bluuebunny/crossref_metadata_2025 huggingface dataset:
Mitochondria Targeting Fluorescent Probes Based on through Bond‐Energy Transfer for Mutually Imaging Signaling Molecules H2S and H2O2
Authors: Sun Jian , Li Xiao , Cao Jia , Sun Qi , Zhang Yajie , Wang Xuewei , Wu Tiantian , Hu Xiantao , Feng Fude
Published: April 2019

Reactive signaling molecules participate in varieties of biochemical reactions, and methods to detect their mutual existence and crosstalk are in urgent demand. A benzothiadiazole‐based handle was designed to fluorescently respond to the co‐existence of H2S and H2O2 under pseudo‐physiological conditions on a basis of a thiyl‐radical‐mediated mechanism that accounts for the rapid and efficient domino‐like reaction processes. Then the handle motif was attached to a rhodamine moiety by means of an ethynylene linkage, and achieved a significant H2S–H2O2 mutual response in the mitochondria of living cells. Theoretical calculations supported that a through bond energy transfer mechanism contributes to the drastic fluorescence response.
Catalytic Chemosensing Assay for Selective Detection of Methyl Parathion Organophosphate Pesticide
Authors: Zheng Anxun , Shen Chang , Tang Qian , Gong Cheng‐Bin , Chow Cheuk‐Fai
Published: April 2019

Herein, a catalytic chemosensing assay (CCA), based on a bimetallic complex, [RuII(bpy)2(CN)2]2(CuII)2 (bpy=2,2′‐bipyridine), is described. This complex integrates a task‐specific catalyst (CuI‐catalyst) and a signaling unit ([RuII(bpy)2(CN)2]) to specifically hydrolyze methyl parathion, a highly toxic organophosphate (OP) pesticide. The bimetallic complex catalyzed the hydrolysis of the phosphate ester to generate o,o‐dimethyl thiophosphate (DTP) anion and 4‐nitrophenolate. Intrinsically, 4‐nitrophenolate absorbed UV/Vis light at λmax=400 nm, creating the first level of the chemosensing signal. DTP interacted with the original complex to displace the chromophore, [RuII(bpy)2(CN)2], which was monitored by spectrofluorometry; this was classified as the second level of chemosensing signal. By integrating both spectroscopic and spectrofluorometric signals with a simple AND logic gate, only methyl parathion was able to provide a positive response. Other aromatic and aliphatic OP pesticides (diazinon, fenthion, meviphos, terbufos, and phosalone) and 4‐nitrophenyl acetate provided negative responses. Furthermore, owing to the metal‐catalyzed hydrolysis of methyl parathion, the CCA system led to the detoxification of the pesticide. The CCA system also demonstrated its catalytic chemosensing properties in the detection of methyl parathion in real samples, including tap water, river water, and underground water.
Chemo‐ and Regioselective Catalyst‐Controlled Carbocyclization of Alkynyl Ketones: Rapid Synthesis of 1‐Indanones and 1‐Naphthols
Authors: Song Liangliang , Tian Guilong , Van der Eycken Erik V.
Published: April 2019

A catalyst‐controlled intramolecular carbocyclization of 2‐alkynyl aryl ketones is presented. Under rhodium(III) catalysis, 1‐indanones are formed through 5‐exo‐dig carbocyclizations with exclusive chemo‐, regio‐ and stereoselectivity. When catalyzed by copper(I), 1‐naphthols are obtained through 6‐endo‐dig carbocyclizations with exclusive chemo‐ and regioselectivity.
Enantiomeric resolution, thermodynamic parameters, and modeling of clausenamidone and neoclausenamidone on polysaccharide‐based chiral stationary phases
Authors: Luo Xuna , Fang Chengqiao , Mi Junru , Xu Jingzi , Lin Hansen
Published: April 2019

The aim of the paper is to describe a new synthesis route to obtain synthetic optically active clausenamidone and neoclausenamidone and then use high‐performance liquid chromatography (HPLC) to determine the optical purities of these isomers. In the process, we investigated the different chromatographic conditions so as to provide the best separation method. At the same time, a thermodynamic study and molecular simulations were also carried out to validate the experimental results; a brief probe into the separation mechanism was also performed. Two chiral stationary phases (CSPs) were compared with separate the enantiomers. Elution was conducted in the organic mode with n‐hexane and iso‐propanol (IPA) (80/20 v/v) as the mobile phases; the enantiomeric excess (ee) values of the synthetic R‐clausenamidone and S‐clausenamidone and R‐neoclausenamidone and S‐ neoclausenamidone were higher than 99.9%, and the enantiomeric ratio (er) values of these isomers were 100:0. Enantioselectivity and resolution (α and Rs, respectively) levels with values ranging from 1.03 to 1.99 and from 1.54 to 17.51, respectively, were achieved. The limits of detection and quantitation were 3.6 to 12.0 and 12.0 to 40.0 ug/mL, respectively. In addition, the thermodynamics study showed that the result of the mechanism of chiral separation was enthalpically controlled at a temperature ranging from 288.15 to 308.15 K. Furthermore, docking modeling showed that the hydrogen bonds and π‐π interactions were the major forces for chiral separation. The present chiral HPLC method will be used for the enantiomeric resolution of the clausenamidone derivatives.
Systematic Experimental Study on Quantum Sieving of Hydrogen Isotopes in Metal‐Amide‐Imidazolate Frameworks with narrow 1‐D Channels
Authors: Mondal Suvendu Sekhar , Kreuzer Alex , Behrens Karsten , Schütz Gisela , Holdt Hans‐Jürgen , Hirscher Michael
Published: April 2019

