bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial Enzymes for Diels‐Alder Reactions
Authors: Ghattas Wadih , Mahy Jean‐Pierre , Réglier Marius , Simaan A. Jalila 
Published: September 2020

AbstractThe Diels‐Alder (DA) reaction is a cycloaddition of a conjugated diene and an alkene (dienophile) leading to the formation of a cyclohexene derivative through a concerted mechanism. As DA reactions generally proceed with a high degree of regio‐ and stereoselectivity, they are widely used in synthetic organic chemistry. Considering eco‐conscious public and governmental movements, efforts are now directed towards the development of synthetic processes that meet environmental concerns. Artificial enzymes, which can be developed to catalyze abiotic reactions, appear to be important synthetic tools in the synthetic biology field. This review describes the different strategies used to develop protein‐based artificial enzymes for DA reactions, including for in cellulo approaches.
Probing the Conformation States of Neurotensin Receptor 1 Variants by NMR Site‐Directed Methyl Labeling
Authors: Goba Inguna , Goricanec David , Schum Dominik , Hillenbrand Matthias , Plückthun Andreas , Hagn Franz 
Published: September 2020

AbstractG protein‐coupled receptors (GPCRs) are key players in mediating signal transduction across the cell membrane. However, due to their intrinsic instability, many GPCRs are not suitable for structural investigations. Various approaches have been developed in recent years to remedy this situation, ranging from the use of more native membrane mimetics to protein‐stabilization methods. The latter approach typically results in GPCRs that contain various numbers of mutations. However, probing the functionality of such variants by in vitro and in vivo assays is often time consuming. In addition, to validate the suitability of such GPCRs for structural investigations, an assessment of their conformation state is required. NMR spectroscopy has been proven to be suitable to probe the conformation state of GPCRs in solution. Here, by using chemical labeling with an isotope‐labeled methyl probe, we show that the activity and the conformation state of stabilized neurotensin receptor 1 variants obtained from directed evolution can be efficiently assayed in 2D NMR experiments. This strategy enables the quantification of the active and inactive conformation states and the derivation of an estimation of the basal as well as agonist‐induced activity of the receptor. Furthermore, this assay can be used as a readout when re‐introducing agonist‐dependent signaling into a highly stabilized, and thus rigidified, receptor by mutagenesis. This approach will be useful in cases where low production yields do not permit the addition of labeled compounds to the growth medium and where 1D NMR spectra of selectively 19F‐labeled receptors are not sufficient to resolve signal overlap for a more detailed analysis.
Outcomes of retrograde chronic total occlusion percutaneous coronary intervention: A report from the OPEN‐CTO registry
Authors: Kalra Sanjog , Doshi Darshan , Sapontis James , Kosmidou Ioanna , Kirtane Ajay J. , Moses Jeffrey W. , Riley Robert F. , Jones Philip , Nicholson William J. , Salisbury Adam C. , Lombardi William L. , McCabe James M. , Pershad Ashish , Hirai Taishi , Hakemi Emad , Russo Juan J. , Prasad Megha , Ahmad Yousif , Hatem Raja , Gkargkoulas Fotis , Spertus John A. , Wyman R. Michael , Jaffer Farouc , Spaedy Anthony , Cook Stephen , Marso Steven P. , Nugent Karen , Federici Robert , Yeh Robert W. , Leon Martin B. , Stone Gregg W. , Ali Ziad A. , Parikh Manish A. , Maehara Akiko , Cohen David J. , Batres Candido , Grantham J. Aaron , Karmpaliotis Dimitri 
Published: September 2020

