bluuebunny/crossref_metadata_2025 huggingface dataset:
Tailoring Therapeutic Responses via Engineering Microenvironments with a Novel Synthetic Fluid Gel
Authors: Foster Nicola C. , Allen Piers , El Haj Alicia J. , Grover Liam M. , Moakes Richard J. A.
Published: June 2021

This study reports the first fully synthetic fluid gel (SyMGels) using a simple poly(ethylene glycol) polymer. Fluid gels are an interesting class of materials: structured during gelation via shear‐confinement to form microparticulate suspensions, through a bottom‐up approach. Structuring in this way, when compared to first forming a gel and subsequently breaking it down, results in the formation of a particulate dispersion with particles “grown” in the shear flow. Resultantly, systems form a complex microstructure, where gelled particles concentrate remaining non‐gelled polymer within the continuous phase, creating an amorphous‐like interstitial phase. As such, these materials demonstrate mechanical characteristics typical of colloidal glasses, presenting solid‐like behaviors at rest with defined yielding; likely through intrinsic particle‐particle and particle‐polymer interactions. To date, fluid gels have been fabricated using polysaccharides with relatively complex chemistries, making further modifications challenging. SyMGels are easily functionalised, using simple click‐chemistry. This chemical flexibility, allows the creation of microenvironments with discrete biological decoration. Cellular control is demonstrated using MSC (mesenchymal stem cells)/chondrocytes and enables the regulation of key biomarkers such as aggrecan and SOX9. These potential therapeutic platforms demonstrate an important advancement in the biomaterial field, underpinning the mechanisms which drive their mechanical properties, and providing a versatile delivery system for advanced therapeutics.
Biomimetic Liposome with Surface‐Bound Elastase for Enhanced Tumor Penetration and Chemo‐Immumotherapy
Authors: Li Yong‐Jiang , Wu Jun‐Yong , Hu Xiong‐Bin , Ding Tianjinhao , Tang Tiantian , Xiang Da‐Xiong
Published: June 2021

Dense extracellular matrix (ECM) in the tumor stroma has been a challenge for drug penetration and cytotoxic T lymphocyte (CTL) infiltration. Neutrophil elastase (NE), in surface‐bound form, can destruct ECM rapidly, may be used for remodeling tumor ECM, and overcoming tumor stromal barrier. Focusing on elastosis in triple‐negative breast tumor, biomimetic liposomes with chimeric cell membrane proteins (LMP) are developed and for the first time, it is demonstrated that LMP with surface‐bound elastase (NE‐LMP) can target and degrade ECM effectively in tumor stroma, with minimal toxicity to normal tissues. The pretreatment of NE‐LMP increases the accumulation of chemotherapeutics at the tumor site and enhances antitumor effects. Also, NE‐LMP facilitates CTL infiltration in tumors and exhibits enhanced chemo‐immunotherapy in combination of PD‐1 immune checkpoint blockade treatment in orthotopic 4T1 tumor‐bearing mice, with significantly prolonged survival. Moreover, the remodeling of the tumor ECM by NE‐LMP shows inhibiting effects on metastasis in the lung. Findings from this study suggest that NE‐LMP holds promise for enhancing deep penetration of drug and infiltration of CTL in desmoplastic tumor by effective degrading ECM in the tumor stroma.
A Reversible Tuning of High Absorption in Chalcogenide–Metal Stacked‐Layer Structure and Its Application for Multichannel Biosensing
Authors: Behera Jitendra K. , Liu Kuan , Lian Meng , Cao Tun
Published: June 2021

Perfect absorption ranging from visible, infrared, terahertz, to microwave is desirable for solar cell, photodetection, telecommunications, and molecular sensing. Recently, the air/dielectric–metal stacks/substrate‐based asymmetric Fabry–Pérot (FP) cavity has attracted much attention owing to lithography‐free design which is scalable and low cost. Herein, a reversibly tunable asymmetric FP cavity high absorber in the near‐infrared (NIR) region is experimentally demonstrated, relying on chalcogenide (Ge2Sb2Te5)–metal (Au) stacked layers. It exhibits an extremely high absorptance of 0.99 at a resonant wavelength of 1180 nm for amorphous (AM) state; yet, the peak absorptance redshifts to 1680 nm for crystalline (CR) state. Importantly, it takes about 5 ns to reversibly transit the peak absorptance by reamorphizing the GST225. It is also experimentally shown the Brewster modes can be excited in the cavity absorber, and a wide tuning of Brewster modes (from 820 to 1500 nm) is realized as switching the state between AM and CR. The Goos–Hänchen (GH) shift can be observed at the Brewster angle for each state. For the proof of concept multibiosensing application, the cavity to detect two different solutions of the copper sulfate and glucose in both AM and CR states is numerically functionalized, respectively.
Thienothiophenyl‐Isoquinoline Iridium Complex‐Based Deep Red to Near‐Infrared Organic Light‐Emitting Diodes with Low Driving Voltage and High Radiant Emittance for Practical Biomedical Applications
Authors: Park Yongjin , Lee Gyeong Seok , Choi Hye-Ryung , Jeon Yongmin , Jeong So Yeong , Noh Byeongju , Park Kyoung-Chan , Kim Yun-Hi , Choi Kyung-Cheol
Published: June 2021

