bluuebunny/crossref_metadata_2025 huggingface dataset:
High Performance Flexible Lithium‐Ion Battery Electrodes: Ion Exchange Assisted Fabrication of Carbon Coated Nickel Oxide Nanosheet Arrays on Carbon Cloth
Authors: Chen Shengrui , Tao Runming , Tu Ji , Guo Pingmei , Yang Guang , Wang Wenjun , Liang Jiyuan , Lu Shih‐Yuan
Published: April 2021

Transition metal oxides (TMOs)‐based anode materials of high theoretical capacities have been intensively studied for lithium‐ion storage. However, their poor high‐rate capability and cycling stability remain to be effectively resolved. Herein, a novel ion exchange (IE)‐assisted indirect carbon coating strategy is proposed to realize high performance freestanding TMO‐based anodes for flexible lithium‐ion batteries (FLIBs). This approach effectively avoids the possible side reaction of oxide reduction, enhances degrees of graphitization of the carbon coating, and preserves advantageous nanostructure of the starting template, leading to enhanced electrical conductivities, alleviated volume variation induced structural instability, fast lithium‐ion diffusion pathways and enhanced electron transfer kinetics. As a proof of concept, IE‐prepared carbon coated NiO nanosheet arrays with excellent structural and electrochemical stability are developed as freestanding anodes for LIBs and FLIBs, which exhibit outstanding electrochemical performances superior to most state‐of‐the‐art NiO‐based anodes reported in recent years. The product anode delivers a high areal capacity (3.08 mAh cm−2 at 0.25 mA cm−2), outstanding high‐rate capability (1.78 mAh cm−2 at 8 mA cm−2) and excellent cycling stability (over 300 cycles). Further pouch cell tests confirm the excellent flexibility of the freestanding electrode against mechanical deformation with well‐maintained electrochemical performance under folding.
Electrocatalysts by Electrodeposition: Recent Advances, Synthesis Methods, and Applications in Energy Conversion
Authors: Kale Manoj B. , Borse Rahul Anil , Gomaa Abdelkader Mohamed Aya , Wang Yaobing
Published: April 2021

The conventional environment polluting energy sources and the continuous growing energy demand compelled researchers to find alternative energy sources. Therefore, in recent years, extensive research has been carried out in synthesizing catalysts for energy conversion applications. This review focuses on the application of various electrodeposition methods in the synthesis of energy‐related electrocatalyst and briefly discusses different electrocatalyst characterization techniques. Further, the influence of various parameters on the electrocatalyst activity and stability is highlighted. Electrocatalyst application in clean energy conversion reactions, such as the hydrogen evolution reaction, oxygen evolution reaction, oxygen reduction reaction, carbon dioxide reduction reaction, nitrogen reduction reaction along with the metal‐air/CO2 battery, are reviewed. Finally, the comparative experimental data are provided as a reference to synthesize the next‐generation electrodeposited electrocatalyst in clean energy conversions and beyond.
Nitrogen‐Doped Accordion‐Like Soft Carbon Anodes with Exposed Hierarchical Pores for Advanced Potassium‐Ion Hybrid Capacitors
Authors: Zhang Chen , Liu Xing , Li Zhen , Zhang Chenying , Chen Zhiwen , Pan Dengyu , Wu Minghong
Published: April 2021

Soft carbon (SC) is a promising anode material for potassium‐ion hybrid capacitors (PIHCs), but there are limited K+ storage sites in common SC due to a skin‐like carbon film covering on the surface. To address this issue, a simple oxidization method to completely remove the skin‐like carbon film is reported and a novel accordion‐like architecture of SC (ASC) is constructed with a hierarchical porous framework composed of micropores, mesopores, and macropores, all of which can be exposed to K+ electrolytes for enhanced energy storage. Importantly, this exposed structure facilitates pseudocapacitance modification by electro‐deposition of highly electrochemically active nitrogen‐doped graphene quantum dots (N‐GQDs) to enhance kinetic performance and additional K+ storage. After annealing treatment to regulate N‐doping type, the accordion‐like N‐GQD@ASC‐500 exhibits excellent reversible capacity of 360 mAh g−1 as well as superior rate capability and cycle stability. Kinetic, in situ Raman/electrochemical impedance spectroscopy analysis, and density functional theory calculation elucidate the K+ storage mechanism. As expected, the PIHC assembled with N‐GQD@ASC‐500 anode and porous carbon cathode delivers an ultrahigh energy/power density (171 Wh kg−1 and 20 000 W kg−1) with long cycle life. This work suggests that ASC is a promising anode material for designing of high‐performance PIHCs.
Polycatechol Mediated Small Interfering RNA Delivery for the Treatment of Ulcerative Colitis
Authors: Fan Qianqian , Yang Zhen , Li Yuhan , Cheng Yiyun , Li Yiwen
Published: April 2021