AbstractObjectivesWe sought to assess in‐hospital and long‐term outcomes of retrograde compared with antegrade‐only percutaneous coronary intervention for chronic total occlusion (CTO PCI).BackgroundProcedural and clinical outcomes following retrograde compared with antegrade‐only CTO PCI remain unknown.MethodsUsing the core‐lab adjudicated OPEN‐CTO registry, we compared the outcomes of retrograde to antegrade‐only CTO PCI. Primary endpoints included were in‐hospital major adverse cardiac and cerebrovascular events (MACCE) (all‐cause death, stroke, myocardial infarction [MI], emergency cardiac surgery, or clinically significant perforation) and MACCE at 1‐year (all‐cause death, MI, stroke, target lesion revascularization, or target vessel reocclusion).ResultsAmong 885 single CTO procedures from the OPEN‐CTO registry, 454 were retrograde and 431 were antegrade‐only. Lesion complexity was higher (J‐CTO score: 2.7 vs. 1.9; p < .001) and technical success lower (82.4 vs. 94.2%; p < .001) in retrograde compared with antegrade‐only procedures. All‐cause death was higher in the retrograde group in‐hospital (2 vs. 0%; p = .003), but not at 1‐year (4.9 vs. 3.3%; p = .29). Compared with antegrade‐only procedures, in‐hospital MACCE rates (composite of all‐cause death, stroke, MI, emergency cardiac surgery, and clinically significant perforation) were higher in the retrograde group (10.8 vs. 3.3%; p < .001) and at 1‐year (19.5 vs. 13.9%; p = .03). In sensitivity analyses landmarked at discharge, there was no difference in MACCE rates at 1 year following retrograde versus antegrade‐only CTO PCI. Improvements in Seattle Angina Questionnaire Quality of Life scores at 1‐year were similar between the retrograde and antegrade‐only groups (29.9 vs 30.4; p = .58).ConclusionsIn the OPEN‐CTO registry, retrograde CTO procedures were associated with higher rates of in‐hospital MACCE compared with antegrade‐only; however, post‐discharge outcomes, including quality of life improvements, were similar between technical modalities.
Rosai Dorfman Disease —A rare case of cervical lymphadenopathy
Authors: Amiji Insiyah , Mohammed Ummulkheir , Salum Hajaj , Karugaba Emilia , Mkeni Luka , Mumburi Livin , Msafiri Anna , Massawe Higgins 
Published: September 2020

AbstractRosai Dorfman disease is a rare cause of sinus histiocytosis with massive lymphadenopathy. In developing countries, it often mimics some infectious diseases and malignancies and is often mismanaged. A high index of suspicion is necessary for its diagnosis. It is seldom life threatening therefore observation is currently the best advocated approach for its management.
Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis**
Authors: Buchter Valentin , Ong Yih Ching , Mouvet François , Ladaycia Abdallah , Lepeltier Elise , Rothlisberger Ursula , Keiser Jennifer , Gasser Gilles 
Published: September 2020

AbstractSchistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene‐containing (Fc‐CH2‐OXA), ruthenocene‐containing (Rc‐CH2‐OXA) and benzene‐containing (Ph‐CH2‐OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both Schistosoma mansoni larvae and adult worms and S. haematobium adult worms, and were also active in vivo against adult S. mansoni. Encouraged by these promising results, we conducted additional in‐depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on S. haematobium and juvenile S. mansoni, computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on S. haematobium. This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.
Solid‐State Properties of Hexaazatriphenylenehexacarbonitrile HAT(CN)6.− Radical Anions in Crystalline Salts Containing Cryptand(M+) and Crystal Violet Cations
Authors: Konarev Dmitri V. , Khasanov Salavat S. , Kuzmin Alexey V. , Mikhailenko Maxim V. , Otsuka Akihiro , Yamochi Hideki , Kitagawa Hiroshi , Lyubovskaya Rimma N. 
Published: September 2020

AbstractCrystalline {Cryptand[2.2.2](Na+)}{HAT(CN)6.−}⋅0.5C6H4Cl2 (1), {Cryptand[2.2.2](K+)}{HAT(CN)6.−} (2), (CV+){HAT(CN)6.−} (3), and (CV+){HAT(CN)6.−}⋅2C6H4Cl2 (4) salts (where CV+ is the crystal violet cation) containing hexaazatriphenylenehexacarbonitrile radical anions have been obtained. The solid‐state molecular structure as well as the optical and magnetic properties of HAT(CN)6.− are studied. The formation of HAT(CN)6.− in 1–4 leads to the appearance of new bands in the visible range, at 694 and 740 nm. The HAT(CN)6.− radical anions have spin state S=1/2 and are packed in one‐dimensional stacks containing the {HAT(CN)6.−}2 dimers alternated with weaker interacting pairs of HAT(CN)6.− in 1 and nearly isolated {HAT(CN)6.−}2 dimers in 2. The {HAT(CN)6.−}2 dimers are diamagnetic in 1 but they effectively mediate one‐dimensional antiferromagnetic coupling of spins within the stacks with moderate exchange interaction of J/kB = −80 K. The behaviour of salt 2 is described by a singlet–triplet model for the {HAT(CN)6.−}2 dimers with an energy gap of 434(±7) K. Magnetic behaviour of both salts agree well with the data of extended Hückel calculations. Salts 3 and 4 contain isolated stacks of alternated HAT(CN)6.− and CV+ ions, and in this case, nearly paramagnetic behaviour is observed with Weiss temperatures of −1 and −7 K, respectively. Narrow Lorentzian EPR signals with g = 2.0033–2.0039 were found for the HAT(CN)6.− radical anions in 1 and 4 but in solution g‐factor shifts to 1.9964. The electronic structure of HAT(CN)6.− is analysed based on X‐ray diffraction data for 2, showing a Jahn–Teller distortion of the radical anion that reduces the symmetry from D3h to Cs and splits the initially degenerated LUMOs.
Catalytic Processes for the Neutralization of Sulfur Mustard
Authors: Oheix Emmanuel , Gravel Edmond , Doris Eric 
Published: September 2020