It is extremely rare that near‐infrared organic light‐emitting diodes (NIR OLEDs) have been actually applied to various fields such as sensors, night‐vision displays, or phototherapy owing to device reliability and stability. Therefore, developing a novel deep red to NIR (DR/NIR) emitter for the high‐performance DR/NIR OLED has become a prominent research area. Herein, a novel thienothiophene‐isoquinoline‐based Ir(III) complex DR/NIR emitter with narrow full width half maximum (FWHM, 38 nm), a shallow highest occupied molecular orbital (HOMO) energy level, and short radiative lifetime of 0.66  is designed and synthesized. The best device based on a new Ir(III) complex yields record‐high radiant emittance (> 5 mW cm−2) at low voltage (6 V), low external quantum efficiency (EQE) roll‐off, low driving voltage (2.5–6 V), and stable operational lifetime for biomedical application with an emission peak wavelength of 696 nm. From all perspectives, this is notably an outstanding performance among other reported Ir(III)‐based DR/NIR OLEDs. Moreover, DR/NIR OLEDs are applied to the biomedical field and an in vitro experiment shows an increase in cell proliferation effect of up to 24% under diverse conditions.
Manganese Catalyzed Hydrogenation of Azo (N=N) Bonds to Amines
Authors: Das Uttam Kumar , Kar Sayan , Ben‐David Yehoshoa , Diskin‐Posner Yael , Milstein David
Published: June 2021

We report the first example of homogeneously catalyzed hydrogenation of the N=N bond of azo compounds using a complex of an earth‐abundant‐metal. The hydrogenation reaction is catalyzed by a manganese pincer complex, proceeds under mild conditions, and yields amines, which makes this methodology a sustainable alternative route for the conversion of azo compounds. A plausible mechanism involving metal‐ligand cooperation and hydrazine intermediacy is proposed based on mechanistic studies.

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Visible‐Light‐Induced Radical Cascade Cyclization of o‐Diisocyanoarenes: Synthesis of Diethyl Benzo[a]phenazine‐6,6(5H)‐Dicarboxylate
Authors: Yuan Yao , Zhang Si‐Yuan , Dong Wu‐Heng , Wu Feng , Xie Xiao‐Min , Zhang Zhao‐Guo
Published: June 2021

A visible‐light‐induced radical cascade cyclization of ortho‐diisocyanoarenes for the synthesis of diethyl benzo[a]phenazine‐6,6(5H)‐dicarboxylates has been developed. This process provides an efficient and convenient protocol for the construction of benzo[a]phenazine skeleton that widely present in biologically active molecules and pharmaceuticals. The reaction takes place under mild conditions and the products are obtained in moderate to excellent yields.

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Vertically Aligned Nanostructured Topographies for Human Neural Stem Cell Differentiation and Neuronal Cell Interrogation
Authors: Lestrell Esther , O'Brien Carmel M. , Elnathan Roey , Voelcker Nicolas H.
Published: June 2021

Neurodegenerative disorders are a widespread global health concern caused by aging, disease, and trauma, for which there are limited treatment options. Stem cell therapies, tissue engineering, and nanobiotechnologies offer hope for improved therapeutic delivery approaches, as well as tissue repair and regenerative medicine interventions. The complexity of the human brain, coupled with its limited availability for research, makes human neural lineage cells and their precursor stem cells integral to the further understanding of brain functions in health, development, and disease.

Engineered nanomaterials provide highly specialized microenvironments, enabling precise interrogation of the impact of external and spatial stimuli on human neural cells in vitro, greatly advancing the knowledge of human neural function. Interacting with neural cells at the nanoscale, vertically aligned nanostructured (VA‐NS) arrays can influence cell fate and aid in more efficient cell reprogramming, and lend themselves to the development of highly targeted, sensitive signal transducer platforms suitable for in vivo monitoring of neural cell health and activity.

This perspective highlights the current state of stem cell nanoneurobiology, specifically focusing on interdisciplinary advances made by VA‐NS arrays to manipulate human neural stem cells in translatable research applications. Current challenges and identify are discussed underexplored and emerging future research areas.
Self‐Selective Organic Memristor by Engineered Conductive Nanofilament Diffusion for Realization of Practical Neuromorphic System
Authors: Park Hea‐Lim , Kim Min‐Hwi , Kim Hyungjin , Lee Sin‐Hyung
Published: June 2021

Solution‐processed organic memristors are promising ingredients to realize smart wearable electronics including neural networks. In organic memristors, tunable functionality of materials allows for realizing bio‐realistic neuromorphic electronics in the view point of the mechanical and electrical characteristics. However, it is challenging to achieve high‐density crossbar arrays of organic memristors due to undesirable sneak currents arising from unselected cells. For inorganic systems, considerable effort has been made to fabricate practical arrays by employing external components to suppress sneak current. By contrast, in organic memristors, it is barely possible to achieve practical systems due to the solvent orthogonality limiting the integration of the devices. Herein, an unprecedented structure of organic memristors with high self‐selectivity is developed to realize practical crossbar arrays. In the developed memristor, the self‐selective characteristics are achieved by systematically engineering the conductive nanofilament diffusion in the polymer. The maximum size of the memristor arrays is found to be more than 1 Mbits, and the neural networks based on the developed device showed reliable recognition performance similar to ideal software systems. This novel concept of developing the organic memristor with high self‐selectivity will open a new platform for realizing next‐generation flexible memory and practical neuromorphic systems linked to artificial intelligence.
Laser Processing Methods for Perovskite Solar Cells and Modules
Authors: Brooks Keith G. , Nazeeruddin Mohammad Khaja
Published: June 2021

The perovskite photovoltaic technology is now transitioning from basic research to the pre‐industrialization phase. In order to achieve reliable and high‐performance commercial perovskite solar modules, high throughput manufacturing technologies must now be adapted to the specific constraints and requirements imposed by the perovskite solar cells unique new chemistries, film deposition methodologies, and encapsulation requirements. Laser technologies will play an important role in the industrialization of these devices, both to achieve high active surface area modules and for the deposition and/or treatment of the critical layers. Industrial lasers will be essential to achieve active areas greater than 95% of the total area to retain the benefits of the very high performances reported for <1 cm2 laboratory cells. The speed of laser processing for the preparation of interconnects is unrivalled by comparison to other structuring methods. Recent reports of the use of lasers in upscaling perovskite solar cells are presented and analyzed here.
Fluoroethylamine Engineering for Effective Passivation to Attain 23.4% Efficiency Perovskite Solar Cells with Superior Stability
Authors: Su Hang , Zhang Jing , Hu Yingjie , Du Xinyi , Yang Ying , You Jiaxue , Gao Lili , (Frank) Liu Shengzhong
Published: June 2021