Quantum sieving of hydrogen isotopes is experimentally studied in isostructural hexagonal metal‐organic frameworks having 1‐D channels, named IFP‐1, −3, −4 and −7. Inside the channels, different molecules or atoms restrict the channel diameter periodically with apertures larger (4.2 Å for IFP‐1, 3.1 Å for IFP‐3) and smaller (2.1 Å for IFP‐7, 1.7 Å for IFP‐4) than the kinetic diameter of hydrogen isotopes. From a geometrical point of view, no gas should penetrate into IFP‐7 and IFP‐4, but due to the thermally induced flexibility, so‐called gate‐opening effect of the apertures, penetration becomes possible with increasing temperature. Thermal desorption spectroscopy (TDS) measurements with pure H2 or D2 have been applied to study isotope adsorption. Further TDS experiments after exposure to an equimolar H2/D2 mixture allow to determine directly the selectivity of isotope separation by quantum sieving. IFP‐7 shows a very low selectivity not higher than S=2. The selectivity of the materials with the smallest pore aperture IFP‐4 has a constant value of S≈2 for different exposure times and pressures, which can be explained by the 1‐D channel structure. Due to the relatively small cavities between the apertures of IFP‐4 and IFP‐7, molecules in the channels cannot pass each other, which leads to a single‐file filling. Therefore, no time dependence is observed, since the quantum sieving effect occurs only at the outermost pore aperture, resulting in a low separation selectivity.
Electronically Tuned Asymmetric meso‐Substituted Porphyrins for p‐Type Solar Cells
Authors: Grzegorzek Norbert , Zieleniewska Anna , Schür Annika , Maichle‐Mössmer Cäcilia , Killian Manuela S. , Guldi Dirk M. , Chernick Erin T.
Published: April 2019

A series of electronically tuned asymmetric porphyrins have been synthesized for use in p‐type solar cells. The porphyrin derivatives were strategically designed with electron‐withdrawing capability and an electronic dipole gradient to aid in electron‐harvesting capacity from a nickel oxide cathode. Specifically, the porphyrins were substituted at the meso position with different arrangements of the electron‐withdrawing pentafluorobenzene moiety, electron‐donating/coordinating 4‐pyridyl ligand, and an electron withdrawing/synthetically modifiable 4‐cyanophenyl unit. Two distinct free‐base porphyrins were synthesized, one of which was further metallated with nickel(II). The porphyrins were fully characterized and their electronic properties explored experimentally by electrochemistry, and both steady state and time‐resolved spectroscopy. Finally, the porphyrins were incorporated into a p‐type solar cell device utilizing NiO as the cathode, and demonstrating a preliminary maximum performance of η(%)=0.082 and IPCEMAX(%)=26.0 without co‐sensitization.
Cytomorphologic features of malignant solitary fibrous tumor with mediastinal involvement sampled by endoscopic and endobronchial ultrasound‐guided fine‐needle aspiration: A comparison of two cases
Authors: Hupp Meghan , Najmuddin Mufaddal , Dincer Huseyin Erhan , Mallery James Shawn , Amin Khalid , Stewart Jimmie
Published: April 2019

Solitary fibrous tumor (SFT) is an uncommon fibroblastic neoplasm with considerable risk of local recurrence. SFT is histologically characterized by bland spindled‐to‐epithelioid cells in alternating hyper‐ and hypocellular zones, a “patternless pattern,” ectatic “staghorn” vessels with variable edematous perivascular stroma, and thick ropey collagen. Cytologically, smears are variably cellular with spindled‐to‐epithelioid cells with oval nuclei, wispy cytoplasm, multiple inconspicuous nucleoli, and occasional nuclear pseudoinclusions. Small vessels and bare/stripped nuclei are generally present while mild atypia is not uncommon. STAT6 nuclear expression is the most useful immunohistochemical stain and is the product of a NAB2‐STAT6 gene fusion. SFTs with mediastinal involvement may be diagnostically challenging due to proximity to vital structures and anticipated patient risks. Endobronchial and endoscopic ultrasound‐guided fine‐needle aspiration (EBUS/EUS‐FNA) are minimally‐invasive tissue sampling methods that provide diagnostic material while minimizing patient risk, and the mediastinum is accessible by both procedures. Small aspirate samples and SFT nonspecific features can compound the diagnostic difficulty, although familiarity with the cytologic, morphologic, immunophenotypic, and genetic features of SFTs assist the pathologist in confirming the diagnosis. Pathologists must also be aware of high‐risk SFT features to ensure appropriate therapy and management. Case #1 describes a recurrent mediastinal SFT with high‐risk features sampled by EUS‐FNA. Case #2 describes a primary diagnosis of mediastinal SFT with malignant behavior made on an EBUS‐FNA specimen.
Tissue resident T cell memory or how the magnificent seven are chilling in the bone
Authors: Zens Kyra , Münz Christian
Published: April 2019

Following infection, tissue‐resident memory T cells (Trm) are thought to be left behind at sites of antigen encounter to protect affected tissues against subsequent reinfection. In this issue of the European Journal of Immunology, however, Pascutti et al. demonstrate that both murine and human CD8+ Trm specific to seven different pathogens, including systemic, skin, and lung tissue‐localized pathogens, accumulate in the bone marrow (BM). These cells have a CD69+ phenotype, develop independently of local antigen, and require IL‐15, Blimp‐1, and Hobit for their differentiation and maintenance. Following restimulation, these cells expand and rapidly produce cytokines. While some of these responses may protect the BM from infection, the consideration that some of these pathogens or their antigens might never reach the BM suggests additional functional roles of BM Trm, possibly in supporting hematopoietic functions via cytokine production following infection. It will be further interesting to determine whether BM Trm contribute to the circulating effector pool following reinfection with tissue‐localized or systemic pathogens and whether these cells can be elicited by vaccination.
[2]Rotaxanes Bearing a Tetralactam Macrocycle: The Role of a Trifurcated Hydrogen Bond in the Crystalline State
Authors: Salbego Paulo R. S. , Orlando Tainára , Farias Fellipe F. S. , Bonacorso Helio G. , Martins Marcos A. P.
Published: April 2019

