bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating resting energy expenditure from dual‐energy X‐ray absorptiometry: A cross‐sectional study in healthy young adults
Authors: Venturini Ana Cláudia Rossini , Silva Analiza Mónica , Abdalla Pedro Pugliesi , dos Santos André Pereira , Borges Franciane Goes , Alves Thiago Cândido , Siqueira Vitor Antonio Assis Alves , da Cruz Alves Natália Maíra , Ferriolli Eduardo , Coelho Eduardo Barbosa , Duncan Michael , Mota Jorge , Machado Dalmo Roberto Lopes
Published: July 2020

Objective

To qualify a 3C approach model of dual‐energy X‐ray absorptiometry (DXA) to estimate multicomponent resting energy expenditure (REE) referenced by indirect calorimetry (IC).

Methods

A sample of 155 college students, of both sexes (18‐30 years old) was evaluated. Anthropometric measures, REE by IC, and whole‐body DXA‐scans were performed. The REE for each body component was determined after transforming the components from the molecular (DXA) to the organ tissue level. Bland‐Altman and proportional bias analyses were used to verify agreement between REE measured (REEIC) and estimated (REEDXA).

Results

Statistically significant differences were found for all sex comparisons (P < .001), except for age (P = .950). Differences from the final sex‐specific models' were not found between REEIC and REEDXA (P > .05). Men also presented greater expenditure (P < .001) in each component, except for adipose tissue. The plots confirmed the validity of the model for both sexes, with low difference values between the measured and estimated REE. The mean of the differences of REEIC and REEDXA showed heteroscedasticity of the data for men (P = .004). The same error tendency was not evident for women (P = .333).

Conclusions

This 3C model, estimating REE from a multicomponent approach, allows a new application of DXA as tool for understanding intraindividual differences in terms of the mass of metabolically active tissue. Sex and populational differences should be taken in account. Consequently, we present qualified sex‐specific DXA models that can be applied in different contexts such as health and sports, besides considering interpersonal differences in terms of energy expenditure.
Large duplication in LMBR1 gene in a large Chinese pedigree with triphalangeal thumb polysyndactyly syndrome
Authors: Xu Jihai , Wu Jing , Teng Xiaofeng , Cai Libing , Yuan Huizong , Chen Xiaokun , Hu Mu , Wang Xin , Jiang Ning , Chen Hong
Published: July 2020

Polydactyly and syndactyly are digital abnormalities in limb‐associated birth defects usually caused by genetic disorders. In this study, a five‐generation Chinese pedigree was found with triphalangeal thumb polysyndactyly syndrome (TPTPS), showing an autosomal dominant pattern of inheritance. We utilized linkage analysis and whole genome sequencing (WGS) for the genetic diagnosis of this pedigree. Linkage analysis was performed using a genome‐wide single nucleotide polymorphism (SNP) chip and three genomic regions were identified in chromosomes 2, 6, and 7 with significant linkage signals. WGS discovered a copy number variation (CNV) mutation caused by a large duplication region at the tail of chromosome 7 located in exons 1–5 of the LMBR1 gene, including the zone of polarizing activity regulatory sequence (ZRS), with a length of approximately 180 kb. A real‐time polymerase chain reaction (PCR) assay confirmed the duplication. The findings of our study supported the notion that large duplications including the ZRS caused TPTPS. Our study showed that linkage analysis in combination with WGS could successfully identify the disease locus and causative mutation in TPTPS, which could help elucidate the molecular mechanisms and genotype–phenotype correlations in polydactyly.
Die Evolution des Diels‐Alder‐Reaktionsmechanismus seit den 1930er Jahren: Woodward, Houk zusammen mit Woodward und der Einfluss der Computerchemie auf das Verständnis von Cycloadditionen
Authors: Houk Kendall N. , Liu Fang , Yang Zhongyue , Seeman Jeffrey I.
Published: July 2020

Dieser Aufsatz beschreibt die Entwicklung von Woodwards mechanistischem Denken, beginnend in den späten 1930er und frühen 1940er Jahren mit seinem Vorschlag eines Ladungsübertragungsmechanismus in der Diels‐Alder‐Reaktion, der zum zweistufigen konzertierten Woodward‐Katz‐Mechanismus und schließlich zur mechanistischen Lösung in Bezug auf die Orbitalsymmetrie führte. Houks Zeit in den Woodward‐Labors, in der diese Theorie getestet wurde, wird beschrieben. Nachfolgende moderne Rechnungen haben gezeigt, dass Woodward nicht nur den Cyclopentadien‐Dimerisierungsmechanismus perfekt beschrieben hatte, sondern auch eine neue Klasse von Übergangszuständen – ambimodale oder bispericyclische Übergangszustände. In den letzten Jahren fand Houks Gruppe heraus, dass ambimodale Reaktionen in der [6+4]‐Cycloaddition wirksam sind. Moleküldynamik‐Simulationen vieler Diels‐Alder‐ und ambimodaler Cycloadditionen liefern ein zeitaufgelöstes Bild davon, wie diese Reaktionen ablaufen. Den Schluss bildet eine Coda von Roald Hoffmann, in der er seine Freude ausdrückt, auf die Reise der Cycloadditionsgeschichte von Woodwards Jugend bis zu den heutigen rechnergestützten Simulationen mitgenommen zu werden.
Ferroelectricity‐Driven Self‐Powered Ultraviolet Photodetection with Strong Polarization Sensitivity in a Two‐Dimensional Halide Hybrid Perovskite
Authors: Ji Chengmin , Dey Dhananjay , Peng Yu , Liu Xitao , Li Lina , Luo Junhua
Published: July 2020