Defects in perovskite layers usually cause nonradiative recombination, impairing device performance and stability. Here, fluoroethylamine (FC2H4NH3, FEA) is integrated into the perovskite film to passivate defects. By engineering of different amounts of fluorine in the molecule, it is found that when 2‐fluoroethylamine (1FEA), in which one F bonds to the first carbon atom at the end of the molecule's structure, is used, the F atoms appear to be distributed throughout the bulk to the very surface. When 2,2‐difluoroethylamine (2FEA) and 2, 2, 2‐trifluoroethylamine (3FEA) are used, F is prone to distribution in the bulk of the perovskite film, while there appears to be no detectable F content on the surface. With the FEA passivation, the nonradiative recombination is suppressed, the carrier‐lifetime is improved to 840.01 ns, and the film‐air interface offers greater hydrophobicity, especially in the case of 1FEA, where because it is distributed throughout the film thickness, it passivates more defects and delivers the highest efficiency, as much as 23.40%. The device with 3FEA shows the best environmental stability; specifically, the bare cell without any encapsulation maintains 87% of its initial efficiency after exposure to the ambient environment for 1200 h.
A High‐Speed True Random Number Generator Based on a CuxTe1−x Diffusive Memristor
Authors: Woo Kyung Seok , Kim Jaehyun , Han Janguk , Choi Jin Myung , Kim Woohyun , Hwang Cheol Seong
Published: June 2021

Herein, a true random number generator (TRNG) based on a CuxTe1−x diffusive memristor (DM) using its threshold switching (TS) behavior is reported. The intrinsic stochasticity of the TS behavior contributes to the randomness of the TRNG system. The switching behavior is discussed through field‐induced nucleation theory and surface diffusion dynamics. Demonstrating the performance of TRNG as a hardware security application, the DM‐based TRNG passes all 15 National Institute of Standards and Technology randomness tests without any post‐processing step, even in high‐temperature conditions. Moreover, a nonlinear‐feedback shift register is implemented for a high‐speed TRNG, producing the highest rate among the reported volatile‐memristor‐based TRNGs.
Genome sequencing for detection of pathogenic deep intronic variation: A clinical case report illustrating opportunities and challenges
Authors: Walker Susan , Lamoureux Sylvia , Khan Tayyaba , Joynt Alyssa C. M. , Bradley Melissa , Branson Helen M. , Carter Melissa T. , Hayeems Robin Z. , Jagiello Lukasz , Marshall Christian R. , Meyn M. Stephen , Miller Steven P. , Wilson Diane , Scherer Stephen W. , Blaser Susan , Mireskandari Kamiar , Costain Gregory
Published: June 2021

Variants in JAM3 have been reported in four families manifesting a severe autosomal recessive disorder characterized by hemorrhagic destruction of the brain, subependymal calcification, and cataracts. We describe a 7‐year‐old male with a similar presentation found by research‐based quad genome sequencing to have two novel splicing variants in trans in JAM3, including one deep intronic variant (NM_032801.4: c.256+1260G>C) not detectable by standard exome sequencing. Targeted sequencing of RNA isolated from transformed lymphoblastoid cell lines confirmed that each of the two variants has a deleterious effect on JAM3 mRNA splicing. The role for genome sequencing as a clinical diagnostic test extends to those patients with phenotypes strongly suggestive of a specific Mendelian disorder, especially when the causal genetic variant(s) are not found by a more targeted approach. Barriers to diagnosis via identification of pathogenic deep intronic variation include lack of laboratory consensus regarding in silico splicing prediction tools and limited access to clinically validated confirmatory RNA experiments.
Broadening the phenotypic spectrum of Beta3GalT6‐associated phenotypes
Authors: Leoni Chiara , Tedesco Marta , Radio Francesca Clementina , Chillemi Giovanni , Leone Antonio , Bruselles Alessandro , Ciolfi Andrea , Stellacci Emilia , Pantaleoni Francesca , Butera Gianfranco , Rigante Donato , Onesimo Roberta , Tartaglia Marco , Zampino Giuseppe
Published: June 2021

Biallelic mutations in B3GALT6, coding for a galactosyltransferase involved in the synthesis of glycosaminoglycans (GAGs), have been associated with various clinical conditions, causing spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1 or SEMDJL Beighton type), Al‐Gazali syndrome (ALGAZ), and a severe progeroid form of Ehlers‐Danlos syndrome (EDSSPD2). In the 2017 Ehlers‐Danlos syndrome (EDS) classification, Beta3GalT6‐related disorders were grouped in the spondylodysplastic EDSs together with spondylodysplastic EDSs due to B4GALT7 and SLC39A13 mutations. Herein, we describe a patient with a previously unreported homozygous pathogenic B3GALT6 variant resulting in a complex phenotype more severe than spondyloepimetaphyseal dysplasia with joint laxity type 1, and having dural ectasia and aortic dilation as additionally associated features, further broadening the phenotypic spectrum of the Beta3GalT6‐related syndromes. We also document the utility of repeating sequencing in patients with uninformative exomes, particularly when performed by using “first generations” enrichment capture methods.
Surface Plasmon Resonance Assay for Label‐Free and Selective Detection of Xylella Fastidiosa
Authors: Sarcina Lucia , Macchia Eleonora , Loconsole Giuliana , D’Attoma Giusy , Saldarelli Pasquale , Elicio Vito , Palazzo Gerardo , Torsi Luisa
Published: June 2021

