene hexacarbonitrile (HAT-CN), is found that it can be used not only as a hole-injecting material but also a surface modification material to clean contaminated substrate electrodes for the fabrication of organic electronic devices. As an example, HAT-CN can modify or “clean” indium-tin-oxide (ITO) anode surface in organic light-emitting diodes (OLEDs). Negative effect from ITO surface contamination on the electroluminescence performance of OLEDs can be dramatically reduced with this modification layer. As a result, the OLEDs with the same device architecture but with different ITO surface conditions, even with intentional contamination, can all exhibit substantially identical and superior electroluminescence performance. The surface modification function of this material is feasibly useful for the real fabrications of OLEDs as well as for advanced research on other organic electronic devices. [ABSTRACT FROM AUTHOR]

Both Cluster of Differentiation 166 (CD166) and Melanoma Cell Adhesion Molecule (MCAM) play critical roles in maintaining transformative phenotype of Hepatocellular Carcinoma (HCC) cells. However, the relationship between these two membrane proteins remains unknown. Here, we found that CD166 has a positive impact on the expression of MCAM, while MCAM has no feedback on CD166. Tissue microarray analysis (TMA) also showed a positive correlation between CD166 and MCAM. Depletion of CD166-induced anti-carcinogenic phenotype could be reversed by overexpression of MCAM, suggesting MCAM is functional important in the CD166-induced liver tumorigenesis. Furthermore, we found CD166 regulates MCAM mainly through protecting MCAM from ubiquitin-mediated protein degradation. Mechanically, CD166 down-regulated two ubiquitin E3 ligases, βTrCP and Smurf1, which play critical roles in the destability of MCAM protein. In addition, overexpression of βTrCP and Smurf1-reduced transformative phenotype could be partially reversed by MCAM, providing evidence that MCAM is a target of βTrCP and Smurf1. Moreover, we identified c-Raf/MEK/ERK signaling acts as a downstream effecter of CD166/PI3K/AKT axis to stimulate ubiquitination and destability of βTrCP and Smurf1. Taken together, we establish a model that CD166 regulates MCAM through a signaling flow from activation of PI3K/AKT and c-Raf/MEK/ERK signaling to the inhibition of potential MCAM ubiquitin E3 ligases, βTrCP and Smurf1, blockage of this signaling cascade may be useful in the treatment of CD166 and MCAM-dependent HCC. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index (BMI), and estimate their interactions with soybean food intake. Methods: A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model. Results: The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly higher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 (95% confidence interval: 1.15–2.34, P<0.01) after adjusting for the common confounders. Conclusion: Our study has suggested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake. [Copyright &y& Elsevier]

Among the catalysts for hydrogen evolution reaction (HER) in alkaline media, Ni–Mo turns out to be the most active one. Conventional preparations of Ni–Mo electrode involve repeated spraying of dilute solutions of precursors onto the electrode substrate, which is time-consuming and usually results in cracking and brittle electrodes. Here we report a noble fabrication of Ni–Mo electrode for HER. NiMoO4 powder was synthesized and used as the precursor. After reduction in H2 at 500 °C, the NiMoO4 powder layer was converted to a uniform and robust electrode containing metallic Ni and amorphous Mo(IV) oxides. The distribution of Ni and Mo components in this electrode is naturally uniform, which can maximize the interaction between Ni and Mo and benefit the electrocatalysis. The thus-obtained Ni–Mo electrode exhibits a very high catalytic activity toward the HER: the current density reaches 700 mA/cm2 at 150 mV overpotential in 5 M KOH solution at 70 °C. This new fabrication method of Ni–Mo electrode is not only suitable for alkaline water electrolysis (AWE), but also applicable to the alkaline polymer electrolyte water electrolysis (APEWE), an emerging technique for efficient production of H2. [ABSTRACT FROM AUTHOR]