This study investigated the proper classification and quantification of intercomponent trifurcated hydrogen bonds, in the crystalline state, of rotaxanes bearing a tetralactam Leigh‐type macrocycle. Quantum mechanical calculations were carried out to obtain the interaction paths and their stabilization energies. In general, the use and necessity of fragmentation in types of interaction have been reported in the literature, although they are commonly performed only using a geometric approach. This results in N–H···O interactions that are indicated as the main interactions between components, neglecting other possible interactions. The use of energetic fragmentation was demonstrated here under an appropriate demarcation considering all interactions and showing the existence and role of the C–H···O interaction. The C–H···O interactions showed similar energy to N–H···O interactions with average values around –4.75 kcal mol–1and –4.60 kcal mol–1, respectively. This revealed that the three hydrogen bonds are part of a cooperative set of interactions with a similar contribution. The trifurcated hydrogen bonds presented high contribution in the total intercomponent stabilization energy of the rotaxanes, with an average value of 51 % in the studied series.
Electrooxidative C–H Functionalization of Heteroarenes. Thiocyanation of Pyrazolo[1,5‐a]pyrimidines
Authors: Kokorekin Vladimir A. , Yaubasarova Rauza R. , Neverov Sergei V. , Petrosyan Vladimir A.
Published: April 2019

Efficient electrooxidative C–H thiocyanation of both high and low reactive pyrazolo[1,5‐a]pyrimidines using a new system of complementary approaches has been developed. Advantages of this promising strategy are the undivided cell, mild conditions, and readily available reagents as well as feasible scaling up process and transformation of the synthesized aryl thiocyanates to new thiols. Also, target thiocyanates were found to have pronounced antifungal activity.
The Synthesis of Chitosan Decorated Reduced Graphene Oxide‐Ferrocene Nanocomposite and its Application in Electrochemical Detection Rhodamine B
Authors: Yang Xing , Niu Xiaohui , Mo Zunli , Liu Nijuan , Guo Ruibin , Zhao Pan , Liu Zhenyu , Ouyang Meixuan
Published: April 2019

Chitosan (CS) decorated reduced graphene oxide‐Ferrocene nanocomposite (RGO−Fc−CS) was synthesized by a one‐pot reaction. In the synthesis process of RGO−Fc−CS, GO−Fc was successfully self‐assembled via the π–π interaction, which had the features of large surface area and the high load. Then GO‐Fc and CS linked via one‐pot under alkaline conditions. The FT−IR, TGA, SEM were employed to characterize the successful synthesis of RGO−Fc−CS composites. A miniature electrochemical system was fabricated by RGO−Fc−CS modified glassy carbon electrode (expressed as RGO−Fc−CS/GCE) for the sensitive detection of RhB enantiomers via DPV. Electrochemical results revealed that the RGO−Fc−CS/GCE exhibited high molecular recognition toward RhB. Due to the synergy between the RGO−Fc and CS, the RGO−Fc−CS/GCE showed a linear range of 0.001–70 μM with a LOD of 0.5 nM, indicating that RGO−Fc−CS/GCE has broad application prospects to simplify monitor RhB real‐time.
Weight trajectories and disordered eating behaviours in 11‐ to 12‐year‐olds: A longitudinal study within the Danish National Birth Cohort
Authors: Stemann Larsen Pernille , Nybo Andersen Anne‐Marie , Olsen Else Marie , Kragh Andersen Per , Micali Nadia , Strandberg‐Larsen Katrine
Published: April 2019

Objective

To examine how childhood weight trajectories are associated with disordered eating behaviours (DEBs) in early adolescence.

Methods

Self‐reports on DEBs (fasting, purging, and binge eating) were obtained from 18,337 children in the 11‐year follow‐up of the Danish National Birth Cohort. For this population, birth register information on gestational age and birth weight was categorized into the following: small, appropriate, and large for gestational age. Prospective parent‐reported height and weight data at child ages 1 and 7 years were dichotomized using standardized cut‐offs into non‐overweight and overweight. A 12‐category weight trajectory variable was created, and the associations between weight trajectory and DEBs were estimated using logistic regression.

Results

In total, 7.0% 11‐ to 12‐year olds reported DEBs. Compared with children born appropriate for gestational age and being non‐overweight at age 1 and 7 years, children born small for gestational age and who were overweight at age 1 and 7 years had a very high risk of disordered eating (OR 7.00; CI [2.57, 19.40]). The statistical analyses revealed, however, that overweight at age 7 years was the main contributor and independently of trajectory increased the risk of disordered eating at age 11–12 years significantly (OR 3.16 CI [2.73, 3.65]).

