bluuebunny/crossref_metadata_2025 huggingface dataset:
Ferromagnetic Resonance Vector Magnetic Sensor with High Sensitivity and Ultrawide Working Range
Authors: Wen Tao , Wang Zhiguang , Du Qin , Su Wei , Guan Mengmeng , Zhao Shishun , Wu Jingen , Hu Zhongqiang , Zhou Ziyao , Liu Ming
Published: October 2021

Large working range is of vital importance for magnetic sensors when exposed to complicated magnetic field profile, especially in automation and power industry where large field variation is frequently encountered. The design for traditional magnetic sensors, e.g., magnetoresistive and fluxgate magnetometers, utilizes ferromagnetic materials with ultrahigh permeability to maximize the field sensitivity, resulting in strictly confined dynamic range due to limited saturation field. Here, an integratable ferromagnetic resonance (FMR) prototype magnetic sensor with high sensitivity and theoretically unlimited working range is reported. An ultrawide working range (>450 mT) which is more than two orders larger than that of commercial sensors with similar field resolution is experimentally verified. Moreover, the FMR magnetometer is a vector sensor in contrast to the traditional scalar sensors based on magnetic resonance. With a navigating magnetic field of 50 μT (ca. the Earth's magnetic field), the resolution for azimuth angle is 0.006°. Compared with traditional nuclear magnetic resonance and electron paramagnetic resonance sensors with large size and high power consumption, the compact FMR sensor with large dynamic range and high sensitivity has much broader application prospects, especially in magnetically harsh environments.
Catalytic Asymmetric Halogenation/Semipinacol Rearrangement of 3‐Hydroxyl‐3‐vinyl Oxindoles: A Stereodivergent Kinetic Resolution Process
Authors: Dai Li , Liu Wen , Zhou Yuqiao , Zeng Zi , Hu Xinyue , Cao Weidi , Feng Xiaoming
Published: October 2021

A highly enantioselective halogenation/semipinacol rearrangement of isatin‐derived allylic alcohols has been developed with a chiral N,N′‐dioxide/ScIII complex as catalyst. This strategy involved a pivotal stereodivergent kinetic resolution process and provided a facile and efficient entry to optically active halo‐substituted quinolone derivatives and quinoline alkaloids with a quaternary stereocenter simultaneously under mild reaction conditions. Based on the control experiments together with kinetic studies and DFT calculations, a possible catalytic cycle was proposed to illustrate the reaction process and enantiocontrol.
Enantioselective Tertiary Electrophile (Hetero)Benzylation: Pd‐Catalyzed Substitution of Isoprene Monoxide with Arylacetates**
Authors: Doyle Michael G. J. , Gabbey Alexis L. , McNutt Wesley , Lundgren Rylan J.
Published: October 2021

The enantioselective generation of quaternary carbon centers remains challenging but is of growing importance for the preparation of functional molecules. Metal catalyzed allylic alkylations of tertiary electrophiles can provide access to these substructures but remain generally incompatible with organometallic benzyl nucleophiles. Here we demonstrate that electron‐deficient arylacetates can serve as benzyl nucleophile surrogates to generate enantioenriched acyclic molecules containing a quaternary carbon center via a two‐step substitution–decarboxylation process using isoprene monoxide. Products are often obtained in >90 % ee using a commercially available catalyst. An array of electron‐withdrawing functional groups on the arylacetate moiety are tolerated. The lactone generated by the initial substitution reaction can be used in further stereoselective transformations to prepare molecules with acyclic vicinal quaternary stereocenters.
Quantifying Mechanical Properties of Molecular Crystals: A Critical Overview of Experimental Elastic Tensors
Authors: Spackman Peter R. , Grosjean Arnaud , Thomas Sajesh P. , Karothu Durga Prasad , Naumov Panče , Spackman Mark A.
Published: October 2021

This review presents a critical and comprehensive overview of current experimental measurements of complete elastic constant tensors for molecular crystals. For a large fraction of these molecular crystals, detailed comparisons are made with elastic tensors obtained using the corrected small basis set Hartree–Fock method S‐HF‐3c, and these are shown to be competitive with many of those obtained from more sophisticated density functional theory plus dispersion (DFT‐D) approaches. These detailed comparisons between S‐HF‐3c, experimental and DFT‐D computed tensors make use of a novel rotation‐invariant spherical harmonic description of the Young's modulus, and identify outliers among sets of independent experimental results. The result is a curated database of experimental elastic tensors for molecular crystals, which we hope will stimulate more extensive use of elastic tensor information—experimental and computational—in studies aimed at correlating mechanical properties of molecular crystals with their underlying crystal structure.
Magnetization Dynamics on Isotope‐Isomorphic Holmium Single‐Molecule Magnets
Authors: Liu Yang , Ho Le Tuan Anh , Huang Guo‐Zhang , Chen Yan‐Cong , Ungur Liviu , Liu Jun‐Liang , Tong Ming‐Liang
Published: October 2021

Here we reported the deuteration of the metal‐binding equatorial water molecules in a reported HoIII single‐molecule magnet (SMM) with pentagonal‐bipyramidal geometry, from [Ho(CyPh2PO)2(H2O)5]3+ to [Ho(CyPh2PO)2(D2O)5]3+. The hyperfine structures originating from the nuclear spin of 165HoIII can be clearly observed. Moreover, the resulting magnetization dynamics revealed the switch of the relative relaxation rates for the two isotope‐isomorphic complexes—respectively faster/slower at low/high temperature. The noticeable isotope effect arises from not only the paramagnetic metal center but also the diamagnetic ligands, which can be explained by the ab initio calculated tunnel splitting and the involvement of the super‐hyperfine interaction related to the difference in the nuclear spin number of protium (1H, I=1/2) and deuterium (2H, I=1).
An on‐surface Diels–Alder reaction
Authors: Castro‐Esteban Jesús , Albrecht Florian , Fatayer Shadi , Pérez Dolores , Gross Leo , Peña Diego
Published: October 2021