Polarization‐sensitive ultraviolet (UV) photodetection is highly indispensable in military and civilian applications and has been demonstrated with various wide‐band photodetectors. However, it still remains elusive to achieve the self‐powered devices, which can be operated in the absence of external bias. Herein, for the first time, ferroelectricity‐driven self‐powered photodetection towards polarized UV light was successfully demonstrated in a 2D wide‐band gap hybrid ferroelectric (BPA)2PbBr4 (BPA=3‐bromopropylammonium) (1). We found that the prominent spontaneous polarization in 1 results in a bulk photovoltaic effect (BPVE) of 0.85 V, that independently drives photoexcited carriers separation and transport and thus supports self‐powered ability. This self‐powered detector shows strong polarization sensitivity to linearly polarized UV illumination with a polarization ratio up to 6.8, which is superior to that of previously reported UV‐polarized photodetectors (ZnO, GaN, and GeS2).
In Vitro Reconstitution Reveals a Central Role for the N‐Oxygenase PvfB in (Dihydro)pyrazine‐N‐oxide and Valdiazen Biosynthesis
Authors: Morgan Gina L. , Li Bo
Published: July 2020

The Pseudomonas virulence factor (pvf) operon is essential for the biosynthesis of two very different natural product scaffolds: the (dihydro)pyrazine‐N‐oxides and the diazeniumdiolate, valdiazen. PvfB is a member of the non‐heme diiron N‐oxygenase enzyme family that commonly convert anilines to their nitroaromatic counterparts. In contrast, we show that PvfB catalyzes N‐oxygenation of the α‐amine of valine, first to the hydroxylamine and then the nitroso, while linked to the carrier protein of PvfC. PvfB modification of PvfC‐tethered valine was observed directly by protein NMR spectroscopy, establishing the intermediacy of the hydroxylamine. This work reveals a central role for PvfB in the biosynthesis of (dihydro)pyrazine‐N‐oxides and valdiazen.
Quest for Zeolite‐like Supramolecular Assemblies: Self‐Assembly of Metal–Organic Squares via Directed Hydrogen Bonding
Authors: Li Jiantang , Kan Liang , Li Jiyang , Liu Yunling , Eddaoudi Mohamed
Published: July 2020

Our conceived approach based on the directed assembly of functional metal–organic squares (MOSs), 4‐membered ring (4MR) building units, permitted the construction of two novel zeolite‐like supramolecular assemblies (ZSAs), namely [Co4(ImDC)4(En)4]⋅9 H2O⋅1.5 DMF (ZSA‐10) and [Co4(ImDC)4(En)4]⋅7 H2O (ZSA‐11) (H3ImDC=4,5‐imidazoledicarboxylic acid, En=ethylenediamine, DMF=N,N‐dimethylformamide). The elected MOSs encompass both trans‐ and cis‐coordinated nodes, offering complementary peripheral functional groups for their directed assembly into zeolite‐like topologies via supramolecular hydrogen bonding interactions. Distinctly, ZSA‐10 possesses the underling MER zeolite topology and is the only pure MER framework material (without any supporting templates) exhibiting permanent porosity up to now. ZSA‐11 has the underlying ABW topology together with one type of narrow channel.
Duale Funktionalisierung von Fluorophoren für die Konstruktion zielgerichteter und selektiver Fluoreszenz‐Sensoren
Authors: Trinh Natalie , Jolliffe Katrina A. , New Elizabeth J.
Published: July 2020

Eine Schlüsselfrage in der gegenwärtigen biologischen Forschung ist, welche Rolle gewisse Chemikalien und chemische Reaktionen im Zusammenhang mit dem regulären zellulären Betrieb, als auch mit zellulären Störungen spielen. Von den gebräulichen Imaging‐Verfahren bietet das Fluoreszenz‐Imaging den Vorteil, dass es die Balance zwischen Sensitivität und Auflösung hält, und somit die kosteneffiziente und rapide Visualisierung biologischer Modell‐Systeme ermöglicht. Insbesondere ist die Verwendung responsiver Fluoreszenz‐Sensoren in Verbindung mit der technisch immerzu fortschreitenden Mikroskopie‐ und Durchflusszytometrie‐Technik vorteilhaft: Sie ermöglicht die Visualisierung von spezifischen chemischen Spezies als auch von chemischen Reaktionen mit hoher raum‐zeitlicher Auflösung in lebenden Zellen. Ein idealer responsiver Fluoreszenz‐Sensor besteht aus einem Fluorophor, der mit einer Fühler‐Gruppe, die die Selektivität der Rückmeldung sicherstellt, und einer Zielausrichtungs‐Gruppe, die die sub‐zelluläre Lokalisierung des Sensors kontrolliert, ausgestattet ist. Bis dato sind Fluoreszenz‐Sensoren, die zielgerichtet und selektiv sind, relativ rar und die meisten dieser Sensoren werden eher durch Zufall als durch rationales Design entdeckt. Eine zentrale Herausforderung in diesem Forschungsgebiet ist daher die Identifizierung geeigneter Fluorophor‐Grundgerüste, die ohne Weiteres mit Fühler‐ und Zielausrichtungs‐Gruppen versehen werden können. In diesem Kurzaufsatz besprechen wir gegenwärtige Strategien zur dualen Funktionalisierung von Fluorophoren und heben Schlüsselbeispiele zielgerichteter, responsiver Sensoren hervor.
Responsive Four‐Coordinate Iron(II) Nodes in FePd(CN)4
Authors: Ohtani Ryo , Matsunari Hiromu , Yamamoto Takafumi , Kimoto Koji , Isobe Masaaki , Fujii Kotaro , Yashima Masatomo , Fujii Susumu , Kuwabara Akihide , Hijikata Yuh , Noro Shin‐ichiro , Ohba Masaaki , Kageyama Hiroshi , Hayami Shinya
Published: July 2020