Conclusion

Overweight not in the first year of life, but at age 7 years was more predictive for DEBs.
Metal Toxicity During Short-Term Sediment Resuspension and Redeposition in a Tropical Reservoir
Authors: Cervi Eduardo Cimino , Hudson Michelle , Rentschler Alison , Burton G. Allen
Published: April 2019

Billings Complex is the largest water-storage reservoir in São Paulo, Brazil, and has been contaminated since the 1960s. Periodically, Billings sediments are subjected to currents causing resuspension and subsequent release of metals. A short-term (4-h) resuspension was simulated using sediment flux exposure chambers (SeFECs) to better understand the fate, bioavailability, and transport of iron (Fe), manganese (Mn), and zinc (Zn) during these events, as well as possible organism toxicity. Daphnia magna and Hyalella azteca were exposed during the 4-h resuspension, and were monitored after exposure for survival, growth, and reproduction. Resuspension rapidly deoxygenated the overlying water, decreased the pH, and resulted in elevated dissolved Zn above the US Environmental Protection Agency's (2002) criteria for acute toxicity (120 µg L–1). However, Zn was scavenged (after 20 h) from solution as new sorption sites formed. Dissolved Mn increased during and after resuspension, with maximum values at 20 h post exposure. An initial release of Fe occurred, likely associated with oxidation of acid-volatile sulfides, but decreased after 1 h of resuspension. The Fe decrease is likely due to precipitation as oxyhydroxides. No acute toxicity was observed during resuspension; however, mortality of D. magna and H. azteca occurred during the postexposure period. Daphnia magna also exhibited chronic toxicity, with decreased neonate production after exposure. This sublethal effect could lead to decreased zooplankton populations over a longer period in the reservoir. Environ Toxicol Chem 2019;38:1476–1485. © 2019 SETAC

Abstract

Conceptual model of metal (Me) speciation under different sediment redox states. During bedded conditions (A) metals are mainly bounded as insoluble sulfides or associated with organic carbon (OC). When resuspended (B), sulfide species are oxidized, mobilizing metals (such as Zn) into the overlying water (OW). However, the mobilized metal is scavenged by OC and freshly-precipitated FexOx. As particles redeposit (C), and are returned to the benthic environment, further oxidation can occur in the aerobic sediment layer releasing Fe. High dissolved Fe concentrations in OW caused acute and chronic toxicity to D. magna. Ingestion of Zn caused growth inhibition and mortality to H. azteca.
Shrinkage sinusoidal phase estimation based on spherical simplex unscented transform and bootstrap method
Authors: Park Chee‐Hyun , Chang Joon‐Hyuk
Published: April 2019

This paper presents novel shrinkage‐based sinusoidal phase estimation algorithms. The main contributions of this paper are two‐fold. First, the shrinkage factor is found using the spherical simplex unscented transform (SSUT) and the combination of bootstrap and SSUT to reduce the computational complexity of the Monte Carlo method. The computational burden of the proposed methods is relatively low due to the use of SSUT, resulting from the carefully selected sigma points. Second, the accuracy of the novel shrinkage estimator is better than that of the maximum likelihood estimator (MLE) and existing shrinkage estimator under the low signal‐to‐noise ratio (SNR) and small sample number conditions. It is demonstrated that the resulting accuracies of the proposed shrinkage‐based phase estimation methods are superior to those of existing shrinkage algorithm and MLE in low SNR and small sample number conditions.
Purification and identification of an antioxidant peptide from perilla seed (Perilla frutescens) meal protein hydrolysate
Authors: Kim Ja Min , Liceaga Andrea M. , Yoon Kyung Young
Published: April 2019

This study aimed to obtain antioxidant peptides from perilla seed meal (PSM), which is normally discarded as an industrial waste during seed oil extraction. PSM protein was hydrolyzed using trypsin and fractionated by ultrafiltration. Molecular weight fraction (<3 kDa) with the highest antioxidant activity was purified using prep‐HPLC and analytical HPLC. The purification fold of the peptide (fraction V) obtained from PSM protein hydrolysate on DPPH radical scavenging activity, ABTS radical scavenging activity, and reducing power was 1.79‐, 1.59‐, and 1.81‐fold, respectively, after the three‐step purification procedure. The sequence of the purified peptide from fraction V that exhibited free radical scavenging activity and reducing power was identified as Ile‐Ser‐Pro‐Arg‐Ile‐Leu‐Ser‐Tyr‐Asn‐Leu‐Arg (1,330.77 Da). These results demonstrate that PSM protein, a by‐product from the oil seed extraction, can be used as a source of natural antioxidant peptides for food and/or nutraceutical applications.
Altered dynamics of brain segregation and integration in poststroke aphasia
Authors: Guo Jing , Biswal Bharat B. , Han Shaoqiang , Li Jiao , Yang Siqi , Yang Mi , Chen Huafu
Published: April 2019

Poststroke aphasia (PSA) results from direct effect of focal lesions and dysfunction of distributed language networks. However, how flexible the activity at specific nodes control global dynamics is currently unknown. In this study, we demonstrate that alterations in the regional activity may cause imbalances between segregation and integration in temporo‐spatial pattern, and the transient dynamics are disrupted in PSA patients. Specifically, we applied dynamic framework to eyes‐closed resting‐state functional MRI data from PSA patients (n= 17), and age‐, gender‐, and education‐matched healthy controls (HCs,n= 20). Subsequently, we calculated two basis brain organizational principles: “dynamic segregation,” obtained from dynamic amplitude of low‐frequency fluctuations (dALFF), which represent the specialized processing within interconnected brain regions; and “dynamic integration,” obtained from dynamic functional connectivity, which measures the efficient communication between interconnected brain regions. We found that both measures were decreased in the PSA patients within the left frontal and temporal subregions compared to the HCs. PSA patients displayed increased flexibility of interaction between left temporo‐frontal subregions and right temporo‐parieto‐frontal subnetworks. Furthermore, we found that dALFF in the pars triangularis of left inferior frontal gyrus was associated with aphasia quotient. These findings suggest that the reduced temporal flexibility of regional activity in language‐relevant cortical regions in PSA is related to the disrupted organization of intrahemispheric networks, leading to a loss of the corresponding functions. By using dynamic framework, our results offer valuable information about the alterations in segregation and integration of spatiotemporal information across networks and illuminate how dysfunction in flexible activity may underlie language deficits in PSA.
Addition of S‐Heterocyclic Carbenes to Fullerenes: Formation and Characterization of Dithiomethano‐Bridged Derivatives
Authors: Kako Masahiro , Arikawa Yuki , Kanzawa Shinji , Yamada Michio , Maeda Yutaka , Furukawa Makoto , Akasaka Takeshi
Published: April 2019