Small interfering RNA (siRNA)‐based therapeutics has high potency and specificity in silencing target genes for the treatment of various diseases; however, the design of efficient and safe carriers for siRNA delivery remains grand challenges. In this study, a family of cationic polycatechols are designed and synthesized using different direct polymerization methods for siRNA delivery in vitro and in vivo. It is observed that the introduction of multiple catechol moieties into cationic polymers could enhance their siRNA binding capability, thus greatly improving the biological stability, cell internalization, and gene silencing efficiency of their complexes. The flexibility of the backbone in polycatechols is also found to influence the whole siRNA delivery process. After screening, the lead cationic polycatechol P1 with a 50% catechol molar ratio could efficiently deliver siRNAs into different cell lines and downregulate various target genes even in the presence of serum proteins. Besides, P1 is also able to successfully silence tumor necrosis factor‐α in macrophages in vitro and in vivo, and efficiently mitigate the symptoms without causing adverse effects in a dextran sodium sulfate‐induced ulcerative colitis model. The results demonstrate that those polycatechols could be developed as a promising class of siRNA delivery systems for gene therapy.
Near‐Infrared II Light‐Triggered Robust Carbon Radical Generation for Combined Photothermal and Thermodynamic Therapy of Hypoxic Tumors
Authors: Liu Xin , Yang Yuanyuan , Ling Mingjian , Sun Rui , Zhu Meiyan , Chen Jianjun , Yu Meng , Peng Zhenwei , Yu Zhiqiang , Liu Xiqiang
Published: April 2021

Tumor hypoxia is a major cause of failure in cancer therapy, and there is almost no efficacious treatment for hypoxic tumors. Herein, an azo‐containing polymer (P2) is designed to encapsulate IR1061, and further covalently grafted with a tumor‐targeting tripeptide RGD to form P2@IR1061‐RGD NPs for combined photothermal and thermodynamic therapy (PTT/TDT) in the near‐infrared II (NIR II) biowindow (1000–1700 nm). Upon 1064 nm laser irradiation, IR1061 generates heat to break the azo bonds of P2, achieving robust carbon radical generation, which induces cancer cell death even under a hypoxic tumor microenvironment. RNA‐sequencing is first adopted to unveil the impact of combined PTT/TDT on the cell transcriptome and the corresponding pathways using 4T1 breast cancer cells. The dysregulated genes are involved in protein processing within the endoplasmic reticulum, cell cycle regulation, ubiquitin‐mediated proteolysis, and DNA replication pathways. The tumor inhibition rates on a 4T1 breast cancer model as well as on a patient‐derived xenograft model of hepatocellular carcinoma (PDXHCC) are 97% and 100%, and negligible systematic toxicity is observed. This study proposes the application of an azo‐containing polymer for safe and efficient combined PTT/TDT in the NIR II biowindow, as a promising strategy for clinical treatment of hypoxic tumors.
Ultrathin 2D Copper(I) 1,2,4‐Triazolate Coordination Polymer Nanosheets for Efficient and Selective Gene Silencing and Photodynamic Therapy
Authors: Liu Si‐Yang , Xu Yuzhi , Yang Huihui , Liu Liping , Zhao Meiting , Yin Wen , Xu Yan‐Tong , Huang Ying , Tan Chaoliang , Dai Zong , Zhang Hua , Zhang Jie‐Peng , Chen Xiao‐Ming
Published: April 2021

Gene silencing holds promise for cancer therapeutics because of its potential to inhibit genes involved in tumor development. However, gene silencing is still restricted by its limited efficacy and safety. Nanoscale coordination polymers (CPs) emerge as promising nanocarriers for gene delivery, but their responsiveness and potential therapeutic properties have rarely been explored simultaneously. Here, multifunctional ultrathin 2D nanosheets of Cu(I) 1,2,4‐triazolate CP with a thickness of 4.5 ± 0.8 nm are synthesized using a bottom‐up method. These CP nanosheets can act as both an effective DNAzyme nanocarrier for gene therapy and an intrinsic photosensitizer for hypoxia‐tolerant type I photodynamic therapy (PDT), which is ascribed to the Fenton‐like reaction. Because of the glutathione (GSH)‐responsiveness of the CP nanosheets, DNAzyme‐loaded CP nanosheets exhibit excellent cancer‐cell‐targeting gene silencing of the early growth response factor‐1 (EGR‐1), with messenger RNA inhibited by 84% in MCF‐7 (human breast cancer cells) and only 6% in MCF‐10A (normal human mammary epithelial cells). After tail intravenous injection into MCF‐7‐tumor‐bearing mice, the CP nanosheets loaded with chlorin‐e6‐modified DNAzyme under photoirradiation show a high antitumor efficacy (88.0% tumor regression), demonstrating a promising therapeutic platform with efficient and selective gene silencing and PDT of cancer.
AMYQ: An index to standardize quantitative amyloid load across PET tracers
Authors: Pegueroles Jordi , Montal Victor , Bejanin Alexandre , Vilaplana Eduard , Aranha Mateus , Santos‐Santos Miguel Angel , Alcolea Daniel , Carrió Ignasi , Camacho Valle , Blesa Rafael , Lleó Alberto , Fortea Juan ,   for the Alzheimer Disease Neuroimaging Initiative,   Australian Imaging, Biomarkers and Lifestyle Research Group
Published: April 2021

Introduction

Positron emission tomography (PET) amyloid quantification methods require magnetic resonance imaging (MRI) for spatial registration and a priori reference region to scale the images. Furthermore, different tracers have distinct thresholds for positivity. We propose the AMYQ index, a new measure of amyloid burden, to overcome these limitations.

Methods

We selected 18F‐amyloid scans from ADNI and Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL) with the corresponding T1‐MRI. A subset also had neuropathological data. PET images were normalized, and the AMYQ was calculated based on an adaptive template. We compared AMYQ with the Centiloid scale on clinical and neuropathological diagnostic performance.