The Diels–Alder reaction is one of the most popular reactions in organic chemistry. However, its use in the field of on‐surface synthesis is hampered by the spatial restrictions of this cycloaddition reaction. Herein we selected a cyclic strained triyne to demonstrate an on‐surface hexadehydro‐Diels–Alder reaction in a single molecule. The reaction was studied in detail by means of atomic force microscopy (AFM) with CO‐functionalized tips. Our results pave the way to use this iconic pericyclic reaction for on‐surface synthesis, introducing the concept of atom economy in the field.
A Strategy for Site‐ and Chemoselective C−H Alkenylation through Osmaelectrooxidative Catalysis
Authors: Choi Isaac , Messinis Antonis M. , Hou Xiaoyan , Ackermann Lutz
Published: October 2021

Herein, we disclose osmaelectrocatalyzed C−H activations that set the stage for electrooxidative alkyne annulations by benzoic acids. The osmium electrocatalysis enables site‐ and chemoselective electrooxidative C−H activations with unique levels of selectivity. The isolation of unprecedented osmium(0) and osmium(II) intermediates, along with crystallographic characterization and analyses by spectrometric and spectroscopic in operando techniques delineate a synergistic osmium redox catalyst regime. Detailed mechanistic studies revealed a facile C−H cleavage, which allows for an ample substrate scope, providing provide robust and user‐friendly access to annulated heterocycles.
Catalytic Asymmetric Inverse‐Electron‐Demand Diels–Alder Reactions of 2‐Pyrones with Indenes: Total Syntheses of Cephanolides A and B
Authors: Lu Yang , Xu Meng‐Meng , Zhang Zhi‐Mao , Zhang Junliang , Cai Quan
Published: October 2021

An inverse‐electron‐demand Diels–Alder (IEDDA) reaction could complement the conventional normal‐electron‐demand Diels–Alder reaction in the synthesis of six‐membered carbocycles. However, catalytic asymmetric all‐carbon‐based IEDDA reactions are underdeveloped. Herein, we disclosed a copper‐catalyzed asymmetric IEDDA reaction using electron‐deficient 3‐carboalkoxyl‐2‐pyrones and electronically unbiased indenes as reactants. This method enables the rapid and enantioselective construction of a wide range of hexahydrofluorenyl bridged‐lactone scaffolds. Using this method, asymmetric total syntheses of cephanolides A and B were accomplished.
Evolution of Cationic Vacancy Defects: A Motif for Surface Restructuration of OER Precatalyst
Authors: Wu Yi‐jin , Yang Jian , Tu Teng‐xiu , Li Wei‐qiong , Zhang Peng‐fang , Zhou Yao , Li Jian‐feng , Li Jun‐tao , Sun Shi‐Gang
Published: October 2021

Defects have been found to enhance the electrocatalytic performance of NiFe‐LDH for oxygen evolution reaction (OER). Nevertheless, their specific configuration and the role played in regulating the surface reconstruction of electrocatalysts remain ambiguous. Herein, cationic vacancy defects are generated via aprotic‐solvent‐solvation‐induced leaking of metal cations from NiFe‐LDH nanosheets. DFT calculation and in situ Raman spectroscopic observation both reveal that the as‐generated cationic vacancy defects tend to exist as VM (M=Ni/Fe); under increasing applied voltage, they tend to assume the configuration VMOH, and eventually transform into VMOH‐H which is the most active yet most difficult to form thermodynamically. Meanwhile, with increasing voltage the surface crystalline Ni(OH)x in the NiFe‐LDH is gradually converted into disordered status; under sufficiently high voltage when oxygen bubbles start to evolve, local NiOOH species become appearing, which is the residual product from the formation of vacancy VMOH‐H. Thus, we demonstrate that the cationic defects evolve along with increasing applied voltage (VM → VMOH → VMOH‐H), and reveal the essential motif for the surface restructuration process of NiFe‐LDH (crystalline Ni(OH)x → disordered Ni(OH)x → NiOOH). Our work provides insight into defect‐induced surface restructuration behaviors of NiFe‐LDH as a typical precatalyst for efficient OER electrocatalysis.
3D Binary Mesocrystals from Anisotropic Nanoparticles
Authors: Jenewein Christian , Avaro Jonathan , Appel Christian , Liebi Marianne , Cölfen Helmut
Published: October 2021

Binary mesocrystals offer the combination of nanocrystal properties in an ordered superstructure. Here, we demonstrate the simultaneous self‐assembly of platinum and iron oxide nanocubes into micrometer‐sized 3D mesocrystals using the gas‐phase diffusion technique. By the addition of minor amounts of a secondary particle type tailored to nearly identical size, shape and surface chemistry, we were able to promote a random incorporation of foreign particles into a self‐assembling host lattice. The random distribution of the binary particle types on the surface and within its bulk has been visualized using advanced transmission and scanning electron microscopy techniques. The 20–40 μm sized binary mesocrystals have been further characterized through wide and small angle scattering techniques to reveal a long‐range ordering on the atomic scale throughout the crystal while showing clear evidence that the material consists of individual building blocks. Through careful adjustments of the crystallization parameters, we could further obtain a reverse superstructure, where incorporated particles and host lattice switch roles.
General Tolerance of Galactosyltransferases toward UDP‐galactosamine Expands Their Synthetic Capability
Authors: Fu Xuan , Gadi Madhusudhan Reddy , Wang Shuaishuai , Han Jinghua , Liu Ding , Chen Xi , Yin Jun , Li Lei
Published: October 2021