The reactions of novel S‐heterocyclic carbenes (SHCs), which were prepared by the cycloaddition of disilenes and digermenes to CS2, with C60 and Sc3N@Ih‐C80 afforded the corresponding methano‐bridged fullerenes. The [6,6]‐closed and [6,6]‐open structures were characterized for the SHC adducts of C60 and Sc3N@Ih‐C80, respectively. These derivatives exhibited relatively low oxidation potentials, indicative of the electron‐donating effects of the SHC addends. The electronic properties of the SHC derivatives were clarified by the density functional theory calculations.
PD‐(L)1 inhibitors vs. chemotherapy vs. their combination in front‐line treatment for NSCLC: An indirect comparison
Authors: Liang Hengrui , Liu Zhichao , Cai Xiuyu , Pan Zhenkui , Chen Difei , Li Caichen , Chen Yingying , He Jianxing , Liang Wenhua
Published: April 2019

We comprehensively compared the therapeutic effects and safety of PD‐1/L1 antibodies (I), chemotherapy (C) or their combination (I + C) as first‐line treatments for advanced NSCLC. Online databases were searched to identify RCTs. Survival outcomes and safety events were pooled by indirect treatment comparison. Main subgroup analyses were conducted according to PD‐L1 expression. A total of 11 RCTs involving 6,731 patients were included. Overall, PD‐1/L1 inhibitors showed no difference to chemotherapy in PFS (HR 0.90, 0.65–1.24) and OS (HR 0.84, 0.64–1.09), while I + C was superior to chemotherapy both in PFS (HR 0.64, 0.58–0.71) and OS (HR 0.74, 0.62–0.89). I + C also showed advantages over PD‐1/L1 in PFS (HR 0.71, 0.51–0.99) but not OS (HR 0.88, 0.64–1.22). In the PD‐L1 < 1% subgroup, I + C was beneficial both in OS (HR 0.78, 0.67–0.90) and PFS (HR 0.72, 0.65–0.80) than chemotherapy. In PD‐L1 ≥ 50% population, PD‐1/L1 had longer OS than chemotherapy (HR 0.71, 0.60–0.84); I + C also had longer OS (HR 0.61, 0.49–0.77) and PFS (HR 0.41,0.34–0.49) than chemotherapy. In indirect analysis (PD‐L1 ≥ 50%), I + C was superior to PD‐1/L1 in terms of PFS (HR 0.54, 0.35–0.82), but not OS (HR 0.86, 0.65–1.14). Both treatment‐related and immune‐mediated adverse events occurred most frequently in the combination therapy group. We suggest that a combination regimen is preferable as first‐line treatment for NSCLC patients with different PD‐L1 expression, in the meanwhile, in cautious of side effects.
Brightness preserving optimized weighted bi‐histogram equalization algorithm and its application to MR brain image segmentation
Authors: Veluchamy Magudeeswaran , Mayathevar Krishnamurthy , Subramani Bharath
Published: April 2019

Medical image segmentation is crucial for neuroscience research and computer‐aided diagnosis. However, intensity inhomogeneity and existence of noise in magnetic resonance images lead to incorrect segmentation. In this article, an effective method called enhanced fuzzy level set algorithm is presented to segment the white matter, gray matter, and cerebrospinal fluid automatically in contrast‐enhanced brain images. In this method, first, exposure threshold is computed to divide the input histogram into two sub‐histograms of different gray levels. The input histogram is clipped using a mean gray level to control the excessive enhancement rate. Then, these two sub‐histograms are modified and equalized independently to get a better contrast enhanced image. Finally, an enhanced fuzzy level set algorithm is employed to facilitate image segmentation. The extensive experimental results proved the outstanding performance of the proposed algorithm compared with other existing methods. The results conform its effectiveness for MR brain image segmentation.
miR‐146a‐5p enhances hepatitis B virus replication through autophagy to promote aggravation of chronic hepatitis B
Authors: Fu Lei , Fu Xiaoyu , Mo Juan , Li Xiaomei , Li Ronghua , Peng Shifang
Published: April 2019

The objective of this study was to investigate the mechanism by which miR‐146a‐5p mediated autophagy and hepatitis B virus (HBV) replication. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to determine the mRNA expression levels of miR‐146a‐5p and X‐linked inhibitor of apoptosis (XIAP) and HBV DNA and RNA. The protein expression levels of XIAP, IκB‐α, murine double minute 2 oncoprotein (MDM2) and p53, the phosphorylation of p65, and the conversion of light chain 3 (LC3)‐I to LC3‐II were detected by Western blotting. The expression levels of XIAP, HBV‐related pro‐inflammatory cytokines, and serum markers were detected by enzyme‐linked immunosorbent assay (ELISA). miR‐146a‐5p was highly expressed in patients with chronic hepatitis B (CHB) and HBV‐expressing hepatocytes. HBV core protein (HBc) and HBV X protein (HBx) were responsible for its effects on miR‐146a‐5p expression through the nuclear factor‐κB pathway. Furthermore, the miR‐146a‐5p inhibitor suppressed autophagic response and HBV replication as well as MDM2/p53 expression. Luciferase reporter assay confirmed that XIAP was a direct target of miR‐146a‐5p. We therefore demonstrated that miR‐146a‐5p mediated positive feedback loop by regulating autophagy‐induced HBV replication via targeting the XIAP‐mediated MDM2/p53 axis. © 2019 IUBMB Life, 71(9):1336–1346, 2019
Moderate activation of Wnt/β‐catenin signaling promotes the survival of rat nucleus pulposus cells via regulating apoptosis, autophagy, and senescence
Authors: Li Zhiliang , Chen Songfeng , Chen Sheng , Huang Donghua , Ma Kaige , Shao Zengwu
Published: April 2019