Excessive iron has emerged in a large population of patients suffering from degenerative or hematological diseases with a common outcome, osteoporosis. However, its underlying mechanism remains to be clarified in order to formulate effective prevention and intervention against the loss of bone-forming osteoblasts. We show herein that increased intracellular iron by ferric ammonium citrate (FAC) mimicking the so-called non-transferrin bound iron concentrations leads to ferroptosis and impaired osteoblast differentiation. FAC upregulates the expression of Trfr and DMT1 genes to increase iron uptake, accumulating intracellular labile ferrous iron for iron overload status. Then, the excessive ferrous iron generates reactive oxygen species (ROS) and lipid peroxidation products (LPO), causing ferroptosis with its typical mitochondrial morphological changes, such as shrinkaged and condensed membrane with diminution and loss of crista and outer membrane rupture. We further examined that ferroptosis is the main cause responsible for FAC-disrupted osteoblast differentiation, although apoptosis and senescence are concurrently induced as well. Mechanistically, we revealed that iron dose-dependently down-regulates the expression of Wnt target genes and inhibits the transcription of Wnt reporter TopFlash construct, so as to inhibit the canonical Wnt signaling. Wnt agonist, ferroptosis inhibitor, or antioxidant melatonin reverses iron-inhibited canonical Wnt signaling to restore osteoblast differentiation by reducing ROS and LPO production to prevent ferroptosis notably without reducing iron overload. This study proposes a working model against excessive iron-induced osteoporosis: iron chelator deferoxamine or the above three drugs prevent ferroptosis, restore traditional Wnt signaling to maintain osteoblast differentiation no matter whether iron overload is removed or not. Additionally, iron chelator should be used to a suitable extent because iron itself is necessary for osteogenic differentiation. [Display omitted] • Excessive iron induces ferroptosis to disrupt osteoblast differentiation, although it also induces apoptosis and senescence. • Downregulation of canonical Wnt signaling may be the reason for excessive iron to disrupt osteoblast differentiation. • Iron chelator and Wnt agonist, ferroptosis inhibitor, and melatonin act on the upstream and downstream of iron overload. • The later three drugs restore canonical Wnt signaling to maintain osteoblast differentiation without changing iron overload. [ABSTRACT FROM AUTHOR]

Many professional athletes, after the end of their careers, cannot fully carry out daily social activities due to problems with health. The main problem is a significant rate of cardiovascular diseases. Therefore, the choice of rehabilitation techniques for former athletes is of primary importance. The aim of the paper is to create a model that increases the ability to predict both relapses and remissions during rehabilitation in cardiovascular diseases. The model takes into account the features of the cardiovascular function in athletes and their recovery. The article shows that the reliability of the implemented model can predict both necessary rehabilitation duration and time to complete recovery of an athlete's functional condition. The novelty of this study is that rehabilitation is based on the approximation of exercise load to the optimal levels during disease monitoring. The practical significance of the study is that during the rehabilitation of athletes, the obtained model to predict the course of the disease is aimed at the minimization of negative consequences for the athlete's cardiovascular system following professional activities. This model is recommended for use in medical prediction. • Experiments were different resulted in model parameters; • A prediction method during rehabilitation process is proposed. [ABSTRACT FROM AUTHOR]

• Optimal control policies are calculated for two applications in crystallization. • The policies can be learned from simulation data or experimental data. • Desired crystallinity targets can be achieved robustly using feedback. This paper reviews a previously-reported methodology for establishing feedback control of self-assembly. The methodology combines dimension reduction, supervised learning, and dynamic programming to obtain an optimal feedback control policy for reaching a desired assembled state. Sampled data are used in calculating the optimal feedback policy; this data can be generated using a predictive model (i.e. "simulated data") or using experimental data. The control strategy is demonstrated, with both simulation and experimental results, for two applications: control of colloidal assembly (to produce perfect colloidal crystals) and control of crystallization from solution (to produce crystals of desired average size). [ABSTRACT FROM AUTHOR]