Accessing large numbers of structurally diverse glycans and derivatives is essential to functional glycomics. We showed a general tolerance of galactosyltransferases toward uridine‐diphosphate‐galactosamine (UDP‐GalN), which is not a commonly used sugar nucleotide donor. The property was harnessed to develop a two‐step chemoenzymatic strategy for facile synthesis of novel and divergent N‐acetylgalactosamine (GalNAc)‐glycosides and derivatives in preparative scales. The discovery and the application of the new property of existing glycosyltransferases expand their catalytic capabilities in generating novel carbohydrate linkages, thus prompting the synthesis of diverse glycans and glycoconjugates for biological studies.
Co(II), Ni(II), Cu(II), and Zn(II) metal complexes of chalcone: Synthesis, characterization, thermal, antimicrobial, photocatalytic degradation of dye and molecular modeling studies
Authors: Johnson Jino , Yardily Amose
Published: October 2021

A thiazole‐based chalcone ligand and its bidentate Co(II), Ni(II), Cu(II), and Zn(II) complexes of general formula [M (DMTP)2], (DMTP = (E)‐3‐(3,4‐dimethoxyphenyl)‐1‐(thiazol‐2‐yl)prop‐2‐en‐1‐one) have been synthesized. The compounds were characterized by elemental analyses, molar conductance, fourier‐transform infrared (FTIR) spectra, 1H NMR, 13C NMR, mass, UV–Vis., magnetic susceptibility, and thermal and powder X‐ray diffraction (XRD) techniques. Based on spectral data, tetrahedral geometry is assigned for Co(II), Ni(II), and Zn(II) complexes. Square planar geometry was observed for Cu(II) complex. Molecular geometries of the compounds were fully optimized with density functional theory (DFT) computations. Additionally, the Lewis base character of DMTP, flexibility toward metal ions, structural stabilization on coordination, frontier molecular orbitals (FMO), quantum chemical parameters, and theoretical vibrational frequencies were evaluated. The antibacterial and antifungal (in vitro and in silico) activities of the complexes were studied and compared with those of DMTP. Finally, the metal(II) complexes of DMTP were successfully used to enhance the removal of methylene blue (MB) dye from an aqueous solution.
Pd (II) complexes bearing “SNS” pincer‐type thioether ligands: Application as catalysts in the synthesis of vitamin K3
Authors: Sogukomerogullari Hatice Gamze , Taskin Tok Tugba , Uruş Serhan , Sönmez Mehmet
Published: October 2021

The novel four SNS pincer‐type thioether containing Pd (II) complexes were synthesized and characterized by using FT‐IR, UV‐Vis, mass, elemental analysis techniques. The complexes were used as catalysts in the synthesis of vitamin K3 (2‐methyl‐1,4‐naphthoquinone) from 2‐methyl naphthalene. Hydrogen peroxide was used as green oxidant in acetic acid and sulfuric acid medium. L2‐Pd (II) and L3‐Pd (II) complexes showed the best catalytic activity with 62.63% and 61.05% selectivities in the conversions of 82.61% and 87.84%, respectively. Moreover, in silico studies on Pd (II) complexes have shown that L2‐Pd (II) and L3‐Pd (II) complexes have low band gaps between LUMO and HOMO energy levels and their electrostatic energy values are higher than other complex structures. This reveals that they have better chemical activity than other complexes and also supports the experimental studies carried out in this research. The conversions and the selectivities of these complexes are one of the best compared to the literature. Peroxyacetic acid with sulfuric acid is a very important oxidant in the oxidation of 2‐methyl naphthalene to 2‐methyl‐1,4‐naphthoquinone.
The challenge of detecting adverse events in adults with autism spectrum disorder who have intellectual disability
Authors: Ballester Pura , Espadas Cristina , Londoño Ana C. , Almenara Susana , Aguilar Victor , Belda Cesar , Pérez Enrique , Muriel Javier , Peiró Ana M.
Published: October 2021

Adults with autism spectrum disorder (ASD) and associated intellectual disability (ID) take a high number of different psychotropic drugs simultaneously. Nowadays, little is known about this multidrug pattern efficacy and safety. The present study has endeavored to fill this gap creating a local pharmacovigilance system. A 36‐month, retrospective and prospective, observational, and multicenter pharmacovigilance study was carried out in adults with ASD and ID (n = 83). Information regarding ongoing medications (polypharmacy: taking simultaneously >4 drugs; safety profile: adverse events' number, adverse drug reactions' number, and affected system; and observed‐to‐expected [O/E] ratio using the summary of product characteristics), and current diagnoses were recorded. A median of four ongoing medications per participant was registered, half of the sample was under polypharmacy regimen. Regarding all ongoing medications, 50% were antipsychotic drugs, and 47% of participants had >1 antipsychotic prescribed. In contrast, only 64 adverse events were identified from electronic health records, mostly due to risperidone. Half of them were related either to nervous or metabolic systems, and almost a third were not previously described in the corresponding drug summary of products characteristics. Extrapyramidalism, gynecomastia, hypercholesterolemia, and urinary retention were some AEs that occurred more frequently than expected (O/E ratio > 6 times) according to our data. The highest O/E ratio scores (>120 times) were for hypercholesterolemia and rhabdomyolysis caused by valproic acid. According to the number of adverse events and adverse drug reactions reported in electronic health records locally and nationally by clinicians, we need to increase awareness about medications safety.

