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Purpose: To evaluate the rate of presumed endophthalmitis (EO) after intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections performed in an operating room (OR) under sterile conditions in mainland China., Methods: Retrospective single-center study between September 2012 and December 2017 at Beijing Tongren Eye Center, Beijing, China. Intravitreal injection database was reviewed. All anti-VEGF injections were performed using a standardized sterile technique in an OR. Injection protocols included antibiotics for 3 days pre-injection, topical 5% povidone-iodine rinsing before the procedure, and post-injection antibiotics for 3 days., Results: A total of 37,830 intravitreal injections were performed at Beijing Tongren Eye Center. Three cases were managed as presumed EO (0.0079%). Positive cultures were documented in 2 of 3 cases. EO incidence following ranibizumab and conbercept administration was 0.0088% (3 in 33,930) and 0% (0 in 3,900), respectively. No significant difference was detected between the two drugs ( P = 0.745)., Conclusions: Very low EO rates were seen in mainland China using a standardized sterile technique in an OR. However, EO could not be completely avoided., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Yanyun Chen et al.)

Objectives: We aimed to explore the relationship of hypertensive retinopathy with carotid intima--media thickness (CIMT), and to examine the possible effect modifiers in Chinese adults with hypertension., Methods: We conducted a cross-sectional study of 12 342 hypertensive patients with complete exit site visit data from the China Stroke Primary Prevention Trial. CIMT was measured by carotid ultrasonography. Hypertensive retinopathy was diagnosed according to the Keith--Wagener--Barker classification., Results: The mean (SD) CIMT among study participants was 739.9 (111.4) μm. Compared with patients with grade 1 hypertensive retinopathy or without hypertensive retinopathy, a significantly higher CIMT level (β, 7.63, 95% CI: 2.54--12.73) was observed in patients with grade 2-4 hypertensive retinopathy. Moreover, the association between hypertensive retinopathy (grade 2-4 versus grade 1 or normal) and CIMT was stronger in participants of younger age (<60 years; β, 13.70, 95% CI: 5.65--21.75; versus ≥60 years; β, 1.03, 95% CI: -5.58 to 7.63; P interaction = 0.006); or with lower total homocysteine levels [<12.1 μmol/l (median); β, 12.70, 95% CI: 5.98--19.42; versus ≥12.1 μmol/l; β, 2.07, 95% CI: -5.63 to 9.78; P interaction = 0.030). None of the other variables, including sex, BMI, study centers, treatment group, SBP, triglycerides, total cholesterol, fasting blood glucose, folate, serum creatinine, current smoking and alcohol drinking, significantly modified the relation of hypertensive retinopathy with CIMT levels., Conclusion: Hypertensive retinopathy (grade 2 and higher) was significantly associated with increased CIMT in hypertensive patients. The association was stronger in those of younger age or with lower total homocysteine levels.

In this work, TC4/TNTZO multi-layered composite as well as TNTZO and TC4 alloys were prepared by direct laser deposition (DLD) to investigate the microstructure, mechanical properties and in vitro bioactivity. The microstructure characterization shows that the multi-layered material is free of cracks and intermetallics while the interface is metallurgically bonded. The fine microstructure was observed in TC4 layer of the TC4/TNTZO multi-layered material, and a large amount of α' martensite exists in the transition zone. Different from the single β phase cellular arrays in the DLD-ed TNTZO alloy, α″ martensite with high volume content formed at the cellular grain boundary in TNTZO zone of DLD-ed TC4/TNTZO. The elastic modulus of the DLD-ed TC4/TNTZO is 64 GPa, decreased about 45% compared to the DLD-ed TC4. The tensile yield strength and elongation along the printing direction are up to 789 MPa and 7%, which are 12% higher than the tensile yield strength of DLD-ed TNTZO and 61% higher than the elongation of DLD-ed TC4 respectively. Moreover, the DLD-ed TC4/TNTZO shows good in vitro bioactivity. The TC4/TNTZO multi-layered composite fabricated by DLD can be regarded as a potential candidate to integrate the advantages of the two Ti-base alloys for application in the biomedical field., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

A novel sensitive method for the determination of the five primary metabolites of phthalate esters (PAEs) in urine was developed by combining dispersive liquid-liquid microextraction (DLLME) using ionic liquids with high performance liquid chromatography (HPLC). The factors affecting the efficiency of DLLME were optimized. The types and proportions of extraction solvent and dispersants, as well the ultrasonic extraction time, cooling time, and centrifugal time, were determined. The optimal conditions were as follows:extraction solvent[C 8 MIM]PF 6 ] 35 μL; dispersants[BSO 3 HMIm]OTf] 30 μL,[C 4 MIM]BF 6 ] 120 μL; NH 4 PF 6 0.1 g, extraction at 35℃, ultrasonic dispersion for 5 min, cooling in ice water for 5 min, centrifugation at 4000 r/min for 5 min. After optimization, the five primary metabolites of PAEs were determined. The method showed a good linear relationship within the concentration range of 0.5-1000 μg/L. The determination coefficients ( R 2 ) were greater than 0.9955. The detection limit was in the range of 0.16-0.19 μg/L. Under the optimized conditions, the extraction recoveries for the PAEs were 92.9%-105.0%, and the relative standard deviations (RSDs) of the intra- and inter-day precisions were < 5.96%. Urine samples collected from 10 diabetic patients were tested, and the exposure level of the population to the PAE metabolites was evaluated. All the PAE metabolites were detected in these samples, and the detection rate of 2-ethylhexyl hydrogen phthalate (MEHP) was 100%. In conclusion, no toxic organic reagents were added during the extraction process in this method, and multifunctional ionic liquids were used as the extraction agent, dispersant, and salting-out agent. In other words, the extraction process was demonstrated to be green, simple, and efficient. The developed method has high sensitivity and stability, and it is suitable for the determination of trace PAE metabolites in human urine.

