bluuebunny/crossref_metadata_2025 huggingface dataset:
Separation of Xe from Kr with Record Selectivity and Productivity in Anion‐Pillared Ultramicroporous Materials by Inverse Size‐Sieving
Authors: Wang Qingju , Ke Tian , Yang Lifeng , Zhang Zhaoqiang , Cui Xili , Bao Zongbi , Ren Qilong , Yang Qiwei , Xing Huabin
Published: November 2019

The separation of xenon/krypton (Xe/Kr) mixture is of great importance to industry, but the available porous materials allow the adsorption of both, Xe and Kr only with limited selectivity. Herein we report an anion‐pillared ultramicroporous material NbOFFIVE‐2‐Cu‐i (ZU‐62) with finely tuned pore aperture size and structure flexibility, which for the first time enables an inverse size‐sieving effect in separation along with record Xe/Kr selectivity and ultrahigh Xe capacity. Evidenced by single‐crystal X‐ray diffraction, the rotation of anions and pyridine rings upon contact of larger‐size Xe atoms adapts cavities to the shape/size of Xe and allows strong host‐Xe interaction, while the smaller‐size Kr is excluded. Breakthrough experiments confirmed that ZU‐62 has a real practical potential for producing high‐purity Kr and Xe from air‐separation byproducts, showing record Kr productivity (206 mL g−1) and Xe productivity (42 mL g−1, in desorption) as well as good recyclability.
Eine auf dem Benzophenongerüst basierende Strategie für die Photoschützung der N7‐Position des Guanosins
Authors: Anhäuser Lea , Klöcker Nils , Muttach Fabian , Mäsing Florian , Špaček Petr , Studer Armido , Rentmeister Andrea
Published: November 2019

Die selektive Modifikation von Nukleobasen mit lichtempfindlichen Schutzgruppen erlaubt es, Prozesse und Wechselwirkungen von Nukleinsäuren zu untersuchen und zu kontrollieren. Zahlreiche Positionen von Nukleobasen wurden bereits geschützt, allerdings wurde stets Wasserstoff durch eine Photoschutzgruppe ersetzt. Die Natur nutzt aber auch explizit die Methylierung von Ringstickstoffatomen wie m7G und m1A, um elektronische Struktur und Eigenschaften der RNA zu verändern und biomolekulare Wechselwirkungen zu steuern, die für Translation und RNA‐Abbau unerlässlich sind. Wir berichten, dass Arylketone wie Benzophenon und α‐Hydroxyalkylketon lichtempfindliche Schutzgruppen für die N7‐Position des Guanosins oder die N1‐Position des Adenosins sind. Gängige, auf ortho‐Nitrobenzyl basierende Photoschutzgruppen waren für diese Positionen hingegen nicht geeignet. Chemische und enzymatische Methoden zur ortsspezifischen Modifikation von N7G in Nukleosiden, Dinukleotiden und RNA wurden entwickelt, um die molekularen Wechselwirkungen von m7G und m1A mit räumlich‐zeitlicher Kontrolle zu untersuchen.
Molecule‐Induced Radical Formation (MIRF) Reactions—A Reappraisal
Authors: Sandhiya Lakshmanan , Jangra Harish , Zipse Hendrik
Published: November 2019

Radical chain reactions are commonly initiated through the thermal or photochemical activation of purpose‐built initiators, through photochemical activation of substrates, or through well‐designed redox processes. Where radicals come from in the absence of these initiation strategies is much less obvious and are often assumed to derive from unknown impurities. In this situation, molecule‐induced radical formation (MIRF) reactions should be considered as well‐defined alternative initiation modes. In the most general definition of MIRF reactions, two closed‐shell molecules react to give a radical pair or biradical. The exact nature of this transformation depends on the σ‐ or π‐bonds involved in the MIRF process, and this Minireview specifically focuses on reactions that transform two σ‐bonds into two radicals and a closed‐shell product molecule.
Structure‐Based Design of a Macrocyclic PROTAC
Authors: Testa Andrea , Hughes Scott J. , Lucas Xavier , Wright Jane E. , Ciulli Alessio
Published: November 2019

Constraining a molecule in its bioactive conformation via macrocyclization represents an attractive strategy to rationally design functional chemical probes. While this approach has been applied to enzyme inhibitors or receptor antagonists, to date it remains unprecedented for bifunctional molecules that bring proteins together, such as PROTAC degraders. Herein, we report the design and synthesis of a macrocyclic PROTAC by adding a cyclizing linker to the BET degrader MZ1. A co‐crystal structure of macroPROTAC‐1 bound in a ternary complex with VHL and the second bromodomain of Brd4 validated the rational design. Biophysical studies revealed enhanced discrimination between the second and the first bromodomains of BET proteins. Despite a 12‐fold loss of binary binding affinity for Brd4, macroPROTAC‐1 exhibited cellular activity comparable to MZ1. Our findings support macrocyclization as an advantageous strategy to enhance PROTAC degradation potency and selectivity between homologous targets.
Performance comparison of feedforward neural network training algorithms in modelling microwave pyrolysis of oil palm fibre for hydrogen and biochar production
Authors: Nasrudin Nor Anisa , Jewaratnam Jegalakshimi , Hossain Md Arafat , Ganeson Poo Balan
Published: November 2019