Results

AMYQ was related with amyloid neuropathological burden and had excellent diagnostic performance to discriminate controls from patients with Alzheimer's disease (AD) (area under the curve [AUC] = 0.86). AMYQ had a high agreement with the Centiloid scale (intraclass correlation coefficient [ICC] = 0.88) and AUC between 0.94 and 0.99 to discriminate PET positivity when using different Centiloid cutoffs.

Discussion

AMYQ is a new MRI‐independent index for standardizing and quantifying amyloid load across tracers.
Long‐Term Tracking and Dynamically Quantifying of Reversible Changes of Extracellular Ca2+ in Multiple Brain Regions of Freely Moving Animals
Authors: Liu Yuandong , Liu Zhichao , Zhao Fan , Tian Yang
Published: April 2021

Understanding physiological and pathological processes in the brain requires tracking the reversible changes in chemical signals with long‐term stability. We developed a new anti‐biofouling microfiber array to real‐time quantify extracellular Ca2+ concentrations together with neuron activity across many regions in the mammalian brain for 60 days, in which the signal degradation was < ca. 8 %. The microarray with high tempo‐spatial resolution (ca. 10 μm, ca. 1.3 s) was implanted into 7 brain regions of free‐moving mice to monitor reversible changes of extracellular Ca2+ upon ischemia‐reperfusion processes. The changing sequence and rate of Ca2+ in 7 brain regions were different during the stroke. ROS scavenger could protect Ca2+ influx and neuronal activity after stroke, suggesting the significant influence of ROS on Ca2+ overload and neuron death. We demonstrated this microarray is a versatile tool for investigating brain dynamic during pathological processes and drug treatment.
High‐Throughput Counting and Superresolution Mapping of Tetraspanins on Exosomes Using a Single‐Molecule Sensitive Flow Technique and Transistor‐like Semiconducting Polymer Dots
Authors: Jiang Yifei , Andronico Luca A. , Jung Seung‐Ryoung , Chen Haobin , Fujimoto Bryant , Vojtech Lucia , Chiu Daniel T.
Published: April 2021

A method for high‐throughput counting and superresolution mapping of surface proteins on exosomes is described. The method combines a single‐molecule sensitive flow technique and an adaptive superresolution imaging method. Exosomes stained with membrane dye and dye‐conjugated antibodies were analyzed using a microfluidic platform at a flow rate of 100 exosome s−1 to determine size and protein copy number. Superresolution mapping was performed with exosomes labeled with novel transistor‐like, semiconducting polymer dots (Pdots), which exhibit spontaneous blinking with <5 nm localization error and a broad range of optical‐adjustable duty cycles. Based on the copy numbers extracted from the flow analysis, the switch‐on frequency of the Pdots were finely adjusted so that structures of hundreds of exosomes were obtained within five minutes. The high throughput and high sensitivity of this method offer clear advantages for characterization of exosomes and similar biological vesicles.
Additive‐free, robust and superelastic dual‐network graphene/melamine composite sponge for motion sensing
Authors: Zhang Linjiong , Feng Lianfang , Gu Xueping , Zhang Cailiang
Published: April 2021

Graphene aerogel (GA) has a large potential in many fields such as energy storage, catalyst support, and sensors. However, its poor mechanical property has restricted the wide application. In this work, superelastic and robust melamine/graphene composite sponges are prepared by constructing a dual‐network structure of melamine and graphene without any chemical additives. The strength of as‐prepared composite sponge at 50% strain can reach 40 times higher than that of controlled GA. After 50 compressive cycles, the strain and strength recovery ratios of composite sponge are about 97% and 90%, respectively. More importantly, the excellent compression performance combines with the good electrical conductivity of the graphene network enable it as a dynamic piezo‐resistive material, which can provide immediate responses to dynamic stresses and strains with different frequencies. Benefitting by these excellent performances, the dual‐network composite sponge shows a great potential application in the field of motion sensing.
Ablation properties of zinc borate and aluminum hypophosphite filled silicone rubber composites
Authors: Zhang Hao , Yan Liwei , Wang Yuan , Zhou Shengtai , Liang Mei , Zou Huawei , Chen Yang
Published: April 2021

The ablative properties of epoxy modified silicone rubber composites filled with zinc borate (ZB) and aluminum hypophosphite (AHP) were studied. The decomposition of the added fillers and covering connection of residual on the substrate contribute to the improvement of heat insulation. The ablation test shows that the formation of a dense char layer with certain strength is key to improving the ablative properties. The optimal ablative performance is achieved when the concentration of ZB and AHP is 10 and 5 phr, respectively. Under such circumstances, the linear ablation rate is as low as 0.032 mm/s, which is about 61% lower than the pure silicone rubber. Furthermore, the structure and composition of the formed char layer were analyzed using X‐ray diffraction analysis, scanning electron microscopy, and Fourier transform infrared spectroscopy.
Spatial Visualization of Human Anatomy through Art Using Technical Drawing Exercises
Authors: Na Youjin , Clary Derek W. , Rose‐Reneau Zakary B. , Segars Larry , Hanson Andrea , Brauer Philip , Wright Barth W. , Keim Sarah A.
Published: April 2021