Metal node design is crucial for obtaining structurally diverse coordination polymers (CPs) and metal–organic frameworks with desirable properties; however, FeII ions are exclusively six‐coordinated. Herein, we present a cyanide‐bridged three‐dimensional (3D) CP, FePd(CN)4, bearing four‐coordinate FeII ions, which is synthesized by thermal treatment of a two‐dimensional (2D) six‐coordinate FeII CP, Fe(H2O)2Pd(CN)4⋅4 H2O, to remove water molecules. Atomic‐resolution transmission electron microscopy and powder X‐ray and neutron diffraction measurements revealed that the FePd(CN)4 structure is composed of a two‐fold interpenetrated PtS topology network, where the FeII center demonstrates an intermediate geometry between tetrahedral and square‐planar coordination. This four‐coordinate FeII center with the distorted geometry can act as a thermo‐responsive flexible node in the PtS network.
Current Status of COVID‐19 (Pre)Clinical Vaccine Development
Authors: Ye Tingting , Zhong Zifu , García‐Sastre Adolfo , Schotsaert Michael , De Geest Bruno G.
Published: July 2020

The current COVID‐19 pandemic has a tremendous impact on daily life world‐wide. Despite the ability to dampen the spread of SARS‐CoV‐2, the causative agent of the diseases, through restrictive interventions, it is believed that only effective vaccines will provide sufficient control over the disease and revert societal live back to normal. At present, a double‐digit number of efforts are devoted to the development of a vaccine against COVID‐19. Here, we provide an overview of these (pre)clinical efforts and provide background information on the technologies behind these vaccines. In addition, we discuss potential hurdles that need to be addressed prior to mass scale clinical translation of successful vaccine candidates.
Electrocatalytic Deuteration of Halides with D2O as the Deuterium Source over a Copper Nanowire Arrays Cathode
Authors: Liu Cuibo , Han Shuyan , Li Mengyang , Chong Xiaodan , Zhang Bin
Published: July 2020

Precise deuterium incorporation with controllable deuterated sites is extremely desirable. Here, a facile and efficient electrocatalytic deuterodehalogenation of halides using D2O as the deuteration reagent and copper nanowire arrays (Cu NWAs) electrochemically formed in situ as the cathode was demonstrated. A cross‐coupling of carbon and deuterium free radicals might be involved for this ipso‐selective deuteration. This method exhibited excellent chemoselectivity and high compatibility with the easily reducible functional groups (C=C, C≡C, C=O, C=N, C≡N). The C−H to C−D transformations were achieved with high yields and deuterium ratios through a one‐pot halogenation–deuterodehalogenation process. Efficient deuteration of less‐active bromide substrates, specific deuterium incorporation into top‐selling pharmaceuticals, and oxidant‐free paired anodic synthesis of high‐value chemicals with low energy input highlighted the potential practicality.
Enantioselective Synthesis of cis‐Decalin Derivatives by the Inverse‐Electron‐Demand Diels–Alder Reaction of 2‐Pyrones
Authors: Si Xu‐Ge , Zhang Zhi‐Mao , Zheng Cheng‐Gong , Li Zhan‐Ting , Cai Quan
Published: July 2020

A novel strategy for the synthesis of cis‐decalins by an ytterbium‐catalyzed asymmetric inverse‐electron‐demand Diels–Alder reaction of 2‐pyrones and silyl cyclohexadienol ethers is reported here. A broad range of synthetically important cis‐decalin derivatives with multiple contiguous stereogenic centers and functionalities are obtained in good yields and stereoselectivities. A full set of diastereomeric substituted cis‐decalin motifs are readily accessible by tuning the absolute configurations of substituted silyl cyclohexadienol ethers (R or S) as well as the ligands (R or S). The synthetic potential is showcased by the enantioselective total synthesis of 4‐amorphen‐11‐ol, and further demonstrated by the first total synthesis of cis‐crotonin.
Designing AI‐Aided Analysis and Prediction Models for Nonprecious Metal Electrocatalyst‐Based Proton‐Exchange Membrane Fuel Cells
Authors: Ding Rui , Wang Ran , Ding Yiqin , Yin Wenjuan , Liu Yide , Li Jia , Liu Jianguo
Published: July 2020

Traditionally, a larger number of experiments are needed to optimize the performance of the membrane electrode assembly (MEA) in proton‐exchange membrane fuel cells (PEMFCs) since it involves complex electrochemical, thermodynamic, and hydrodynamic processes. Herein, we introduce artificial intelligence (AI)‐aided models for the first time to determine key parameters for nonprecious metal electrocatalyst‐based PEMFCs, thus avoiding unnecessary experiments during MEA development. Among 16 competing algorithms widely applied in the AI field, decision tree and XGBoost showed good accuracy (86.7 % and 91.4 %) in determining key factors for high‐performance MEA. Artificial neural network (ANN) shows the best accuracy (R2=0.9621) in terms of predictions of the maximum power density and a decent reproducibility (R2>0.99) on uncharted I–V polarization curves with 26 input features. Hence, machine learning is shown to be an excellent method for improving the efficiency of MEA design and experiments.
Dual‐Functionalisation of Fluorophores for the Preparation of Targeted and Selective Probes
Authors: Trinh Natalie , Jolliffe Katrina A. , New Elizabeth J.
Published: July 2020