Microwave pyrolysis of oil palm fibre (OPF) was conducted to study the effect of microwave power, temperature, and nitrogen (N2) flow rate on the production of hydrogen and biochar. The effect of microwave power ranging from 400 to 900 W, reaction temperatures ranging from 450°C to 700°C, and N2 flow rates ranging 200 to 1,200 cm3 min−1 were investigated. The microwave power, reaction temperature, and N2 flow rates are directly proportional to hydrogen and inversely proportional to biochar yield. The characteristics of the biochar were analysed using CHNOS, scanning electron microscopy, and Brunauer–Emmett–Teller results. Central composite design was used to optimize the number of experiment. The optimized experimental datasets were used as inputs for developing a model that can predict the weight of hydrogen and biochar from microwave pyrolysis of OPF. A multilayer feedforward neural network model was developed by comparing the performance of 11 different types of backpropagation training algorithms. The 11 training algorithms belong to six classes, which are (a) additive momentum, (b) self‐adaptive learning rate, (c) resilient backpropagation, (d) conjugate gradient, (e) quasi‐Newton, and (f) Bayesian regulation (BR). Best performing training algorithm was selected based on the lowest error values computed. The objective of this research is to identify the most suitable training algorithm for this process. Levenberg–Marquardt and BR exhibited very good performance. BR exhibited best performance with lowest error values in predicting weight of hydrogen and biochar. The testing data error values for hydrogen weight is 0.216 root mean square error (RMSE), 0.144 mean absolute error (MAE), and 0.020 mean absolute percentage error (MAPE), and biochar is 0.886 RMSE, 0.489 MAE, and 0.019 MAPE. The optimum number of hidden neuron for this algorithm is 19 with mean square error 0.23. The biochar exhibits porous structure suggesting possible land application.
Study on the formation process of low‐temperature ash deposition induced by ammonium bisulfate in pulverized coal‐fired boiler
Authors: Wang Limin , Bu Yufan , Tang Chunli , Lv Cheng , Chen Xun , Che Defu
Published: November 2019

In order to explore the mechanism of low‐temperature ash deposition induced by ammonium bisulfate (ABS), ash deposits, and a corroded heat transfer plate in the rotary air preheater (RAPH) of a 1,000‐MW pulverized coal‐fired power plant in China were analyzed by X‐ray fluorescence, ion chromatography, X‐ray diffraction, and scanning electron microscope equipped with energy dispersive X‐ray spectroscopy. The element composition, main compounds, and ammonium ion in the samples were analyzed. The thermal gravimetric analysis of ash samples was conducted to infer the type of ammonium salt ultimately existing in the ash. The prediction of the ABS deposition range coincides well with both the area of serious ash deposition and the area of NH4+ distribution obtained by ion chromatography. The cause for corrosion and plugging in the RAPH was proposed by analyzing the reactions or mineral transformations involved in the ash deposits. The results indicate that ABS can form in a large height range in the RAPH. The ammonium induces the sulfur trioxide to deposit on and react with the metal plate or the ash particles to form sulfates, which act as the bridging agent, finally leading to serious plugging problems in the RAPH.
Lanthanide‐Based Luminescent Materials for Waveguide and Lasing
Authors: Chen Xian , Sun Tianying , Wang Feng
Published: November 2019

Microlasers and waveguides have wide applications in the fields of photonics and optoelectronics. Lanthanide‐doped luminescent materials featuring large Stokes/anti‐Stokes shift, long excited‐state lifetime as well as sharp emission bandwidth are excellent optical components for photonic applications. In the past few years, great progress has been made in the design and fabrication of lanthanide‐based waveguides and lasers at the micrometer length scale. Waveguide structures and microcavities can be fabricated from lanthanide‐doped amorphous materials through top‐down process. Alternatively, lanthanide‐doped organic compounds featuring large absorption cross‐section can self‐assemble into low‐dimensional structures of well‐defined size and morphology. In recent years, lanthanide‐doped crystalline structures displaying highly tunable excitation and emission properties have emerged as promising waveguide and lasing materials, which substantially extends the range of lasing wavelength. In this minireview, we discuss recent advances in lanthanide‐based luminescent materials that are designed for waveguide and lasing applications. We also attempt to highlight challenging problems of these materials that obstacle further development of this field.
State‐feedback stabilization and inverse optimal control for stochastic high‐order nonlinear systems with time‐varying powers
Authors: Li Wuquan , Liu Ying , Yao Xiaoxiao
Published: November 2019

This paper considers the stability and optimality problems associated with stochastic high‐order nonlinear systems with time‐varying powers. This research extends previous studies on the plant with constant powers. In this paper, we firstly construct a state‐feedback controller to ensure that the equilibrium at the origin of the closed‐loop system is globally asymptotically stable (GAS) in probability. Then we redesign a new optimal controller with infinite gain margin to solve the inverse optimal stabilization (IOS) problem. Specifically, the optimal controller is not only optimal with respect to a meaningful cost functional but also globally asymptotically stabilizes the closed‐loop system. The efficiency of the designed controllers is demonstrated by a simulation example.
Sulfolane‐Based Ethylene Carbonate‐Free Electrolytes for LiNi0.6Mn0.2Co0.2O2−Li4Ti5O12 Batteries
Authors: Björklund Erik , Göttlinger Mara , Edström Kristina , Younesi Reza , Brandell Daniel
Published: November 2019

Most electrolytes in today's lithium‐ion batteries contain a large proportion of ethylene carbonate (EC) mixed with other alkyl carbonate‐based solvents. EC has, however, been shown to be unstable at the high potentials at which several novel cathode materials are electrochemically active. Here, different mixtures of sulfolane and DMC are investigated in this context. The electrochemical stability is explored in addition to galvanostatic cycling of LiNi0.6Mn0.2Co0.2O2‐Li4Ti5O12 (NMC‐LTO) cells. The measurement of the ionic conductivity showed that mixing 25 % sulfolane into DMC improved the electrolyte properties as compared to pure DMC, making the conductivity similar to EC:DEC electrolytes and therefore fully functional. Moreover, the addition of sulfolane slightly enhanced the capacity retention, likely caused by formation of thinner and more stable surface layers on the LTO electrodes as determined by X‐ray photoelectron spectroscopy (XPS). The cycling performance is especially improved for sulfolane‐based electrolytes during cycling at sub‐zero temperatures.
Cellular Adaptation Relies on Regulatory Proteins Having Episodic Memory
Authors: Stan Razvan C. , Bhatt Darshak K. , de Camargo Maristela M.
Published: November 2019

