bluuebunny/crossref_metadata_2025 huggingface dataset:
Polystyrene Nanopillars with Inbuilt Carbon Nanotubes Enable Synaptic Modulation and Stimulation in Interfaced Neuronal Networks
Authors: Calaresu Ivo , Hernandez Jaime , Rauti Rossana , Rodilla Beatriz L. , Arché‐Núñez Ana , Perez Lucas , Camarero Julio , Miranda Rodolfo , González M. Teresa , Rodríguez Isabel , Scaini Denis , Ballerini Laura
Published: February 2021

The use of nanostructured materials and nanosized‐topographies has the potential to impact the performance of implantable biodevices, including neural interfaces, enhancing their sensitivity and selectivity, while reducing tissue reactivity. As a result, current trends in biosensor technology require the effective ability to improve devices with controlled nanostructures. Nanoimprint lithography to pattern surfaces with high‐density and high aspect ratio nanopillars (NPs) made of polystyrene (PS‐NP, insulating), or of a polystyrene/carbon‐nanotube nanocomposite (PS‐CNT‐NP, electrically conductive) are exploited. Both substrates are challenged with cultured primary neurons. They are demonstrated to support the development of suspended synaptic networks at the NPs’ interfaces characterized by a reduction in proliferating neuroglia, and a boost in neuronal emergent electrical activity when compared to flat controls. The authors successfully exploit their conductive PS‐CNT‐NPs to stimulate cultured cells electrically. The ability of both nanostructured surfaces to interface tissue explants isolated from the mouse spinal cord is then tested. The integration of the neuronal circuits with the NP topology, the suspended nature of the cultured networks, the reduced neuroglia formation, and the higher network activity together with the ability to deliver electrical stimuli via PS‐CNT‐NP reveal such platforms as promising designs to implement on neuro‐prosthetic or neurostimulation devices.
Full‐Space Manipulations of Electromagnetic Wavefronts at Two Frequencies by Encoding Both Amplitude and Phase of Metasurface
Authors: Bao Lei , Fu Xiaojian , Wu Rui Yuan , Ma Qian , Cui Tie Jun
Published: February 2021

In recent years, metasurfaces have not only provided new mechanisms to effectively control the electromagnetic waves but also maintained lower profiles and easy fabrication. Based on metasurfaces, many novel devices and applications have been reported and realized successively. Here, a dual‐band metasurface operating at microwave frequencies to achieve independent manipulations of reflected and transmitted waves in two half‐spaces at two frequencies is proposed. The designed C‐shaped metaparticle consists of two C‐shaped patterns and a C‐shaped slot on three layers, which can modulate both amplitude and phase responses of the reflected and transmitted waves simultaneously by altering the opening and orientation angles at 7 and 17 GHz. The transmission mode works at 7 GHz, in which multifocal points can be formed on focal planes with different distances and intensities using the amplitude and phase modulations. While the reflection mode works at 17 GHz, the reflected beams can be generated and controlled with different intensities in far‐field. All experimental results have good agreements with numerical simulations. This proposed metasurface paves the way for attaining multifunctional metadevices with amplitude and phase modulations in the full space, which have potential applications in imaging and communication systems.
ε‐Ga2O3 Thin Film Avalanche Low‐Energy X‐Ray Detectors for Highly Sensitive Detection and Fast‐Response Applications
Authors: Zhang Zhipeng , Chen Zimin , Chen Manni , Wang Kai , Chen Huanjun , Deng Shaozhi , Wang Gang , Chen Jun
Published: February 2021