Developing new materials with high strength and ductility, low modulus and high biocompatibility is a continuing demand in the field of surgical implants. Inspired by the high-entropy design philosophy, two medium entropy alloys (MEAs), i.e. equiatomic TiZrHf and equi-weight Ti 40 Zr 20 Hf 10 Nb 20 Ta 10 were designed and their mechanical properties and biocompatibility were assessed. Both the single-phase hexagonal close-packed (HCP) structured TiZrHf alloy and the single-phase body-centered cubic (BCC) structured Ti 40 Zr 20 Hf 10 Nb 20 Ta 10 alloy show high strength-ductility combinations close to commercial Ti-6Al-4V wrought alloy and remarkably lower young's modulus than commercial pure titanium (CP-Ti) and Ti-6Al-4V. From the aspects of adhesion, proliferation, toxicity and related gene expression of human gingival fibroblasts (HGFs), the Ti 40 Zr 20 Hf 10 Nb 20 Ta 10 alloy exhibits distinctively better biocompatibility than that of CP-Ti while the TiZrHf shows only slightly better biocompatibility as compared with CP-Ti. These results indicate that these two ductile MEAs are potential candidates for dental application., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Myelin water fraction (MWF) can be quantified with analysis of the T 2 * distribution, whereas deducing the T 2 * spectrum from several echoes is an underdetermined and ill-posed problem., Purpose: To improve the quantification of myelin water content by using nonnegative jointly sparse (NNJS) optimization., Study Type: Prospective., Subjects: Nine healthy subjects., Field Strength/sequence: 3T, multiecho gradient echo., Assessment: The results of NNJS were compared with that of the nonnegative least square (NNLS)-based algorithms. Simulated models with varied MWF at different noise levels were used to evaluate the accuracy of estimations. In human data, the MWF values of different regions were compared with previous studies and the coefficient of variation (COV) was used to assess the spatial coherence., Statistical Test: Paired t-test., Results: In simulation, the relative errors of MWF obtained from synthesized data with signal-to-noise ratio (SNR) at 500, 200, 150, and 100 were 0.08, 0.09, 0.10, and 0.12 for NNJS, 0.29, 0.43, 0.48, and 0.53 for regularized NNLS (rNNLS), and 0.19, 0.24, 0.25, and 0.26 for spatially-regularized NNLS (srNNLS). In human data, the mean values of MWF produced by NNJS in different regions were consistent with previous studies. Compared with the NNLS-based algorithms, lower COVs generated by NNJS were observed in genu, forceps minor, forceps major, and internal capsule, which were 0.44 ± 0.08, 0.48 ± 0.07, 0.46 ± 0.03, and 0.48 ± 0.09 in NNJS, 0.88 ± 0.28, 0.96 ± 0.18, 0.72 ± 0.03, and 0.85 ± 0.15 in rNNLS, and 0.56 ± 0.17, 0.64 ± 0.14, 0.50 ± 0.04 and 0.58 ± 0.13 in srNNLS., Data Conclusion: Quantitative results of both simulated and human data show that NNJS provides more plausible estimation than the NNLS-based algorithms. Visual advantages of NNJS in spatial consistency can be confirmed by the comparative COV index. The proposed algorithm might improve the quantification of myelin water content., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;52:146-158., (© 2019 International Society for Magnetic Resonance in Medicine.)

Cobalt oxide is an excellent water oxidation cocatalyst used in photoelectrochemical (PEC) water splitting field. Finding a facial way to load cobalt oxide on a semiconductor anode is important to effectively realize PEC water splitting on a large scale. In this work, a simple impregnation and calcination method is developed to fabricate CoO x /BiVO 4 anode. The constructed CoO x /BiVO 4 anode provides a photocurrent of 3.1 mA cm -2 at 1.23 V vs. RHE, about 2.8 times that of BiVO 4 anode (1.1 mA cm -2 ). Furthermore, both the charge separation and injection efficiency are improved by loading CoO x nanoparticles onto the BiVO 4 layer. Importantly, input voltage-output current characteristic curves are used for the first time to prove the formation of p-n junction between CoO x and BiVO 4 , which benefits to the separation of photogenerated holes and electrons. All results indicate that the impregnation and calcination method is efficacious for facile fabrication of CoO x /BiVO 4 photoanode with high performance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Accurate preoperative assessment of the pathological grade of hepatocellular carcinoma (HCC) could greatly benefit prognostic predictions., Purpose: To assess and compare the diagnostic accuracy of the apparent diffusion coefficient (ADC) and tissue diffusivity (D) for the noninvasive pathological grading of HCC., Study Type: Meta-analysis., Data Sources: PubMed/Medline, EMBASE, the Web of Science, and the Cochrane Library were searched to find related original articles published up to May 30, 2019., Field Strength/sequence: Diffusion-weighted imaging (DWI) and/or intravoxel incoherent motion (IVIM) were performed with a 1.5T or 3.0T scanner., Assessment: The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the methodologic quality., Statistical Tests: The bivariate random-effects model was used to obtain the pooled sensitivity and specificity, and the area under summary receiver operating characteristic curve (AUROC) was obtained. Subgroup analyses were performed., Results: A total of 16 original articles (1428 HCCs) were included. Most studies had a low to unclear risk of bias and minimal concerns regarding applicability. For the discrimination of well-differentiated HCCs, the pooled sensitivity and specificity of the ADC value were 85% and 92%, respectively. For the discrimination of poorly differentiated HCCs, the pooled sensitivity and specificity of the ADC value and D were 84% and 80%, and 92% and 77%, respectively. The summary AUROC of D (0.94) was significantly higher than that of ADC (0.89) (z = -2.718, P = 0.007). The subgroup analyses identified three covariates including size, number of included lesions in the studies, and blindness to the reference standard as possible sources of heterogeneity., Data Conclusion: This meta-analysis showed that the ADC and D values had a high to excellent accuracy for the noninvasive pathological grading of HCCs and that the D value was superior to the ADC value for discriminating poorly differentiated HCCs., Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2020;51:1581-1593., (© 2019 International Society for Magnetic Resonance in Medicine.)

Using construction and demolition waste (CDW) as road subgrade filling materials is an excellent way to solve the disparity between increased demand and road construction aggregate shortages. However, a key quality control problem is predicting the subgrade settlement, primarily because the CDW subgrade settlement prediction methods are not yet mature. To go some way in overcoming this problem, in this paper we developed a three-point hyperbolic combination model to predict CDW subgrade settlement, in which three appropriate points for the measured settlement curve were selected in the prediction samples to improve the hyperbolic model. Then, common prediction models-namely, the hyperbolic model, the three-point model, and the Hushino model-were compared with the proposed combination model to assess its viability. Finally, the three-point hyperbolic combination prediction accuracy was analyzed for different start points t 0 and time intervals Δ t . The analyses found that the proposed model was in good agreement with the measured data, had a high correlation coefficient, and had only small errors. However, the time interval Δ t needed to be greater than 80 days and the start point t 0 needed to be selected at the beginning of the stable post-filling period, that is, t 0 = 90-100 days. The application parameters were also determined to provide a reference for the large-scale application and settlement predictions of CDW subgrade.

Known as the 'third polar region', the Qinghai-Tibet Plateau represents one of the harshest highland environments in the world and yet a number of organisms thrive there. Previous studies of birds, animals and humans have focused on well-differentiated populations in later stages of phenotypic divergence. The adaptive processes during the initial phase of highland adaptation remain poorly understood. We studied a human commensal, the Eurasian Tree Sparrow, which has followed human agriculture to the Qinghai-Tibet Plateau. Despite strong phenotypic differentiation at multiple levels, in particular in muscle-related phenotypes, highland and lowland populations show shallow genomic divergence and the colonization event occurred within the past few thousand years. In a one-month acclimation experiment investigating phenotypic plasticity, we exposed adult lowland tree sparrows to a hypoxic environment and did not observe muscle changes. Through population genetic analyses, we identified a signature of polygenic adaptation, whereby shifts in allele frequencies are spread across multiple loci, many of which are associated with muscle-related processes. Our results reveal a case of positive selection in which polygenic adaptation appears to drive rapid phenotypic evolution, shedding light on early stages of adaptive evolution to a novel environment., (© The Author(s) 2019. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

Feature extraction, as an important method for extracting useful information from surfaceelectromyography (SEMG), can significantly improve pattern recognition accuracy. Time andfrequency analysis methods have been widely used for feature extraction, but these methods analyzeSEMG signals only from the time or frequency domain. Recent studies have shown that featureextraction based on time-frequency analysis methods can extract more useful information fromSEMG signals. This paper proposes a novel time-frequency analysis method based on the Stockwelltransform (S-transform) to improve hand movement recognition accuracy from forearm SEMGsignals. First, the time-frequency analysis method, S-transform, is used for extracting a feature vectorfrom forearm SEMG signals. Second, to reduce the amount of calculations and improve the runningspeed of the classifier, principal component analysis (PCA) is used for dimensionality reduction of thefeature vector. Finally, an artificial neural network (ANN)-based multilayer perceptron (MLP) is usedfor recognizing hand movements. Experimental results show that the proposed feature extractionbased on the S-transform analysis method can improve the class separability and hand movementrecognition accuracy compared with wavelet transform and power spectral density methods.