Recent studies are indicative for strong carcinogenetic roles of Runt related transcription factor 2 (Runx2) and Yes associated protein (YAP) in several cancer types. However, whether and how the interaction between Runx2 and YAP plays a role in liver tumorigenesis still remain illusive. Here, we identified a close relationship between Runx2 and YAP in liver cancer cells. Runx2 had a positive role on YAP expression and vice versa. We also found that Rux2 and YAP were capable of inhibiting long non-coding RNA (lncRNA), Metallothionein 1D, Pseudogene (MT1DP) expression through direct promoter binding. Overexpression of MT1DP resulted in reduced cell proliferation and colony formation in soft agar, but increased apoptosis in liver cancer cells, whereas knockdown of this lncRNA had the opposite effect, indicating that MT1DP acts as a tumor suppressor. Furthermore, MT1DP was revealed as a negative regulator of Alfa-fetoprotein (AFP), a classic liver cancer tumor marker, through inhibiting protein synthesis of Forkhead box A1 (FoxA1), an important transcription factor in liver development and cancer progression. Furthermore, we found that FoxA1 plays a positive role on YAP and Runx2 expression. Specially, opening the compacted chromatin by FoxA1 around CREB binding site within the YAP promoter facilitates CREB-mediated YAP transcription. Finally, MT1DP-inhibited in vivo liver cancer cell growth could be rescued by a combination of overexpression of FoxA1, Runx2 and YAP. Taken together, the close relationship between Rnux2 and YAP plays a pro-carcinogenetic role in liver cancer cells through inhibiting tumor suppressor lncRNA, MT1DP in a FoxA1 dependent manner. [ABSTRACT FROM AUTHOR]

• A Bayesian optimization approach is proposed to reduce the computational cost of dynamic concentration operating condition design. • Fixed temperature difference control strategy outperforms other conventional control strategies, and is convenient for industrial operation. • A surrogate model is developed based on the first principles model for further optimization. • The method can be applied to similar dynamic operation with different solutes and solvents. In the synthesis of pharmaceutical intermediates, concentration is commonly employed to separate the product and recycle the solvents. To achieve a cost-effective manufacturing, operating parameters shall be adjusted over time, which could traditionally be achieved based on dynamic simulation, but with significant computation cost. In this work, we introduced a Bayesian optimization approach to design the optimal operating condition of a pharmaceutical intermediate in the production of Lamivudine. Using a Gaussian process regression as the surrogate model, the approach tremendously reduced the computational cost in searching for the optimal design. In comparison to other commonly used intelligent optimization algorithms, the results demonstrate that the presented approach confers evident advantages, especially in reducing the tendency of getting trapped in local optima and in improving the speed of convergence to an optimal solution. [ABSTRACT FROM AUTHOR]

tRNA-derived fragments offer a recently identified group of non-coding single-stranded RNAs that are often as abundant as microRNAs in cancer cells and play important roles in carcinogenesis. However, the biological functions of them in breast cancer are still unclear. Hence, we focused on investigating whether tiRNAs could play a key role in the progression of breast cancer. We have identified 5'-tiRNAVal with significantly low expression in breast cancer tissues. The down-regulation of serum 5'-tiRNAVal was positively correlated with stage progression and lymph node metastasis. Overexpression of 5'-tiRNAVal suppressed cells malignant activities. FZD3 was confirmed to be a direct target of 5'-tiRNAVal in breast cancer. In addition, FZD3, β-Catenin, c-myc and cyclinD1 levels in 5'-tiRNAVal overexpressing cells were downregulated while APC was inversely upregulated. Moreover, 5'-tiRNAVal inhibited the FZD3-mediated Wnt/β-Catenin signaling pathway in breast cancer cells. Finally, 5'-tiRNAVal levels differentiated breast cancer from healthy controls with a sensitivity of 90.0% and specificity of 62.7%. This is the first study to show that 5'-tiRNAVal as a new tumor-suppressor through inhibition of FZD3/Wnt/β-Catenin signaling pathway, which could be as a potential diagnostic biomarker for breast cancer. [ABSTRACT FROM AUTHOR]