Lay Summary

A 36‐month study in adults with autism, ID, and polypharmacy (>4 drugs) was done to investigate drug safety on everyone. A median of four medications per person was registered, half were antipsychotic drugs, and 47% of participants had >1 antipsychotic medication simultaneously. Only 64 adverse events were identified from electronic health records, mostly due to risperidone. Half of them were related to nervous or metabolic systems and a third were not previously described in the drug information sheet.
New Insights into Structural Evolution of LiNiO2 Revealed by Operando Neutron Diffraction
Authors: Chien Po‐Hsiu , Wu Xianyang , Song Bohang , Yang Zhijie , Waters Crystal K. , Everett Michelle S. , Lin Feng , Du Zhijia , Liu Jue
Published: October 2021

Invited for this month's cover picture is the group of Jue Liu and co‐workers. The front cover shows the operando neutron diffraction study of structural evolution of LiNiO2 cathode in a jelly‐type full cell. The anomalous increase of Ni−O bond length at high degrees of charge is successfully captured, bringing new insights into the structure and electronic structure evolution of LiNiO2 at deep charging states. Read the full text of the Article at 10.1002/batt.202100135.
What happens when someone violates FERPA
Authors: Rainsberger Richard
Published: October 2021

What has to happen for a school official to violate the Family Educational Rights and Privacy Act? That person has disclosed a student's education records illegally.
Trust and commitment: Effect of applying consumer data rights on U.S. Consumers' attitudes toward online retailers in big data era
Authors: Willis Brooke , Jai Tunmin (Catherine) , Lauderdale Mitzi
Published: October 2021

Applying the Commitment‐Trust Theory, this study investigates how a U.S.‐based online retailer's choice to apply (or not to apply) General Data Protection Regulation (GDPR) data subject rights to consumers in the United States affect the retailer‐customer relationship. This study conducted an online survey through Amazon Mechanical Turk (MTurk) with a total of 659 respondents. The findings provide empirical evidence that consumers perceived higher trust and lower privacy concerns toward online retailers when a retailer voluntarily applied the GDPR consumer data rights to U.S. consumers, thereby increasing brand commitment. The post hoc analyzes also revealed that when a global retailer chose to apply the GDPR consumer data rights to U.S. customers, the respondents' comments exhibited positive emotions and indicated they would be more willing to give the retailer their future business. These results are particularly relevant to international marketers and brands that serve both European and U.S. consumers.
Biomimetic DNA Nanotechnology to Understand and Control Cellular Responses
Authors: Sethi Soumya , Sugiyama Hiroshi , Endo Masayuki
Published: October 2021

At the cellular level, numerous nanocues guide the cells to adhere, interact, proliferate, differentiate, etc. Understanding and manipulating the cellular functions in vitro, necessitates the elucidation of these nanocues provided to the cells by the extracellular matrix (ECM), neighbouring cells or in the form of ligands. DNA nanotechnology is a biocompatible, flexible and a promising molecular level toolkit for mimicking cell‐cell and cell‐matrix interactions. In this review, we summarize various advances in cell‐matrix, cell‐cell and cell receptor‐ligand interactions using DNA nanotechnology as a tool. We also provide a brief outlook on the current challenges and the future potentials of these DNA‐based nanostructures so as to inspire novel innovations in the field.
Predictive Engineering of Class I Terpene Synthases Using Experimental and Computational Approaches
Authors: Leferink Nicole G. H. , Scrutton Nigel S.
Published: October 2021

Terpenoids are a highly diverse group of natural products with considerable industrial interest. Increasingly, engineered microbes are used for the production of terpenoids to replace natural extracts and chemical synthesis. Terpene synthases (TSs) show a high level of functional plasticity and are responsible for the vast structural diversity observed in natural terpenoids. Their relatively inert active sites guide intrinsically reactive linear carbocation intermediates along one of many cyclisation paths via exertion of subtle steric and electrostatic control. Due to the absence of a strong protein interaction with these intermediates, there is a remarkable lack of sequence‐function relationship within the TS family, making product‐outcome predictions from sequences alone challenging. This, in combination with the fact that many TSs produce multiple products from a single substrate hampers the design and use of TSs in the biomanufacturing of terpenoids. This review highlights recent advances in genome mining, computational modelling, high‐throughput screening, and machine‐learning that will allow more predictive engineering of these fascinating enzymes in the near future.
Impacts of Particle Properties on Gas Holdup under Four Flow Regimes in Three‐Phase Bubble Columns
Authors: Li Weiling , Zhou Genfu , Sun Jian , Guo Yafei , Wang Ruilin
Published: October 2021

The impacts of the solid volume fraction Vs and particle size dp on the total and local gas holdups in gas‐liquid‐solid bubble columns under different flow regimes were investigated. The flow regimes discussed were the discrete bubble regime (DBR), transition regime (TR), bubble coalescence regime (BCR), and strong turbulent regime (STR). The results demonstrated that the bed average gas holdup εg decreased with higher solid volume fraction in DBR, TR, and BCR. The increment of the solid volume fraction promoted bubble coalescence and also can enhance the particle effect on the average gas holdup. The εg changed slightly when shifting the Vs or dp in STR. A new correlation for εg was developed considering the particle properties and the flow regimes studied.
Incorporation of β‐Alanine in Cu(II) ATCUN Peptide Complexes Increases ROS Levels, DNA Cleavage and Antiproliferative Activity**
Authors: Heinrich Julian , Bossak‐Ahmad Karolina , Riisom Mie , Haeri Haleh H. , Steel Tasha R. , Hergl Vinja , Langhans Alexander , Schattschneider Corinna , Barrera Jannis , Jamieson Stephen M. F. , Stein Matthias , Hinderberger Dariush , Hartinger Christian G. , Bal Wojciech , Kulak Nora
Published: October 2021