Xylella fastidiosa is among the most dangerous plant bacteria worldwide causing a variety of diseases, with huge economic impact on agriculture and environment. A surveillance tool, ensuring the highest possible sensitivity enabling the early detection of X. fastidiosa outbreaks, would be of paramount importance. So far, a variety of plant pathogen biomarkers are studied by means of surface plasmon resonance (SPR). Herein, multiparameter SPR (MP‐SPR) is used for the first time to develop a reliable and label‐free detection method for X. fastidiosa. The real‐time monitoring of the bioaffinity reactions is provided as well. Selectivity is guaranteed by biofunctionalizing the gold transducing interface with polyclonal antibodies for X. fastidiosa and it is assessed by means of a negative control experiment involving the nonbinding Paraburkholderia phytofirmans bacterium strain PsJN. Limit of detection of 105 CFU mL−1 is achieved by transducing the direct interaction between the bacterium and its affinity antibody. Moreover, the binding affinity between polyclonal antibodies and X. fastidiosa bacteria is also evaluated, returning an affinity constant of 3.5 × 107 m−1, comparable with those given in the literature for bacteria detection against affinity antibodies.
Exploring the Druggability of Conserved RNA Regulatory Elements in the SARS‐CoV‐2 Genome
Authors: Sreeramulu Sridhar , Richter Christian , Berg Hannes , Wirtz Martin Maria A. , Ceylan Betül , Matzel Tobias , Adam Jennifer , Altincekic Nadide , Azzaoui Kamal , Bains Jasleen Kaur , Blommers Marcel J. J. , Ferner Jan , Fürtig Boris , Göbel Michael , Grün J. Tassilo , Hengesbach Martin , Hohmann Katharina F. , Hymon Daniel , Knezic Bozana , Martins Jason N. , Mertinkus Klara R. , Niesteruk Anna , Peter Stephen A. , Pyper Dennis J. , Qureshi Nusrat S. , Scheffer Ute , Schlundt Andreas , Schnieders Robbin , Stirnal Elke , Sudakov Alexey , Tröster Alix , Vögele Jennifer , Wacker Anna , Weigand Julia E. , Wirmer‐Bartoschek Julia , Wöhnert Jens , Schwalbe Harald
Published: June 2021

SARS‐CoV‐2 contains a positive single‐stranded RNA genome of approximately 30 000 nucleotides. Within this genome, 15 RNA elements were identified as conserved between SARS‐CoV and SARS‐CoV‐2. By nuclear magnetic resonance (NMR) spectroscopy, we previously determined that these elements fold independently, in line with data from in vivo and ex‐vivo structural probing experiments. These elements contain non‐base‐paired regions that potentially harbor ligand‐binding pockets. Here, we performed an NMR‐based screening of a poised fragment library of 768 compounds for binding to these RNAs, employing three different 1H‐based 1D NMR binding assays. The screening identified common as well as RNA‐element specific hits. The results allow selection of the most promising of the 15 RNA elements as putative drug targets. Based on the identified hits, we derive key functional units and groups in ligands for effective targeting of the RNA of SARS‐CoV‐2.
A Unified Catalytic Asymmetric (4+1) and (5+1) Annulation Strategy to Access Chiral Spirooxindole‐Fused Oxacycles
Authors: Gao Min , Luo Yanshu , Xu Qianlan , Zhao Yukun , Gong Xiangnan , Xia Yuanzhi , Hu Lin
Published: June 2021

A unified catalytic asymmetric (N+1) (N=4, 5) annulation reaction of oxindoles with bifunctional peroxides has been achieved in the presence of a chiral phase‐transfer catalyst (PTC). This general strategy utilizes peroxides as unique bielectrophilic four‐ or five‐atom synthons to participate in the C−C and the subsequent umpolung C−O bond‐forming reactions with one‐carbon unit nucleophiles, thus providing a distinct method to access the valuable chiral spirooxindole‐tetrahydrofurans and ‐tetrahydropyrans with good yields and high enantioselectivities under mild conditions. DFT calculations were performed to rationalize the origin of high enantioselectivity. The gram‐scale syntheses and synthetic utility of the resultant products were also demonstrated.
1,3‐Alkyl Transposition in Allylic Alcohols Enabled by Proton‐Coupled Electron Transfer
Authors: Zhao Kuo , Seidler Gesa , Knowles Robert R.
Published: June 2021

A method is described for the isomerization of acyclic allylic alcohols into β‐functionalized ketones via 1,3‐alkyl transposition. This reaction proceeds via light‐driven proton‐coupled electron transfer (PCET) activation of the O−H bond in the allylic alcohol substrate, followed by C−C β‐scission of the resulting alkoxy radical. The transient alkyl radical and enone acceptor generated in the scission event subsequently recombine via radical conjugate addition to deliver β‐functionalized ketone products. A variety of allylic alcohol substrates bearing alkyl and acyl migratory groups were successfully accommodated. Insights from mechanistic studies led to a modified reaction protocol that improves reaction performance for challenging substrates.
Strained and Reactive Donor/Acceptor‐Supported Metallasilanone
Authors: Takahashi Shintaro , Ramos‐Enríquez Manuel A. , Bellan Ekaterina , Baceiredo Antoine , Saffon‐Merceron Nathalie , Nakata Norio , Hashizume Daisuke , Branchadell Vicenç , Kato Tsuyoshi
Published: June 2021

A novel stable donor/acceptor‐supported MnI‐metallasilanone 3 was synthesized. The intramolecular silanone‐MnI interaction induces a highly strained three‐membered cyclic structure, leading to an exceptionally high reactivity of 3 as a donor/acceptor complex of silanone. Indeed, metallasilanone 3 readily reacts with various small molecules such as H2 or ethylene gas in mild conditions.
Cyclic (Alkyl)(amino)carbene Ligands Enable Cu‐Catalyzed Markovnikov Protoboration and Protosilylation of Terminal Alkynes: A Versatile Portal to Functionalized Alkenes**
Authors: Gao Yang , Yazdani Sima , Kendrick Aaron , Junor Glen P. , Kang Taeho , Grotjahn Douglas B. , Bertrand Guy , Jazzar Rodolphe , Engle Keary M.
Published: June 2021