The ability to memorize changes in the environment is present at all biological levels, from social groups and individuals, down to single cells. Trans‐generational memory is embedded subcellularly through genetic and epigenetic mechanisms. Evidence that cells process and remember features of the immediate environment using protein sensors is reviewed. It is argued that this mnemonic ability is encapsulated within the protein conformational space and lasts throughout its lifetime, which can overlap with the lifespan of the organism. Means to determine diachronic changes in protein activity are presented.
Treatment patterns and survival in patients with hepatocellular carcinoma in the Swedish national registry SweLiv
Authors: Henriksson M. , Björnsson B. , Sternby Eilard M. , Lindell G. , Strömberg C. , Hemmingsson O. , Isaksson B. , Rizell M. , Sandström P.
Published: November 2019

Background

Consistent data on clinical features, treatment modalities and long-term survival in patients with hepatocellular carcinoma (HCC) using nationwide quality registers are lacking. This study aimed to describe treatment patterns and survival outcomes in patients diagnosed with HCC using a national maintained database.

Methods

Characteristics and treatment patterns in patients diagnosed with HCC and registered in the national register of liver and bile duct tumours (SweLiv) between 2009 and 2016 were reviewed. Overall survival (OS) was estimated using Kaplan–Meier analysis and the log rank test to compare subgroups for clinical features, treatment modalities and outcomes according to the year of treatment.

Results

A total of 3376 patients with HCC were registered over 8 years, 246 (7·3 per cent) of whom underwent transplantation. Some 501 (14·8 per cent) and 390 patients (11·6 per cent) had resection and ablation as primary treatment. Transarterial chemoembolization and systemic sorafenib treatment were intended in 476 (14·1 per cent) and 426 patients (12·6 per cent) respectively; the remaining 1337 (39·6 per cent) were registered but referred for best supportive care (BSC). The 5-year survival rate was approximately 75 per cent in the transplantation group. Median OS was 4·6 (i.q.r. 2·0 to not reached) years after resection and 3·1 (2·3–6·7) years following ablation. In patients referred for palliative treatment, median survival was 1·4 (0·8–2·9), 0·5 (0·3–1·2) and 0·3 (0·1–1·0) years for the TACE, sorafenib and BSC groups respectively (P < 0·001). Median survival was 0·9 years for the total HCC cohort in 2009–2012, before publication of the Swedish national treatment programme, increasing to 1·4 years in 2013–2016 (P < 0·001).

Conclusion

The survival outcomes reported were in line with previous results from smaller cohorts. The introduction of national guidelines may have contributed to improved survival among patients with HCC in Sweden.
Computational simulation and experimental validation of an engineering problem: A case study on heat transfer in cylindrical fin with phase‐change material
Authors: R. Prithvi Raj , M. P. Midhun , D. Prakash
Published: November 2019

In this study, an extensive numerical simulation on the fins with a phase‐change material (PCM) has been conducted under various design aspects to understand the heat transfer mechanism through a project‐based learning system. A detailed methodology on the use of computational fluid dynamics (CFD) tools for an engineering problem is discussed along with experimental validation. Initially, a required experimental test setup has been developed, and a cylindrical fin with PCM is fabricated and tested for heat transfer. Cylindrical fin is made from aluminum material, and paraffin is used as PCM since its application is widely spread in energy industries. Later, CFD simulation is performed on the cylindrical fin in ANSYS Workbench by including both heat transfer and phase‐change phenomenon of PCM. The CFD solver solves the partial differential equation through the finite volume method and the results obtained from the CFD simulation are checked for grid independence. Also, the obtained results are compared with experimental results for validation and found a good agreement. After validation, the influence of the PCM zone aspect ratio, PCM zone location, and groove over fin on heat transfer are numerically studied. From the obtained results, it is noticed that increasing the PCM volume increases the melting time and also lowers the fin tip temperature. Finally, fins with peripheral grooves and PCM proves as a good combination for a better heat transfer rate. This kind of simulation studies helps the students to understand the complex heat transfer mechanism through project‐based learning and also expertise the students.
Know how to comply with legal guidance for accommodating pregnant, parenting students
Authors: Hope Joan
Published: November 2019

BOSTON — Pregnancy itself is not a disability. But even temporary limitations can trigger the need to provide accommodations, said Ida Dilwood, Director of the Office of Disability Services and the University Test Center at the University of Colorado, Colorado Springs. Dilwood, along with Amanda Allee, Director of the Office of Institutional Equity and Title IX Coordinator, also at UCCS, explained best practices for accommodating pregnant and parenting students at the Association for Higher Education And Disability annual conference.
CD44‐associated radioresistance of glioblastoma in irradiated brain areas with optimal tumor coverage
Authors: Liu Wei‐Hsiu , Lin Jang‐Chun , Chou Yu‐Ching , Li Ming‐Hsien , Tsai Jo‐Ting
Published: November 2019