The DWARF4 ( DWF4 ) gene encodes a C-22 hydroxylase which is pivotal for brassinosteroids (BRs) biosynthesis. In this research, aimed to understand the molecular mechanism of DWF4 on regulation of potatoes tolerance to salt stress, DWF4 was cloned from potato, named as StDWF4 . Its 1476 bp open reading frame encodes a protein of 491 amino acids. The StDWF4 -overexpressing (OE) and interference-expressing (RNAi) transgenic potato plants were acquired using Agrobacterium -mediated transformation, respectively. Tissue specific analysis using Quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated that the StDWF4 gene expressed in the leaves, stems and roots of the transgenic and un-transgenic (NT) plants, with specially increased ( StDWF4 -OE)/reduced ( StDWF4 -RNAi) expression in the roots. The content of malondialdehyde (MDA) in StDWF4 -OE potato plants was lower than that of NT, and proline content was higher than that of NT. MDA and proline content in StDWF4 -OE and NT under salt-stress was significantly higher than that of the control and was increased at different sampling times. The content of soluble protein, soluble sugar and the activities of superoxide dismutase (SOD), peroxidase (POD) and ascorbate peroxidase (APX) was higher in the StDWF4 -OE plantlets at varied salt treatment time than in the NT potatoes. Reduction of H 2 O 2 content in the StDWF4 -OE plants was observed. All above plant physiology indicators in the StDWF4 -RNAi potatoes showed opposite variation trends. The results proved that the overexpressing of StDWF4 in potato plantlets can enhance the salt resistance by alleviating the negative effects of salt-stress. However, its interference expression in potato plants depresses the salt resistance. The results lay the groundwork for intensive study of BRs regulation in potato growth and development, and will help us to reveal the molecular mechanisms of how the BRs signaling regulate potato salt tolerance. [ABSTRACT FROM AUTHOR]

Endothelial-to-mesenchymal transition (EndMT) in renal glomerular endothelial cells plays a critical role in the pathogenesis of diabetic nephropathy (DN). Furthermore, advanced oxidation protein products (AOPPs) have been shown to contribute to the progression of DN. However, whether AOPPs induce EndMT in renal glomerular endothelial cells remains unclear. Thus, we investigated the effect of AOPPs on human renal glomerular endothelial cells (HRGECs) and the mechanisms underlying the effects. Our results showed that AOPP treatment lowered the expression of vascular endothelial cadherin, CD31, and claudin 5 and induced the overexpression of α-smooth muscle actin, vimentin, and fibroblast-specific protein 1, which indicated that AOPPs induced EndMT in HRGECs. Furthermore, AOPP stimulation increased the expression of glucose-regulated protein 78 and CCAAT/enhancer-binding protein-homologous protein, which suggested that AOPPs triggered endoplasmic reticulum (ER) stress in HRGECs. Notably, the aforementioned AOPP effects were reversed following the treatment of cells with salubrinal, an inhibitor of ER stress, whereas the effects were reproduced after exposure to thapsigargin, an inducer of ER stress. Collectively, our results indicate that AOPPs trigger EndMT in HRGECs through the induction of ER stress. These findings suggest novel therapeutic strategies for inhibiting renal fibrosis by targeting ER stress. [ABSTRACT FROM AUTHOR]