Low‐energy X‐ray detectors are widely used in diverse areas, including medical diagnosis, space exploration, environmental monitoring, industrial inspection, and scientific research. Developing large area, highly sensitive, and fast low‐energy X‐ray detectors is challenging owing to material and device operation mechanism limitation. Herein, an epitaxial ε‐Ga2O3 thin film over a large area (2 in.) is prepared by metal–organic chemical vapor deposition and applied in the efficient low‐energy X‐ray detectors. The detectors are highly sensitive to detecting low‐energy X‐rays owing to the high mass attenuation coefficients achieved in the low‐energy X‐ray range (1–30 keV). The avalanche multiplication mechanism in back‐to‐back Au–Ga2O3 Schottky diodes is explored to realize high carrier multiplication and photocurrent gain. The charge collection efficiency is improved by reducing the spacing gap of the fingers within the coplanar interdigitated Au electrodes in the film, thus achieving a high detection sensitivity of up to 1.9 × 104 μCGyair−1 cm−2 for 30 keV X‐ray. Furthermore, the ε‐Ga2O3 thin films demonstrate high crystallization quality with low trap density and high breakdown voltage with a low noise current that enable their usage in applications requiring fast response time (e.g., 37 ms) and low detectable dose rate (e.g., 42.3 μGyair s−1).
Recent Advances in the Development of Direct Trifluoromethylselenolation Reagents and Methods
Authors: Wang Yanan , Ye Zhegao , Zhang Han , Yuan Zheliang
Published: February 2021

The introduction of trifluoromethylchalcogen group (CF3O, CF3S and CF3Se) has attracted growing attention in the field of modern organofluorine chemistry. Compared with the CF3S and CF3O chemistry, methods for trifluoromethylselenolation are much less developed owing to the limited availability of CF3Se transfer reagents and synthetic methods. The CF3Se group introduces promising lipophilicity (Hansch‐Leo parameter=1.29) and strong electron‐withdrawing effect (Hammett constants σm=0.44, σp=0.45) which are important parameters for the development of new pharmaceutically relevant compounds. Traditionally, the CF3Se compounds were synthesized by the nucleophilic trifluoromethylation of diselenides and selenocyanates, which suffered from harsh conditions and/or limited substrates scope. Compared with the indirect methods, the direct formation of C−SeCF3 constitutes is a more efficient approach. In recent years, new reagents and methods were developed which enabled the incorporation of the trifluoromethylselenyl group directly under mild conditions, specifically in transition metal catalysis and photoredox catalysis. In this review, we will focus on direct trifluoromethylselenolation strategies based on the development of new trifluoromethylselenolation reagents and methods.

magnified image
Electrochemical‐Induced Hydrogenation of Electron‐Deficient Internal Olefins and Alkynes with CH3OH as Hydrogen Donor
Authors: Qin Hongyun , Yang Jianjing , Yan Kelu , Xue Yaxuan , Zhang Meichen , Sun Xuejun , Wen Jiangwei , Wang Hua
Published: February 2021

Efficient hydrogenation of electron‐deficient internal olefins and alkynes access to saturate ketone with CH3OH as a single hydrogen donor under electrochemical conditions has been successfully developed. This hydrogenation strategy can be used to convert electron‐deficient internal olefins and alkynes to saturate ketone under electrochemical conditions with exogenous‐reductant and a metal catalyst. Mechanistic studies reveal that radical hydrogenation was involved in this transformation. Notably, various electron‐deficient internal olefins and alkynes could be tolerated in such an electrochemical hydrogenation synthetic strategy and can be easily scaled up with good efficiency.

magnified image
Dose‐Dependent Carbon‐Dot‐Induced ROS Promote Uveal Melanoma Cell Tumorigenicity via Activation of mTOR Signaling and Glutamine Metabolism
Authors: Ding Yi , Yu Jie , Chen Xingyu , Wang Shaoyun , Tu Zhaoxu , Shen Guangxia , Wang Huixue , Jia Renbing , Ge Shengfang , Ruan Jing , Leong Kam W. , Fan Xianqun
Published: February 2021

Uveal melanoma (UM) is the most common intraocular malignant tumor in adults and has a low survival rate following metastasis; it is derived from melanocytes susceptible to reactive oxygen species (ROS). Carbon dot (Cdot) nanoparticles are a promising tool in cancer detection and therapy due to their unique photophysical properties, low cytotoxicity, and efficient ROS productivity. However, the effects of Cdots on tumor metabolism and growth are not well characterized. Here, the effects of Cdots on UM cell metabolomics, growth, invasiveness, and tumorigenicity are investigated in vitro and in vivo zebrafish and nude mouse xenograft model. Cdots dose‐dependently increase ROS levels in UM cells. At Cdots concentrations below 100 µg mL−1, Cdot‐induced ROS promote UM cell growth, invasiveness, and tumorigenicity; at 200 µg mL−1, UM cells undergo apoptosis. The addition of antioxidants reverses the protumorigenic effects of Cdots. Cdots at 25–100 µg mL−1 activate Akt/mammalian target of rapamycin (mTOR) signaling and enhance glutamine metabolism, generating a cascade that promotes UM cell growth. These results demonstrate that moderate, subapoptotic doses of Cdots can promote UM cell tumorigenicity. This study lays the foundation for the rational application of ROS‐producing nanoparticles in tumor imaging and therapy.
Hotter and sicker: External energy expenditure and the tangled evolutionary roots of anthropogenic climate change and chronic disease
Authors: Pontzer Herman
Published: February 2021