A key current challenge in biological research is the elucidation of the that roles chemicals and chemical reactions play in cellular function and dysfunction. Of the available cellular imaging techniques, fluorescence imaging offers a balance between sensitivity and resolution, enabling the cost‐effective and rapid visualisation of model biological systems. Importantly, the use of responsive fluorescent probes in conjunction with ever‐advancing microscopy and flow cytometry techniques enables the visualisation, with high spatiotemporal resolution, of both specific chemical species and chemical reactions in living cells. Ideal responsive fluorescent probes are those that contain a fluorophore tethered to both a sensing unit, to ensure selectivity of response, and a targeting group, to control the sub‐cellular localisation of the probe. To date, probes that are both targeted and selective are relatively rare and most localised probes are discovered serendipitously rather than by design. A challenge in this field is therefore the identification of suitable fluorophore scaffolds that can be readily attached to both sensing and targeting groups. Here we review current strategies for dual‐functionalisation of fluorophores, highlighting key examples of targeted, responsive probes.
Multiple‐Color Platinum Complex with Super‐Large Stokes Shift for Super‐Resolution Imaging of Autolysosome Escape
Authors: Liu Liu‐Yi , Fang Hongbao , Chen Qixin , Chan Michael Ho‐Yeung , Ng Maggie , Wang Kang‐Nan , Liu Wenting , Tian Zhiqi , Diao Jiajie , Mao Zong‐Wan , Yam Vivian Wing‐Wah
Published: July 2020

It is of great significance to track the platinum drugs in real time with super‐resolution to elucidate their mechanism of action, such as their behavior and distribution in live cells. Such information is required for further drug development. However, it is always challenging to design platinum complexes suitable for such research. Herein, we design a luminescent building block (L) for metal complexes and a dinuclear platinum complex (Pt2L) for super‐resolution imaging. Because of its super‐large Stokes shift and excellent photophysical properties, Pt2L is capable of serving as an ideal candidate for super‐resolution imaging with extremely low luminescence background and high photobleaching resistance. Moreover, upon light stimulation, a matter flux of Pt2L escaping from autolysosomes to nucleus was observed, which represents a new transportation path. Utilizing the photoactivated escape properties, we can regulate the nuclear accessibility of Pt2L form autolysosomes with photo‐selectivity, which provides a new way to improve the targeting of platinum drugs.
A Dearomatization/Debromination Strategy for the [4+1] Spiroannulation of Bromophenols with α,β‐Unsaturated Imines
Authors: Ge Yicong , Qin Cheng , Bai Lu , Hao Jiamao , Liu Jingjing , Luan Xinjun
Published: July 2020

A novel [4+1] spiroannulation ofo‐ &p‐bromophenols with α,β‐unsaturated imines has been developed for the direct synthesis of a new family of azaspirocyclic molecules. Notably, several other halophenols (X=Cl, I) were also applicable for this transformation. Moreover, a catalytic asymmetric version of the reaction was realized with 1‐bromo‐2‐naphthols by using a chiral ScIII/Py‐Box catalyst. Mechanistic studies revealed that this domino reaction proceeded through electrophile‐triggered dearomatization of phenol derivatives at their halogenated positions and followed by halogen‐displacement withN‐nucleophiles via a radical‐based SRN1 mechanism.
A Synergistic Enhancement Strategy for Realizing Ultralong and Efficient Room‐Temperature Phosphorescence
Authors: Zhang Zhi‐Yuan , Xu Wen‐Wen , Xu Wen‐Shi , Niu Jie , Sun Xiao‐Han , Liu Yu
Published: July 2020

An enhancement strategy is realized for ultralong bright room‐temperature phosphorescence (RTP), involving polymerization between phosphor monomers and acrylamide and host–guest complexation interaction between phosphors and cucurbit[6,7,8]urils (CB[6,7,8]). The non‐phosphorescent monomers exhibit 2.46 s ultralong lifetime after copolymerizing with acrylamide. The improvement is due to the rich hydrogen bond and carbonyl within the polymers which promote intersystem crossing, suppress nonradiative relaxation and shield quenchers effectively. By tuning the ratio of chromophores, a series of phosphorescent copolymers with different lifetimes and quantum yields are prepared. The complexation of macrocyclic hosts CB[6,7,8] promote the RTP of polymers by blocking aggregation‐caused quenching, and offsetting the losses of aforementioned interaction provided by polymer. Multiple lifetime‐encoding for digit and character encryption are achieved by utilizing the difference of their lifetimes.
Pendant Alkoxy Groups on N‐Aryl Substitutions Drive the Efficiency of Imidazolylidene Catalysts for Homoenolate Annulation from Enal and Aldehyde
Authors: Kyan Ryuji , Sato Kohei , Mase Nobuyuki , Narumi Tetsuo
Published: July 2020

Hydrogen‐transfer in the tetrahedral intermediate generated from an imidazolylidene catalyst and α,β‐unsaturated aldehyde forms a conjugated Breslow intermediate. This is a critical step affecting the efficiency of the NHC‐catalyzed γ‐butyrolactone formation via homoenolate addition to aryl aldehydes. A novel type of imidazolylidene catalyst with pendant alkoxy groups on the ortho‐N‐aryl groups is described. Catalyst of this sort facilitates the formation of the conjugated Breslow intermediate. Studies of the rate constants for homoenolate annulation affording γ‐butyrolactones, reveal that introduction of the oxygen atoms in the appropriate position of the N‐aryl substituents can increase the efficiency of imidazolylidene catalysts. Structural and mechanistic studies revealed that pendant alkoxy groups can be located close to the proton of the tetrahedral intermediate, thereby facilitating the proton transfer.
α‐FeOOH−MoO3 Nanorod for Effective Photo‐Fenton Degradation of Dyes and Antibiotics at a Wide Range of pH
Authors: Xing Wenxin , Zhou Liang , Chen Bin , Lei Juying , Wang Lingzhi , Zhang Jinlong
Published: July 2020