The performance of BiVO 4 for photoelectrocatalytic (PEC) water decomposition is commonly limited by reaction kinetics. In this work, NiS and CoS nanospheres were respectively loaded on BiVO 4 thin films (NiS/BiVO 4 and CoS/BiVO 4 composites) to improve its reaction kinetics for PEC water decomposition. Both physical and chemical properties of these composites were characterized by XRD, SEM, TEM, PL and UV-DRS. The photoelectric properties of the samples were verified by testing LSV, i-t, EIS and IPCE. The formation of the composites can effectively prevent the recombination of carriers and consequently accelerate the separation of electrons and holes. NiS/BiVO 4 and CoS/BiVO 4 can reach photocurrent of 2.1 mA cm -2 and 2.7 mA cm -2 under light respectively, at 1.23 V vs. RHE, which are 1.75 times and 2.25 times that of BiVO 4 (1.2 mA cm -2 ). The hydrogen production of the NiS/BiVO 4 and CoS/BiVO 4 photoanodes was 4.7 and 7.3 times higher than that of BiVO 4 photoanode, respectively., (Copyright © 2019 Elsevier Inc. All rights reserved.)

As one of the highly effective methods to prepare catalysts for photocatalytic reduction of CO 2 into value-added chemicals, using metalloporphyrin as light-harvesting mixed ligand to modify metal-organic framework (MOF) is very valuable since it can greatly improve the prophyrin dispersibility and consequently inhibit its potential agglomeration. Herein, we employed a one-pot synthetic strategy to chemically immobilize Cu(II) tetra(4-carboxylphenyl)porphyrin (CuTCPP) into UiO-66 MOF structure through coordination mode. Meanwhile, in-situ growth of TiO 2 nanoparticles onto the MOF is actualized with the generation of CuTCPP ⊂ UiO-66/TiO 2 (CTU/TiO 2 ) composites. Under Xe lamp irradiation (λ > 300 nm), the catalytic result presents that an optimal value of 31.32 μmol g -  h 1  h - 1 CO evolution amount, about 7 times higher than that of pure TiO 2 was obtained through the photocatalysis. It is supposed owning to a consistent augment of light absorption derived from chemically implanted porphyrin derivative, which is simultaneously functioning with an efficacious separation of photo-induced carries given by the newly engendered composites between MOF and TiO 2 , an effective catalytic activity and approving recyclability of CTU/TiO 2 can be achieved in the photocatalytic reduction of CO 2 into CO., (Copyright © 2019 Science China Press. Published by Elsevier B.V. All rights reserved.)

Background: Macroautophagy (hereafter autophagy) is a tightly regulated process that delivers cellular components to lysosomes for degradation. Damage-regulated autophagy modulator 1 (DRAM1) induces autophagy and is necessary for p53-mediated apoptosis. However, the signalling pathways regulated by DRAM1 are not fully understood., Methods: HEK293T cells were transfected with FLAG-DRAM1 plasmid. Autophagic proteins (LC3 and p62), phosphorylated p53 and the phosphorylated proteins of the class I PI3K-Akt-mTOR-ribosomal protein S6 (rpS6) signalling pathway were detected with Western blot analysis. Cellular distribution of DRAM1 was determined with immunostaining. DRAM1 was knocked down in HEK293T cells using siRNA oligos which is confirmed by quantitative RT-PCR. Cells were serum starved for 18 h after overexpression or knockdown of DRAM1 to decrease the rpS6 activity to the basal level, and then the cells were stimulated with insulin growth factor, epidermal growth factor or serum. rpS6 phosphorylation and rpS6 were detected with Western blotting. Similarly, after overexpression or knockdown of DRAM1, phosphorylation of IGF-1Rβ and IGF-1R were examined with Western blotting. Cell viability was determined with CCK-8 assay and colony formation assay. Finally, human cancer cells Hela, SW480, and HCT116 were transfected with the FLAG-DRAM1 plasmid and phosphorylated rpS6 and rpS6 were detected with Western blot analysis., Results: DRAM1 induced autophagy and inhibited rpS6 phosphorylation in an mTORC1-dependent manner in HEK293T cells. DRAM1 didn't affect the phosphorylated and total levels of p53. Furthermore, DRAM1 inhibited the activation of the PI3K-Akt pathway stimulated with growth factors or serum. DRAM1 was localized at the plasma membrane and regulate the phosphorylation of IGF-1 receptor. DRAM1 decreased cell viability and colony numbers upon serum starvation. Additionally, DRAM1 inhibited rpS6 phosphorylation in several human cancer cells., Conclusions: Here we provided evidence that DRAM1 inhibited rpS6 phosphorylation in multiple cell types. DRAM1 inhibited the phosphorylation of Akt and the activation of Akt-rpS6 pathway stimulated with growth factors and serum. Furthermore, DRAM1 regulated the activation of IGF-1 receptor. Thus, our results identify that the class I PI3K-Akt-rpS6 pathway is regulated by DRAM1 and may provide new insight into the potential role of DRAM1 in human cancers.