Glioblastoma multiforme (GBM) requires radiotherapy (RT) as its definitive management. However, GBM still has a high local recurrence rate even after RT. Cancer stem‐like cells (CSCs) might enable GBM to evade irradiation damage and cause therapeutic failure. The optimal RT plan should achieve a planning target volume (PTV) coverage of more than 95% but cannot always meet the requirements. Here, we demonstrate that irradiation with different tumor coverage rates to different brain areas has similar effects on GBM. To retrospectively analyze the relationship between PTV coverage and the survival rate in 26 malignant glioblastoma patients, we established primary cell lines from patient‐derived malignant glioblastoma cells with the PTV95 (PTV coverage of more than 95%) program (GBM‐MG1 cells) and the Non‐PTV95 (poor PTV coverage of less than 95%) program (GBM‐MG2 cells). The clinical results of PTV95 and Non‐PTV95 showed no difference in the overall survival (OS) rate (P = .390) between the two different levels of PTV coverage. GBM‐MG1 (PTV95 program) cells exhibited higher radioresistance than GBM‐MG2 (Non‐PTV95 program) cells. CD44 promotes radioresistance, CSC properties, angiogenesis and cell proliferation in GBM‐MG1 (PTV95 program) cells. GBM patients receiving RT with the PTV95 program exhibited higher radioresistance, CSC properties, angiogenesis and cell proliferation than GBM patients receiving RT with the Non‐PTV95 program. Moreover, CD44 plays a crucial role in these properties of GBM patients with the PTV95 program.
A V‐Nitrogenase Variant Containing a Citrate‐Substituted Cofactor
Authors: Newcomb Megan P. , Lee Chi Chung , Tanifuji Kazuki , Jasniewski Andrew J. , Liedtke Jasper , Ribbe Markus W. , Hu Yilin
Published: November 2019

Nitrogenases catalyze the ambient reduction of N2 and CO at its cofactor site. Herein we present a biochemical and spectroscopic characterization of an Azotobacter vinelandii V nitrogenase variant expressing a citrate‐substituted cofactor. Designated VnfDGKCit, the catalytic component of this V nitrogenase variant has an αβ2(δ) subunit composition and carries an 8Fe P* cluster and a citrate‐substituted V cluster analogue in the αβ dimer, as well as a 4Fe cluster in the “orphaned” β‐subunit. Interestingly, when normalized based on the amount of cofactor, VnfDGKCit shows a shift of N2 reduction from H2 evolution toward NH3 formation and an opposite shift of CO reduction from hydrocarbon formation toward H2 evolution. These observations point to a role of the organic ligand in proton delivery during catalysis and imply the use of different reaction sites/mechanisms by nitrogenase for different substrate reductions. Moreover, the increased NH3/H2 ratio upon citrate substitution suggests the possibility to modify the organic ligand for improved ammonia synthesis in the future.
A case of giant cell arteritis simultaneously diagnosed with chronic subdural hematoma
Authors: Otani Yuichiro , Kanno Keishi , Kikuchi Yuka , Kametani Takahiro , Kobayashi Tomoki , Tazuma Susumu
Published: November 2019

Here, we describe a case of giant cell arteritis (GCA) simultaneously diagnosed with chronic subdural hematoma. In this case, head to chest computed tomography angiography was useful for the diagnosis and treatment of GCA.
Two‐Dimensional Metal–Organic Framework Nanosheets with Cobalt‐Porphyrins for High‐Performance CO2 Electroreduction
Authors: Zhang Xiang‐Da , Hou Shu‐Zhen , Wu Jian‐Xiang , Gu Zhi‐Yuan
Published: November 2019

The electrochemical reduction of CO2 presents a promising strategy to mitigate the greenhouse effect and reduce excess carbon dioxide emission to realize a carbon‐neutral energy cycle, but it suffers from the lack of high‐performance electrocatalysts. In this work, catalytic active cobalt porphyrin [TCPP(Co)=(5,10,15,20)‐tetrakis(4‐carboxyphenyl)porphyrin‐CoII] was precisely anchored onto water‐stable 2D metal–organic framework (MOF) nanosheets (Zr‐BTB) to obtain ultrathin 2D MOF nanosheets [TCPP(Co)/Zr‐BTB] with accessible catalytic sites for the CO2 reduction reaction. Compared with molecular cobalt porphyrin, the TCPP(Co)/Zr‐BTB exhibits an ultrahigh turnover frequency (TOF=4768 h−1 at −0.919 V vs. reversible hydrogen electrode, RHE) owing to high active‐site utilization. In addition, three post‐modified 2D MOF nanosheets [TCPP(Co)/Zr‐BTB‐PABA, TCPP(Co)/Zr‐BTB‐PSBA, TCPP(Co)/Zr‐BTB‐PSABA] were obtained, with the modifiers of p‐(aminomethyl)benzoic acid (PABA), p‐sulfobenzoic acid potassium (PSBA), and p‐sulfamidobenzoic acid (PSABA), to change the micro‐environments around TCPP(Co) through the tuning of steric effects. Among them, the TCPP(Co)/Zr‐BTB‐PSABA exhibited the best performance with a faradaic efficiency (FECO) of 85.1 %, TOF of 5315 h−1, and jtotal of 6 mA cm−2 at −0.769 V (vs. RHE). In addition, the long‐term durability of the electrocatalysts is evaluated and the role of pH buffer is revealed.
A Mild and Versatile Friedel–Crafts Methodology for the Diversity‐Oriented Synthesis of Redox‐Active 3‐Benzoylmenadiones with Tunable Redox Potentials
Authors: Cotos Leandro , Donzel Maxime , Elhabiri Mourad , Davioud‐Charvet Elisabeth
Published: November 2019