It's highly significant to develop a novel catalyst, which can be active at a wide range of pH, for an effective photo‐Fenton reaction. In this work, α‐FeOOH−MoO3 nanorod was prepared by a one‐step hydrothermal method and applied in photo‐Fenton degradation of organic pollutants. Benefit from the electron migration mechanism of Z‐scheme and excellent photoelectric performance, the catalyst exhibited superior photo‐Fenton activity in degradation of organic pollutants. In addition, the catalyst holds good stability after 5 recycles. These results demonstrated that this catalyst has wide application prospect in organic wastewater treatment.
Exosomal LINC01005 derived from oxidized low‐density lipoprotein‐treated endothelial cells regulates vascular smooth muscle cell phenotypic switch
Authors: Zhang Zhiliang , Yi Dasong , Zhou Jiamin , Zheng Yaofu , Gao Zhiming , Hu Xiaoliang , Ying Guoqiu , Peng Xiaoping , Wen Tong
Published: July 2020

Phenotype switch of vascular smooth muscle cells (VSMCs) plays an important role in the development of atherosclerosis (AS). Endothelial cells can regulate VSMC phenotypic switch by secreting exosomes, crucial mediators of intracellular communication. This study aimed to determine whether exosomal LINC01005 from oxidized low‐density lipoprotein (ox‐LDL)‐treated human umbilical vein endothelial cells (HUVECs) plays a role in regulating VSMC phenotypic switch and to validate the underlying molecular mechanism. Exosomes were extracted from ox‐LDL‐treated HUVECs (ox‐LDL‐Exo) and then administered into VSMCs. VSMC phenotypic switch was assessed by determining VSMC phenotypic markers using western blot. VSMC cell proliferation and migration were evaluated by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay and wound healing assay, respectively. The interaction between miR‐128‐3p and LINC01005 or Krüppel‐like factor 4 (KLF4) was analyzed by luciferase reporter assay. ox‐LDL‐Exo contained high expression of LINC01005. Inhibition of LINC01005 expression in ox‐LDL‐Exo abrogated the ox‐LDL‐Exo‐induced VSMC phenotypic switch, proliferation, and migration. Furthermore, LINC01005 acted as a sponge of miR‐128‐3p to upregulate KLF4 expression. Moreover, miR‐128‐3p overexpression and KLF4 silencing in VSMCs attenuated the ox‐LDL‐Exo‐induced VSMC phenotypic switch, proliferation, and migration. Collectively, exosomal LINC01005 from ox‐LDL‐treated HUVECs promotes VSMC phenotype switch, proliferation, and migration by regulating the miR‐128‐3p/KLF4 axis.
Biocompatibility of Biomaterials for Tissue Regeneration or Replacement
Authors: Raut Hemant Kumar , Das Rupambika , Liu Ziqian , Liu Xiaoling , Ramakrishna Seeram
Published: July 2020

Emerging biomaterials for tissue engineering applications witness a multitude of interaction (both along their interface and internally) with human tissue. Insufficient consideration of the spatial and temporal aspects of these biomaterial‐tissue interactions often raise biocompatibility concerns. This review focuses on strategies implemented in some of the recently developed biomaterials—particularly for soft and hard tissue regeneration or replacement—to overcome potential foreign body response and ensure effective functioning of the biomaterial.
Random epigenetic modulation of CHO cells by repeated knockdown of DNA methyltransferases increases population diversity and enables sorting of cells with higher production capacities
Authors: Weinguny Marcus , Eisenhut Peter , Klanert Gerald , Virgolini Nikolaus , Marx Nicolas , Jonsson Andreas , Ivansson Daniel , Lövgren Ann , Borth Nicole
Published: July 2020

Chinese hamster ovary (CHO) cells produce a large share of today's biopharmaceuticals. Still, the generation of satisfactory producer cell lines is a tedious undertaking. Recently, it was found that CHO cells, when exposed to new environmental conditions, modify their epigenome, suggesting that cells adapt their gene expression pattern to handle new challenges. The major aim of the present study was to employ artificially induced, random changes in the DNA‐methylation pattern of CHO cells to diversify cell populations and consequently increase the finding of cell lines with improved cellular characteristics. To achieve this, DNA methyltransferases and/or the ten‐eleven translocation enzymes were downregulated by RNA interference over a time span of ∼16 days. Methylation analysis of the resulting cell pools revealed that the knockdown of DNA methyltransferases was highly effective in randomly demethylating the genome. The same approach, when applied to stable CHO producer cells resulted in (a) an increased productivity diversity in the cell population, and (b) a higher number of outliers within the population, which resulted in higher specific productivity and titer in the sorted cells. These findings suggest that epigenetics play a previously underestimated, but actually important role in defining the overall cellular behavior of production clones.
Media supplementation for targeted manipulation of monoclonal antibody galactosylation and fucosylation
Authors: Wells Evan , Song Liqing , Greer Madison , Luo Yu , Kurian Varghese , Ogunnaike Babatunde , Robinson Anne S.
Published: July 2020