Redox‐active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades. High complex stability results in silencing of the Cu(II)/Cu(I) redox cycle and therefore leads to low ROS generation. In this work, we demonstrate that an exchange of the α‐amino acid Gly with the β‐amino acid β‐Ala at position 2 (Gly2→β‐Ala2) of the ATCUN motif reinstates ROS production (•OH and H2O2). Potentiometry, cyclic voltammetry, EPR spectroscopy and DFT simulations were utilized to explain the increased ROS generation of these β‐Ala2‐containing ATCUN complexes. We also observed enhanced oxidative cleavage activity towards plasmid DNA for β‐Ala2 compared to the Gly2 complexes. Modifications with positively charged Lys residues increased the DNA affinity through electrostatic interactions as determined by UV/VIS, fluorescence, and CD spectroscopy, and consequently led to a further increase in nuclease activity. A similar trend was observed regarding the cytotoxic activity of the complexes against several human cancer cell lines where β‐Ala2 peptide complexes had lower IC50 values compared to Gly2. The higher cytotoxicity could be attributed to an increased cellular uptake as determined by ICP‐MS measurements.
In Situ Observation of Ferroelastic Domain and Phase Transition in a Three‐Dimensional Molecular Crystal
Authors: Cheng Sai‐Nan , Ding Kun , Zhang Tie , Zhang Zhi‐Xu , Su Chang‐Yuan , Ge Jia‐Zhen , Zhang Yi , Fu Da‐Wei
Published: October 2021

Massive efforts have been devoted to designing molecular ferroic materials by molecular modification. For molecular ferroelastic, previous work is focused on the temperature‐dependent ferroelastic domains, however, few are related to controlling the ferroelastic domain by the stress. Inspired by the “quasi‐spherical theory” and fluorination effect, we designed a more flexible (MedabcoF)2+ (MedabcoF=1‐fluoro‐4‐methyl‐1,4‐diazoniabicyclo[2.2.2]octane) cation by introducing a methyl group and a fluorine atom at the two symmetrical ends of the Dabco (1,4‐diazoniabicyclo[2.2.2]octane) and synthesized a hybrid 3D perovskite (MedabcoF)Rb(BF4)3 (1) which displays three reversible phase transitions accompanying dual ferroelastic behavior. Besides, it not only exhibits ferroelastic domains switching by the thermal stimulation, and the sensitive reaction of in situ domains under the stress of it is also realized. This work not only achieves a force‐controlled ferroelastic domain but develops a more profound comprehension of the relationship between the thermal motion behavior of guest cations and the intriguing properties of materials.
Diverse Ring‐seco Limonoids from Munronia unifoliolata and Their Biological Activities
Authors: Sun Yunpeng , Li Qiurong , Cui Letian , Tang Pengfei , Li Yongyi , Kong Lingyi , Luo Jun
Published: October 2021

Comprehensive Summary

Twenty‐two new limonoids, mufolinoids A—V (1—22), including six rings A, B‐seco limonoids (1—6), twelve ring A‐seco limonoids (7—18), four ring‐intact limonoids (19—22), together with thirteen known compounds (23—35) were isolated from Munronia unifoliolata. Their structures including absolute configurations were elucidated by combination of NMR, HR‐MS, single‐crystal X‐ray diffraction and calculations of ECD and NMR technologies. Compounds 24, 25, 33, 34 could be significantly reversed the multidrug resistance of MCF‐7/doxorubicin (DOX) cells, and the reversal fold (RF) was much higher than that of positive drug Verapamil. Compounds 24, 28, and 29 exhibited significant anti‐inflammatory activity with the IC50 values in the range of 17.7—39.4 μmol/L. Furthermore, compound 29 could markedly inhibit the release of IL‐1β by inhibiting the initiation and assembly of NLRP3 inflammasome, which demonstrates the great potential of limonoids as an anti‐inflammatory agent.
Blood Pressure Recovery After Dobutamine Antagonism: Partial With Landiolol, None With Esmolol
Authors: Krumpl Günther , Ulč Ivan , Trebs Michaela , Kadlecová Pavla , Hodisch Juri , Husch Bernhard
Published: October 2021

We investigated the hemodynamic effects of 2 short‐acting β1‐blockers, landiolol and esmolol, in the continuous presence of dobutamine in a prospective, single‐center, randomized, crossover study in 16 healthy White volunteers. Dobutamine was infused at a rate sufficient to increase the heart rate by at least 30 beats per minute, followed by a 60‐minute infusion of 50 μg/kg/min esmolol or 10 μg/kg/min landiolol on top of the unchanged dobutamine infusion. Concentrations of β‐blockers and their metabolites in blood, heart rate, and blood pressure were followed for 180 minutes. Landiolol reduced the dobutamine‐induced heart rate and blood pressure increases better than esmolol. After discontinuation of β‐blocker administration, heart rate recovered swiftly to preinfusion values in both study arms. Systolic and diastolic blood pressure recovered partially after landiolol but showed a continued reduction after esmolol. No serious adverse events were observed. The heart rate effect is characteristic for β‐blockers, whereas the blood pressure effects are likely due to direct and indirect β‐blocker effects as well as influences on various ion channels. This may explain why landiolol that is devoid of effects on renin and sodium, calcium, and potassium channels behaves different from esmolol with respect to blood pressure recovery.
Real‐Time, In Vivo Measurement of Protein Kinase A Activity in Deep Brain Structures Using Fluorescence Lifetime Photometry (FLiP)
Authors: Lodder Bart , Lee Suk Joon , Sabatini Bernardo L.
Published: October 2021