A series of highly diversified 3‐aroylmenadiones was prepared by a new Friedel–Crafts acylation variant/oxidative demethylation strategy. A mild and versatile acylation was performed between 1,4‐dimethoxy‐2‐methylnaphthalene and various activated/deactivated benzoic and heteroaromatic carboxylic acids, in the presence of mixed trifluoroacetic anhydride and triflic acid, at room temperature and in air. The 1,4‐dimethoxy‐2‐methylnaphthalene‐derived benzophenones were isolated in high yield, and submitted to oxidative demethylation with cerium ammonium nitrate to produce 3‐benzoylmenadiones. All 1,4‐naphthoquinone derivatives were investigated as redox‐active electrophores by cyclic voltammetry. The electrochemical data recorded for 3‐acylated menadiones are characterized by a second redox process, the potentials of which cover a wide range of values (500 mV). These data emphasize the ability of the generated structural diversity at the 3‐aroyl chain of these electrophores to fine‐tune their corresponding redox potentials. These properties are of significance in the context of antimalarial drug development and understanding of the mechanism of bioactivation/action.
Designing Molecular Spanners to Throw in the Protein Networks
Authors: Serapian Stefano A. , Colombo Giorgio
Published: November 2019

Proteins govern most aspects of cellular life and, through specific interfaces, are typically involved in intricate protein–protein interaction (PPI) networks and signaling pathways. Subtle up‐ or downregulation of key protein functions and PPIs results in disease; still, the preferred option to contrast the role of a protein in disease and healthy conditions alike remains its outright shutdown through orthosteric ligands that block its active site. Here, we explore subtler alternatives to modulate proteins and PPIs. Driven by a view of proteins as dynamic entities, we discuss ways to identify allosteric binding sites, which, when targeted by tailored ligands, can induce significant changes in the active site of a protein, and lead to agonistic or antagonistic effects. We also summarize the selective regulation of specific PPIs—either direct or allosteric—and show that effects can be stabilizing as well as destabilizing, depending on how the conformational equilibrium of a protein is shifted.
Spiro‐Carbon: A Metallic Carbon Allotrope Predicted from First Principles Calculations
Authors: Oliveira Felipe L. , Capaz Rodrigo B. , Esteves Pierre M.
Published: November 2019

A structurally stable microporous metallic carbon allotrope, poly(spiro[2.2]penta‐1,4‐diyne) or, for short, spiro‐carbon, withI41/amd(D4h) symmetry is predicted by first‐principles calculations using density functional theory (DFT). The calculations of electronic, vibrational, and structural properties show that spiro‐carbon has lower relative energy than other elusive carbon allotropes such as T‐Carbon and 1‐diamondyne (Y‐Carbon). Its structure can be pictured as a set oftrans‐cisoid‐polyacetylene chains tangled and interconnected together bysp3carbon atoms. Calculations reveal a metallic electronic structure arising from an “intrinsic doping” oftrans‐cisoid‐polyacetylene chains withsp3carbon atoms. Possible synthetic routes and various simulated spectra (XRD, NMR, and IR absorption) are provided in order to guide future efforts to synthesize this novel material.
Preparation of Lipid Nanodiscs with Lipid Mixtures
Authors: Li Mavis Jiarong , Atkins William M. , McClary Wynton D.
Published: November 2019

Lipid nanodiscs provide a native‐like lipid environment for membrane proteins, and they have become a valuable platform for the study of membrane biophysics. A range of biophysical and biochemical analyses are enabled when membrane proteins are captured in lipid nanodiscs. Two parameters that can be controlled when capturing membrane proteins in lipid nanodiscs are the radius, and hence the surface area of the lipid surface, and the composition of the lipid bilayer. Despite their emergence as a versatile tool, most studies with lipid nanodiscs in the literature have focused on nanodiscs of a single radius with a single lipid. In light of the complexity of biological membranes, it is likely that nanodiscs with multiple membrane components would be more sophisticated models for membrane research. It is possible to prepare nanodiscs with more complex lipid mixtures to probe the effects of lipid composition on several aspects of membrane biochemistry. Detailed protocols are described here for the preparation of nanodiscs with mixtures of phospholipids, incorporation of cholesterol, and incorporation of a spectroscopic lipid probe. These protocols provide starting points for the construction of nanodiscs with more physiological membrane compositions or with useful biophysical probes. © 2019 by John Wiley & Sons, Inc.

Basic Protocol 1: Assembly of mixed lipid nanodiscs

Basic Protocol 2: Assembly of nanodiscs with cholesterol

Basic Protocol 3: Incorporation of laurdan into nanodiscs for membrane fluidity measurements
The Generation of Growth Dislocations by Inclusions and Growth‐Face Damages: An Experimental Study
Authors: Neuroth Gero , Klapper Helmut
Published: November 2019

The generation of growth dislocations in crystals by intentionally introduced foreign‐particle inclusions and by mechanical damaging (scratching) of the growth face is reported. The formation of dislocations is studied by in situ observation of the step pattern on the involved growth face by optical microscopy and—after growth—by X‐ray diffraction topography. This is performed on three different growth faces of orthorhombic salol (C13H10O3, melting temperature Tm = 41.5 °C) growing from the melt supercooled by 1–2 °C. The development of the growth pattern after the closure of the inclusion by overgrowing layers and after the scratching is recorded by videos. Particularly instructive is the inclusion experiment on the fast‐growing (100) face: immediately after the closure a big pyramid and fast step source appears, which dominates and sporadically overflows neighbored secondary step sources. In the sequel the big pyramid splits into a row of small hills which gradually diverge. This indicates that the associated dislocations fan out within the (010) plane of the crystal, as is confirmed by X‐ray topography. The in situ scratching of the growth face triggers the immediate appearance and fast development of a complex hill structure associated with numerous dislocations.
Evolution Process and Controlled Synthesis of Humins with 5‐Hydroxymethylfurfural (HMF) as Model Molecule
Authors: Shen Haiyan , Shan Haozhe , Liu Li
Published: November 2019