Monoclonal antibodies are critically important biologics as the largest class of molecules used to treat cancers, rheumatoid arthritis, and other chronic diseases. Antibody glycosylation is a critical quality attribute that has ramifications for patient safety and physiological efficacy—one that can be modified by such factors as media formulation and process conditions during production. Using a design‐of‐experiments approach, we examined the effect of 2‐F‐peracetyl fucose (2FP), uridine, and galactose on cell growth and metabolism, titer, and gene expression of key glycosylation‐related proteins, and report how the glycoform distribution changed from Days 4 to 7 in a batch process used for IgG1 production from Chinese hamster ovary cells. We observed major glycosylation changes upon supplement addition, where the addition of 2FP decreased antibody fucosylation by up to 48%, galactose addition increased galactosylation by up to 21%, and uridine addition decreased fucosylation and increased galactosylation by 6% and 2%, respectively. Despite having major effects on glycosylation, neither galactose nor 2FP significantly affected cell culture growth, metabolism, or titer. Uridine improved peak cell densities by 23% but also reduced titer by ∼30%. The supplements caused significant changes in gene expression by Day 4 of the cultures where 2FP addition significantly reduced fucosyltransferase 8 and nucleotide sugar transporter gene expression (by ∼2‐fold), and uridine addition significantly increased expression of UDP‐GlcNAcT (SLC35A3) and B4GALT1–6 genes (by 1.5–3‐fold). These gene expression data alongside glycosylation, metabolic, and growth data improve our understanding of the cellular mechanisms affected by media supplementation and suggest approaches for modifying antibody glycosylation in antibody production processes.
Metabolome responses of Enterococcus faecium to acid shock and nitrite stress
Authors: Yu Zhong , Shi Dongchen , Liu Wencong , Meng Yabing , Meng Fangang
Published: July 2020

Enterococcus faecium is gaining increasing interest due to its virulence and tolerance to a range of stresses (e.g., acid shock and nitrite stress in human stomach). The chemical taxonomy and basic structural features of cellular metabolite can provide us a deeper understanding of bacterial tolerance at molecular level. Here, we used hierarchical classification and molecular composition analysis to investigate the metabolome responses of E. faecium to acid shock and nitrite stress. Our results showed that considerable high biodegradable compounds (e.g., dipeptides) were produced by E. faecium under acid shock, while nitrite stress induced the accumulations of some low biodegradable compounds (e.g., organoheterocyclic compounds and benzenoids). Complete genome analysis and metabolic pathway profiling suggested that E. faecium produced high biodegradable metabolites responsible for the proton‐translocation and biofilm formation, which increase its tolerance to acid shock. Yet, the presence of low biodegradable metabolites due to the nitrite exposure could disturb the bacterial productions of surface proteins, and thus inhibiting biofilm formation. Our approach uncovered the hidden interactions between intracellular metabolites and exogenous stress, and will improve the understanding of host‐microbe interactions.
Addressing endogeneity by proposing novel instrumental variables in the nexus of sustainability reporting and firm financial performance: A step‐by‐step procedure for non‐experts
Authors: Zahid Muhammad , Rahman Haseeb Ur , Khan Musa , Ali Wajahat , Shad Fazaila
Published: July 2020

Most of the prior literature that investigated the nexus between corporate sustainability disclosures (CSD) and firm financial performance (FFP) has largely been ignored the potential problem of endogeneity. The omitted variable(s), measurement error, and reverse causality, which are the known causes of endogeneity, may also be the possible reasons for the indecisive and inconsistent relationship between CSD and FFP. Accordingly, this study reinvestigates the relationship by addressing the problem of endogeneity through applying the two‐stage least squares (2SLS) estimator to data collected from the annual reports of the top 10 Pakistani banks through content analysis from 2013 to 2017. The results show a positive impact of the CSD and social sustainability on FFP. However, environmental sustainability exerted a negative impact on FFP. The statistics for 2SLS are much different than those of the ordinary least squares (OLS), which explain the importance of addressing the endogeneity bias. The study offers a methodological procedure that identifies and addresses the endogeneity through a step‐by‐step process in Stata 13.0. Besides, the study also has a novelty to propose and validate additional instrumental variables for the research in the future. Overall, the study has many contributions and implications for different stakeholders such as academia, regulatory bodies, and practitioners in the field of corporate sustainability.
An optimization‐based decision support system for students' personalized long‐term course planning
Authors: Shakhsi‐Niaei Majid , Abuei‐Mehrizi Hossein
Published: July 2020

This paper intends to facilitate academic advising by means of optimal long‐term course planning (LTCP), which is instrumental in students' retention and success. LTCP ensures that students will satisfy the educational requirements without facing unnecessary delays. The proposed decision support system is based on an optimization model which deals with several student preferences, that is, maximum credits per semester, difficulty of courses, graduation semester, and elective courses priorities. The proposed system has been implemented in an industrial engineering department, and several improvements and modifications have been done based on student feedback. The developed system supports two kind of users, that is, educational staff and the students. The courses, their relationships, and regulation parameters are defined/set by educational staff, whereas students determine their own information and preferences, for example, finished courses, graduation target, interest for each elective course, complexity of courses, course load and complexity for each semester, and relative weights of objective functions. Considering theoretical issues, common applications have been integrated to form this system with simple and user‐friendly interfaces.
Review process for complying with new Title IX regulations
Authors: McCarthy Claudine
Published: July 2020

Your institution has until Aug. 14 to comply with the new Title IX regulations issued by the Department of Education. To help colleges and universities comply with the changes, a webinar panel of education and employment attorneys with McGuireWoods LLP discussed the topic.
Understand IP considerations regarding online instruction
Authors: Rooksby Jacob H.
Published: July 2020