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra. Prevailing evidence suggests that abnormal autophagy and mitochondrial dysfunction participate in the process of PD. However, many damages of neuronal functions are regulated by intracellular Ca 2+ signaling and the contribution of mitochondrial Ca 2+ to the process of neurodegeneration is still unclear. MPP + , the metabolite of a neurotoxin MPTP, causes symptom of PD in animal models by selectively destroying dopaminergic neurons in substantia nigra. Here we report that mitochondrial Ca 2+ uniporter (MCU) participated in MPP + -induced autophagic cell death in SH-SY5Y cells. Pharmacological agonist of MCU or exogenous expressed MCU can partially reduce MPP + -induced autophagic cell death. Down-regulation of MCU enhanced autophagic cell death via AMPK activation, which was independent of Beclin1 and PI3K. These findings show that the mitochondrial calcium dyshomeostasis contributes to MPP + -induced neuronal degeneration, and MCU may be a potential therapeutic target of PD through the prevention of pathological autophagy., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background & Objective: Amyotrophic lateral sclerosis is a progressive neurodegenerative disease that specifically affects motor neurons in the brain and in the spinal cord. Patients with amyotrophic lateral sclerosis usually die from respiratory failure within 3 to 5 years from when the symptoms first appear. Currently, there is no cure for amyotrophic lateral sclerosis. Accumulating evidence suggests that dismantling of neuromuscular junction is an early event in the pathogenesis of amyotrophic lateral sclerosis., Conclusion: It is starting to realized that macrophage malfunction contributes to the disruption of neuromuscular junction. Modulation of macrophage activation states may stabilize neuromuscular junction and provide protection against motor neuron degeneration in amyotrophic lateral sclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: Chemical exchange saturation transfer is a novel and promising MRI contrast method, but it can be time-consuming. Common parallel imaging methods, like SENSE, can lead to reduced quality of CEST. Here, parallel blind compressed sensing (PBCS), combining blind compressed sensing (BCS) and parallel imaging, is evaluated for the acceleration of CEST in brain and breast., Methods: The CEST data were collected in phantoms, brain (N = 3), and breast (N = 2). Retrospective Cartesian undersampling was implemented and the reconstruction results of PBCS-CEST were compared with BCS-CEST and k-t sparse-SENSE CEST. The normalized RMSE and the high-frequency error norm were used for quantitative comparison., Results: In phantom and in vivo brain experiments, the acceleration factor of R = 10 (24 k-space lines) was achieved and in breast R = 5 (30 k-space lines), without compromising the quality of the PBCS-reconstructed magnetization transfer rate asymmetry maps and Z-spectra. Parallel BCS provides better reconstruction quality when compared with BCS, k-t sparse-SENSE, and SENSE methods using the same number of samples. Parallel BCS overperforms BCS, indicating that the inclusion of coil sensitivity improves the reconstruction of the CEST data., Conclusion: The PBCS method accelerates CEST without compromising its quality. Compressed sensing in combination with parallel imaging can provide a valuable alternative to parallel imaging alone for accelerating CEST experiments., (© 2018 International Society for Magnetic Resonance in Medicine.)

Key Message: A SLAF-BSA approach was used to locate the RPF1 locus. The three most likely candidate genes were identified which provide a basic for cloning the resistance gene at the RPF1 locus. Spinach downy mildew is a globally devastating oomycete disease. The use of downy mildew resistance genes constitutes the most effective approach for disease management. Hence, the objective of the present study was to fine map the first-reported resistance locus RPF1. The resistance allele at this resistance locus was effective against races 1-7, 9, 11, 13, and 15 of Peronospora farinosa f. sp. spinaciae (P. effusa). The approach fine mapped RPF1 using specific-locus amplified fragment sequencing (SLAF-Seq) technology combined with bulked segregant analysis. A 1.72 Mb region localized on chromosome 3 was found to contain RPF1 based on association analysis. After screening recombinants with the SLAF markers within the region, the region was narrowed down to 0.89 Mb. Within this region, 14 R genes were identified based on the annotation information. To identify the genes involved in resistance, resequencing of two resistant inbred lines (12S2 and 12S3) and three susceptible inbred lines (12S1, 12S4, and 10S2) was performed. The three most likely candidate genes were identified via amino acid sequence analysis and conserved domain analysis between resistant and susceptible inbred lines. These included Spo12729, encoding a receptor-like protein, and Spo12784 and Spo12903, encoding a nucleotide-binding site and leucine-rich repeat domains. Additionally, based on the sequence variation in the three genes between the resistant and susceptible lines, molecular markers were developed for marker-assisted selection. The results could be valuable in cloning the RPF1 alleles and improving our understanding of the interaction between the host and pathogen.

Background : This cross-section investigation included 2,199 participants with hypertension complicated by diabetes mellitus, a cohort of the China Stroke Primary Prevention Trial in which 20,702 patients with essential hypertension were given enalapril with folic acid or enalapril-only double-blind treatment for 5 years. This study aimed to explore the correlation between folic acid supplementation and retinal atherosclerosis (RA) in adults with hypertension complicated by diabetes mellitus. Methods: The diagnosis of RA was determined by non-mydriatic fundus photography and classified by the Keith-Wagener-Barker system. The statistical correlation of folic acid supplementation with RA prevalence and severity was assessed. Results: Of our cohort, 1,698 (77.6%) participants were diagnosed with RA, and the prevalence in males and females was 78.0 and 75.6%, respectively. Participants in the enalapril group had higher total homocysteine (tHcy) levels than those in enalapril-folic acid group. Compared with the enalapril group in the tHcy > 15 μmol/L group of females, the odds ratio for the enalapril-folic acid group was 0.28 (95% confidence interval, 0.11-0.67, P = 0.0061). Conclusions: The prevalence of RA was high (77.6%) in our cohort of adults with hypertension complicated by diabetes mellitus. Folic acid supplementation was significantly associated with reduced risk of RA in females with hyperhomocysteinemia. No significant association were seen in males.

Selective activation of saturated C-H bond in hydrocarbons to produce high-value-added chemicals is of great significance for chemical synthesis and transformation. Herein, we present a facile procedure to achieve Ni-doped CdS nanoparticles with mixed (cubic and hexagonal) phases, as well as its application to the photocatalytic activation of saturated primary C-H bond of toluene and its derivatives. The photocatalytic oxidation rate of toluene into benzaldehyde of formation reached up to 216.7 μmolh -1 g -1 under visible light irradiation. The excellent photocatalytic performance of Ni(II)-doped CdS [Ni(II)/CdS] can be attributed to its unique structural assembly with cubic and hexagonal phases and also the addition of Ni ions, together taking effect in promoting the separation of photogenerated charge carriers. The possible reaction mechanism for the photocatalytic selective oxidation is illustrated in this work. The band width of the as-prepared mixed phase CdS is reduced, which can effectively expand the response range and improve photocatalytic performance.

Purpose of the Review: To reason that targeting chaperone-mediated autophagy (CMA) represents a promising approach for disease therapy, we will summarize advances in researches on the relationship between CMA and diseases and discuss relevant strategies for disease therapy by targeting the CMA process., Recent Findings: CMA is a unique kind of selective autophagy in lysosomes. Under physiological conditions, CMA participates in the maintenance of cellular homeostasis by protein quality control, bioenergetics, and timely regulated specific substrate-associated cellular processes. Under pathological conditions, CMA interplays with various disease conditions. CMA makes adaptive machinery to address stress, while disease-associated proteins alter CMA which is involved in pathogeneses of diseases. As more proteins are identified as CMA substrates and regulators, dysregulation of CMA has been implicated in an increasing number of diseases, while rectifying CMA alteration may be a benefit for these diseases., Summary: Alterations of CMA in diseases mainly including neurodegenerative diseases and many cancers raise the possibility of targeting CMA to recover cellular homeostasis as one potential strategy for therapy of relevant diseases., Competing Interests: Conflict of Interest On behalf of all authors, the corresponding author states that there is no conflict interest.