Regioselective hydrofunctionalization of alkynes represents a straightforward route to access alkenyl boronate and silane building blocks. In previously reported catalytic systems, high selectivity is achieved with a limited scope of substrates and/or reagents, with general solutions lacking. Herein, we describe a selective copper‐catalyzed Markovnikov hydrofunctionalization of terminal alkynes that is facilitated by strongly donating cyclic (alkyl)(amino)carbene (CAAC) ligands. Using this method, both alkyl‐ and aryl‐substituted alkynes are coupled with a variety of boryl and silyl reagents with high α‐selectivity. The reaction is scalable, and the products are versatile intermediates that can participate in various downstream transformations. Preliminary mechanistic experiments shed light on the role of CAAC ligands in this process.
Iridium(III)‐Catalyzed Diarylation/Annulation of Benzoic Acids: Facile Access to Multi‐Aryl Spirobifluorenes as Pure Hydrocarbon Hosts for High‐Performance OLEDs
Authors: Luo Yuanyuan , Liu Zheng , Yang Ge , Wang Tianhong , Bin Zhengyang , Lan Jingbo , Wu Di , You Jingsong
Published: June 2021

Herein disclosed is the first example of diarylation/annulation of benzoic acids via an iridium catalyst system. This protocol provides a step‐economic and highly efficient pathway to 1‐aryl, 1,3‐diaryl, 1,7‐diaryl and 1,3,7‐triaryl spirobifluorenes from readily available starting materials. The applications of multi‐aryl spirobifluorenes as pure hydrocarbon (PHC) hosts for red, green, and blue (RGB) phosphorescent organic light‐emitting diodes (PhOLEDs) were explored. Due to high triplet energies, 1,3‐diaryl spirobifluorenes exhibit the potential as the host material of blue PhOLEDs. 1,7‐Diaryl spirobifluorene can serve as the host of green PhOLEDs. 1,3,7‐Triaryl spirobifluorene is a high‐performance host for red PhOLEDs, which exhibits a high external quantum efficiency (EQE) up to 27.3 %. This work not only exemplifies the great potential of multi‐aryl spirobifluorenes as PHC hosts, but also offers a new approach for the synthesis of these PHC hosts.
Silicon Naphthalocyanine Tetraimides: Cathode Interlayer Materials for Highly Efficient Organic Solar Cells
Authors: Cai Chunsheng , Yao Jia , Chen Lie , Yuan Zhongyi , Zhang Zhi‐Guo , Hu Yu , Zhao Xiaohong , Zhang Youdi , Chen Yiwang , Li Yongfang
Published: June 2021

Naphthalocyanine derivatives (SiNcTI‐N and SiNcTI‐Br) were firstly used as excellent cathode interlayer materials (CIMs) in organic solar cells, via introducing four electron‐withdrawing imide groups and two hydrophilic alkyls. Both of them showed deep LUMO energy levels (below −3.90 eV), good thermal stability (Td >210 °C), and strong self‐doping property. The SiNcTI‐Br CIM displayed high conductivity (4.5×10−5 S cm−1) and electron mobility (7.81×10−5 cm2 V−1 s−1), which could boost the efficiencies of the PM6:Y6‐based OSCs over a wide range of CIM layer thicknesses (4–25 nm), with maximum efficiency of 16.71 %.
A Chemiluminescent Tetraaryl Diborane(4) Tetraanion
Authors: Budy Hendrik , Kaese Thomas , Bolte Michael , Lerner Hans‐Wolfram , Wagner Matthias
Published: June 2021

Two subvalent, redox‐active diborane(4) anions, [3]4− and [3]2−, carrying exceptionally high negative charge densities are reported: Reduction of 9‐methoxy‐9‐borafluorene with Li granules without stirring leads to the crystallization of the B(sp3)−B(sp2) diborane(5) anion salt Li[5]. [5]− contains a 2,2′‐biphenyldiyl‐bridged B−B core, a chelating 2,2′‐biphenyldiyl moiety, and a MeO substituent. Reduction of Li[5] with Na metal gives the Na+ salt of the tetraanion [3]4− in which two doubly reduced 9‐borafluorenyl fragments are linked via a B−B single bond. Comproportionation of Li[5] and Na4[3] quantitatively furnishes the diborane(4) dianion salt Na2[3], the doubly boron‐doped congener of 9,9′‐bis(fluorenylidene). Under acid catalysis, Na2[3] undergoes a formal Stone–Wales rearrangement to yield a dibenzo[g,p]chrysene derivative with B=B core. Na2[3] shows boron‐centered nucleophilicity toward n‐butyl chloride. Na4[3] produces bright blue chemiluminescence when exposed to air.
Ruthenium‐Nanoparticle‐Loaded Hollow Carbon Spheres as Nanoreactors for Hydrogenation of Levulinic Acid: Explicitly Recognizing the Void‐Confinement Effect
Authors: Yu Zhihao , Ji Na , Xiong Jian , Li Xiaoyun , Zhang Rui , Zhang Lidong , Lu Xuebin
Published: June 2021

As a typical class of man‐made nanoreactors, metal‐loaded hollow carbon nanostructures (MHC nanoreactors) exhibit competitive potentials in the heterogeneous catalysis due to their tailorable microenvironment effects, in which the void‐confinement effect is one of the most fundamental functions in boosting the catalytic performance. Herein this paper, Ru‐loaded hollow carbon spheres are employed as nanoreactors with a crucial biomass hydrogenation process, levulinic acid (LA) hydrogenation into γ‐valerolactone, as the probe reaction to further recognize the forming mechanism of this pivotal effect. We demonstrated that the void‐confinement effect of the selected MHC nanoreactors is essentially driven by an integrating action of electronic metal‐support interaction, reactant enrichment and diffusion, which are mainly ascribed to peculiar properties of hollow nanoreactors both in electronic and structural aspects, respectively. This work offers a distinct case for interpreting the catalytic behaviour of MHC nanoreactors, which could potentially promise broader insights into the microenvironment engineering strategies of hollow nanostructures.
Lineage‐specific vs. universal: A comparison of the Compositae1061 and Angiosperms353 enrichment panels in the sunflower family
Authors: Siniscalchi Carolina M. , Hidalgo Oriane , Palazzesi Luis , Pellicer Jaume , Pokorny Lisa , Maurin Olivier , Leitch Ilia J. , Forest Felix , Baker William J. , Mandel Jennifer R.
Published: June 2021