When higher education moved online this past spring because of the outbreak of the novel coronavirus, few faculty or administrators had time to stop and ponder the intellectual property–related questions regarding remote instruction. Do faculty own materials used when teaching remotely, or does the university (as employer and software provider) have a claim? Can faculty use material protected by copyright in a remote‐learning course? What's the role of university IP policies? Who owns class recordings?
Towards Zwitterionic Oligonucleotides with Improved Properties: the NAA/LNA‐Gapmer Approach
Authors: Wojtyniak Melissa , Schmidtgall Boris , Kirsch Philine , Ducho Christian
Published: July 2020

Oligonucleotides (ON) are promising therapeutic candidates, for instance by blocking endogenous mRNA (antisense mechanism). However, ON usually require structural modifications of the native nucleic acid backbone to ensure satisfying pharmacokinetic properties. One such strategy to design novel antisense oligonucleotides is to replace native phosphate diester units by positively charged artificial linkages, thus leading to (partially) zwitterionic backbone structures. Herein, we report a “gapmer” architecture comprised of one zwitterionic central segment (“gap”) containing nucleosyl amino acid (NAA) modifications and two outer segments of locked nucleic acid (LNA). This NAA/LNA‐gapmer approach furnished a partially zwitterionic ON with optimised properties: i) the formation of stable ON‐RNA duplexes with base‐pairing fidelity and superior target selectivity at 37 °C; and ii) excellent stability in complex biological media. Overall, the NAA/LNA‐gapmer approach is thus established as a strategy to design partially zwitterionic ON for the future development of novel antisense agents.
Analysis of the expression and association of retinoblastoma binding protein 6 with the JNK signaling pathway in prostate cancers
Authors: Guan Wen‐Ying , Zhao Sheng , Luo Yun‐Na
Published: July 2020

This study aims to investigate the expression of retinoblastoma binding protein 6 (RBBP6) in prostate cancer (PCa) and its association with the c‐Jun N‐terminal kinase (JNK) pathway. Immunohistochemistry was used to detect RBBP6 and JNK1/2 expression in PCa and benign prostatic hyperplasia tissues. RBBP6 expression in PCa cells (LNCap, PC3, and DU145) and noncancerous prostate epithelial cells (RWPE‐1) was determined by quantitative real‐time polymerase chain reaction and western blot analysis. PC3 and DU145 cells were transfected with RBBP6 small interfering RNAs (siRNAs) to examine the biological characteristics. Anisomycin (a JNK activator) with/without RBBP6 siRNA was used to treat PC3 cells for further investigating the ramification of the RBBP6‐mediated JNK pathway in PCa. PCa tissues and cells showed higher RBBP6 and JNK1/2 expression. RBBP6 was positively correlated with JNK1/2 in PCa tissues. Besides, RBBP6 expression was correlated to clinical tumor stage, lymph node metastasis, Gleason grade, preoperative prostate‐specific antigen level, as well as prognosis of PCa. RBBP6 siRNA reduced cell proliferation, arrested cells at G2/M, and promoted cell apoptosis, and suppressed JNK pathway. In addition, migration and invasion decreased after the RBBP6 siRNA transfection with downregulated matrix metallopeptidase‐2 (MMP‐2) and MMP‐9. Anisomycin promoted the proliferation, invasion, and migration of PC3 cells and inhibited PC3 cell apoptosis, which could be reversed by RBBP6 siRNA. RBBP6 expression was upregulated in PCa tissues and positively correlated with expression level of JNK1/2. With inhibition of RBBP6 expression, the proliferation, invasion, and migration of PCa cells decreased dramatically, while PC3 cell apoptosis increased appreciably, accompanied by the suppression of the JNK pathway.
Macroscopic MXene ribbon with oriented sheet stacking for high‐performance flexible supercapacitors
Authors: Zhu Chao , Geng Fengxia
Published: July 2020

Flexible and wearable fiber electrodes with high conductivity and acceptable electrochemical behavior are crucial for extending the application of next‐generation portable electronics, the development of which, however, is very challenging. Two‐dimensional sheets are known to be excellent units for assembling fiber entities, particularly when sheets are oriented in a stacking manner, which helps integrate their intrinsic in‐plane advantages, especially those related with mechanical and electronic performances. In this study, we developed a flexible macroscopic and continuous fiber in an unusual ribbon shape composed solely of Ti3C2 sheets, a typical member of the MXene family. The ribbon morphology was realized through highly ordered stacking of Ti3C2, which imparts fibers with favorable mechanical characteristics. Based on the intrinsic metallic conductivity of Ti3C2 sheets and the oriented stacking structure, the developed macroscopic ribbon exhibited excellent conductivity for both electrons (up to 2458 S/cm) and ions. A fiber‐shaped asymmetric supercapacitor using the developed macroscopic ribbon as a cathode coupled with reduced graphene oxide fibers as an anode delivered a competitive maximum volumetric energy density of 58.4 mWh/cm3 (20.0 Wh/kg) while maintaining a power level of 1679.0 mW/cm3 (581.0 W/kg) and excellent cycling stability (92.4% retention after 10 000 cycles at 10 A/g). This study highlights the excellent potential of MXene as a platform for macroscopic assembly and definitely broadens the applications of MXene materials in wearable electronics.
Insight into the Effect of ZIF‐8 Particle Size on the Performance in Nanocarbon‐Based Supercapacitors
Authors: Wen Yanliang , Chen Xuecheng , Mijowska Ewa
Published: July 2020