Elucidation of the chemical structure and formation mechanism of humins is a requisite to further improve the efficiency of acid‐catalyzed biomass conversion. Through a low‐temperature approach, the key intermediates resulting in the formation of 5‐hydroxymethylfurfural (HMF)‐derived humins were captured, revealing multiple elementary reactions such as etherification, esterification, aldol condensation, and acetalization. Through humin characterization, it was found out that the aldol condensation moiety between aldehyde group and levulinic acid is critical to justify the characteristic IR peaks (1620 and 1710 cm−1) and aromatic fragments from pyrolysis GC–MS. Based on the investigations by means of HPLC–MS/MS, IR, pyrolysis GC–MS, and SEM, the structural models of humins at different temperatures were proposed, which are comprised of the elementary reaction types confirmed by the key intermediates. Humin structures with varying content of aldol condensation could be controllably synthesized under different reaction conditions (temperature and time), demonstrating the evolution process of HMF‐derived humins.
Fantastic bees and where to find them: locating the cryptic overwintering queens of a western bumble bee
Authors: Williams Neal M. , Mola John M. , Stuligross Clara , Harrison Tina , Page Maureen L. , Brennan Ross M. , Rosenberger Nick M. , Rundlöf Maj
Published: November 2019

Bumble bees are among the best‐studied bee groups worldwide, yet surprisingly we know almost nothing about their overwintering habitats nor the microsite characteristics that govern selection of these sites. This gap represents a critical barrier for their conservation, especially if preferred overwintering habitats differ from foraging and nesting habitats. Current conservation plans focus on foraging habitat, potentially creating a problem of partial habitats where improved forage might fail to prevent population declines due to limited overwintering sites. We provide the first data on the overwintering habitat for any western North American bumble bee. Our data suggest that overwintering and foraging habitats are likely distinct, and queens’ selection of overwintering sites may be shaped by environmental stressors of the year. In our study area, queens overwintered in litter beneath cypress trees, where no floral resources exist. Whether this separation of overwintering and foraging habitat holds for other bumble bee species remains to be discovered. Our data highlight the need to consider the whole life cycle for understanding population dynamics and conservation planning. This need is underscored by growing evidence for the decline of multiple North American bumble bee species.
Amido Silicon Chalcogenide Compounds with Unprecedented Cluster Cores and Low Oxidation State Silicon Atoms
Authors: Schwedtmann Kevin , Hepp Alexander , Schwedtmann Kai , Weigand Jan J. , Lips Felicitas
Published: November 2019

Invited for the cover of this issue is Felicitas Lips from the University of Münster, Germany. The cover image shows butterflies trapped in a series of silicon‐based cages. The color of each cage compound is represented by the color of the butterfly in it.
Higher Carbon Analogues of 1,4‐Dihydropyridines as Potent TGFβ/Smad Inhibitors
Authors: Barth Eva R. , Längle Daniel , Wesseler Fabian , Golz Christopher , Krupp Anna , Schade Dennis , Strohmann Carsten
Published: November 2019

The C to Si and Ge exchange in bioactive compounds has often led to positive changes in the molecular properties, whereby Ge analogues are underrepresented. This is only possible at tetrahedral positions, and it is necessary for the analogue building blocks to withstand the synthetic conditions. Here, we present the synthesis of Si and Ge analogues of a TGFβ inhibiting 1,4‐dihydropyridine, which has a tetrahedral carbon in an important position for its activity. The molecular properties are compared by the discussion of the single X‐ray crystal structures and the electrostatic potential on the molecule surface which could play a role in the target interaction. Biological activities show that the C to Si and Ge exchange goes with full preservation of the potency, thus representing good starting points to modify physicochemical features and pharmacokinetics of these TGFβ inhibitors.
2,3,3,3‐Tetrafluoropropene (HFO‐1234yf) as a CF3‐Building Block: Synthesis of Enol Ethers and Vinyl Sulfides
Authors: Murray Ben J. , Ball Ellis D. , Harsanyi Antal , Sandford Graham
Published: November 2019

2,3,3,3‐Tetrafluoropropene (HFO‐1234yf) is an inexpensive and readily available fluorinated building block, owing to its growing use as a low global warming potential 4th generation refrigerant, but there have so far been few reported uses of this fluoroalkene in organic synthesis. Herein, we report our investigations into nucleophilic substitution reactions of HFO‐1234yf with alkoxide and thiolate derivatives. The regiochemistry of these transformations varies with conditions and we propose these reactions proceed through addition–elimination with reversible formation of a carbanion intermediate. The regioselectivity is dictated by hard/soft nucleophile/electrophile control. This is supported by deuterium trapping of the proposed reactive intermediate. The effect of solvent and base choice was examined and the substrate scope for the synthesis of α‐trifluoromethyl enol ethers was expanded.
Methane Activation and Utilization: Current Status and Future Challenges
Authors: Sun Lanlan , Wang Yu , Guan Naijia , Li Landong
Published: November 2019

Methane, an abundant and clean fossil energy source, can provide the highest specific energy compared with other hydrocarbons. Exploiting an efficient way to convert methane to fuel or chemicals is, therefore, of significant importance economically as well as in terms of sustainability. Generally, methane is first converted to syngas in industry, which is further transformed to liquid hydrocarbons via a Fischer–Tropsch process. Methane is also directly pyrolyzed to olefins or aromatic hydrocarbons or coupled to C2 products at very high temperatures. Among all the direct routes, the selective oxidation of methane to methanol is noteworthy as it is thermodynamically favorable under relatively mild reaction conditions. However, restricted by the high C—H bond energy, the activation and utilization of methane still encounters great challenges despite the developments in recent years. Based on this background, this Review highlights the recent advances and forthcoming challenges in the process of methane activation and utilization. Catalysis plays a key role in the process of methane activation and it is focused on here. This Review is expected to be useful for scientists and engineers working in this field and is timely to boost further research.
Yield and nitrogen uptake of sole and intercropped maize and peanut in response to N fertilizer input
Authors: Gao Huaxin , Meng Weiwei , Zhang Chaochun , van der Werf Wopke , Zhang Zheng , Wan Shubo , Zhang Fusuo
Published: November 2019