AbstractResearch on the decontamination of the chemical warfare agent sulfur mustard pursues several objectives that include the neutralization of spared ammunition, the cleaning of affected areas, and also the development of protective equipment or tools. Neutralization of vesicant sulfur mustard involves different chemical routes such as hydrolysis, dehydrochlorination, oxidation, or complete mineralization. This review weighs the pros and cons associated with the different systems reported in the literature, with an emphasis on catalytic procedures, to selectively convert sulfur mustard or its simulants into harmless products.
PROTOCOL: Psychosocial, pharmacological and legal interventions for improving the psychosocial outcomes of children with substance misusing parents
Authors: Eggins Elizabeth , Dawe Sharon , Wilson David B. , Chandler‐Mather Ned , Betts Joseph 
Published: September 2020

AbstractThis review aims to first enhance and update existing reviews by comprehensively synthesising the full array of psychosocial, pharmacological and legal interventions that aim to improve the psychosocial outcomes of children with substance misusing parents. Second, the review aims to use network meta‐analysis to integrate and examine the comparative impact of these interventions. Specifically, the review will address the following research questions: (1) What is the comparative impact of psychosocial, pharmacological, and legal interventions for improving the psychosocial outcomes of children with substance misusing parents? (2) Does the impact of interventions vary according to the child developmental period (e.g., infancy, early childhood, adolescence) or the type of (a) outcome measure; (b) substance misuse; (c) practitioner implementing the intervention; or (d) intervention setting? (3) Does the impact of interventions vary by the country of implementation?
Luminescent Sulfur Quantum Dots: Synthesis, Properties and Potential Applications
Authors: Gao Pengxiang , Wang Guan , Zhou Li 
Published: September 2020

AbstractSulfur quantum dots (SQDs) represent a new class of luminescent nanomaterials. They have shown great potential in numerous application fields including sensing, cell imaging, photocatalysis, light emitting diodes and polymer nanocomposites, due to their unique composition, favorable optical properties, low toxicity, fine processability and low cost. This Minireview summarizes the recent research progress on the synthesis, characterization, properties and applications of SQDs, especially those synthesized from elemental sulfur. Critical yet unsolved issues in the synthesis and applications of SQDs are also discussed. In addition, an outlook for future research trends of SQDs is presented.
A Protocol to Study Mitochondrial Function in Human Neural Progenitors and iPSC‐Derived Astrocytes
Authors: Assis‐de‐Lemos Gabriela , Ledur Pítia Flores , Karmirian Karina , Rehen Stevens Kastrup , Galina Antonio 
Published: September 2020