Spatial visualization, the ability to mentally rotate three‐dimensional (3D) images, plays a significant role in anatomy education. This study examines the impact of technical drawing exercises on the improvement of spatial visualization and anatomy education in a Neuroscience course. First‐year medical students (n = 84) were randomly allocated into a control group (n = 41) or art‐training group (n = 43). Variables including self‐reported artistic drawing ability, previous technical drawing experience, or previous anatomy laboratory exposure were gathered. Participants who self‐identified as artistic individuals were equally distributed between the two groups. Students in the art‐training group attended four 1‐hour sessions to solve technical drawing worksheets. All participants completed two Mental Rotations Tests (MRT), which were used to assess spatial visualization. Data were also collected from two neuroscience written examinations and an anatomical “tag test” practical examination. Participants in the art‐training and control groups improved on the MRT. The mean of written examination two was significantly higher (P = 0.007) in the art‐training group (12.95) than the control group (11.48), and higher (P = 0.027) in those without technical drawing experience (12.44) than those with (11.00). The mean of the anatomical practical was significantly higher (P = 0.010) in those without artistic ability (46.24) than those with (42.00). These results suggest that completing technical drawing worksheets may aid in solving anatomy‐based written examination questions on complex brain regions, but further research is needed to determine its implication on anatomy practical scores. These results propose a simple method of improving spatial visualization in anatomy education.
Polymerization via Insertion of Ethylene into Al−C bond under Mild Conditions: Mechanistic Studies on the Promotion Exerted by a Catalytic Amount of Cationic Gadolinium Metallocene
Authors: Fukushima Rika , Tardif Olivier , Kaita Shojiro , Wakatsuki Yasuo , Koga Nobuaki
Published: April 2021

The cationic gadolinium metallocene [(C5Me5)2Gd][B(C6F5)4], when combined with an excess amount of Al(iBu)3, efficiently produces polyethylene at 80 °C under 0.8 MPa pressure of ethylene. After quenching, the resulting polyethylene has ethyl group at one end and isobutyl group at the other terminal. Because no Gd‐alkyl species appears to be involved, a mechanism with conventional coordinative chain transfer polymerization (CCTP) is not feasible. Density functional theory (DFT) analyses indicate a novel mechanism in which the cationic Gd plays a crucial role by coordinating ethylene and assists the insertion of the coordinated ethylene into Al−C bond.
Silence at school: Uses and experiences of silence in pedagogy at a secondary school
Authors: Hanna Amy
Published: April 2021

Silence infuses all aspects of our daily communications: what we say and what remains unspoken; those to whom we speak, and those we ignore; those we trust and respect, and those we do not. In the school environment, interactions between students and teachers lie at the heart of pedagogy. This relationship is also marked by its silences, and the concept of ‘student voice’ arose out of these silences on matters that affect students. However, the role of silence in such interactions has yet to receive comprehensive attention. This article presents the findings of a study on the uses and experiences of silence in the classroom with secondary school students aged 14–15 years and their teachers. Drawing on nine group discussions and 33 interviews with 20 teachers and 35 students, respectively, I argue that an oversight of silence in the student voice discipline has obscured the power dimensions of student voice, and the injustices that become visible when different forms of silence are illuminated. I argue that there are two core ideas which emerge from the findings: firstly, that silent practices manifest in two distinct paradigms of productivity and listening which function as expectations of teaching and learning; secondly, that the conflation of the listening paradigm with respect demonstrates the capacity of silent practices to reinforce the division between teaching and learning to become mediums of injustice. I conclude that this dichotomous relationship between pedagogy and student voice requires a pedagogy based on a critical examination of respect.
Cytoskeletal diversification across 1 billion years: What red algae can teach us about the cytoskeleton, and vice versa
Authors: Goodson Holly V. , Kelley Joshua B. , Brawley Susan H.
Published: April 2021

The cytoskeleton has a central role in eukaryotic biology, enabling cells to organize internally, polarize, and translocate. Studying cytoskeletal machinery across the tree of life can identify common elements, illuminate fundamental mechanisms, and provide insight into processes specific to less‐characterized organisms. Red algae represent an ancient lineage that is diverse, ecologically significant, and biomedically relevant. Recent genomic analysis shows that red algae have a surprising paucity of cytoskeletal elements, particularly molecular motors. Here, we review the genomic and cell biological evidence and propose testable models of how red algal cells might perform processes including cell motility, cytokinesis, intracellular transport, and secretion, given their reduced cytoskeletons. In addition to enhancing understanding of red algae and lineages that evolved from red algal endosymbioses (e.g., apicomplexan parasites), these ideas may also provide insight into cytoskeletal processes in animal cells.
Enzymatic RNA Production from NTPs Synthesized from Nucleosides and Trimetaphosphate**
Authors: Chizzolini Fabio , Kent Alexandra D. , Passalacqua Luiz F. M. , Lupták Andrej
Published: April 2021