An adsorbent with multiple interaction sites for the adsorption of nitrogen-containing compounds (NCCs) has been realized in a silver ion functionalized Cr 3+ based metal-organic framework (Cr)-MIL-101-SO 3 Ag. The adsorptive denitrogenation performance of (Cr)-MIL-101-SO 3 Ag was evaluated in a batch adsorption system in terms of both its adsorption capacity and selectivity, of which, quinoline and indole were selected as representative organonitrogen contaminants in liquid fuels. (Cr)-MIL-101-SO 3 Ag could interact with NCCs through multiple ways simultaneously, which exhibited about 50% higher adsorption capacity compared to (Cr)-MIL-101-SO 3 H, and a still high level of adsorption amount could be remained even in a model fuel where toluene (15% v) was added as a co-solvent and benzothiophene (BT) was added as a competitive adsorbate. The highly efficient and selective denitrogenation performance, we speculated was a combined results of these multiple interaction sites. The immobilized Ag(I) sites could strongly interact with NCCs through π-complexation, which was thought to be responsible for its high adsorption capacity, meanwhile, the hard lewis acid site (Cr 3+ ), which could preferentially interact with the hard nitrogen bases and the acid-base interaction between nitrogen bases and remaining -SO 3 H groups endowed (Cr)-MIL-101-SO 3 Ag with high selectivity over BT and other aromatic compounds. Futhermore, the enhanced interaction of (Cr)-MIL-101-SO 3 Ag with NCCs was also confirmed from the IR spectra with the significantly enhanced absorbance peak at 806 or 745 cm -1 observed for QUI and IND, respectively when compared to BT. After five successive adsorption-desorption cycles, the adsorption capacity of (Cr)-MIL-101-SO 3 Ag was almost unchanged, and the structural stability was well maintained, making it a potential adsorbent for deep denitrogenation of liquid fuels., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Endobronchial one-way valves have been proposed as treatment for persistent air leak complicating spontaneous pneumothorax in which surgical intervention is not feasible. However, published data on efficacy, safety, and factors associated with success are scanty., Methods: This is a retrospective study of 37 patients at a general hospital from 2008 to 2016. The impact of endobronchial valve implantation on the time to air-leak cessation after bronchoscopy was evaluated., Results: The median patient age was 71 years. The majority of patients were males (92%), were ever-smokers (83%), had at least one co-morbidity (97%), and had secondary spontaneous pneumothorax (89%). Nineteen patients (51%) had a mean of 2.6 endobronchial valves implanted (range, 1-6). The air leak ceased within 72 hours for only eight patients (22% of the complete cohort), with immediate air-leak cessation after completion of endobronchial valve implantation. All six successful cases that had computed tomographic data of the thorax were shown to have bilateral intact interlobar fissures. The median (interquartile range) Charlson co-morbidity index was 1 (0.25-1) and 2 (1-3) for the success group and failure group, respectively (P=0.029). All patients in the no-endobronchial valve group survived, whereas three patients in the endobronchial valve group died within 30 days of endobronchial valve implantation., Conclusion: Only a small proportion of cases of endobronchial valve implantation for air leak complicating pneumothorax had unequivocal success. Intact bilateral interlobar fissures appear to be a necessary, though not sufficient, condition for success. Patients with fewer medical co-morbidities and immediate air-leak cessation after endobronchial valve implantation have a higher likelihood of success.

Inflammation and autophagy are two critical cellular processes. The relationship between these two processes is complex and includes the suppression of inflammation by autophagy. However, the signaling mechanisms that relieve this autophagy-mediated inhibition of inflammation to permit a beneficial inflammatory response remain unknown. We find that LPS triggers p38α mitogen-activated protein kinase (MAPK)-dependent phosphorylation of ULK1 in microglial cells. This phosphorylation inhibited ULK1 kinase activity, preventing it from binding to the downstream effector ATG13, and reduced autophagy in microglia. Consistently, p38α MAPK activity is required for LPS-induced morphological changes and the production of IL-1β by primary microglia in vitro and in the brain, which correlates with the p38α MAPK-dependent inhibition of autophagy. Furthermore, inhibition of ULK1 alone was sufficient to promote an inflammatory response in the absence of any overt inflammatory stimulation. Thus, our study reveals a molecular mechanism that enables the initial TLR4-triggered signaling pathway to inhibit autophagy and optimize inflammatory responses, providing new understanding into the mechanistic basis of the neuroinflammatory process., (© 2018 He et al.)

Macroautophagy/autophagy and inflammation are 2 intertwined processes vital for immune cells to perform their functions. Under resting conditions, autophagy acts as a brake to suppress inflammation in microglia. Upon signal stimulation, their fine-tuned interplay is pivotal for proper response to stress. How inflammatory signals remove this autophagy brake on inflammation remains unclear. In a recent study, we showed that the stress kinase MAPK14/p38α in microglia senses the inflammatory cue lipopolysaccharide (LPS), directly phosphorylates and inhibits ULK1, relieves the autophagic inhibition on the inflammatory machinery, and thus allows for a full immune response.

Autophagy and inflammation are two processes vital for immune cells to perform their functions. Their proper interplay upon signal is pivotal for proper response to stress. The stress kinase p38α MAPK in microglia senses inflammatory cue LPS, directly phosphorylates ULK1, relieves the autophagic inhibition on the inflammatory machinery, and thus allows for a full immune response., Competing Interests: Conflicting interests The authors have declared that no conflict of interests exist.

Endoplasmic reticulum (ER) and lysosomes coordinate a network of key cellular processes including unfolded protein response (UPR) and autophagy in response to stress. How ER stress is signaled to lysosomes remains elusive. Here we find that ER disturbance activates chaperone-mediated autophagy (CMA). ER stressors lead to a PERK-dependent activation and recruitment of MKK4 to lysosomes, activating p38 MAPK at lysosomes. Lysosomal p38 MAPK directly phosphorylates the CMA receptor LAMP2A at T211 and T213, which causes its membrane accumulation and active conformational change, activating CMA. Loss of ER stress-induced CMA activation sensitizes cells to ER stress-induced death. Neurotoxins associated with Parkinson's disease fully engages ER-p38 MAPK-CMA pathway in the mouse brain and uncoupling it results in a greater loss of SNc dopaminergic neurons. This work identifies the coupling of ER and CMA as a critical regulatory axis fundamental for physiological and pathological stress response.

Background: This cross sectional investigation included 12,966 subjects with hypertension, a cohort of the China Stroke Primary Prevention Trial (CSPPT), a randomized, multicenter clinical trial. This study aimed to explore the correlation between serum uric acid (SUA) concentration and hypertensive retinopathy in hypertensive adults., Methods: Diagnosis of hypertensive retinopathy was determined by non-mydriatic fundus photography and classified with Keith-Wagener-Barker (KWB) system. The correlation of SUA levels with hypertensive retinopathy prevalence and severity was assessed by statistical analysis., Results: 9848 (75.95%) subjects were diagnosed with hypertensive retinopathy with the following retinopathy grade distribution: grade 1: 58.80%, grade 2: 14.81%, and grade 3-4: 2.34%. SUA levels were significantly associated with hypertensive retinopathy prevalence. Patients with hypertensive retinopathy had higher SUA levels than those without hypertensive retinopathy. Patients in the highest uric acid quartile had an odds ratio for hypertensive retinopathy of 1.21 compared to patients in the lowest uric acid quartile (OR = 1.21, 95% CI: 1.05-1.40, P = 0.008). When compared to the non-hyperuricemia group, those in the hyperuricemia group had an odds ratio for hypertensive retinopathy of 1.18(OR = 1.18, 95% CI: 1.05-1.33, P = 0.004). Every 1 mg/dl increase in uric acid concentration was significantly associated with a 6% higher odds of hypertensive retinopathy (OR = 1.06, 95% CI: 1.02-1.10, P = 0.002)., Conclusions: The prevalence of hypertensive retinopathy was high (75.95%) among hypertensives in our patients cohort. In addition, SUA concentration was significantly associated with hypertensive retinopathy.