AbstractMitochondrial dysfunction is a central component in the pathophysiology of multiple neuropsychiatric and degenerative disorders. Evaluating mitochondrial function in human‐derived neural cells can help characterize dysregulation in oxidative metabolism associated with the onset of brain disorders, and may also help define targeted therapies. Astrocytes play a number of different key roles in the brain, being implicated in neurogenesis, synaptogenesis, blood‐brain‐barrier permeability, and homeostasis, and, consequently, the malfunctioning of astrocytes is related to many neuropathologies. Here we describe protocols for generating induced pluripotent stem cell (iPSC)−derived astrocytes and evaluating multiple aspects of mitochondrial function. We use a high‐resolution respirometry assay that measures real‐time variations in mitochondrial oxygen flow, allowing the evaluation of cellular respiration in the context of an intact intracellular microenvironment, something not possible with permeabilized cells or isolated mitochondria, where the cellular microenvironment is disrupted. Given that an impairment in the mitochondrial regulation of intracellular calcium homeostasis is involved in many pathologic stresses, we also describe a protocol to evaluate mitochondrial calcium dynamics in human neural cells, by fluorimetry. Lastly, we outline a mitochondrial function assay that allows for the measurement of the enzymatic activity of mitochondrial hexokinase (mt‐HK), an enzyme that is functionally coupled to oxidative phosphorylation and is involved in redox homeostasis, particularly in the brain. In all, these protocols allow a detailed characterization of mitochondrial function in human neural cells. High‐resolution respirometry, calcium dynamics, and mt‐HK activity assays provide data regarding the functional status of mitochondria, which may reflect mitochondrial stress or dysfunction. © 2020 Wiley Periodicals LLC.Basic Protocol 1: Generation of iPSC‐derived human astrocytesBasic Protocol 2: Measuring real‐time oxygen flux in human iPSC‐derived astrocytes using a high‐resolution OROBOROS Oxygraph 2k (O2k)Basic Protocol 3: Measuring mitochondrial calcium dynamics fluorometrically in permeabilized human neural cellsBasic Protocol 4: Measuring OXPHOS‐dependent activity of mitochondrial hexokinase in permeabilized human neural cells using a spectrophotometer
Lignin Intermediates on Palladium: Insights into Keto‐Enol Tautomerization from Theoretical Modelling
Authors: de Andrade Ageo Meier , Srifa Pemikar , Broqvist Peter , Hermansson Kersti 
Published: September 2020

AbstractIt has been suggested in the literature that keto‐to‐enol tautomerization plays a vital role for lignin fragmentation under mild conditions. On the other hand, previous modelling has shown that the adsorbed keto form is more stable than enol on the Pd(111) catalyst. The current density functional theory study of lignin model molecules shows that, in the gas‐phase, keto is more stable than enol, but on the Pd surface, we find enol conformers that are at least as stable as keto. This supports the experimental result that the favourable reaction pathway for lignin depolymerization involves keto‐enol tautomerization. An energy decomposition analysis gives insights concerning the origin of the fine energy balance between the keto and enol forms, where the molecule–surface interaction (−7 eV) and the molecular strain energy (+3 eV) are the main contributors to the adsorption energy.
NbOPO4Supported Rh Nanoparticles with Strong Metal−Support Interactions for Selective CO2Hydrogenation
Authors: Wang Lingxiang , Fang Wei , Wang Liang , Xiao Feng‐Shou 
Published: September 2020

AbstractStrong metal−support interactions (SMSI) could improve the performance of nanoparticle catalysts through the electronic and geometric modulation of the reducible metal oxide supports. Here, SMSI is demonstrated to occur for catalysts with non‐oxide carrier, such as NbOPO4‐supported Rh nanoparticles, under reduction treatment at low temperature. During CO2hydrogenation, this Rh/NbOPO4catalyst with SMSI exhibits impressive CO selectivity at high CO2conversion in a wide temperature range with hindered methanation. For example, over 98.9 % CO selectivity was obtained with 39.9 % CO2conversion at 500 °C. Mechanism investigations demonstrate that the SMSI results in the formation of a metal−support interface with weaker CO adsorption than the metallic Rh sites, thus accelerating the CO desorption, which hinders deep hydrogenation. Rh nanoparticles with small diameter of about 1.1 nm is sinter‐resistant with unchanged performance during a long‐period test. This work might extend the investigation of SMSI from oxides to phosphate supports, which helps optimizing the selectivity and stability of metal nanoparticle catalysts.
Natural HDAC‐1/8 inhibitor baicalein exerts therapeutic effect in CBF‐AML
Authors: Yu Xiaoxuan , Li Hui , Hu Po , Qing Yingjie , Wang Xiangyuan , Zhu Mengyuan , Wang Hongzheng , Wang Zhanyu , Xu Jingyan , Guo Qinglong , Hui Hui 
Published: September 2020