Background

The dual crises of climate change and chronic, or non‐communicable, disease (NCD) have emerged worldwide as the global economy has industrialized over the past two centuries.

Aims

In this synthesis I examine humans’ dependence on external (non‐metabolic) energy expenditure (e.g., fire, fossil fuels) as a common, root cause in these modern crises.

Materials and Methods

Using fossil, archeological, and historical evidence I show that the human lineage has been dependent on external energy sources since the control of fire in the Paleolithic. This reliance has grown with the development of agriculture, the use of wind‐ and water‐power, and the most recently with industrialization and the transition to fossil fuels. To place industrialization in context I develop a Rule of 50, whereby individuals in industrialized economies consume roughly 50‐times more external energy and manufacture roughly 50‐times more material than do hunter‐gatherers.

Results

Industrialization and mechanization, powered by fossil fuels, have promoted centralization and processing in food production, reduced physical activity, and increased air pollution (including greenhouse gas emissions). These developments have led in turn to NCD and climate change.

Discussion and Conclusion

Climate change and NCD are connected both to one another and to our species’ deep evolutionary dependence on external energy. Transitioning to carbon‐free energy is essential to reduce the existential risks of climate change, but will likely have only modest effects on NCD. With the impending exhaustion of oil, coal, and natural gas reserves, developing replacements for fossil fuels is also critical to maintaining our species’ external energy portfolio.
Conjugated Copolymers That Shouldn't Be
Authors: Guan Jun , Sun Zejun , Ansari Ramin , Liu Yujia , Endo Aimi , Unno Masafumi , Ouali Armelle , Mahbub Shahrea , Furgal Joseph C. , Yodsin Nuttapon , Jungsuttiwong Siriporn , Hashemi Daniel , Kieffer John , Laine Richard M.
Published: February 2021

Multiple studies have explored using cage silsesquioxanes (SQs) as backbone elements in hybrid polymers motivated by their well‐defined structures and physical and mechanical properties. As part of this general exploration, we report unexpected photophysical properties of copolymers derived from divinyl double decker (DD) SQs, [vinyl(Me)Si(O0.5)2][PhSiO1.5]8[(O0.5)2Si(Me)vinyl] (vinylDDvinyl). These copolymers exhibit strong emission red‐shifts relative to model compounds, implying unconventional conjugation, despite vinyl(Me)Si(O‐)2 siloxane bridges. In an effort to identify minimum SQ structures that do/do not offer extended conjugation, we explored Heck catalyzed co‐polymerization of vinyl‐ladder(LL)‐vinyl compounds, vinyl(Me/Ph)Si(O0.5)2[PhSiO1.5]4(O0.5)2Si(Me/Ph)vinyl, with Br‐Ar‐Br. Most surprising, the resulting oligomers show 30–60 nm emission red‐shifts beyond those seen with vinylDDvinyl analogs despite lacking a true cage. Further evidence for unconventional conjugation includes apparent integer charge transfer (ICT) between LL‐co‐thiophene, bithiophene, and thienothiophene with 10 mol % F4TCNQ, suggesting potential as p‐type doped organic/inorganic semiconductors.
Post‐Functionalization of Supramolecular Polymers on Surface and the Chiral Assembly‐Induced Enantioselective Reaction
Authors: Li Deng‐Yuan , Zhu Ya‐Cheng , Li Shi‐Wen , Shu Chen‐Hui , Liu Pei‐Nian
Published: February 2021