Background: Human umbilical cord mesenchymal stem cells (hUCMSCs) are a type of pluripotent stem cell which are isolated from the umbilical cord of newborns. hUCMSCs have great therapeutic potential. We designed this experimental study in order to investigate whether the transplantation of hUCMSCs can improve the ovarian reserve function of perimenopausal rats and delay ovarian senescence., Method: We selected naturally aging rats confirmed by vaginal smears as models of perimenopausal rats, divided into the control group and the treatment group, and selected young fertile female rats as normal controls. hUCMSCs were transplanted into rats of the treatment group through tail veins. Enzyme-linked immunosorbent assay (ELISA) detected serum levels of sex hormones, H&E staining showed ovarian tissue structure and allowed follicle counting, immunohistochemistry and western blot analysis revealed ovarian expression of hepatocyte growth factor (HGF), vascular endothelial cell growth factor (VEGF), and insulin-like growth factor-1 (IGF-1), polymerase chain reaction (PCR) and western blot analysis revealed hUCMSCs expression of HGF, VEGF, and IGF-1., Results: At time points of 14, 21, and 28 days after hUCMSCs transplantation, estradiol (E 2 ) and anti-Müllerian hormone (AMH) increased while follicle-stimulating hormone (FSH) decreased; ovarian structure improved and follicle number increased; ovarian expression of HGF, VEGF, and IGF-1 protein elevated significantly. Meanwhile, PCR and western blot analysis indicated hUCMSCs have the capacity of secreting HGF, VEGF, and IGF-1 cytokines., Conclusions: Our results suggest that hUCMSCs can promote ovarian expression of HGF, VEGF, and IGF-1 through secreting those cytokines, resulting in improving ovarian reserve function and withstanding ovarian senescence.

Raf kinase inhibitory protein (RKIP) regulates multiple cellular processes, and its downregulation is associated with distinct human cancers. In the present study, the status of RKIP promoter methylation, as well as its expression and clinical significance in esophageal squamous cell carcinoma (ESCC), were examined. The promoter methylation status in the 5'-CpG island of the RKIP gene and the expression level of the RKIP protein were examined using a modified methylation-specific polymerase chain reaction (MSP) method and immunohistochemical staining, respectively, in 77 ESCC samples and matched paratumor normal tissues. The incidence of RKIP promoter methylation was significantly higher in tumor samples (75.3%) than in the matched normal tissues (27.3%; P<0.001). A higher incidence of promoter methylation was also detected in poorly differentiated cancers (93.5%) compared with well-differentiated cancers (50.0%; P<0.001), as well as in tumor samples with positive lymph node metastasis (86.7%) compared with those with negative lymph node metastasis (59.4%; P<0.001). Consistent with the promoter methylation status, the expression level of RKIP was significantly reduced in cancer tissues (36.4%) compared with matched normal tissues (76.6%; P<0.01), as well as in cancers with positive lymph node metastasis (24.4%) compared with those with negative lymph node metastasis (53.1%; P=0.01). Promoter methylation-induced gene silencing significantly correlated with the down regulation of RKIP and the development of ESCC. The results of the present study suggested that the methylation status of the RKIP promoter, when combined with its expression level, may serve as a biomarker for predicting the biological behaviors of ESCC.

The phosphatidylinositol-3-kinase-like kinase ATM (ataxia-telangiectasia mutated) plays a central role in coordinating the DNA damage responses including cell cycle checkpoint control, DNA repair, and apoptosis. Mutations of ATM cause a spectrum of defects ranging from neurodegeneration to cancer predisposition. We previously showed that Cdk5 (cyclin-dependent kinase 5) is activated by DNA damage and directly phosphorylates ATM at serine 794 in postmitotic neurons. Phosphorylation at serine 794 precedes and is required for ATM autophosphorylation at serine 1981, and activates ATM kinase activity. Cdk5-ATM pathway plays a crucial role in DNA damage-induced neuronal injury. This chapter describes protocols used in analyzing ATM phosphorylation by Cdk5 in CGNs (cerebellar granule neurons) and its effects on neuronal survival.

The Grey-headed Lapwing (Vanellus cinereus) is a Vanellus bird belonging to the group Ciconiiformes, which breeds in northeast China and Japan. In this study, we sequenced its complete mitochondrial genome by PCR-based method. The mitochondrial DNA is packaged in a compact 17,135 based pair (bp) circular molecule with A + T content of 55.14%. It contains 37 typical mitochondrial genes, including 13 protein-coding genes, 2 rRNAs and 22 tRNAs and a non-coding control region (D-loop). All protein-coding genes are initiated by ATG codon, except for the COI gene and ND5 gene starting with GTG codon, and ND3 uses ATC codon. TAA is the most frequent stop codon. All tRNAs possess the classic cloverleaf secondary structure except for tRNA(Ser(AGY)) and tRNA(Leu(CUN)), which lack the ''DHU'' stem. The D-loop is a 1563 bp long A + T-rich region, which is located between tRNA(Glu) and tRNA(Phe).

Oil-polluted water has become a worldwide problem due to increasing industrial oily wastewater as well as frequent oil-spill pollution. Compared with underwater superoleophobic (water-removing) filtration membranes, superhydrophobic/superoleophilic (oil-removing) materials have advantages as they can be used for the filtration of heavy oil or the absorption of floating oil from water/oil mixtures. However, most of the superhydrophobic materials used for oil/water separation lose their superhydrophobicity when exposed to hot (e.g. >50 °C) water and strong corrosive liquids. Herein, we demonstrate superhydrophobic overlapped candle soot (CS) and silica coated meshes that can repel hot water (about 92 °C) and strong corrosive liquids, and were used for the gravity driven separation of oil-water mixtures in hot water and strong acidic, alkaline, and salty environments. To the best of our knowledge, we are unaware of any previously reported studies on the use of superhydrophobic materials for the separation of oil from hot water and corrosive aqueous media. In addition, the as-prepared robust superhydrophobic CS and silica coated meshes can separate a series of oils and organic solvents like kerosene, toluene, petroleum ether, heptane and chloroform from water with a separation efficiency larger than 99.0%. Moreover, the as-prepared coated mesh still maintained a separation efficiency above 98.5% and stable recyclability after 55 cycles of separation. The robust superhydrophobic meshes developed in this work can therefore be practically used as a highly efficient filtration membrane for the separation of oil from harsh water conditions, benefiting the environment and human health.