The biochemical state of neurons, and of cells in general, is regulated by extracellular factors, including neurotransmitters, neuromodulators, and growth hormones. Interactions of an animal with its environment trigger neuromodulator release and engage biochemical transduction cascades to modulate synapse and cell function. Although these processes are thought to enact behavioral adaption to changing environments, when and where in the brain they are induced has been mysterious because of the challenge of monitoring biochemical state in real time in defined neurons in behaving animals. Here, we describe a method allowing measurement of activity of protein kinase A (PKA), an important intracellular effector for neuromodulators, in freely moving mice. To monitor PKA activity in vivo, we use a genetically targeted sensor (FLIM‐AKAR) and fluorescence lifetime photometry (FLiP). This article describes how to set up a FLiP system and obtain robust recordings of net PKA phosphorylation state in vivo. The methods should be generally useful to monitor other pathways for which fluorescence lifetime reporters exist. © 2021 Wiley Periodicals LLC.

Basic Protocol 1: Building a FLiP system

Basic Protocol 2: FLIM‐AKAR viral injection and fiber implantation for FLiP measurement

Basic Protocol 3: Performing measurements using FLiP
Discovery in clinical and translational medicine
Authors: Wang Diane C , Wang Xiangdong
Published: October 2021

With the rapid development of biotechnologies and deep improvement of knowledge, “Discovery” is the initial period and source of innovation of clinical and translational medicine. The international journal of Clinical and Translational Discovery serves to highlight unknown or unclear aspects of clinical and translational medicine‐associated knowledge, technologies, mechanisms, and therapies (https://onlinelibrary.wiley.com/journal/27680622). The Discovery aims to define the interaction between genes, proteins, and cells, and explore molecular mechanisms of intercommunication and inter‐regulation. More discoveries of technologies and equipment are expected to improve method sensitivity, specificity, stability, analysis, and clinical significance. The first priority of Clinical and Translational Discovery is to turn gene‐, protein‐, drug‐, cell‐, and interaction‐based discoveries into health advancements. Clinical and Translational Discovery highly focuses on the discoveries of biological therapies and precision medicine‐based therapy elicited from computational chemistry, DNA libraries, target‐dependent small molecular drugs, high‐throughput screening, vaccination, immune therapy, cell implantations, gene editing, and RNA‐ or protein‐based inhibitors. Thus, Clinical and Translational Discovery sincerely welcome you to join and share the rapid development and future successes to come.
Advances in the detection of growth hormone releasing hormone synthetic analogs
Authors: Memdouh Siham , Gavrilović Ivana , Ng Kelsey , Cowan David , Abbate Vincenzo
Published: October 2021

The administration of growth hormone releasing hormone (GHRH) and its synthetic analogs is prohibited by the World Anti‐Doping Agency (WADA). Although there is evidence of their use, based on admissions and intelligence, they do not appear to have been found in anti‐doping samples by WADA accredited laboratories. This might be due to their small concentration in urine and limited knowledge about their metabolism, especially for unapproved synthetic analogs. This study investigates the in vitro metabolism and detection of four of the larger GHRH synthetic analogs (sermorelin, tesamorelin, CJC‐1295, and CJC‐1295 with drug affinity complex) in fortified urine. Nineteen major in vitro metabolites were identified, selected for synthesis, purified, and characterized in house. These were used as reference materials to spike into urine together with commercially available parent peptides and a metabolite of sermorelin (sermorelin(3‐29)‐NH2) to develop a sensitive liquid chromatography‐tandem mass spectrometry method for their detection to help prove GHRH administration. Limits of detection of the target peptides were generally 1 ng/ml (WADA required performance limit) or less.
Nenitzescu Synthesis of 5‐Hydroxyindoles with Zinc, Iron and Magnesium Salts in Cyclopentyl Methyl Ether
Authors: Satta Giuseppe , Usala Elena , Solinas Angelo , Römer Melina , Livesi Marco , Pira Giovanni Michele , Beccu Andrea , Carboni Silvia , Gaspa Silvia , De Luca Lidia , Pisano Luisa , Azzena Ugo , Carraro Massimo
Published: October 2021

In this work, mild Lewis acids and low environmental impact solvents were investigated for Nenitzescu synthesis. Cyclopentyl methyl ether can be used at room temperature in substitution of halogenated solvents with zinc, iron and magnesium salts as homogeneous catalysts to give 5‐hydroxyindoles in fair to good yields. The reaction features a straightforward workup and excellent solvent recycle.
Enantioselective Allylation of Cyclic and In Situ Formed N‐Unsubstituted Imines with Tetraol‐Protected Allylboronates
Authors: Ullrich Patrick , Schlamkow Max A. , Choi Ching‐Yi , Kerkenpaß Hannah , Henßen Birgit , Pietruszka Jörg
Published: October 2021