Although post‐functionalization is extensively used to introduce diverse functional groups into supramolecular polymers (SPs) in solution, post‐functionalization of SPs on surfaces still remains unexplored. Here we achieved the on‐surface post‐functionalization of two SPs derived from 5,10,15‐tri‐(4‐pyridyl)‐20‐bromophenyl porphyrin (Br‐TPyP) via cross‐coupling reactions on Au(111). The ladder‐shaped, Cu‐coordinated SPs preformed from Br‐TPyP were functionalized through Heck reaction with 4‐vinyl‐1,1′‐biphenyl. In the absence of Cu, Br‐TPyP formed chiral SPs as two enantiomers via self‐assembly, which were functionalized via divergent cross‐coupling reaction with 4‐isocyano‐1,1′‐biphenyl (ICBP). Surprisingly, this reaction was discovered as an enantioselective on‐surface reaction induced by the chirality of SPs. Mechanistic analysis and DFT calculations indicated that after debromination of Br‐TPyP and the first addition of ICBP, only one attack direction of ICBP to the chiral SP intermediate is permissive in the second addition step due to the steric hindrance, which guaranteed the high enantioselectivity of the reaction.
Selective Crystallization of Rare‐Earth Ions into Cationic Metal‐Organic Frameworks for Rare‐Earth Separation
Authors: Yang Huajun , Peng Fang , Schier Danielle E. , Markotic Stipe A. , Zhao Xiang , Hong Anh N. , Wang Yanxiang , Feng Pingyun , Bu Xianhui
Published: February 2021

For rare‐earth separation, selective crystallization into metal‐organic frameworks (MOFs) offers new opportunities. Especially important is the development of MOF platforms with high selectivity toward target ions. Here we report a MOF platform (CPM‐66) with low‐coordination‐number environment for rare‐earth ions. This platform is highly responsive to the size variation of rare‐earth ions and shows exceptional ion‐size selectivity during crystallization. CPM‐66 family are based on M3O trimers (M=6‐coordinated Sc, In, Er‐Lu) that are rare for lanthanides. We show that the size matching between urea‐type solvents and metal ions is crucial for their successful synthesis. We further show that CPM‐66 enables a dramatic multi‐fold increase in separation efficiency over CPM‐29 with 7‐coordinated ions. This work provides some insights into methods to prepare low‐coordinate MOFs from large ions and such MOFs could serve as high‐efficiency platforms for lanthanide separation, as well as other applications.
Effect of Zinc‐Doping on the Reduction of the Hot‐Carrier Cooling Rate in Halide Perovskites
Authors: Wei Qi , Yin Jun , Bakr Osman M. , Wang Ze , Wang Chenhao , Mohammed Omar F. , Li Mingjie , Xing Guichuan
Published: February 2021

The fast hot‐carrier cooling process in the solar‐absorbers fundamentally limits their photon‐conversion efficiencies. It is highly desirable to develop a solar absorber with long‐lived hot‐carriers at sun‐illumination intensity, which can be used to develop the hot‐carrier solar cells with enhanced efficiency. Herein, we reveal that zinc‐doped (0.34 %) halide perovskites have the slower hot‐carrier cooling compared with the pristine sample through the transient absorption spectroscopy measurements and theoretical calculations. The hot‐carrier energy loss rate at the low photoexcitation level of 1017 cm−3 is found to be ≈3 times smaller than that of un‐doped perovskites for T=500 K hot carriers, and up to ten times when the hot‐carrier temperature approaches the lattice temperature. The incorporation of zinc‐dopant into perovskites can reduce the nonadiabatic couplings between conduction bands, which retards the photogenerated hot‐carriers relaxation processes. Our findings present a practical strategy to slow down the hot‐carrier cooling in perovskites at low carrier densities, which would be invaluable for the further development of practical hot‐carrier photovoltaics based on perovskites.
Untersuchung elektroenzymatischer H2‐Produktion mithilfe von Rotierende‐Ring‐Scheiben‐Elektrochemie und Massenspektrometrie**
Authors: Khushvakov Jaloliddin , Nussbaum Robin , Cadoux Cécile , Duan Jifu , Stripp Sven T. , Milton Ross D.
Published: February 2021