Blood-brain barrier (BBB) disruption is pivotal in the pathophysiological process of ischemic stroke and is often measured in rodent stroke studies. Traditionally, rodent BBB permeability increase is determined by measuring cerebral leakage of certain dyes such as Evans Blue or sodium fluorescein (NaFL). However, due to the special processing of samples for BBB permeability measurement, they cannot be used afterward for determining other essential parameters such as cerebral infarction volume. Therefore, using different batches of animals for assessing BBB permeability and infarction volume is typical. However, this would limit the stroke study's statistical power and scientific value while hindering the implementation of procedures for high standard animal welfare. The rats subjected to middle cerebral artery occlusion (MCAO) were intraperitoneally injected with NaFL during the reperfusion phase. The brains were sliced and measured for BBB permeability using the small animal optical imaging system (IVIS® Lumia series III). Afterward, the same brain samples were either sliced or homogenized for tests that assessed infarction volume or other molecular changes. The sum fluorescence intensity of the ischemic brain slices under the IVIS® Lumia series Ⅲ showed a strong correlation with the infarction volume determined by 2,3,5-triphenyl tetrazolium chloride (TTC) staining (r = 0.7440, P = 0.0087). The fluorescence intensity of the whole ischemic brain was correlated with the NaFL concentration of brain tissue homogenates (r = 0.8653, P = 0.0026) and cerebral infarction volume (r = 0.7282, P = 0.0072). The new method enables concurrent measurement of BBB permeability and infarction volume on the same batch of brain tissue samples without affecting most downstream biochemical assays. By applying the new method, we could use the same batch of ischemic rodent brain tissue for multiple assays, including BBB permeability and infarction volume. Through this, we would reduce the animal numbers in each study and help to maximize the scientific and statistical potential of future rodent ischemic studies. • The IVIS System could detect BBB permeability through brain tissue in MCAO rats. • BBB permeability and cerebral infarction volume could be detected in the same rats. • The area of BBB injury roughly matched the location of cerebral infarction volume. • The imaged brain tissue can continue to be used for molecular biology analyses. • The new method reduces the animal numbers and improves the statistical power. [ABSTRACT FROM AUTHOR]

[Display omitted] Evidence for the association between long-term exposure to ozone (O 3) and cause-specific cardiovascular disease (CVD) mortality is inconclusive, and this association has rarely been evaluated at high O 3 concentrations. We aim to evaluate the associations between long-term O 3 exposure and cause-specific CVD mortality in a Chinese population. From 2009 to 2018, 744,882 subjects (median follow-up of 7.72 years) were included in the CHinese Electronic health Records Research in Yinzhou (CHERRY) study. The annual average concentrations of O 3 and fine particulate matter (PM 2.5), which were estimated using grids with a resolution up to 1 × 1 km, were assigned to the community address for each subject. The outcomes were deaths from CVD, ischemic heart disease (IHD), myocardial infarction (MI), stroke, and hemorrhagic/ischemic stroke. Time-varying Cox model adjusted for PM 2.5 and individual-level covariates was used. The mean of annual average O 3 concentrations was 68.05 μg/m3. The adjusted hazard ratio per 10 μg/m3 O 3 increase was 1.22 (95% confidence interval [CI]: 1.13–1.33) for overall CVD mortality, 1.08 (0.91–1.29) for IHD, 1.21 (0.90–1.63) for MI, 1.28 (1.15–1.43) for overall stroke, 1.39 (1.16–1.67) for hemorrhagic stroke and 1.22 (1.00–1.49) for ischemic stroke, respectively. The study showed that subjects without hypertension had a higher risk for CVD mortality associated with long-term O 3 exposure (1.66 vs. 1.15, p = 0.01). We observed the association between long-term exposure to high O 3 concentrations and cause-specific CVD mortality in China, independent of PM 2.5 and other CVD risk factors. This suggested an urgent need to control O 3 pollution, especially in developing countries. [ABSTRACT FROM AUTHOR]

A computational study is presented in which real-time manipulation of the interaction potential between particles in a colloidal system is used to control their assembly into a close-packed crystalline object. The basic model used throughout the study is a high-fidelity representation of a real experimental system in which 32 colloidal silica particles are suspended in aqueous solution with polymer hydrogel providing a temperature-tunable attractive force between the particles. Diffusion mapping is used to determine a set of coarse variables that provide an appropriate low-dimensional representation of this system at four discrete values of the attraction strength. In this case the diffusion mapping process identified two dimensions; one correlates well with the radius of gyration of the entire set of particles and the other correlates well with the average distance between distinct clusters of particles. Two different stochastic models are then built in the two-dimensional (2D) space of these variables, using data from a large number of short Brownian dynamics simulations of the full 32-particle system. The first 2D model is based on a Smoluchowski framework and is used to characterize the overall equilibrium and diffusive properties of the system. The second 2D model is based on a transition rate matrix and is used for process control. A control policy based on an infinite-horizon Markov decision process is developed using the four different attraction strengths as the input variables. The resulting policy is non-trivial; rather than simply selecting the strongest level of attraction, some mix of weak and strong attractions generally provides the optimal approach to the target close-packed state. This study, while focused on the particular mechanism of tunable depletion attraction, suggests a general strategy that could be adapted to different mechanisms of actuating colloidal assembly. [ABSTRACT FROM AUTHOR]