In this paper we consider image reconstruction from fully sampled multichannel phased array MRI data without knowledge of the coil sensitivities. To overcome the non-uniformity of the conventional sum-of-square reconstruction, a new framework based on multichannel blind deconvolution (MBD) is developed for joint estimation of the image function and the sensitivity functions in image domain. The proposed approach addresses the non-uniqueness of the MBD problem by exploiting the smoothness of both functions in the image domain through regularization. Results using simulation, phantom and in vivo experiments demonstrate that the reconstructions by the proposed algorithm are more uniform than those by the existing methods., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: To characterize Bietti crystalline dystrophy (BCD) in different stages using multiple imaging modalities., Methods: Sixteen participants clinically diagnosed as BCD were included in the retrospective study and were categorized into 3 stages according to fundus photography. Eleven patients were genetically confirmed. Fundus autofluorescence, spectral domain optical coherence tomography, and enhanced depth imaging features of BCD were analyzed., Results: On fundus autofluorescence, the abnormal autofluorescence was shown to enlarge in area and decrease in intensity with stages. Using spectral domain optical coherence tomography, the abnormalities in Stage 1 were observed to localize in outer retinal layers, whereas in Stage 2 and Stage 3, more extensive retinal atrophy was seen. In enhanced depth imaging, the subfoveal choroidal layers were delineated clearly in Stage 1; in Stage 2, destructions were primarily found in the choriocapillaris with associated alterations in the outer vessels; Stage 3 BCD displayed severe choroidal thinning. Choroidal neovascularization and macular edema were exhibited with high incidence. IVS6-8del17bp/inGC of the CYP4V2 gene was the most common mutant allele., Conclusion: Noninvasive fundus autofluorescence, spectral domain optical coherence tomography, and enhanced depth imaging may help to characterize the chorioretinal pathology of BCD at different degrees, and therefore, we propose staging of BCD depending on those methods. Physicians should be cautious of the vision-threatening complications of the disease.

The Mn-catalyzed C-H alkenylation reactions of indole with terminal- and internal-alkynes have been developed. In the presence of a catalytic amount of acid, the procedure efficiently affords bis/trisubstituted indolyl-alkenes in a highly regio- and stereo-selective manner. Without the addition of acid, the reaction undergoes a [2+2+2] cyclization process to give carbazoles with release of hydrogen gas. Notably, the directing pyrimidyl group can be readily removed. Experimental studies reveal that the reaction is initiated by a C-H activation step and the acid is the selectivity controller via a hydrogen transfer process.

MicroRNAs (miRNAs) regulate the translational potential of their mRNA targets and control many cellular processes. The key step in canonical miRNA biogenesis is the cleavage of the primary transcripts by the nuclear RNase III enzyme Drosha. Emerging evidence suggests that the miRNA biogenic cascade is tightly controlled. However, little is known whether Drosha is regulated. Here, we show that Drosha is targeted by stress. Under stress, p38 MAPK directly phosphorylates Drosha at its N terminus. This reduces its interaction with DiGeorge syndrome critical region gene 8 and promotes its nuclear export and degradation by calpain. This regulatory mechanism mediates stress-induced inhibition of Drosha function. Reduction of Drosha sensitizes cells to stress and increases death. In contrast, increase in Drosha attenuates stress-induced death. These findings reveal a critical regulatory mechanism by which stress engages p38 MAPK pathway to destabilize Drosha and inhibit Drosha-mediated cellular survival., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments.

Aims: Dysfunction of myocyte enhancer factor 2D (MEF2D), a key survival protein and transcription factor, underlies the pathogenic loss of dopaminergic (DA) neurons in Parkinson's disease (PD). Both genetic factors and neurotoxins associated with PD impair MEF2D function in vitro and in animal models of PD. We investigated whether distinct stress conditions target MEF2D via converging mechanisms., Results: We showed that exposure of a DA neuronal cell line to 6-hyroxydopamine (6-OHDA), which causes PD in animals models, led to direct oxidative modifications of MEF2D. Oxidized MEF2D bound to heat-shock cognate protein 70 kDa, the key regulator for chaperone-mediated autophagy (CMA), at a higher affinity. Oxidative stress also increased the level of lysosomal-associated membrane protein 2A (LAMP2A), the rate-limiting receptor for CMA substrate flux, and stimulated CMA activity. These changes resulted in accelerated degradation of MEF2D. Importantly, 6-OHDA induced MEF2D oxidation and increased LAMP2A in the substantia nigra pars compacta region of the mouse brain. Consistently, the levels of oxidized MEF2D were much higher in postmortem PD brains compared with the controls. Functionally, reducing the levels of either MEF2D or LAMP2A exacerbated 6-OHDA-induced death of the DA neuronal cell line. Expression of an MEF2D mutant that is resistant to oxidative modification protected cells from 6-OHDA-induced death., Innovation: This study showed that oxidization of survival protein MEF2D is one of the pathogenic mechanisms involved in oxidative stress-induced DA neuronal death., Conclusion: Oxidation of survival factor MEF2D inhibits its function, underlies oxidative stress-induced neurotoxicity, and may be a part of the PD pathogenic process.

The title mol-ecule, C32H30F2N2, a product of the condensation reaction of butane-2,3-dione and 4-fluoro-2-(1-phenyl-eth-yl)aniline, is located about an inversion centre. In the asymmetric unit, the dihedral angle between the planes of the benzene and phenyl rings is 84.27 (5)°. Neither hydrogen bonding nor aromatic stacking is observed in the crystal structure.

Purpose: To develop a sensitivity-based parallel imaging reconstruction method to reconstruct iteratively both the coil sensitivities and MR image simultaneously based on their prior information., Methods: Parallel magnetic resonance imaging reconstruction problem can be formulated as a multichannel sampling problem where solutions are sought analytically. However, the channel functions given by the coil sensitivities in parallel imaging are not known exactly and the estimation error usually leads to artifacts. In this study, we propose a new reconstruction algorithm, termed Sparse BLind Iterative Parallel, for blind iterative parallel imaging reconstruction using compressed sensing. The proposed algorithm reconstructs both the sensitivity functions and the image simultaneously from undersampled data. It enforces the sparseness constraint in the image as done in compressed sensing, but is different from compressed sensing in that the sensing matrix is unknown and additional constraint is enforced on the sensitivities as well. Both phantom and in vivo imaging experiments were carried out with retrospective undersampling to evaluate the performance of the proposed method., Results: Experiments show improvement in Sparse BLind Iterative Parallel reconstruction when compared with Sparse SENSE, JSENSE, IRGN-TV, and L1-SPIRiT reconstructions with the same number of measurements., Conclusion: The proposed Sparse BLind Iterative Parallel algorithm reduces the reconstruction errors when compared to the state-of-the-art parallel imaging methods., (Copyright © 2013 Wiley Periodicals, Inc.)