Tetraol‐protected α‐chiral allylboronates are utilized in diastereo‐ and enantioselective transformations of cyclic imines (up to 98 %, d.r. 97 : 3, e.r. 99 : 1). An application to in situ formed N‐unsubstituted imines gives in a consecutive one‐pot sequence selective access to all four stereoisomers of the homoallylamine within minutes (up to 88 %, d.r. 81 : 19, e.r. 99 : 1). These results underline the usability, tuneability and stability of tetraol‐based allylboronates.
Laboratory and Field Experimental Validation of Two Different Predation Sensors for Instrumenting Acoustic Transmitters in Fisheries Research
Authors: Lennox Robert J , Nilsen Cecilie I , Nash Ainslie , Hanssen Erlend M , Johannesen Hilde L , Berhe Saron , Barlaup Bjørn , Wiik Vollset Knut
Published: October 2021

We validated the performance of two types of predation sensors on acoustic telemetry transmitters in a combined field and laboratory study design using juvenile Atlantic Salmon Salmo salar and a predator large Brown Trout Salmo  trutta. One tag model was outfitted with an acid-sensitive predation sensor, and the other was equipped with a tilt-based orientation sensor. We found similar response times for the two tag types to identify a predation event (time between known ingestion of a tagged fish and triggering of the predation sensor). However, the orientation sensor model was more accurate in laboratory trials, correctly identifying 100% of events in which predators were fed the tagged fish, whereas correct identification of predation events was 50% for the acid-sensitive sensor in similar trials. The acid-sensitive tags were smaller (0.65 g in air), and all 10 were eventually expelled by predators in the laboratory (2–22 d after tag ingestion). By contrast, only two of five tags with orientation sensors (1.4 g in air) were expelled in a similar period (13 and 16 d after tag ingestion). Both tags had distinct benefits: acid-sensitive sensor tags were very small, and orientation sensor tags were seemingly more accurate and transmitted raw orientation data to receivers for postprocessing.
Anwendungsfälle des Fachmodells Baugrund – Empfehlung Nr. 3 des Arbeitskreises 2.14 der DGGT „Digitalisierung in der Geotechnik“
Authors: Molzahn Michael , Bauer Jörg , Henke Sascha , Tilger Klaus
Published: October 2021

Die dritte Empfehlung des Arbeitskreises 2.14 der DGGT „Digitalisierung in der Geotechnik“ definiert die wesentlichen Anwendungsfälle zur Umsetzung mit dem Fachmodell Baugrund. Anwendungsfälle beschreiben abgegrenzte, spezielle Projektleistungen im Lebenszyklus eines Bauprojekts hinsichtlich ihres Zwecks sowie deren Bearbeitungsinhalte und sind im BIM‐Kontext zu standardisieren. Dazu sind die vom BMVI für Infrastrukturbauwerke bereits identifizierten und exemplarisch beschriebenen Anwendungsfälle mit Blick auf einzelne Fachdisziplinen auszugestalten, zu konkretisieren und zu ergänzen. Für das Fachmodell Baugrund ergeben sich damit Anwendungsfälle, die unmittelbar mit diesem umgesetzt werden können, bei denen das Fachmodell Baugrund einen Teil der erforderlichen Eingangsdaten darstellt oder bei denen eine Ableitung (Schnitt) daraus verwendet wird. Bei der Umsetzung konkreter Bauprojekte findet vom Auftraggeber eine Auswahl aus standardisierten Anwendungsfällen statt, die Bestandteil der Auftraggeber‐Informationsanforderungen (AIA) werden. Damit verbunden sind Anforderungen an die digitalen Liefergegenstände zu bestimmten Entwicklungsstufen des Fachmodells Baugrund.
Cirrhosis regression is associated with improved clinical outcomes in patients with nonalcoholic steatohepatitis
Authors: Sanyal Arun J. , Anstee Quentin M. , Trauner Michael , Lawitz Eric J. , Abdelmalek Manal F. , Ding Dora , Han Ling , Jia Catherine , Huss Ryan S. , Chung Chuhan , Wong Vincent Wai‐Sun , Okanoue Takeshi , Romero‐Gomez Manuel , Muir Andrew J. , Afdhal Nezam H. , Bosch Jaime , Goodman Zachary , Harrison Stephen A. , Younossi Zobair M. , Myers Robert P.
Published: October 2021

Background and Aims

Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests (NITs) of fibrosis with liver‐related complications in patients with NASH cirrhosis.

Approach and Results

Patients with compensated cirrhosis due to NASH were enrolled in two placebo‐controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH Clinical Research Network (CRN) and Ishak classifications and a machine learning (ML) approach, hepatic collagen and alpha‐smooth muscle actin (α‐SMA) expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (enhanced liver fibrosis [ELF], NAFLD fibrosis score [NFS], and Fibrosis‐4 index [FIB‐4]) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver‐related clinical events. Among 1,135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow‐up of 16.6 months, 71 (6.3%) had a liver‐related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α‐SMA expression, ML‐based fibrosis parameters, LS, ELF, NFS, and FIB‐4. Cirrhosis regression observed in 16% (176/1,135) between BL and W48 was associated with a lower risk of events versus nonregression (1.1% [2/176] vs. 7.2% [69/957]; HR, 0.16; 95% CI, 0.04, 0.65 [p = 0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α‐SMA, ML‐based fibrosis parameters, NFS, and LS were associated with an increased risk of events.