Gas‐verarbeitende Metalloenzyme sind für die Entwicklung biotechnologischer und biologisch inspirierter Anwendungen von großer Wichtigkeit. Im Fokus stehen vor allem Hydrogenasen und Nitrogenasen; beides Enzyme, die durch Reduktion von Protonen (H+) Wasserstoffgas (H2) herstellen. Hier demonstrieren wir, wie mithilfe einer Kombination von Rotierende‐Ring‐Scheiben‐Elektrochemie (RRDE) und Massenspektrometrie (MS) die Produktion von H2 und seiner Isotope HD und D2 nachverfolgt werden kann. Als Modell für H2‐produzierende Metalloenzyme verwenden wir die [FeFe]‐Hydrogenase aus Clostridium pasteurianum. Unsere Technik ermöglicht enzymologische Studien ohne Verwendung chemischer Reduktionsmittel, die unerwünschte Nebenwirkungen haben können. Wir gehen davon aus, dass dieser Ansatz einen wertvollen Beitrag zur Aufklärung des Reaktionsmechanismus H2‐produzierender Metalloenzyme leisten wird und die Entwicklung biologisch inspirierter Katalysatoren für H2‐Produktion und N2‐Fixierung begünstigen kann.
Honeycomb Carbon Nanofibers: A Superhydrophilic O2‐Entrapping Electrocatalyst Enables Ultrahigh Mass Activity for the Two‐Electron Oxygen Reduction Reaction
Authors: Dong Kai , Liang Jie , Wang Yuanyuan , Xu Zhaoquan , Liu Qian , Luo Yonglan , Li Tingshuai , Li Lei , Shi Xifeng , Asiri Abdullah M. , Li Quan , Ma Dongwei , Sun Xuping
Published: February 2021

Electrocatalytic two‐electron oxygen reduction has emerged as a promising alternative to the energy‐ and waste‐intensive anthraquinone process for distributed H2O2 production. This process, however, suffers from strong competition from the four‐electron pathway leading to low H2O2 selectivity. Herein, we report using a superhydrophilic O2‐entrapping electrocatalyst to enable superb two‐electron oxygen reduction electrocatalysis. The honeycomb carbon nanofibers (HCNFs) are robust and capable of achieving a high H2O2 selectivity of 97.3 %, much higher than that of its solid carbon nanofiber counterpart. Impressively, this catalyst achieves an ultrahigh mass activity of up to 220 A g−1, surpassing all other catalysts for two‐electron oxygen reduction reaction. The superhydrophilic porous carbon skeleton with rich oxygenated functional groups facilitates efficient electron transfer and better wetting of the catalyst by the electrolyte, and the interconnected cavities allow for more effective entrapping of the gas bubbles. The catalytic mechanism is further revealed by in situ Raman analysis and density functional theory calculations.
Synthesis of a novel lignin‐based epoxy resin curing agent and study of cure kinetics, thermal, and mechanical properties
Authors: Chen Bing , Zhang Qiang , Lu Mangeng , Meng Huifa , Qu Zhencai , Xu Chang'an , Jiao Enxiang
Published: February 2021

In this contribution, first of all, the methoxy groups of organic solvent lignin (OSL) was converted to phenolic hydroxyl groups through demethylation reaction for the purpose of fabricating demethylated organic solvent lignin (DOSL). In addition, the resulting DOSL was utilized as a renewable material to synthesize a novel esterified lignin (EDOSL) by reacting with isobutyryl chloride for curing of epoxy resin. Finally, commercial liquid diglycidyl ether of bisphenol A was cured by EDOSL in the presence of 4‐dimethylaminopyridine (DMAP) used as a catalyst based on dual‐curing mechanism. Dual curing is a processing methodology based upon the alliance of two diverse and compatible polymerization reactions occurring sequentially or simultaneously. According to the FTIR spectra and 1H‐NMR analyses, the demethylation of OSL, esterification of DOSL, and the curing reaction of epoxy resin with EDOSL were successfully conducted. The value of the phenolic hydrogen in the DOSL was approximately 4.89 mmol/g, which increased by 12.64% after demethylation. The thermal and mechanical performances of these cured epoxy samples were measured by DSC, DMA, TGA, and tensile testing. The epoxy system cured by 10%wt esterified lignin with 1%wt DMAP possessed the tensile strength of 71.54 ± 7.50 MPa and the initial degradation temperature (T5%) of 370°C, which can compete fairly with commercial aromatic curing agents or other lignin‐based agents studied currently for the curing of epoxy systems.
Multivariate process trajectories for molecular description of MF thermal curing and correlation with hydrolytic stability
Authors: Weiss Stephanie , Seidl Regina , Kessler Waltraud , Kessler Rudolf W. , Zikulnig‐Rusch Edith M. , Kandelbauer Andreas
Published: February 2021