A mechanism of nucleoside triphosphorylation would have been critical in an evolving “RNA world” to provide high‐energy substrates for reactions such as RNA polymerization. However, synthetic approaches to produce ribonucleoside triphosphates (rNTPs) have suffered from conditions such as high temperatures or high pH that lead to increased RNA degradation, as well as substrate production that cannot sustain replication. Previous reports have demonstrated that cyclic trimetaphosphate (cTmp) can react with nucleosides to form rNTPs under prebiotically‐relevant conditions, but their reaction rates were unknown and the influence of reaction conditions not well‐characterized. Here we established a sensitive assay that allowed for the determination of second‐order rate constants for all four rNTPs, ranging from 1.7×10−6 to 6.5×10−6 M−1 s−1. The ATP reaction shows a linear dependence on pH and Mg2+, and an enthalpy of activation of 88±4 kJ/mol. At millimolar nucleoside and cTmp concentrations, the rNTP production rate is sufficient to facilitate RNA synthesis by both T7 RNA polymerase and a polymerase ribozyme. We suggest that the optimized reaction of cTmp with nucleosides may provide a viable connection between prebiotic nucleotide synthesis and RNA replication.
4‐Nitroanisole Facilitates Proton Reduction: Visible Light‐Induced Oxidative Aryltrifluoromethylation of Alkenes with Hydrogen Evolution
Authors: Kong Rui , Fu Tingfeng , Yang Ruihan , Chen Danna , Liang Deqiang , Dong Ying , Li Weili , Wang Baoling
Published: April 2021

A complementary oxidative photocatalytic strategy is presented. In the presence of 4‐nitroanisole, hexafluoroisopropanol (HFIP) as a proton source is activated and the proton photoreduction is enhanced, enabling a range of cyclizative aryltrifluoromethylations of alkenes and CF3SO2Na (Langlois’ reagent) with hydrogen evolution. Such a protocol is general, for both activated and unactivated olefins could be used as the substrates, affording a variety of CF3‐containing heterocycles such as indolines, indolin‐2‐ones, 3,4‐dihydroisoquinolin‐1‐ones, 5,6‐dihydrobenzoimidazo[2,1‐a]isoquinolines, benzoimidazo[2,1‐a]isoquinolin‐6(5H)‐ones and 1,2,3,4‐tetrahydroisoquinolines, under mild and metal‐ and oxidant‐free conditions with a good functional‐group tolerance. Extensive mechanistic investigations revealed that p‐nitroanisole (p‐NA) does not react with the photocatalyst directly as an oxidant, but rather activates HFIP via proton‐coupled electron transfer (PCET) and scavenges some of the reduced protons to improve proton photoreduction.
Morphology of Flashing Feeds at Critical Fluid Properties in Larger Pipes
Authors: Döß Alexander , Schubert Markus , Wiezorek Michael , Hampel Uwe , Flegiel Felix , Windmeier Christoph , Schleicher Eckhard , Schunk Christoph
Published: April 2021

Tailored conditioning and control of flashing feeds in industrial applications requires knowledge of the evolving flow morphology and phase fractions along the feed pipe. Design methods obtained from reference systems (e.g. water‐air) are hardly applicable for commercial scales and critical fluid properties (e.g. high vapor densities, low surface tension). In this study, the flow morphology of flashing feeds in a novel refrigerant test rig at critical fluid properties was analyzed using wire‐mesh sensors at two locations along the feed pipe and experimental data from the water‐air system.
Recent Advances in Radiometals for Combined Imaging and Therapy in Cancer
Authors: Herrero Álvarez Natalia , Bauer David , Hernández‐Gil Javier , Lewis Jason S.
Published: April 2021

Nuclear medicine is defined as the use of radionuclides for diagnostic and therapeutic applications. The imaging modalities positron emission tomography (PET) and single‐photon emission computed tomography (SPECT) are based on γ‐emissions of specific energies. The therapeutic technologies are based on β−‐particle‐, α‐particle‐, and Auger electron emitters. In oncology, PET and SPECT are used to detect cancer lesions, to determine dosimetry, and to monitor therapy effectiveness. In contrast, radiotherapy is designed to irreparably damage tumor cells in order to eradicate or control the disease‘s progression. Radiometals are being explored for the development of diagnostic and therapeutic radiopharmaceuticals. Strategies that combine both modalities (diagnostic and therapeutic), referred to as theranostics, are promising candidates for clinical applications. This review provides an overview of the basic concepts behind therapeutic and diagnostic radiopharmaceuticals and their significance in contemporary oncology. Select radiometals that significantly impact current and upcoming cancer treatment strategies are grouped as clinically suitable theranostics pairs. The most important physical and chemical properties are discussed. Standard production methods and current radionuclide availability are provided to indicate whether a cost‐efficient use in a clinical routine is feasible. Recent preclinical and clinical developments and outline perspectives for the radiometals are highlighted in each section.
Stereoselective Access to Antimelanoma Agents by Hybridization and Dimerization of Dihydroartemisinin and Artesunic acid
Authors: Botta Lorenzo , Cesarini Silvia , Zippilli Claudio , Filippi Silvia , Bizzarri Bruno Mattia , Baratto Maria Camilla , Pogni Rebecca , Saladino Raffaele
Published: April 2021