Chinese agriculture needs to become less dependent on fertilizer inputs to enhance sustainability. Cereal/legume intercropping is a potential pathway to lower fertilizer inputs, but there is insufficient knowledge on the nitrogen (N) response in species mixtures. Here, we investigated N response in maize/peanut intercropping. Maize showed a stronger yield response to N input than peanut both in sole cropping and in intercropping, and so did sole crops relative to intercrops. Maize yield was the highest at the maximum level tested: 360 kg N/ha. Agronomic efficiency (AE) of sole maize was 7.8 kg/kg N input, averaged across five N levels (0, 90, 180, 270, and 360 kg/ha). Partial land equivalent ratios (pLERs) for maize decreased with N input, from 0.70 at zero to 0.64 at 360 kg/ha. Sole peanut showed an optimum yield response to N input, with the highest yield at 270 kg/ha and lower yield at 360 kg/ha. The average AE of sole peanut was 1.3 kg/kg. The pLER of peanut declined from 0.43 at zero to 0.32 at 360 kg/ha while the overall LER decreased from 1.13 to 0.96, indicating relative better performance of intercropping at low than at high N input. Apparent recovery (RE) for N was 27.2% for sole maize, 12.4% for sole peanut, and 7.2% for intercrops. Mean N uptake was 179 kg/ha in sole maize, 199 kg/ha in intercropping, and 264 kg/ha in sole peanut. Partial economic budgeting indicated that with the current low Chinese N fertilizer prices, gross margin is maximized with high N input in sole crops; however, for intercropping, the highest gross margin was attained at intermediate N inputs of 180 or 270 kg/ha. Fertilizer price incentives may facilitate a transition to intercropping at moderate N input in China.
Modification of DC polarographic antioxidant assay—Application to aromatic plants and their active principles
Authors: Stojićević Aleksandra S. , Pastor Ferenc T. , Gorjanović Stanislava Ž. , Šolević Knudsen Tatjana M. , Antić Mališa P.
Published: November 2019

A direct current (DC) polarographic assay based on the decrease of anodic current of HydroxoPerhydroxoMercury (II) Complex (HPMC) formation in H2O2 solution in Clark Lubs (CL) buffer (pH 9.8) as working solution was previously applied to determine antioxidant (AO) capacity of water‐soluble compounds. Here, the applicability of HPMC assay was extended into samples poorly soluble in water such as the essential oils and extracts of Lamiaceae and Apiaceae species obtained by ultrasound‐assisted maceration (UAM) and Soxhlet extraction (SE) with 70 and 96% ethanol as well as individual compounds present. The influence of solvents miscible with water on HPMC anodic current was studied, and working solution was optimized. A modified HPMC method was applied to measure AO capacity of essential oils and extracts as well as compounds identified using gas chromatography‐mass spectrometer (GC‐MS) and gas chromatography with flame‐ionization detection (GC‐FID) (terpenoids and catechols) or known to be present (phenolic acids and flavonoids). A 1:1 mixture of CL buffer and ethanol was chosen as working solution. AO capacity of essential oils and extracts, established by modified HPMC assay, was in range of 1.2‐2.0 and 9.2‐38.4 (%/mL) while terpenoids and phenolics in range of 0.1‐0.5 and 13.5‐38.5 (%/mol), respectively. The superior AO capacity was ascribed to essential oils and extracts of Lamiaceae species and to extracts obtained with 70% ethanol. A higher AO capacity of extracts in comparison to essential oils was corroborated with a difference in phenolics and terpenoids capacity.
Alpha‐linolenic acid given as an anti‐inflammatory agent in a mouse model of colonic inflammation
Authors: Wen Juan , Khan Israr , Li Anping , Chen Xinjun , Yang Pingrong , Song Pingshun , Jing Yaping , Wei Junshu , Che Tuanjie , Zhang Chunjiang
Published: November 2019

This study examined the relationship between the high‐fat, high‐sugar diet (HFHSD) and trinitrobenzene sulfonic acid (TNBS) induced mouse colitis, the therapeutic effect of alpha‐linolenic acid (ALA) on mouse colitis, and the relationship between HFHSD and hyperlipidemia. We also examined the possible underlying mechanisms behind their interactions. Female BABL/c mice were fed with HFHSD for the 9 weeks. At the same time, ALA treatment (150 or 300 mg/kg) was administered on a daily basis. At the end of the 9 weeks, experimental colitis was induced by the intra‐colonic administration of TNBS. Body weight, spleen weight, disease activity index (DAI), histological changes, T‐cell‐related cytokine level, and lipid profiles were measured after treatment. TNBS induced severe clinical manifestations of colitis and histological damage. Low‐ALA (150 mg/kg) administration profoundly ameliorated TNBS‐induced clinical manifestations, body weight loss, spleen weight loss, and histological damage. On the contrary, the high‐ALA (300 mg/kg) administration did not ameliorate colitis and even exacerbated the symptoms. HFHSD consumption assisted TNBS in changing IL‐12, IFN‐γ, IL‐2, and IL‐17A in the liver. As expected, these changes were recovered through low‐ALA. In addition, HFHSD had a significant impact on the total cholesterol (TC), high‐density lipoprotein cholesterol (HDL‐C), and triglyceride (TG), which related to the increased risk of hyperlipidemia. In summation, HFHSD exacerbated the TNBS‐induced colitis via the Th1/Th17 pathway. The Low‐ALA (150 mg/kg) exhibited protective effects against the TNBS‐induced colitis via the Th1/Th2/Th17 pathway.
The effect of a ban on gender‐based pricing on risk selection in the German health insurance market
Authors: Huang Shan , Salm Martin
Published: November 2019