In this study, the microwave pyrolysis of oil shales (MPOS) from Estonian Kukersite, Moroccan Tarfaya, Chinese Longkou, and Chinese Barkol were investigated. The heating performance of MPOS was also examined. A comparison study between MPOS and conventional oil shale pyrolysis (CPOS) was conducted, which included comparing the temperature profile, heating rate, weight loss at the same temperature, and the organic decomposition kinetic parameters. Results indicate that, under MPOS, both the maximum temperature (T m) and average heating rate (γ) were influenced by the organic matter content in oil shale, and the effects were more significant at higher microwave powers (400–700 W) than at lower powers (200–400 W). Furthermore, both T m or γ were linearly and/or exponentially correlated with microwave power with a breakpoint of 400 W in each correlation. Compared with CPOS, MPOS provided higher γ based on the same input powers and higher weight loss at the same temperatures. This demonstrates that MPOS requires much less processing time and a lower input energy than CPOS. Additionally, the kinetics of oil shale pyrolysis were modelled using the Kissinger method. For organic matter decomposition, MPOS decreased the activation energy by 13–39% and increased the reaction rate constant by at least 65%, compared to CPOS. This implies that under MPOS, higher powers are necessary to establish oil shale thermal reactivity and higher reaction rates can be obtained, thereby causing greater weight loss than with CPOS. [Display omitted] • Heating performance of MPOS was affected by oil shale organic matter content. • T m showed a linear correlation with the microwave power with a breakpoint at 400 W. • γ was exponentially correlated with the microwave power below 400 W. • γ was linearly correlated with the microwave power above 400 W. • Compared with CPOS, MPOS led to lower E a in organic matter decomposition. [ABSTRACT FROM AUTHOR]

Background & Aims: In the Asia–Pacific region, perinatal transmission of the hepatitis B virus (HBV) is the primary cause of chronic hepatitis B infection. Despite the use of HBIG and HBV vaccination, HBV perinatal transmission (PT) occurs in 10–30% of infants born to highly viremic mothers. We evaluated the efficacy and safety of LTD use during late pregnancy in reducing HBV transmission in highly viremic HBeAg+mothers. Methods: Two hundred and twenty-nine HBeAg+HBV DNA levels>1.0×107 copies/ml mothers received telbivudine 600mg/day from week 20 to 32 of gestation (n=135) or served as untreated controls (n=94). All infants in both arms received 200IU of HBIg within 12h postpartum and recombinant HBV vaccine of 20μg at 0, 1, and 6months. HBsAg and HBV DNA results of infants at week 28 were used to determine perinatal transmission rate. All telbivudine treated subjects were registered in the Antiretroviral Pregnancy Registry. Results: Telbivudine treatment was associated with a marked reduction in serum HBV DNA and hepatitis B e antigen (HBeAg) levels and normalization of elevated ALT levels before delivery. A striking decline of HBV DNA levels started from treatment onset to week 4, and sustained in a low level since week 12. Forty-four (33%) of the 135 telbivudine-treated mothers and none (0%) of the untreated controls had polymerase chain reaction-undetectable viremia (DNA<500 copies/ml) at delivery. Seven months after delivery, the incidence of perinatal transmission was lower in the infants that completed follow-up born to the telbivudine-treated mothers than to the controls (0% vs. 8%; p =0.002). HBV DNA levels were only detectable in HBsAg+infants. No significant differences in anti-HBs levels were observed during postnatal follow-up. No serious adverse events were noted in the telbivudine-treated mothers or their infants. Conclusions: Telbivudine used during pregnancy in CHB HBeAg+highly viremic mothers can safely reduce perinatal HBV transmission. Telbivudine was well-tolerated with no safety concerns in the telbivudine-treated mothers or their infants on short term follow up. These data support the use of telbivudine in this special population. [ABSTRACT FROM AUTHOR]