Premise

Phylogenetic studies in the Compositae are challenging due to the sheer size of the family and the challenges they pose for molecular tools, ranging from the genomic impact of polyploid events to their very conserved plastid genomes. The search for better molecular tools for phylogenetic studies led to the development of the family‐specific Compositae1061 probe set, as well as the universal Angiosperms353 probe set designed for all flowering plants. In this study, we evaluate the extent to which data generated using the family‐specific kit and those obtained with the universal kit can be merged for downstream analyses.

Methods

We used comparative methods to verify the presence of shared loci between probe sets. Using two sets of eight samples sequenced with Compositae1061 and Angiosperms353, we ran phylogenetic analyses with and without loci flagged as paralogs, a gene tree discordance analysis, and a complementary phylogenetic analysis mixing samples from both sample sets.

Results

Our results show that the Compositae1061 kit provides an average of 721 loci, with 9–46% of them presenting paralogs, while the Angiosperms353 set yields an average of 287 loci, which are less affected by paralogy. Analyses mixing samples from both sets showed that the presence of 30 shared loci in the probe sets allows the combination of data generated in different ways.

Discussion

Combining data generated using different probe sets opens up the possibility of collaborative efforts and shared data within the synantherological community.
The cardioprotective effects of hydrogen sulfide by targeting endoplasmic reticulum stress and the Nrf2 signaling pathway: A review
Authors: Yarmohammadi Fatemeh , Hayes A. Wallace , Karimi Gholamreza
Published: June 2021

Cardiac diseases are emerging due to lifestyle, urbanization, and the accelerated aging process. Oxidative stress has been associated with cardiac injury progression through interference with antioxidant strategies and endoplasmic reticulum (ER) function. Hydrogen sulfide (H2S) is generated endogenously from l‐cysteine in various tissues including heart tissue. Pharmacological evaluation of H2S has suggested a potential role for H2S against diabetic cardiomyopathy, ischemia/reperfusion injury, myocardial infarction, and cardiotoxicity. Nuclear factor E2‐related factor 2 (Nrf2) activity is crucial for cell survival in response to oxidative stress. H2S up‐regulates Nrf2 expression and its related signaling pathway in myocytes. H2S also suppresses the expression and activity of ER stress‐related proteins. H2S has been reported to improve various cardiac conditions through antioxidant and anti‐ER stress‐related activities.
Mitochondrial transcription factor A plays opposite roles in the initiation and progression of colitis‐associated cancer
Authors: Yang Shirong , He Xianli , Zhao Jing , Wang Dalin , Guo Shanshan , Gao Tian , Wang Gang , Jin Chao , Yan Zeyu , Wang Nan , Wang Yongxing , Zhao Yilin , Xing Jinliang , Huang Qichao
Published: June 2021

Background

Mitochondria are key regulators in cell proliferation and apoptosis. Alterations in mitochondrial function are closely associated with inflammation and tumorigenesis. This study aimed to investigate whether mitochondrial transcription factor A (TFAM), a key regulator of mitochondrial DNA transcription and replication, is involved in the initiation and progression of colitis‐associated cancer (CAC).

Methods

TFAM expression was examined in tissue samples of inflammatory bowel diseases (IBD) and CAC by immunohistochemistry. Intestinal epithelial cell (IEC)‐specific TFAM‐knockout mice (TFAM△IEC) and colorectal cancer (CRC) cells with TFAM knockdown or overexpression were used to evaluate the role of TFAM in colitis and the initiation and progression of CAC. The underlying mechanisms of TFAM were also explored by analyzing mitochondrial respiration function and biogenesis.

Results

The expression of TFAM was downregulated in active IBD and negatively associated with the disease activity. The downregulation of TFAM in IECs was induced by interleukin‐6 in a signal transducer and activator of transcription 3 (STAT3)/miR‐23b‐dependent manner. In addition, TFAM knockout impaired IEC turnover to promote dextran sulfate sodium (DSS)‐induced colitis in mice. Of note, TFAM knockout increased the susceptibility of mice to azoxymethane/DSS‐induced CAC and TFAM overexpression protected mice from intestinal inflammation and colitis‐associated tumorigenesis. By contrast, TFAM expression was upregulated in CAC tissues and contributed to cell growth. Furthermore, it was demonstrated that β‐catenin induced the upregulation of TFAM through c‐Myc in CRC cells. Mechanistically, TFAM promoted the proliferation of both IECs and CRC cells by increasing mitochondrial biogenesis and activity.

Conclusions

TFAM plays a dual role in the initiation and progression of CAC, providing a novel understanding of CAC pathogenesis.
Preliminary Structural Data Revealed That the SARS‐CoV‐2 B.1.617 Variant's RBD Binds to ACE2 Receptor Stronger Than the Wild Type to Enhance the Infectivity
Authors: Khan. Abbas , Wei Dong‐Qing , Kousar Kafila , Abubaker Jehad , Ahmad Sajjad , Ali Javaid , Al‐Mulla Fahd , Ali Syed Shujait , Nizam‐Uddin N. , Mohammad Sayaf Abrar , Mohammad Anwar
Published: June 2021