Carbon materials derived from zeolitic imidazolate framework‐8 (ZIF‐8) and composites thereof have been intensively investigated in supercapacitors. The particle size of the used ZIF‐8 ranges from dozens of nanometers to several microns. However, the influence of the particle size of ZIF‐8 on the capacitive performances is still not clear. A series of ZIF‐8 with different particle sizes (from 25 to 296 nm) has been synthesized and carbonized for supercapacitors. Based on TEM, EDX mapping, XRD, Raman, nitrogen adsorption–desorption, XPS, and the results of electrochemical tests, the optimal particle size (≈70 nm) for superior supercapacitor performances in both acidic and alkaline electrolytes has been obtained. This important result provides a significant reference to guide future ZIF‐8 related research to achieve the best electrochemical performance.
[Ga3+8Sm3+2, Ga3+8Tb3+2] Metallacrowns are Highly Promising Ratiometric Luminescent Molecular Nanothermometers Operating at Physiologically Relevant Temperatures
Authors: Salerno Elvin V. , Zeler Justyna , Eliseeva Svetlana V. , Hernández‐Rodríguez Miguel A. , Carneiro Neto Albano N. , Petoud Stéphane , Pecoraro Vincent L. , Carlos Luís D.
Published: July 2020

Nanothermometry is the study of temperature at the submicron scale with a broad range of potential applications, such as cellular studies or electronics. Molecular luminescent‐based nanothermometers offer a non‐contact means to record these temperatures with high spatial resolution and thermal sensitivity. A luminescent‐based molecular thermometer comprised of visible‐emitting Ga3+/Tb3+ and Ga3+/Sm3+ metallacrowns (MCs) achieved remarkable relative thermal sensitivity associated with very low temperature uncertainty of Sr=1.9 % K−1 and δT<0.045 K, respectively, at 328 K, as an aqueous suspension of polystyrene nanobeads loaded with the corresponding MCs. To date, they are the ratiometric molecular nanothermometers offering the highest level of sensitivity in the physiologically relevant temperature range.
ACE2, the Receptor that Enables Infection by SARS‐CoV‐2: Biochemistry, Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators
Authors: Gross Lissy Z. F. , Sacerdoti Mariana , Piiper Albrecht , Zeuzem Stefan , Leroux Alejandro E. , Biondi Ricardo M.
Published: July 2020

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID‐19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS‐CoV‐2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full‐length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.
The Bouguer‐Beer‐Lambert Law: Shining Light on the Obscure
Authors: Mayerhöfer Thomas G. , Pahlow Susanne , Popp Jürgen
Published: July 2020

The Beer‐Lambert law is unquestionably the most important law in optical spectroscopy and indispensable for the qualitative and quantitative interpretation of spectroscopic data. As such, every spectroscopist should know its limits and potential pitfalls, arising from its application, by heart. It is the goal of this work to review these limits and pitfalls, as well as to provide solutions and explanations to guide the reader. This guidance will allow a deeper understanding of spectral features, which cannot be explained by the Beer‐Lambert law, because they arise from electromagnetic effects/the wave nature of light. Those features include band shifts and intensity changes based exclusively upon optical conditions, i. e. the method chosen to record the spectra, the substrate and the form of the sample. As such, the review will be an essential tool towards a full understanding of optical spectra and their quantitative interpretation based not only on oscillator positions, but also on their strengths and damping constants.
Clinical and radiographic comparative study to evaluate the efficacy of restoring destroyed primary incisors using two different techniques—A pilot study
Authors: Ibrahim Seba , Nourallah Abdul Wahab
Published: July 2020

Objective: The restoration of destroyed maxillary primary incisors is difficult because of the insufficient amount of coronal structure. This pilot study aimed to compare the efficacy of composite posts technique and glass fiber posts technique in restoring destroyed primary incisors.

Materials and Methods: Thirty‐six destroyed maxillary primary incisors in 11 children with early childhood caries were randomly assigned after endodontic treatment into two groups: glass fiber posts (n = 18) and composite resin posts (n = 18). Blinded clinical evaluation was made at 3, 6, 9, and 12 months and Blinded radiographic evaluation was made at 6 and 12 months. The evaluation was according to the FDI criteria. Data were analyzed with Fisher's exact test (α = .05).

Result: After 12 months post‐treatment, the success rates were 88.2% in glass fiber posts group and 70.6% in composite resin posts group. There was no statistically significant difference between the two groups according to the evaluation criteria (p‐value >.05).

Conclusion: Glass fiber posts technique and Composite posts technique may be used in the restoration of destroyed primary incisors.
Crosslinked Resin‐Supported Bifunctional Organocatalyst for Conversion of CO2 into Cyclic Carbonates
Authors: Dong Tongfeng , Zheng Yu‐Jia , Yang Guan‐Wen , Zhang Yao‐Yao , Li Bo , Wu Guang‐Peng
Published: July 2020

The development of solvent‐free, metal‐free, recyclable organic catalysts is required for the current chemical fixation of carbon dioxide converted into cyclic carbonates. With the goal of reducing the cost, time, and energy consumption for the coupling reaction of CO2 and epoxides, a series of highly active heterogeneous catalysts, based on a thiourea and quaternary ammonium salt system, are synthesized by using a thiol‐ene click reaction under ultraviolet light. Benefitting from synergistic interactions of the electrophilic center (thiourea) and the nucleophilic site (ammonium bromide), the catalysts exhibit excellent catalytic selectivity (99 %) for the cycloaddition of carbon dioxide with a diverse range of epoxides under mild conditions (1.2 MPa, 100 °C). Moreover, the catalyst can be easily recycled by facile filtration and reused for 5 times without noticeable loss of activity and selectivity. This work provides a potential heterogeneous catalyst for the conversion of carbon dioxide into high value‐added chemicals with the combined advantages of low cost, easy recovery, and satisfactory catalytic properties.