Recently, shrinking reserves of crude oil have led to increased interest in the utilisation of various unconventional resources. Oil shale is one of these promising alternatives to crude oil. However, the transformation of S/N that takes place during the oil shale pyrolysis cannot be ignored since they contribute to the release of harmful gases and production of poor-quality shale oil. In order to study the mechanism of S/N migration during pyrolysis, S/N species in the pyrolysates produced from the Longkou oil shale were qualitatively and quantitatively examined over a temperature range of 340–520 °C. The results revealed that a majority of the S retained in char during pyrolysis was primarily present as aromatic S, sulfone and sulfate. Aromatic S in the char decreased when at a temperature below 460 °C and increased when in the 460–520 °C range; sulfone in the char increased during the initial stage and decreased in the last stage; and sulfate in the char showed a fluctuating pattern. At lower temperatures (≤400 °C), more gases (H 2 S, CH 3 SH and COS) were produced via the decomposition of pyrite and cleavage reactions of aliphatic and aromatic S, when compared with the liquid S species. At higher temperatures (≥400 °C), an increasing amount of S migrated to shale oil, with the most abundant form being thiophenes. Concerning the transformation of N during pyrolysis, abundant N was present in the char, with a predominant occurrence of pyrrolic N. At temperatures below 340 °C, the pyrrolic N in the char was seen to change slightly, while when the temperature increased from 340 °C to 520 °C, it decreased significantly. By raising the temperature in the tested range, the N compounds were promoted to migrate into both shale oil and gas, and the production of liquid N species was recorded as higher than that of gaseous N (NH 3 and HCN), especially after surpassing 400 °C. More non-basic or weak basic N species, such as indoles, carbazoles and aliphatic nitriles, were present in shale oil than basic N species (anilines and quinolines). These findings suggest that regulating and controlling S/N transformation during oil shale pyrolysis would improve the quality of shale oil. In addition, it would provide basic data to be used in the subsequent processing for the efficient and clean utilisation of oil shale. • S/N migration during oil shale pyrolysis was qualitatively and quantitatively studied. • Most of the S/N was retained in char in primary forms of aromatic S and pyrrolic N. • Temperatures below 400 °C facilitated gaseous S/N emissions. • Temperatures above 400 °C promoted the migration of S/N into shale oil. • S/N was increasingly incorporated into thiophenes/indoles in oil during pyrolysis. [ABSTRACT FROM AUTHOR]

The objective of this study was to detect the selenium level in the environment and the population of Zhoukoudian area, Beijing, and to discuss the influence of various factors on serum selenium level. The soil, drinking water, and foodstuff samples and venous blood samples of 401 individuals were obtained to determine the selenium level by gas chromatograph equipped with a 63Ni electron capture detector (ECD). The selenium level was 0.210±0.013 μg/g in soil, 0.017 μg/L±0.002 in drinking water, 0.034±0.002 μg/g in rice, and 0.034±0.012 μg/g in wheat flour. This index showed that the Zhoukoudian area of Beijing was a moderate or marginal level selenium ecological landscape. The mean serum selenium level of the population was 75.01±28.35 μg/L, ranging between 35.2 and 160.4 μg/L. A total of 279 (69.6%) individuals exhibited serum selenium level below 80 μg/L, which is the lowest threshold for the activity of glutathione peroxidases (GPx) in vivo. A total of 35 (8.5%) individuals exhibited serum selenium level below 45 μg/L. It is widely recommended that below this value (45 μg/L) there is an increased risk of cardiovascular disease and cancer. Multiple linear regression analysis showed that serum selenium level was positively associated with body mass index (β =0.137; P =0.011), serum total cholesterol TC (β =0.785; P =0.000), however, negatively associated with systolic blood pressure (β =−0.172; P =0.023), serum triglyceride (β =−0.170; P =0.007), high density lipoprotein–cholesterol (β =−0.121; P =0.027), and low high density lipoprotein–cholesterol (β =−0.568; P =0.027). [Copyright &y& Elsevier]