The introduction of Lawesson's reagent into a bis-rhodamine spirolactam system afforded a new fluorescent sensor for Cu(2+) ions, SRR, which contained a new tridentate sulfur ligand. SRR showed excellent specificity for Cu(2+) ions over other cations (including Cu(+), Hg(2+), and Fe(3+)), very high sensitivity (10 nM), and a rapid response time (3 min). The detection mechanism was investigated by (1)H NMR, (13)C NMR, (31)P NMR, and ESR spectroscopy, MS, and Gaussian calculations. Coordination of a Cu(2+) ion to the tridentate sulfur ligand, which promotes ring-opening of the rhodamine groups, followed by a spontaneous reduction reaction (Cu(2+) into Cu(+)), has been proposed as the sensing mechanism., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Parkinson disease (PD) is characterized by the selective demise of dopaminergic (DA) neurons in the substantial nigra pars compacta. Dysregulation of transcriptional factor myocyte enhancer factor 2D (MEF2D) has been implicated in the pathogenic process in in vivo and in vitro models of PD. Here, we identified a small molecule bis(3)-cognitin (B3C) as a potent activator of MEF2D. We showed that B3C attenuated the toxic effects of neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)) by activating MEF2D via multiple mechanisms. B3C significantly reduced MPP(+)-induced oxidative stress and potentiated Akt to down-regulate the activity of MEF2 inhibitor glycogen synthase kinase 3β (GSK3β) in a DA neuronal cell line SN4741. Furthermore, B3C effectively rescued MEF2D from MPP(+)-induced decline in both nucleic and mitochondrial compartments. B3C offered SN4741 cells potent protection against MPP(+)-induced apoptosis via MEF2D. Interestingly, B3C also protected SN4741 cells from wild type or mutant A53T α-synuclein-induced cytotoxicity. Using the in vivo PD model of C57BL/6 mice treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP), we showed that B3C maintained redox homeostasis, promoted Akt function activity, and restored MEF2D level in midbrain neurons. Moreover, B3C greatly prevented the loss of tyrosine hydroxylase signal in substantial nigra pars compacta DA neurons and ameliorated behavioral impairments in mice treated with MPTP. Collectedly, our studies identified B3C as a potent neuroprotective agent whose effectiveness relies on its ability to effectively up-regulate MEF2D in DA neurons against toxic stress in models of PD in vitro and in vivo.

The myocyte enhancer factor 2A-D (MEF2) proteins are members of the MCM1-agamous-deficiens-serum response factor family of transcription factors. Various MEF2 isoform proteins are enriched in neurons and exhibit distinct patterns of expression in different regions of the brain. In neurons, MEF2 functions as a converging factor to regulate many neuronal functions including survival. MEF2 activities are tightly controlled in neurons in response to stress. Whether stress signal may differentially regulate MEF2s remains largely unknown. In this work, we showed that MEF2A, but not MEF2C or MEF2D, was modified by ubiquitination in dopaminergic neuronal cell line SN4741 cells. MEF2A was ubiquitinated at its N'-terminus, and the ubiquitination of MEF2A was first detectable in the nuclear compartment and later in the cytoplasm. Ubiquitination of MEF2A correlated with reduced DNA-binding activity and transcriptional activity. More importantly, disturbing the degradation of ubiquitinated MEF2A through proteasome pathway by neurotoxins known to induce Parkinson's disease features in model animals caused accumulation of ubiquitinated MEF2A, reduced MEF2 activity, and impaired cellular viability. Our work thus provides the first evidence to demonstrate an isoforms-specific regulation of MEF2s by ubiquitination-proteasome pathway in dopaminergic neuronal cell by neurotoxins, suggesting that stress signal and cellular context-dependent dysregulation of MEF2s may underlie the loss of neuronal viability., (© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.)

The role of apoptosis in the formation and regression of neovascularization is largely hypothesized, although the detailed mechanism remains unclear. Inflammatory cells and endothelial cells both participate and interact during neovascularization. During the early stage, these cells may migrate into an angiogenic site and form a pro-angiogenic microenvironment. Some angiogenic vessels appear to regress, whereas some vessels mature and remain. The control mechanisms of these processes, however, remain unknown. Previously, we reported that the prevention of mitochondrial apoptosis contributed to cellular survival via the prevention of the release of proapoptotic factors, such as apoptosis-inducing factor (AIF) and cytochrome c. In this study, we investigated the regulatory role of cellular apoptosis in angiogenesis using two models of ocular neovascularization: laser injury choroidal neovascularization and VEGF-induced corneal neovascularization in AIF-deficient mice. Averting apoptosis in AIF-deficient mice decreased apoptosis of leukocytes and endothelial cells compared to wild-type mice and resulted in the persistence of these cells at angiogenic sites in vitro and in vivo. Consequently, AIF deficiency expanded neovascularization and diminished vessel regression in these two models. We also observed that peritoneal macrophages from AIF-deficient mice showed anti-apoptotic survival compared to wild-type mice under conditions of starvation. Our data suggest that AIF-related apoptosis plays an important role in neovascularization and that mitochondria-regulated apoptosis could offer a new target for the treatment of pathological angiogenesis., (Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is the second most common neurodegenerative disorder due to selective death of neurons in the substantia nigra pars compacta. The cause of cell death remains largely unknown. Myocyte enhancer factor 2 (MEF2) is a group of transcriptional factors required to regulate neuronal development, synaptic plasticity, as well as survival. Recent studies show that MEF2 functions are regulated in multiple subcellular organelles and suggest that dysregulation of MEF2 plays essential roles in the pathogenesis of PD. Many kinases associated with transcription, translation, protein misfolding, autophagy, and cellular energy homeostasis are involved in the neurodegenerative process. Following the first demonstration that mitogen-activated protein kinase p38 (p38 MAPK) directly phosphorylates and activates MEF2 to promote neuronal survival, several other kinase regulators of MEF2s have been identified. These include protein kinase A and extracellular signal regulated kinase 5 as positive MEF2 regulators, and cyclin-dependent kinase 5 (Cdk5) and glycogen synthase kinase 3β as negative regulators in response to diverse toxic signals relevant to PD. It is clear that MEF2 has emerged as a key point where survival and death signals converge to exert their regulatory effects, and dysregulation of MEF2 function in multiple subcellular organelles may underlie PD pathogenesis. Moreover, several other kinases such as leucine-rich repeat kinase 2 and PTEN-induced putative kinase 1 (PINK1) are of particular interest due to their potential interaction with MEF2.

Synaptic and extrasynaptic NMDA receptors (NMDARs) appear to play opposite roles in neuronal survival and death. Here we report the new findings on the dysregulation of survival factor, myocyte enhancer factor 2D (MEF2D), by extrasynaptic NMDARs. Excitotoxicity led to the NMDAR-dependent degradation of MEF2D protein and inhibition of its transactivation activity in mature cortical neurons. The activation of extrasynaptic NMDARs alone was sufficient for degradation of MEF2D. Calpain directly cleaved MEF2D in vitro and blocking this protease activity greatly attenuated NMDAR signaled degradation of MEF2D in neurons. Consistently, inhibition of calpain protected cortical neurons from NMDA-induced excitotoxicity. Furthermore, knockdown of MEF2D sensitized neurons to NMDA-induced excitotoxicity, which was not protected by calpain inhibition. Collectively, these findings suggest that dysregulation of MEF2D by calpain may mediate excitotoxicity via an extrasynaptic NMDAR-dependent manner.