AbstractBackgroundAlthough targeting histone deacetylases (HDACs) may be an effective strategy for core binding factor‐acute myeloid leukemia (CBF‐AML) harboring t(8;21) or inv(16), HDAC inhibitors are reported to be limited by drug‐resistant characteristic. Our purpose is to evaluate the anti‐leukemia effects of Baicalein on CBF‐AML and clarify its underlying mechanism.MethodsEnzyme activity assay was used to measure the activity inhibition of HDACs. Rhodamine123 and RT‐qPCR were employed to evaluate the distribution of drugs and the change of ATP‐binding cassette (ABC) transporter genes. CCK8, Annexin V/PI, and FACS staining certified the effects of Baicalein on cell growth, apoptosis, and differentiation. Duolink and IP assay assessed the interaction between HDAC‐1 and ubiquitin, HSP90 and AML1‐ETO, and Ac‐p53 and CBFβ‐MYH11. AML cell lines and primary AML cells‐bearing NOD/SCID mice models were used to evaluate the anti‐leukemic efficiency and potential mechanism of Baicalein in vivo.ResultsBaicalein showed HDAC‐1/8 inhibition to trigger growth suppression and differentiation induction of AML cell lines and primary AML cells. Although the inhibitory action on HDAC‐1 was mild, Baicalein could induce the degradation of HDAC‐1 via ubiquitin proteasome pathway, thereby upregulating the acetylation of Histone H3 without promoting ABC transporter genes expression. Meanwhile, Baicalein increased the acetylation of HSP90 and lessened its connection to AML1/ETO, consequently leading to degradation of AML1‐ETO in t(8;21)q(22;22) AML cells. In inv(16) AML cells, Baicalein possessed the capacity of apoptosis induction accompanied with p53‐mediated apoptosis genes expression. Moreover, CBFβ‐MYH11‐bound p53 acetylation was restored via HDAC‐8 inhibition induced by Baicalein contributing the diminishing of survival of CD34+ inv(16) AML cells.ConclusionsThese findings improved the understanding of the epigenetic regulation of Baicalein, and warrant therapeutic potential of Baicalein for CBF‐AML.
A three‐lncRNA signature of pretreatment biopsies predicts pathological response and outcome in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy
Authors: Zhang Chaoqi , Zhang Zhihui , Zhang Guochao , Xue Liyan , Yang Haijun , Luo Yuejun , Zheng Xiaoli , Zhang Yonglei , Yuan Yufen , Lei Ruixue , Yang Zhaoyang , Zheng Bo , Zhang Zhen , Wang Le , Che Yun , Wang Sihui , Wang Feng , Fang Lingling , Zeng Qingpeng , Li Jiagen , Gao Shugeng , Xue Qi , Sun Nan , He Jie 
Published: September 2020

AbstractBackgroundCurrent strategies are insufficient to predict pathologically complete response (pCR) for esophageal squamous cell carcinomas (ESCCs) before treatment. Here, we aim to develop a novel long noncoding RNA (lncRNA) signature for pCR and outcome prediction of ESCCs through a multicenter analysis for a Chinese population.MethodsDifferentially expressed lncRNAs (DELs) between pCRs and less than pCR (<pCR) in the pretreated cancer biopsies were identified from 28 cases in Guangzhou cohort and verified from 30 cases in Beijing discovery cohort. Then a prediction model was built through Fisher's linear discriminant analysis (FLDA) of 67 cases in Beijing training cohort. Then an internal cohort and an integrated external cohort (Zhengzhou and Anyang cohorts) were used to validate the predictive accuracy. The prognostic value of this signature was also evaluated.ResultsTwelve DELs were identified from Guangzhou cohort and six lncRNAs were verified. Then, a classifier of three lncRNAs (SCAT1, PRKAG2‐AS1, and FLG‐AS1) was established and achieved a high accuracy with an area under the receiver operating characteristic curve (AUC) of 0.952 in the training cohort, which was well validated in the internal validation cohort and external cohort with the AUCs of 0.856 and 0.817, respectively. Furthermore, the predictive score was identified as the only independent predictor for pCR. Patients with high discriminant score showed a significantly longer overall and relapse‐free survival (P < .05).ConclusionsWe developed the first and applicable three‐lncRNA signature of pCR and outcome prediction, which is robust and reproducible in multicenter cohorts for ESCCs with nCRT.