During curing of thermosetting resins the technologically relevant properties of binders and coatings develop. However, curing is difficult to monitor due to the multitude of chemical and physical processes taking place. Precise prediction of specific technological properties based on molecular properties is very difficult. In this study, the potential of principal component analysis (PCA) and principal component regression (PCR) in the analysis of Fourier transform infrared (FTIR) spectra is demonstrated using the example of melamine‐formaldehyde (MF) resin curing in solid state. FTIR/PCA‐based reaction trajectories are used to visualize the influence of temperature on isothermal cure. An FTIR/PCR model for predicting the hydrolysis resistance of cured MF resin from their spectral fingerprints is presented which illustrates the advantages of FTIR/PCR compared to the combination differential scanning calorimetry/isoconversional kinetic analysis. The presented methodology is transferable to the curing reactions of any thermosetting resin and can be applied to model other technologically relevant final properties as well.
The influence of poly(3,4‐ethylenedioxythiophene) modification on the transport properties and fuel cell performance of Nafion‐117 membranes
Authors: Stenina Irina A. , Yurova Polina A. , Titova Tatyana S. , Polovkova Marina A. , Korchagin Oleg V. , Bogdanovskaya Vera A. , Yaroslavtsev Andrey B.
Published: February 2021

Nafion‐117/PEDOT composite membranes were synthesized by in situ chemical polymerization of 3,4‐ethylenedioxythiophene (EDOT) using ammonium persulfate as an oxidant. The polymerization of EDOT in Nafion membranes for various EDOT/oxidant treatment sequences was studied for the first time. PEDOT introduction leads to a slight decrease in both the ion‐exchange capacity and water uptake of the composite membranes, as well as to an increase in cationic transport. Membranes initially treated with an oxidant exhibit better conductivity and lower hydrogen permeability. The effect of both modification of Nafion‐117 membranes by PEDOT and hot‐pressing of hydrogen‐oxygen membrane‐electrode assemblies (MEAs) on the performance of proton‐exchange membrane fuel cells was studied. The maximum power density of the fabricated MEAs increases 1.5‐fold: from 510 (for a pristine Nafion‐117 membrane) to 810 mW cm−2 (for a membrane modified by PEDOT). The current density at a voltage of 0.4 V reaches 1248 and 2246 mA cm−2, respectively.
Improved Stabilities of Labeling Probes for the Selective Modification of Endogenous Proteins in Living Cells and In Vivo
Authors: Lin Kuan‐Yu , Hin Lam Chak , Lin Xin‐Hui , Hsu Jung‐I , Fan Syuan‐Yun , Gupta Nitesh K. , Lin Yu‐Chun , Khoon Tee Boon , Li Jui‐Ping , Chen Jen‐Kun , Tan Kui‐Thong
Published: February 2021

To date, various affinity‐based protein labeling probes have been developed and applied in biological research to modify endogenous proteins in cell lysates and on the cell surface. However, the reactive groups on the labeling probes are also the cause of probe instability and nonselective labeling in a more complex environment, e. g., intracellular and in vivo. Here, we show that labeling probes composed of a sterically stabilized difluorophenyl pivalate can achieve efficient and selective labeling of endogenous proteins on the cell surface, inside living cells and in vivo. As compared with the existing protein labeling probes, probes with the difluorophenyl pivalate exhibit several advantages, including long‐term stability in stock solutions, resistance to enzymatic hydrolysis and can be customized easily with diverse fluorophores and protein ligands. With this probe design, endogenous hypoxia biomarker in living cells and nude mice were successfully labeled and validated by in vivo, ex vivo, and immunohistochemistry imaging.
Changes in the topology of DNA replication intermediates: Important discrepancies between in vitro and in vivo
Authors: Schvartzman Jorge B. , Martínez Víctor , Hernández Pablo , Krimer Dora B. , Fernández‐Nestosa María‐José
Published: February 2021