This study aimed to investigate the specific role of Wnt/β‐catenin signaling in compression‐induced apoptosis, autophagy, and senescence in rat nucleus pulposus (NP) cells. Initially, the cells underwent various periods of exposure to 1.0 MPa compression. Wnt/β‐catenin signaling associated molecules were assessed in detail, and then 0, 24 and 48 hours exposure periods were selected. The cells were then divided into control, Wnt/β‐catenin inhibitor (IWP‐2), Wnt/β‐catenin activator (LiCl), and β‐catenin overexpression groups. After 0, 24, and 48 hours of compression, apoptosis, autophagy, and senescence were evaluated by Western blot analysis and real‐time polymerase chain reaction and were visually observed by Hoechst33258, monodansylcadaverine, and SA‐β‐gal stainings, respectively. Additionally, the regulatory effect of Wnt/β‐catenin signaling on cell morphology, viability, cell cycle, death ratio, and ultrastructure was detected to thoroughly evaluate the survival capacity of NP cells. The results established that compression elicited a time‐dependent activation of Wnt/β‐catenin signaling. The IWP‐2 treatment decreased cell survival rate, which corresponded to downregulation of autophagy as well as increases in apoptosis and senescence. LiCl treatment enabled more efficient of cell survival accompanied by increased autophagy and downregulated apoptosis and senescence; however, in contrast to LiCl, overexpression of β‐catenin aggravated compression‐induced NP cells death. In conclusion, moderate activation of Wnt/β‐catenin signaling enables more efficient of NP cells survival via downregulation of apoptosis, senescence, and upregulation of autophagy, and overactivation of Wnt/β‐catenin signaling achieved the opposite effect. Treatment strategies that aim to regulate Wnt/β‐catenin signaling might be a novel target for improving compression‐induced NP cells death and potential treatment of intervertebral disc degeneration.
Silencing fibroblast growth factor 7 inhibits krypton laser‐induced choroidal neovascularization in a rat model
Authors: Zhang Chao , Han Mei , Wu Shuai
Published: April 2019

Choroidal neovascularization (CNV), a characteristic of age‐related macular degeneration, is an underlying cause of severe vision loss among elderly patients. Fibroblast growth factor (FGF) is suggested to exert an important role in the pathogenesis of CNV. However, the molecular mechanisms governing this event are not fully elucidated. Herein, we identified the potential role of FGF7 in CNV. To examine the roles of FGF7 in the progression of CNV, rat CNV models were established and treated with small interfering RNA (siRNA) against FGF7 or FGF7 overexpression, followed by identification of expression of FGF7 in the CNV modeled rats. Next, proliferation and migration, and in vitro tube formation of human umbilical vein endothelial cells, as well as expression of vascular endothelial growth factor (VEGF) and transforming growth factor‐beta 2 (TGF‐β2) were evaluated. CNV led to upregulated FGF7 expression. Cells in the presence of FGF7 siRNA showed suppressed proliferation, migration, and tube formation, along with downregulated VEGF and TGF‐β2 expression. Taken together, functional suppression of FGF7 inhibited the onset of CNV, ultimately highlighting a novel therapeutic target for suppressing CNV progression.
Activation of spinal Extacellular Signal‐Regulated Kinases and c‐jun N‐terminal kinase signaling pathways contributes to morphine‐induced acute and chronic hyperalgesia in mice
Authors: Ruan Jia‐Ping , Chen Ling , Ma Zheng‐liang
Published: April 2019

Background

This study investigated the activation of mitogen‐activated protein kinases in the spinal dorsal horn to explore the mechanisms underlying morphine‐induced acute and chronic hyperalgesia in mice.

Methods

Male adult mice were given a single subcutaneous injection (SC) of morphine (1 μg/kg) or twice‐daily administration of morphine (10 mg/kg/day) for 8 days. Thermal hyperalgesia and mechanical allodynia were assessed using the radiant heat and von Frey filament test. Levels of phospho (p)‐extracellular signal–regulated kinases (p‐ERK), p‐c‐Jun N‐terminal kinase (p‐JNK), p‐p38, p‐PKCγ, N‐methyl‐d‐aspartate receptor (NMDAr), and c‐Fos protein in the spinal dorsal horn were examined by Western blot assays.

Results

A single ultra‐low dose or repeated administration of morphine induced hyperalgesia in mice and caused a significant increase in the levels of p‐ERK and p‐JNK, but not p‐p38, in the spinal dorsal horn. The level of c‐Fos protein was significantly elevated following administration of morphine. The protein levels of p‐PKCγ and NMDAr subunits (NR2B and NR2A) were also altered. Pretreatment with the NMDAr antagonist MK‐801 or the protein kinase C (PKC) inhibitor calphostin C (CC) suppressed the morphine‐induced increase in p‐ERK, p‐JNK, and c‐Fos. Administration of MK‐801 and CC also relieved morphine‐induced hyperalgesia.