Conclusions

In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver‐related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis.
Management of pre‐, peri‐, and post‐menopausal abnormal uterine bleeding: When to perform endometrial sampling?
Authors: Papakonstantinou Efthymia , Adonakis Georgios
Published: October 2021

Abnormal uterine bleeding (AUB) is defined as abnormal volume, duration, or frequency of menstrual period and is a common symptom in women of all ages (premenopausal, perimenopausal, and postmenopausal). The acronym PALM‐COEIN, introduced by the International Federation of Gynecology and Obstetrics (FIGO), facilitates the evaluation and differential diagnosis of AUB, mostly in premenopausal women with AUB. Endometrial evaluation (including ultrasound or hysteroscopic imaging and tissue sampling) for subtle pathology is proposed in patients who are at high risk for endometrial cancer and in patients at low risk who present with AUB and who present poor correspondence in medical treatment. Many new diagnostic modalities are available in clinicians in order to help the assessment of women presenting with abnormalities in their menstrual pattern. The present study reviews the optimal management of women presenting with AUB, taking into consideration the actual need for invasive management in these women, who of them require it, and who can be diagnosed without histological verification. The importance of endometrial tissue sampling in women who present with AUB as well as the best timing for a clinician to conduct a biopsy are two axons analyzed below, according to the latest worldwide guidelines and major publications about this subject.
Raman spectroscopy–based water measurements identify the origin of MRI T2 signal in human articular cartilage zones and predict histopathologic score
Authors: Unal Mustafa , Wilson Robert L. , Neu Corey P. , Akkus Ozan
Published: October 2021

We investigated for the first time zonal‐dependent water distribution in articular cartilage by Raman spectroscopy (RS). We further investigated the association of histopathologic score with RS‐ and magnetic resonance imaging (MRI)‐based water measurements. Cadaveric human cartilage plugs (N = 16) with different osteoarthritis (OA) severity were used. Water content distribution in cartilage zones was probed using RS‐ and MRI‐based techniques. Histopathologic scoring was performed by two independent observers blindly. Moderate associations existed between RS‐ and MRI‐based water measurements across all cartilage zones. RS‐based analysis of different water compartments helped assign the origin of the T2 signal collected from the various cartilage zones. RS‐based water parameters significantly correlated with OA‐severity score, whereas MRI‐based water measurements did not. RS can probe different water compartments in cartilage zones and predict up to 66% of the variation observed in the histopathologic score. RS‐based water measurement could be developed further to assess cartilage quality in the clinic.
The clinical significance of vitamin D levels and vitamin D receptor mRNA expression in colorectal neoplasms
Authors: Fang Ying , Song Haojun , Huang Jian , Zhou Jianbo , Ding Xiaoyun
Published: October 2021

Background/Aim

This study aimed to investigate the clinical significance of changes in vitamin D [25(OH)D] levels and vitamin D receptor (VDR) mRNA expression in colorectal adenoma development.

Methods

Plasma concentrations of 25(OH)D and mRNA expression of VDR in tissues were determined by enzyme‐linked immunosorbent assay (ELISA) and real‐time fluorescence quantitative polymerase chain reaction (RT‐qPCR), respectively. In addition, the concentration of plasma 25(OH)D and levels of VDR mRNA in tissues were compared among healthy individuals and adenoma and adenocarcinoma patients.

Results

Vitamin D receptor expression in colorectal adenocarcinoma tissues was significantly lower than that in para‐cancerous tissues that were >5 cm away from malignant tumor sites (p < 0.01). The level of VDR expression in normal colorectal tissues from healthy individuals was significantly higher than that in colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the VDR expression was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.106). The concentration of 25(OH)D in healthy individuals was significantly higher than that in patients with colorectal adenomas (p < 0.01) and colorectal adenocarcinomas (p < 0.01); however, the concentration of 25(OH)D was not significantly different between colorectal adenomas and colorectal adenocarcinomas (p = 0.489). A low concentration of 25(OH)D was considered a risk factor for colorectal adenoma and colorectal adenocarcinoma, with odds ratios of 4.875 and 2.925, respectively.

Conclusions

The 25(OH)D levels and VDR mRNA expression might be associated with the development of colorectal adenoma and its progression to adenocarcinoma.
Child neurocognitive functioning influences the effectiveness of specific techniques in behavioral teacher training for ADHD: Moderator analyses from a randomized controlled microtrial
Authors: Staff Anouck I. , Oosterlaan Jaap , van der Oord Saskia , Königs Marsh , van den Hoofdakker Barbara J. , Luman Marjolein
Published: October 2021

Background

Childhood attention‐deficit/hyperactivity disorder (ADHD) is associated with several neurocognitive impairments. Whether these impairments influence the effectiveness of techniques that are commonly used in behavioral teacher training for ADHD has not been investigated so far.

Method

In this microtrial, teachers of 90 children with ADHD symptoms (6–12 years) were randomly assigned to a short intervention consisting of either antecedent‐based (stimulus‐control) techniques or consequent‐based (contingency management) techniques, or to a waitlist control condition. Primary outcome was the daily assessment of individually selected problem behavior, assessed pre‐ and post‐intervention. Potential neurocognitive moderators of treatment effect included teacher ratings of cognitive control, reward, and punishment sensitivity, and measures derived from computerized neurocognitive tasks, including attentional lapses, interference control, visuospatial working memory, and emotional functioning. Intervention condition by moderator interactions were assessed in separate multilevel mixed models.

Results

Lapses of attention, working memory, and emotional functioning interacted with intervention effectiveness. Antecedent‐based techniques were effective independent of these neurocognitive functions; consequent‐based techniques were (more) effective when these functions were more impaired. The effectiveness of techniques was neither related to interference control nor to teacher‐rated neurocognitive functioning.

Conclusions

This study showed that child neurocognitive functioning influences the effectiveness of behavioral teacher techniques for children with ADHD symptoms. Findings suggest that antecedent‐based techniques may be effective for all children, while consequent‐based techniques have added value particularly for children who suffer from low visuospatial working memory, low emotional functioning, and/or large numbers of attentional lapses.