The evolution of new SARS‐CoV‐2 variants around the globe has made the COVID‐19 pandemic more worrisome, further pressuring the health care system and immunity. Novel variations that are unique to the receptor‐binding motif (RBM) of the receptor‐binding domain (RBD) spike glycoprotein, i. e. L452R‐E484Q, may play a different role in the B.1.617 (also known as G/452R.V3) variant's pathogenicity and better survival compared to the wild type. Therefore, a thorough analysis is needed to understand the impact of these mutations on binding with host receptor (RBD) and to guide new therapeutics development. In this study, we used structural and biomolecular simulation techniques to explore the impact of specific mutations (L452R‐E484Q) in the B.1.617 variant on the binding of RBD to the host receptor ACE2. Our analysis revealed that the B.1.617 variant possesses different dynamic behaviours by altering dynamic‐stability, residual flexibility and structural compactness. Moreover, the new variant had altered the bonding network and structural‐dynamics properties significantly. MM/GBSA technique was used, which further established the binding differences between the wild type and B.1.617 variant. In conclusion, this study provides a strong impetus to develop novel drugs against the new SARS‐CoV‐2 variants.
Direct Visualization of Substitutional Li Doping in Supported Pt Nanoparticles and Their Ultra‐selective Catalytic Hydrogenation Performance
Authors: Chen Tianyi , Foo Christopher , Zheng Jianwei J. W. , Fang Huihuang , Nellist Peter , Tsang Shik Chi Edman
Published: June 2021

It has only recently been established that doping light elements (lithium, boron, and carbon) into supported transition metals can fill interstitial sites, which can be observed by the expanded unit cell. As an example, interstitial lithium (intLi) can block H filling octahedral interstices of palladium metal lattice, which improves partial hydrogenation of alkynes to alkenes under hydrogen. In contrast, herein, we report intLi is not found in the case of Pt/C. Instead, we observe for the first time a direct ‘substitution’ of Pt with substitutional lithium (subLi) in alternating atomic columns using scanning transmission electron microscopy‐annular dark field (STEM‐ADF). This ordered substitutional doping results in a contraction of the unit cell as shown by high‐quality synchrotron X‐ray diffraction (SXRD). The electron donation of d‐band of Pt without higher orbital hybridizations by subLi offers an alternative way for ultra‐selectivity in catalytic hydrogenation of carbonyl compounds by suppressing the facile CO bond breakage that would form alcohols.
Effect of a “Zn Bridge” on the Consecutively Tunable Retention Characteristics of Volatile Random Access Memory Materials
Authors: Guo Jiacong , Zhang Yankun , Tian Guofeng , Ji Deyang , Qi Shengli , Wu Dezhen
Published: June 2021

Polyimide memory materials with a donor–acceptor structure based on a charge‐transfer mechanism exhibit great potential for next‐generation information storage technology due to their outstanding high‐temperature resistance and good dimensional and chemical stability. Precisely controlling memory performance by limited chemical decoration is one of core challenges in this field. Most reported work mainly focuses on designing novel and elaborate electron donors or acceptors for the expected memory behavior of polyimides; this takes a lot of time and is not always efficacious. Herein, we report a series of porphyrinated copolyimides coPI−Znx (x=5, 10, 20, 50, 80), where x represents the mole percentage of Zn ion in the central core of the porphyrin. Experimental and theoretical analysis indicate that the Zn ion could play a vital bridge role in promoting the formation and stabilization of a charge‐transfer complex by enhancing the hybridization of local and charge transfer (HLCT) excitations of porphyrinated polyimides, endowing coPI−Znx with volatile random access memory performance and continuously tunable retention time. This work could provide one simple strategy to precisely regulate memory performance merely by altering the metal content in porphyrinated polyimides.
Driving the Emission Towards Blue by Controlling the HOMO‐LUMO Energy Gap in BF2‐Functionalized 2‐(Imidazo[1,5‐a]pyridin‐3‐yl)phenols
Authors: Colombo Gioele , Attilio Ardizzoia G. , Furrer Julien , Therrien Bruno , Brenna Stefano
Published: June 2021

Several boron compounds with 2‐(imidazo[1,5‐a]pyridin‐3‐yl)phenols, differentiated by the nature of the substituent (R) in the para position of the hydroxy group, have been synthesized and thoroughly characterized both in solution (1H, 13C, 11B, 19F NMR) and in the solid state (X‐ray). All derivatives displayed attractive photophysical properties like very high Stokes shift, high fluorescence quantum yields and a good photostability in solution. Time‐Dependent Density Functional Theory (TD‐DFT) calculations allowed to define the main electronic transitions as intra ligand transitions (1ILT), which was corroborated by the Natural Transition Orbitals (NTOs) shapes. The HOMO‐LUMO energy gap was correlated to the electronic properties of the substituent R on the phenolic ring, as quantified by its σp Hammett constant.
Glycol Chitosan Functionalized with a Gd(III) Chelate as a Redox‐responsive Magnetic Resonance Imaging Probe to Label Cell Embedding Alginate Capsules
Authors: Padovan Sergio , Carrera Carla , Catanzaro Valeria , Grange Cristina , Koni Malvina , Digilio Giuseppe
Published: June 2021

One possibility for the non‐invasive imaging of encapsulated cell grafts is to label the lumen of cell embedding capsules with a redox‐responsive probe, as an increased extracellular reducing potential can be considered as a marker of hypoxia‐induced necrosis. A Gd(III)‐HPDO3A‐like chelate has been conjugated to glycol‐chitosan through a redox‐responsive disulphide bond to obtain a contrast agent for Magnetic Resonance Imaging (MRI). Such a compound can be interspersed with fibroblasts within the lumen of alginate‐chitosan capsules. Increasing reducing conditions within the extracellular microenvironment lead to the reductive cleavage of the disulphide bond and to the release of gadolinium in the form of a low molecular weight, non‐ionic chelate. The efflux of such chelate from capsules is readily detected by a decrease of contrast enhancement in T1‐weighted MR images.
N‐Heterocyclic Iod(az)olium Salts – Potent Halogen‐Bond Donors in Organocatalysis
Authors: Boelke Andreas , Kuczmera Thomas J. , Lork Enno , Nachtsheim Boris J.
Published: June 2021