Conclusion

These findings suggest that activation of the spinal ERK and JNK signaling pathways contribute to morphine‐induced acute and chronic hyperalgesia in mice.
Hydrogen splitting by pyramidalized 13–15 donor–acceptor cryptands: A computational study
Authors: El‐Hamdi Majid , Timoshkin Alexey Y.
Published: April 2019

A series of new donor–acceptor cryptands, where pyramidalized donor (azaadamantane) and acceptor (bora/ala/adamantane) molecules are spatially oriented toward each other and linked via aromatic spacer, are constructed and computationally studied at M06‐2X and ωB97X‐D levels of theory. Kinetic stability of the perfluorinated bora‐ and ala‐adamantane with respect to F migration to group 13 element is demonstrated. The effectiveness of the constructed cryptands, featuring pyramidalized perfluorinated acceptor moieties, in the heterolytic splitting of molecular hydrogen is predicted. Hydrogen splitting is highly exothermic and exergonic and is accompanied by small activation barriers. The most promising candidates for the experimental studies are identified. © 2019 Wiley Periodicals, Inc.
Exploring the “like” in the psychological interaction of users on fan community: A netnography analysis
Authors: Wang Yi‐Sheng
Published: April 2019

Little is known about the psychology behind fans joining fan community pages in a blog context; the factors driving them to like, share, and comment on posts on fan community pages; or the manner in which fans experience and interact with such pages. These topics were not given sufficient explanation in past research. This study aimed to explore the special situations and unique online experiences that fans community experience in a blog context. A netnography analysis was conducted through online interviews and field observations. Three phases of contextual experiences were determined, including observing and collecting data online, active participation, and emergent design. The contribution of this study is its establishment of the fan community experience model, which is a substantive theory, and its suggestion of nine propositions that can provide insights into fan community page interaction and experience models.
Understanding the impact of an after‐school music program with engaged underserved youth
Authors: Sheltzer Joshua M. , Consoli Andrés J.
Published: April 2019

Aims

This study aims to document and understand the benefits of underserved youths' successful involvement in an after‐school music program (ASMP).

Methods

The contents of semi‐structured, individual interviews with 11 alumni and five staff members of an ASMP were coded and analyzed using inductive Thematic Analysis.

Results

Alumni identified several positive program characteristics as most influential (e.g., consistency, opportunity, exposure), and described the program's favorable impact at a personal (e.g., identity development), relational (e.g., improving social skills), and musical level (e.g., acquiring performance skills). Staff members identified similar program characteristics as crucial for the success of the program and singled out their personal, relational, and social motivations as important dimensions that bring about the program's impact.

Conclusions

The study highlights the value of musical experiences and after‐school resources for a group of underserved youth who would otherwise not be exposed to them due to socioeconomic barriers and inequities in opportunities.
The effect of diabetes mellitus on pharmacokinetics, pharmacodynamics and adverse drug reactions of anticancer drugs
Authors: Mashayekhi‐Sardoo Habibeh , Mohammadpour Amir Hooshang , Nomani Homa , Sahebkar Amirhossein
Published: April 2019

Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negatively impact multiple diverse entities including nerves and vascular structures, insulin‐like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP450, Mdr
1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy‐dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.
Retracted: Curcumin ameliorates atherosclerosis through upregulation of miR‐126
Authors: Li Yezhou , Tian Leilei , Sun Dajun , Yin Dexin
Published: April 2019

The potential usage of curcumin in diverse human diseases has been widely studied, including arteriosclerosis (AS). This study focused on investigating the relationship between curcumin and AS‐associated microRNA, which may provide a better understanding of curcumin in a different mechanism. Human microvascular endothelial HMEC‐1 cells were treated by curcumin alone or oxidized low‐density lipoprotein (ox‐LDL) plus curcumin, after which the following parameters were analyzed: cell viability, migration, and the expression of AS‐associated factors. The regulatory effects of curcumin on miR‐126 and signaling pathways involved in AS were then studied. Further, an animal model of AS was stimulated by feeding rabbits with 1% cholesterol diet. The effects of curcumin on the animal model were explored. We found that curcumin treatment significantly reduced HMEC‐1 cells viability, migration, and the protein levels of MMP‐2, MMP‐9, and vascular endothelial growth factor (VEGF) in the presence or absence of ox‐LDL. Meanwhile, the expression of VEGFR1 and VEGFR2 was repressed by curcumin. miR‐126 was upregulated by curcumin. The abovementioned effects of curcumin on HMEC‐1 cells were all attenuated when miR‐126 was silenced. And also, VEGF was a target gene of miR‐126, and curcumin could inhibit the activation of PI3K/AKT JAK2/STAT5 signaling pathways via miR‐126. The effects of curcumin and its regulation on miR‐126 and VEGF were confirmed in the animal model of AS. To sum up, curcumin exerted potent anti‐AS property possibly via upregulating miR‐126 and thereby inhibiting PI3K/AKT and JAK2/STAT5 signaling pathways.
Management of chylous ascites following pancreaticobiliary surgery
Authors: Singh Harjeet , Pandit Narendra , Krishnamurthy Gautham , Gupta Rajesh , Verma Ganga R , Singh Rajinder
Published: April 2019

Background

Chyle leak is an uncommon form of ascites occurring due to the accumulation of lipid‐rich lymph into the peritoneal cavity. Traumatic injury to the lymphatic system due to pancreaticobiliary surgery can lead to this phenomenon.

Method

We retrospectively evaluated the data of 159 patients of pancreticobiliary surgery from January 2012 to December 2016. Five patients (5/137, 3.6%) sustained a chylous leak following pancreaticoduodenectomy and one patient (1/22, 4.5%) sustained a chylous leak following Roux‐en‐Y hepaticojejunostomy for postcholecystectomy biliary stricture.