• INAFM2 rs67839313_T was associated with increased T2DM risk and FBG levels. • Egg consumption interacts with rs67839313 in modifying T2DM risk and elevated FBG. • Consuming more eggs eliminate susceptibility of rs67839313_T to T2DM and higher FBG. INAFM2 rs67839313 was associated with type 2 diabetes (T2DM) in Japanese populations but not in other populations. We aimed to validate the association of rs67839313 with T2DM and explore interactive associations of INAFM2 rs67839313 and egg consumption with T2DM and fasting blood glucose (FBG) in a Chinese population. In total, 7175 participants (4202 T2DM cases) from 3980 families were included and categorized into two groups (<4 and ≥4 eggs/week) according to the median egg consumption. Multilevel logistic regression and linear regression models were performed to estimate the genetic associations of rs67839313 with T2DM and FBG, respectively. The crossproduct term between the variant and egg was included in the models for interaction analysis. We found that rs67839313_T was associated with an increased risk of T2DM (1.22 [95% CI: 1.17–1.27], P < 0.001). Among individuals with the rs67839313_T genotype, those with egg consumption <4/week (1.37 [1.25–1.51]) had a higher T2DM risk than those with egg consumption ≥4/week (1.17 [1.11–1.23]). A significant interactive effect between rs67839313_T and egg consumption on T2DM risk was identified (P = 0.008). Moreover, among participants without T2DM, rs67839313_T was associated with FBG, with a 0.188 mmol/l increase and a 0.152 mmol/l decrease among those consuming <4 eggs/week and ≥4 eggs/week, respectively. The interaction between rs67839313_T and egg consumption was observed to be significantly associated with FBG (P = 0.003). INAFM2 rs67839313_T was associated with increased T2DM risk and FBG levels in Chinese individuals, and consuming more eggs may eliminate the associated genetic risk. This finding has important implications for understanding the genetic pathogenesis of T2DM and for the precision nutrition management of T2DM. [ABSTRACT FROM AUTHOR]

Given instances (spatial points) of different spatial features (categories), significant spatial co-distribution pattern discovery aims to find subsets of spatial features whose spatial distributions are statistically significantly similar to each other. Discovering significant spatial co-distribution patterns is important for many application domains such as identifying spatial associations between diseases and risk factors in spatial epidemiology. Previous methods mostly associated spatial features whose instances are frequently located together; however, this does not necessarily indicate a similarity in the spatial distributions between different features. Thus, this paper defines the significant spatial co-distribution pattern discovery problem and subsequently develops a novel method to solve it effectively. First, we propose a new measure, dissimilarity index, to quantify the difference between spatial distributions of different features under the spatial neighbor relation and then employ it in a distribution clustering method to detect candidate spatial co-distribution patterns. To further remove spurious patterns that occur accidentally, the validity of each candidate spatial co-distribution pattern is verified through a significance test under the null hypothesis that spatial distributions of different features are independent of each other. To model the null hypothesis, a distribution shift-correction method is presented by randomizing the relationships between different features and maintaining spatial structure of each feature (e.g., spatial auto-correlation). Comparisons with baseline methods using synthetic datasets demonstrate the effectiveness of the proposed method. A case study identifying co-morbidities in central Colorado is also presented to illustrate the real-world applicability of the proposed method. • A novel problem of significant spatial co-distribution pattern (SSCDP) discovery is formally defined. • The spatial neighbor relation is modeled in the measurement of difference between spatial distributions of features. • The candidate SSCDPs are detected by clustering spatial distributions of features. • The spatial auto-correlation of each feature is maintained in the significance test of SSCDPs. [ABSTRACT FROM AUTHOR]