A library of five hybrids and six dimers of dihydroartemisinin and artesunic acid has been synthetized in a stereo‐controlled manner and evaluated for the anticancer activity against metastatic melanoma cell line (RPMI7951). Among novel derivatives, three artesunic acid dimers showed antimelanoma activity and cancer selectivity, being not toxic on normal human fibroblast (C3PV) cell line. Among the three dimers, the one bearing 4‐hydroxybenzyl alcohol as a spacer showed no cytotoxic effect (CC50>300 μM) and high antimelanoma activity (IC50=0.05 μM), which was two orders of magnitude higher than that of parent artesunic acid, and of the same order of commercial drug paclitaxel. In addition, this dimer showed cancer‐type selectivity towards melanoma compared to prostate (PC3) and breast (MDA‐MB‐231) tumors. The occurrence of a radical mechanism was hypothesized by DFO and EPR analyses. Qualitative structure activity relationships highlighted the role of artesunic acid scaffold in the control of toxicity and antimelanoma activity.
Examining the ability of the Cancer and Aging Research Group tool to predict toxicity in older men receiving chemotherapy or androgen‐receptor–targeted therapy for metastatic castration‐resistant prostate cancer
Authors: Alibhai Shabbir M. H. , Breunis Henriette , Hansen Aaron R. , Gregg Richard , Warde Padraig , Timilshina Narhari , Tomlinson George , Joshua Anthony M. , Hotte Sebastien , Fleshner Neil , Emmenegger Urban
Published: April 2021

BACKGROUND

Because multiple treatments are available for metastatic castrate‐resistant prostate cancer (mCRPC) and most patients are elderly, the prediction of toxicity risk is important. The Cancer and Aging Research Group (CARG) tool predicts chemotherapy toxicity in older adults with mixed solid tumors, but has not been validated in mCRPC. In this study, its ability to predict toxicity risk with docetaxel chemotherapy (CHEMO) was validated, and its utility was examined in predicting toxicity risk with abiraterone or enzalutamide (A/E) among older adults with mCRPC.

METHODS

Men aged 65+ years were enrolled in a prospective observational study at 4 Canadian academic cancer centers. All clinically relevant grade 2 to 5 toxicities over the course of treatment were documented via structured interviews and chart review. Logistic regression was used to identify predictors of toxicity.

RESULTS

Seventy‐one men starting CHEMO (mean age, 73 years) and 104 men starting A/E (mean age, 76 years) were included. Clinically relevant grade 3+ toxicities occurred in 56% and 37% of CHEMO and A/E patients, respectively. The CARG tool was predictive of grade 3+ toxicities with CHEMO, which occurred in 36%, 67%, and 91% of low, moderate, and high‐risk groups (P = .003). Similarly, grade 3+ toxicities occurred among A/E users in 23%, 48%, and 86% with low, moderate, and high CARG risk (P < .001). However, it was not predictive of grade 2 toxicities with either treatment.

CONCLUSIONS

There is external validation of the CARG tool in predicting grade 3+ toxicity in older men with mCRPC undergoing CHEMO and demonstrated utility during A/E therapy. This may aid with treatment decision‐making.
Colloidal Nanospheres of Amorphous Selenium: Facile Synthesis, Size Control, and Optical Properties
Authors: Cheng Haoyan , Zhou Shan , Xie Minghao , Gilroy Kyle D. , Zhu Zhihong , Xia Younan
Published: April 2021

This article reports a facile method for the colloidal synthesis of nanospheres made of amorphous selenium (ɑ‐Se). The diameters of the nanospheres can be tightly controlled in the range of 45–157 nm by varying the reaction time and temperature, as well as the amount of the reducing agent. The average size of the nanospheres is measured using transmission electron microscopy and dynamic light scattering while their optical properties are characterized using UV‐vis spectroscopy. We also compute their UV‐vis spectra using the discrete dipole approximation (DDA) method and the calculated spectra are consistent with the experimental data based on the UV‐vis spectra and the particle sizes derived from electron microscopy. The data derived from DDA calculations provides a fitting curve for finely controlling the sizes of the ɑ‐Se nanospheres by monitoring the UV‐vis spectra of the reaction solution at different stages of a synthesis.
A Photoionization Reflectron Time‐of‐Flight Mass Spectrometric Study on the Detection of Ethynamine (HCCNH2) and 2H‐Azirine (c‐H2CCHN)
Authors: Turner Andrew M. , Chandra Sankhabrata , Fortenberry Ryan C. , Kaiser Ralf I.
Published: April 2021

Ices of acetylene (C2H2) and ammonia (NH3) were irradiated with energetic electrons to simulate interstellar ices processed by galactic cosmic rays in order to investigate the formation of C2H3N isomers. Supported by quantum chemical calculations, experiments detected product molecules as they sublime from the ices using photoionization reflectron time‐of‐flight mass spectrometry (PI‐ReTOF‐MS). Isotopically‐labeled ices confirmed the C2H3N assignments while photon energies of 8.81 eV, 9.80 eV, and 10.49 eV were utilized to discriminate isomers based on their known ionization energies. Results indicate the formation of ethynamine (HCCNH2) and 2H‐azirine (c‐H2CCHN) in the irradiated C2H2:NH3 ices, and the energetics of their formation mechanisms are discussed. These findings suggest that these two isomers can form in interstellar ices and, upon sublimation during the hot core phase, could be detected using radio astronomy.
Photoinduced Storage and Thermal Release of Singlet Oxygen from 1,2‐Dihydropyridine Endoperoxides
Authors: De Bonfils Paul , Verron Elise , Nun Pierrick , Coeffard Vincent
Published: April 2021