Starting from December 2012, insurers in the European Union were prohibited from charging gender‐discriminatory prices. We examine the effect of this unisex mandate on risk segmentation in the German health insurance market. Although gender used to be a pricing factor in Germany's private health insurance (PHI) sector, it was never used as a pricing factor in the social health insurance (SHI) sector. The unisex mandate makes PHI relatively more attractive for women and less attractive for men. Based on data from the German socio‐economic panel, we analyze how the unisex mandate affects the difference between women and men in switching rates between SHI and PHI. We find that the unisex mandate increases the probability of switching from SHI to PHI for women relative to men. On the other hand, the unisex mandate has no effect on the gender difference in switching rates from PHI to SHI. Because women have on average higher health care expenditures than men, our results imply a worsening of the PHI risk pool and an improvement of the SHI risk pool. Our results demonstrate that regulatory measures such as the unisex mandate can affect risk selection between public and private health insurance sectors.
Development of a chitosan hydrogel containing flavonoids extracted fromPassiflora edulisleaves and the evaluation of its antioxidant and wound healing properties for the treatment of skin lesions in diabetic mice
Authors: Soares Rita D. F. , Campos Maria G. N. , Ribeiro Gislaine P. , Salles Bruno C. C. , Cardoso Naiane S. , Ribeiro Julia R. , Souza Raphaela M. , Leme Krissia C. , Soares Caroline B. , de Oliveira Carla M. , Elston Lilian B. , da Fonseca Clodoaldo C. P. , Ferreira Eric B. , Rodrigues Maria R. , Duarte Stella M. S. , Paula Fernanda B. A.
Published: November 2019

This study aimed to develop a chitosan‐based hydrogel containing a mixture of flavonoids isolated from the leaves ofPassiflora edulisSims and to evaluate its stability, antioxidant properties, and wound healing effects on cutaneous lesions in diabetic rats. in vitro studies were carried out to evaluate the biocompatibility and flavonoid release from the chitosan hydrogel. in vivo wound healing studies were conducted on male Wistar rats, where the injured tissue was removed for histological analysis and determination of lipid peroxidation, superoxide dismutase activity, and glutathione peroxidase activity. From the histological analysis and macroscopic evaluation of the contraction of the wounds, it was observed that the formulation presented wound healing properties. In addition, treatment of the wound with the formulation stimulated the antioxidant defense system, suggesting a beneficial effect during the treatment of skin lesions in diabetic rats, especially in the first few days after wounding. According to these results, we can conclude that the chitosan hydrogel containing the flavonoid analyzed in this study has potential use as dressings in the treatment of wounds.
Stimuli‐responsive nanoparticles for the codelivery of chemotherapeutic agents doxorubicin and siPD‐L1 to enhance the antitumor effect
Authors: Zhou Ye‐juan , Wan Wen‐jun , Tong Yao , Chen Meng‐tian , Wang Dan‐dan , Wang Yu , You Ben‐gang , Liu Yang , Zhang Xue‐nong
Published: November 2019

Cancer cells have been reported to exhibit high resistance against immune system recognition through various cell intrinsic and extrinsic mechanisms. Considerable challenges have been encountered in monotherapy with chemotherapeutics to attain the desired antitumor efficacy. In this study, a nanodelivery system was designed to incorporate doxorubicin (DOX) and programmed death‐ligand 1 (PD‐L1) small interfering RNA (siRNA), that is, siPD‐L1. DOX and siPD‐L1 were formed from a stimuli‐responsive polymer with a poly‐L‐lysine–lipoic acid reduction‐sensitive core and a tumor extracellular pH‐stimulated shedding polyethylene glycol layer. The codelivery system was stable under physiological pH conditions and demonstrated enhanced cellular uptake at the tumor site. Moreover, the combined treatment of DOX and siPD‐L1 exhibited improved antitumor effect in vitro and in vivo compared with either modality alone. The combination of chemotherapy and immunotherapy presented in this work through the codelivery of a chemotherapeutic agent and a gene‐silencing agent (siRNA) may provide a new strategy for cancer treatment.
microRNA‐501‐5p promotes cell proliferation and migration in gastric cancer by downregulating LPAR1
Authors: Ma Xiang , Feng Jiaxi , Lu Ming , Tang Wenjuan , Han Jianbo , Luo XiaGang , Zhao Qinghong , Yang Li
Published: November 2019

In spite of the achievement in treatment, the gastric cancer (GC) mortality still remains high. MicroRNAs (miRNAs) are a group of small noncoding RNAs that play a crucial part in tumor progression. In this study, we explored the expression and function of microRNA‐501‐5p (miR‐501‐5p) in GC cell lines. Quantitative real‐time polymerase chain reaction assay results suggested that miR‐501‐5p was significantly upregulated in GC tissues and cell lines. And, the Cell Counting Kit‐8 colony formation and cell migration assay results showed that the downregulation of miR‐501‐5p decreased GC cell proliferation and migration. Besides that, we found that GC cell cycle was arrested in G2 phase and cell apoptosis rate was increased by silencing the expression of miR‐501‐5p in GC cell lines using the flow cytometry. We also found that miR‐501‐5p could directly target lysophosphatidic acid receptor 1 (LPAR1) and negatively regulate LPAR1 expression in GC cell lines by performing dual‐luciferase reporter gene assay and Western blot analysis. And, LPAR1 was significantly downregulated in GC tissues and inversely correlated with miR‐501‐5p expression. Furthermore, LPAR1 downregulation promoted cell proliferation and migration, which were attenuated by cotransfection of miR‐501‐5p inhibitor in GC cells. In conclusion, miR‐501‐5p can promote GC cell proliferation and migration by targeting and downregulating LPAR1. miR‐501‐5p/LPAR1 may become a potential therapeutic target for GC treatment.