Results

Average daily output was 441 mL (range: 150–800 mL/day), and total duration of output was 16.5 days (range: 4–35 days). Mean hospital stay increased to 19.1 days (range: 10–40 days). All the patients were successfully managed conservatively with a combination of customized enteral feeds, supplemental parenteral nutrition, and octreotide. One patient required additional percutaneous drainage.

Conclusion

Chyle leak can be successfully treated with conservative management but at the cost of increased hospital stay.
Current applications of fecal microbiota transplantation in intestinal disorders
Authors: Hsu Wen‐Hung , Wang Jaw‐Yuan , Kuo Chao‐Hung
Published: April 2019

Fecal microbiota transplantation (FMT) had been an ancient remedy for severe illness several centuries ago. Under modern medical analysis and evidence‐based research, it has been proved as an alternative treatment for recurrent Clostridium difficile infection and recent randomized control study also showed that FMT could be an adjuvant treatment for inflammatory bowel disease. As we get a better understanding of the relationship between gut microbiota and systemic disease, FMT became a potential treatment to explore. This article summarized procedures such as donor selection, fecal material preparation, transplantation delivery methods, and adverse events. We also review the present evidence about FMT in clinical practice.
Alleviation of hypoxia by biologically generated mixing in a stratified water column
Authors: Houghton Isabel A. , Dabiri John O.
Published: April 2019

Daily vertical migrations of zooplankton have been shown to affect nutrient distributions and dissolved gas concentrations in lakes and oceans via active internal transport and metabolic consumption. Additionally, mixing generated by these migrations has been shown to have the capacity to alter the physical structure of a water column, with potential further implications for its biogeochemical structure. In this work, we use laboratory experiments to investigate the importance of biologically generated mixing relative to other processes in determining the biogeochemical structure of a water column inhabited by migrating zooplankton. Specifically, we consider oxygen, a highly ecologically relevant scalar, and the competition between metabolic consumption and biogenic mixing in a stably stratified water column with a hypoxic layer. Using laboratory experiments and a one‐dimensional model informed by those measurements, we illustrate the potential for migrating animals to alleviate hypoxia, introducing complex feedbacks between the presence of animals and the biogeochemical state of their surroundings. Furthermore, we demonstrate the feasibility of oxygen as a potential indicator of biogenic mixing for future in situ investigations given its low diffusivity and higher signal‐to‐noise ratio.
Corrosion of carbon steel underneath a lead/potassium chloride salt mixture
Authors: Talus Annika , Kinnunen Hanna , Norling Rikard , Enestam Sonja
Published: April 2019

High amounts of lead in waste/recycled wood fuel are known to be a contributing factor to the increased corrosion often related to this type of fuel. In combination with potassium, usually present in the fuel, low‐melting point salt mixtures between lead chloride (PbCl
2) and potassium chloride (KCl) are expected to form. The purpose of this study is to investigate reactions in the mixed salt of PbCl
2 and KCl and its interactions with carbon steel P265GH and its oxide. Laboratory exposures were performed in an isothermal tube furnace with a salt mixture of PbCl
2/KCl (50/50 mol%) put on steel samples. The test duration was 24 hr at either 300°C or 340°C in an atmosphere of 100 ppm HCl and 20 vol% H
2O in synthetic air. After exposure, the salt mixture consists of distinct areas of KCl and PbCl
2 but also the compounds K
2PbCl
4 and KPb
2Cl
5. A general observation is that the oxide thickness increases with temperature and that areas with Pb/K‐mixed salt are frequently found in close connection to more corroded areas. Often the more lead‐rich phase KPb
2Cl
5 is located closest to the corrosion product indicating its importance for the corrosion.
Dynamic‐flip‐angle ECG‐gating with nuisance signal regression improves resting‐state BOLD functional connectivity mapping by reducing cardiogenic noise
Authors: Hu Chenxi , Tokoglu Fuyuze , Scheinost Dustin , Qiu Maolin , Shen Xilin , Peters Dana C. , Galiana Gigi , Constable R. Todd
Published: April 2019

Purpose

To investigate an ECG‐gated dynamic‐flip‐angle BOLD sequence with improved robustness against cardiogenic noise in resting‐state fMRI.

Methods

ECG‐gating minimizes the cardiogenic noise but introduces T1‐dependent signal variation, which is minimized by combination of a dynamic‐flip‐angle technique and retrospective nuisance signal regression (NSR) using signals of white matter, CSF, and global average. The technique was studied with simulations in a wide range of T1 and B1 fields and phantom imaging with pre‐programmed TR variations. Resting‐state fMRI of 20 healthy subjects was acquired with non‐gated BOLD (NG), ECG‐gated constant‐flip‐angle BOLD (GCFA), ECG‐gated BOLD with retrospective T1‐correction (GRC), and ECG‐gated dynamic‐flip‐angle BOLD (GDFA), all processed by the same NSR method. GDFA was compared to alternative methods over temporal SNR (tSNR), seed‐based connectivity, and whole‐brain voxelwise connectivity based on intrinsic connectivity distribution (ICD). A previous large‐cohort data set (N = 100) was used as a connectivity gold standard.

Results

Simulations and phantom imaging show substantial reduction of the T1‐dependent signal variation with GDFA alone, and further reduction with NSR. The resting‐state study shows improved tSNR in the basal brain, comparing GDFA to NG, after both processed with NSR. Furthermore, GDFA significantly improved subcortical–subcortical and cortical–subcortical connectivity for several representative seeds and significantly improved ICD in the brainstem, thalamus, striatum, and prefrontal cortex, compared to the other 3 approaches.

Conclusion

GDFA with NSR improves mapping of the resting‐state functional connectivity of the basal–brain regions by reducing cardiogenic noise.