The quest for molecules able to trap, store, and release singlet oxygen is of utmost interest due to their applicability in various domains such as materials science and photomedicine. The aim of this study was to prepare and study a new family of singlet oxygen donors based on the 1,2‐dihydropyridine motif. The experiments demonstrated the influence of substituents and solvents on the photooxygenation rate constants. The process can be operated reversibly by thermolysis of the in situ formed endoperoxide leading to a release of singlet oxygen and formation of the parent 1,2‐dihydropyridine compound. A bifunctional structure based on a phenalenone photosensitizer covalently connected to a 1,2‐dihydropyridine module was synthesized via a multi‐step sequence. Upon irradiation with blue light, singlet oxygen was produced leading to the formation of the endoperoxide intermediate. In the dark cycle, the endoperoxide underwent cycloreversion reaction affording the parent 1,2‐dihydropyridine unit paving the way to a continuous production of singlet oxygen during the light/dark cycles.
Association between dental diseases and history of stroke in the United States
Authors: Alhadainy Hatem A. , Keefe Thomas , Abdel‐Karim Amany H. , Abdulrab Saleem , Halboub Esam
Published: April 2021

Objective

This study aimed to determine the potential association between the dental diseases and self‐reported history of stroke in the United States based on data from the Third National Health and Nutrition Examination Survey (NHANES III).

Methods

Data were extracted from NHANES III. Dental variables were carious tooth surfaces, number of missing teeth, gingival bleeding, and periodontal pockets. Multiple logistic regression modeling was used to estimate the effect of these dental diseases on the self‐reported history of stroke with intent to adjust for the other potential determinants: age, sex, race, marital status, health insurance, education, exercise, body mass index, smoking, alcohol, hypertension, high serum cholesterol, and diabetes.

Results

Number of missing teeth was found to be significantly associated with the self‐reported history of stroke. Associations between the self‐reported history of stroke and caries, gingival bleeding, or periodontal pockets were not statistically significant.

Conclusions

Number of missing teeth was an independent determinant of the self‐reported history of stroke.
Basophil activation test: Assay precision and BI 1002494 SYK inhibition in healthy and mild asthmatics
Authors: Carstensen Saskia , Benediktus Ewald , Litzenburger Tobias , Hohlfeld Jens M. , Müller Meike
Published: April 2021

Background

Application of basophil activation test (BAT) in clinical trials requires assay validity. Whether assay variability differs between healthy and asthmatic subjects is mostly unknown. This study compares basophil stimulation using blood from healthy and asthmatic subjects with or without inhibition of spleen tyrosine kinase (SYK).

Methods

Whole blood of healthy and mild asthmatic subjects was stimulated with anti‐dinitrophenyl (DNP) IgE/DNP bovine serum albumin and anti‐IgE. Basophil activation was detected by CD63 and CD203c expression. CD63 expression levels were compared with serum IgE levels. Three operators repeated experiments with three subjects each from both groups at 3 days to observe assay precision. The effect of the SYK inhibitor BI 1002494 was assessed in BAT for both healthy and asthmatic subjects.

Results

BAT was reproducible in both groups. Acceptance criteria of <25% CV were mostly fulfilled. Stimulation with anti‐DNP (p < 0.001, r = −0.80) but not anti‐IgE (p = 0.74, r = 0.05) was related to serum IgE with levels > 200 IU/ml limiting anti‐DNP stimulation. BI 1002494 IC50 values were 497 nM and 1080 nM in healthy and 287 nM and 683 nM in asthmatics for anti‐DNP and anti‐IgE stimulation, respectively.

Conclusion

BAT, performed with blood from healthy or asthmatic subjects, is a robust test for the measurement of a physiological response in clinical trials. Blood from asthmatic donors with serum IgE > 200 IU/ml is less feasible when using anti‐DNP stimulation. SYK inhibition was not affected by disease status.
Machine learning‐based traffic scheduling techniques for intelligent transportation system: Opportunities and challenges
Authors: Nama Mahima , Nath Ankita , Bechra Nancy , Bhatia Jitendra , Tanwar Sudeep , Chaturvedi Manish , Sadoun Balqies
Published: April 2021

The rise in traffic congestion has become a significant concern in the urban city environment. The conventional traffic control systems with inefficient human resources management fail to control the traffic discipline, leading to increased traffic density and road offenses. However, the intelligent transportation system (ITS) can provide safety, efficiency, and sustainability for large‐scale vehicular traffic dilemmas. ITS unites machine learning with the available traffic control force and performs real‐time police scheduling to ensure the smooth flow of traffic. Many researchers have demonstrated notable work in intelligent traffic police scheduling and deployment using various optimization algorithms. However, the compilation of such praiseworthy work as a whole is still missing. Motivated by these facts, we provide a comprehensive review of the machine learning‐based state‐of‐the‐art technologies that can be used to form a three‐tier solution taxonomy. The first tier describes various tools and technologies that can be utilized to collect traffic data. The second tier highlights the machine learning algorithms and their accuracy, which forms a pattern in the collected data and then yields some crucial information about traffic flow, congestion levels, and so forth. In the third tier, the most vital taxonomy layer, various traffic police scheduling strategies are discussed. The proposed survey also presents the use of cases of traffic police scheduling that elaborates this review's applicability in various domains. Finally, some of the key challenges in the subject being reviewed are discussed, which initiates a further scope of improvement.
TGF‐β superfamily co‐receptors in cancer
Authors: Pawlak John B. , Blobe Gerard C.
Published: April 2021