This article describes the application of N‐heterocyclic iod(az)olium salts (NHISs) as highly reactive organocatalysts. A variety of mono‐ and dicationic NHISs are described and utilized as potent XB‐donors in halogen‐bond catalysis. They were benchmarked in seven diverse test reactions in which the activation of carbon‐ and metal‐chloride bonds as well as carbonyl and nitro groups was achieved.N‐methylated dicationic NHISs rendered the highest reactivity in all investigated catalytic applications with reactivities even higher than all previously described monodentate XB‐donors based on iodine(I) and (III) and the strong Lewis acid BF3.
Mechanosynthesis of Eutectics of Anti‐Inflammatory Drug Ethenzamide – A Comparison with Analogous Cocrystals
Authors: Rajbongshi Trishna , Kumar Sarmah Kashyap , Ganduri Ramesh , Cherukuvada Suryanarayan , Arhangelskis Mihails , Thakuria Ranjit
Published: June 2021

Mechanochemical milling of ethenzamide (ETZ), a nonsteroidal anti‐inflammatory drug, with substituted aromatic carboxylic acids as well as anti‐tuberculosis drug pyrazinamide (PZA) resulted in the formation of eutectics. Although a large number of cocrystals as well as polymorphic cocrystals are reported for ETZ, for the first time we have synthesized six eutectics including an instance of a drug‐drug eutectic system. Supramolecular synthon energy calculations validate the formation of eutectic mixtures over cocrystals with coformers considered in our study.
Assessment of gender representation in clinical trials leading to FDA approval for oncology therapeutics between 2014 and 2019: A systematic review‐based cohort study
Authors: Dymanus Kyle A. , Butaney Mohit , Magee Diana E. , Hird Amanda E. , Luckenbaugh Amy N. , Ma Merry W. , Hall Mary E. , Huelster Heather L. , Laviana Aaron A. , Davis Nancy B. , Terris Martha K. , Klaassen Zachary , Wallis Christopher J. D.
Published: June 2021

Background

Ensuring representative data accrual in clinical trials is important to safeguard the generalizability of results and to minimize disparities in care. This study's goal was to evaluate differences in gender representation in trials leading to US Food and Drug Administration (FDA) cancer drug approvals.

Methods

An observational study was conducted from January 2014 to April 2019 using PubMed and the National Institutes of Health trials registry for primary trial reports. The National Cancer Institute's Surveillance, Epidemiology, and End Results program and US Census were consulted for national cancer incidence. The outcome was an enrollment incidence disparity (EID), which was calculated as the difference between male and female trial enrollment and national incidence, with positive values representing male overrepresentation.

Results

There were 149 clinical trials with 59,988 participants—60.3% and 39.7% were male and female, respectively—leading to 127 oncology drug approvals. The US incidence rates were 55.4% for men versus 44.6% for women. Gender representation varied by specific tumor type. Most notably, women were underrepresented in thyroid cancer (EID, +27.4%), whereas men were underrepresented in soft tissue cancer (EID, –26.1%). Overall, women were underrepresented when compared with expected incidence (EID, +4.9%; 42% of trials).

Conclusions

For many specific tumor types, women are underrepresented in clinical trials leading to FDA oncology drug approvals. It is critical to better align clinical trial cohort demographics and the populations to which these data will be extrapolated.

Lay Summary

This study assesses whether gender disparities exist in clinical trials leading to US Food and Drug Administration (FDA) cancer drug approvals. From January 2014 to April 2019, 149 clinical trials leading to FDA oncology drug approvals showed 60.3% and 39.7% of the enrollees were male and female, respectively.

Gender representation varied by specific tumor when compared with the expected incidence rate of cancer in the United States, although women were more often underrepresented.

Increased efforts are needed with regard to ensuring equitable representation in oncology clinical trials.
The impact of fertility preservation on the timing of breast cancer treatment, recurrence, and survival
Authors: Greer Anna C. , Lanes Andrea , Poorvu Philip D. , Kennedy Patricia , Thomas Ann M. , Partridge Ann H. , Ginsburg Elizabeth S.
Published: June 2021

Background

Many young women with breast cancer undergo fertility preservation (FP) before cancer treatment. This study examined the impact of FP on breast cancer outcomes.

Methods

The authors performed a retrospective cohort study of 272 women aged 20 to 45 years with newly diagnosed stage 0 to III breast cancer who underwent an FP consultation between 2005 and 2017. Among these women, 123 (45.2%) underwent FP (fertility preservation–positive [FP+]). The remaining 149 women did not undergo FP (fertility preservation–negative [FP–]).

Results

The characteristics at enrollment were similar with the exception of ethnicity (FP+, 87.8% White; FP–, 67.8% White; P = .002) and BRCA status (FP+, 27.7% BRCA+; FP–, 15.5% BRCA+; P = .021). The median follow‐up was approximately 4 years. Women who underwent FP had longer times to first treatment (FP+, 37 days; FP–, 31 days; adjusted hazard ratio [aHR], 0.74; confidence interval [CI], 0.56‐0.99) and neoadjuvant chemotherapy (FP+, 36 days; FP–, 26 days; aHR, 0.41; CI, 0.24‐0.68) and from surgery to adjuvant chemotherapy (FP+, 41 days; FP–, 33 days; aHR, 0.58; CI, 0.38‐0.90). Adjusted 3‐ and 5‐year invasive disease–free survival (IDFS) rates were comparable between the 2 groups (3‐year IDFS: FP+, 85.4%; FP–, 79.4%; P = .411; 5‐year IDFS: FP+, 73.7%; FP–, 67.1%; P = .288). Similarly, no difference in overall survival (OS) was observed between the 2 groups (3‐year OS: FP+, 95.5%; FP–, 93.5%; P = .854; 5‐year OS: FP+, 84.2%; FP–, 81.4%; P = .700).

Conclusions

FP after a breast cancer diagnosis delays the time to treatment by a small amount, but this delay does not lead to inferior IDFS or OS.