Transforming growth factor‐β (TGF‐β) superfamily signaling via their cognate receptors is frequently modified by TGF‐β superfamily co‐receptors. Signaling through SMAD‐mediated pathways may be enhanced or depressed depending on the specific co‐receptor and cell context. This dynamic effect on signaling is further modified by the release of many of the co‐receptors from the membrane to generate soluble forms that are often antagonistic to the membrane‐bound receptors. The co‐receptors discussed here include TβRIII (betaglycan), endoglin, BAMBI, CD109, SCUBE proteins, neuropilins, Cripto‐1, MuSK, and RGMs. Dysregulation of these co‐receptors can lead to altered TGF‐β superfamily signaling that contributes to the pathophysiology of many cancers through regulation of growth, metastatic potential, and the tumor microenvironment. Here we describe the role of several TGF‐β superfamily co‐receptors on TGF‐β superfamily signaling and the impact on cellular and physiological functions with a particular focus on cancer, including a discussion on recent pharmacological advances and potential clinical applications targeting these co‐receptors.
Transforming growth factor‐beta1 and myeloid‐derived suppressor cells: A cancerous partnership
Authors: Mojsilovic Slavko , Mojsilovic Sonja S. , Bjelica Suncica , Santibanez Juan F.
Published: April 2021

Transforming growth factor‐beta1 (TGF‐β1) plays a crucial role in tumor progression. It can inhibit early cancer stages but promotes tumor growth and development at the late stages of tumorigenesis. TGF‐β1 has a potent immunosuppressive function within the tumor microenvironment that largely contributes to tumor cells' immune escape and reduction in cancer immunotherapy responses. Likewise, myeloid‐derived suppressor cells (MDSCs) have been postulated as leading tumor promoters and a hallmark of cancer immune evasion mechanisms. This review attempts to analyze the prominent roles of both TGF‐β1 and MDSCs and their interplay in cancer immunity. Furthermore, therapies against either TGF‐β1 or MDSCs, and their potential synergistic combination with immunotherapies are discussed. Simultaneous TGF‐β1 and MDSCs inhibition suggest a potential improvement in immunotherapy or subverted tumor immune resistance.
Population abundance in arctic grayling using genetics and close‐kin mark‐recapture
Authors: Prystupa Samuel , McCracken Gregory R. , Perry Robert , Ruzzante Daniel E.
Published: April 2021

Arctic Grayling (Thymallus arcticus) are among the most widely distributed and abundant freshwater fish in the Yukon Territory of Canada, yet little information exists regarding their broad and fine‐scale population structures or the number and size of these populations. The estimation of population abundance is fundamental for robust management and conservation, yet estimating abundance in the wild is often difficult. Here, we estimated abundance of an Arctic Grayling population using multiple genetic markers and the close‐kin mark‐recapture (CKMR) method. A total of N = 1,104 Arctic Grayling collected from two systems in Yukon were genotyped at 38 sequenced microsatellites. We first identified structure and assessed genetic diversity (effective population size, ). Collections from one of the systems (Lubbock River) comprised adults and young‐of‐the‐year sampled independently allowing the identification of parent–offspring pairs (POPs), and thus, the estimation of abundance using CKMR. We used COLONY and CKMRsim to identify POPs and both provided similar results leading to indistinguishable estimates (95% CI) of census size, that is, = 1858 (1259–2457) and 1812 (1229–2389). The accuracy of the population abundance estimates can in the future be improved with temporal sampling and more precise age or size‐specific fecundity estimates for Arctic Grayling. Our study demonstrates that the method can be used to inform management and conservation policy for Arctic Grayling and likely also for other fish species for which the assumption of random and independent sampling of adults and offspring can be assured.
Testing for functional significance of traits: Effect of the light environment in tropical tree saplings
Authors: Modolo Guilherme Silva , dos Santos Victor Alexandre Hardt Ferreira , Ferreira Marciel José
Published: April 2021

Functional traits have been examined to explain the growth rates of forest communities in different sites. However, weak or nonexistent relations are often found, especially due to the following methodological aspects: 1) lack of an environmental context (e.g., light, water, or nutrient supply), 2) use of nonfunctional traits, 3) an approach that does not contemplate phenotypic integration, and 4) neglect of intraspecific variation.

Here we measured relative growth rates, crown, and leaf traits in saplings of six tropical tree species growing in two light environments (Gap and Understory) to test whether contrasting light environments modulates trait–trait and trait–growth relationships. Moreover, we tested whether models that integrate traits of different dimensions of the plant (crown and leaf) improve the strength of trait–growth relations.

Light availability changed both trait–trait and trait–growth relationships. Overall, in Understory, crown traits (crown length and total leaf area) have a stronger effect on growth rates, while physiological traits related to nutrient acquisition (nitrogen concentration), photochemical efficiency (chlorophyll pigments and chlorophyll a fluorescence), and biochemical efficiency (potassium use efficiency) are strong in Gap. Models including multiple traits explained growth rates better in Gap (up to 62%) and Understory (up to 47%), but just in Gap the best model comprises traits that are representative of different dimensions of the plant.

Synthesis. We advanced the knowledge behind the light effects on tree sapling by posit that trait–trait and trait–growth relationships vary across light environments. Therefore, light availability is a key environmental factor to be considered when choosing the set of traits to be measured in functional approach studies using tropical tree saplings. In compliance with the phenotype integration hypothesis, functional traits are better predictors of growth rates when grouped in a set of traits of different dimensions of the plant that represent different functional mechanisms.