The topology of DNA duplexes changes during replication and also after deproteinization in vitro. Here we describe these changes and then discuss for the first time how the distribution of superhelical stress affects the DNA topology of replication intermediates, taking into account the progression of replication forks. The high processivity of Topo IV to relax the left‐handed (+) supercoiling that transiently accumulates ahead of the forks is not essential, since DNA gyrase and swiveling of the forks cooperate with Topo IV to accomplish this task in vivo. We conclude that despite Topo IV has a lower processivity to unlink the right‐handed (+) crossings of pre‐catenanes and fully replicated catenanes, this is indeed its main role in vivo. This would explain why in the absence of Topo IV replication goes‐on, but fully replicated sister duplexes remain heavily catenated.
Effects of topological constraints on the alignment and maturation of multinucleated myotubes
Authors: Song Ki‐Young , Correia Jorge C. , Ruas Jorge L. , Teixeira Ana I.
Published: February 2021

Microfluidic‐based technologies enable the development of cell culture systems that provide tailored microenvironmental inputs to mammalian cells. Primary myoblasts can be induced to differentiate into multinucleated skeletal muscle cells, myotubes, which are a relevant model system for investigating skeletal muscle metabolism and physiology in vitro. However, it remains challenging to differentiate primary myoblasts into mature myotubes in microfluidics devices. Here we investigated the effects of integrating continuous (solid) and intermittent (dashed) walls in microfluidic channels as topological constraints in devices designed to promote the alignment and maturation of primary myoblast‐derived myotubes. The topological constraints caused alignment of the differentiated myotubes, mimicking the native anisotropic organization of skeletal muscle cells. Interestingly, dashed walls facilitated the maturation of skeletal muscle cells, as measured by quantifying myotube cell area and the number of nuclei per myotube. Together, our results suggest that integrating dashed walls as topographic constraints in microfluidic devices supports the alignment and maturation of primary myoblast‐derived myotubes.
An antitumor peptide RS17‐targeted CD47, design, synthesis, and antitumor activity
Authors: Wang Xinmin , Wang Ying , Hu Jialiang , Xu Hanmei
Published: February 2021

Background

CD47 is a widely expressed transmembrane protein located on the surface of somatic cells. It mediates a variety of cellular processes including apoptosis, proliferation, adhesion, and migration. An important role for CD47 is the transmission of a “Don't eat me” signal by interacting with SIRPα on the macrophage surface membrane, thereby preventing the phagocytosis of normal cells. However, cancer cells can take advantage of this autogenous signal to protect themselves from phagocytosis, thus enabling immune escape. Blocking the interaction between CD47 and SIRPα has proven to be effective in removing cancer cells. The treatment of various cancers with CD47 monoclonal antibodies has also been validated.

Methods

We designed and synthesized a peptide (RS17), which can specifically bind to CD47 and block CD47‐SIRPα signaling. The affinity of RS17 for CD47‐expressing tumor cells was determined, while the inhibition of CD47‐SIRPα signaling was evaluated in vitro and in vivo.

Results

The results indicated that RS17 significantly promotes the phagocytosis of tumor cells by macrophages and had a similar therapeutic effect compared with a positive control (CD47 monoclonal antibodies). In addition, a cancer xenograft mouse model was established using CD47‐expressing HepG2 cells to evaluate the effect of RS17 on tumor growth in vivo. Using ex vivo and in vivo mouse models, RS17 demonstrated a high inhibitory effect on tumor growth.

Conclusions

Based on our results, RS17 may represent a novel therapeutic peptide for cancer therapy.
Giant saccular abdominal aortic aneurysm with manifestation of gastric inlet obstruction mimicking a fundal gastrointestinal stromal tumor: A report on an unexpected case
Authors: Maleki Farid , Jahanshahi Fatemeh , Vahedian‐Ardakani Jalal
Published: February 2021

We present an extremely rare report on gastric inlet obstruction due to giant abdominal aortic aneurysm. Despite the rare occurrence of this manifestation, it should be considered in the differential diagnosis of gastric inlet obstructions.
Comparative study between Partial Least Squares and Rational function Ridge Regression models for the prediction of moisture content of woodchip samples using a handheld spectrophotometer
Authors: Mancini Manuela , Taavitsainen Veli‐Matti , Toscano Giuseppe
Published: February 2021

The use of woodchip for energy use is expected to increase in the next years because of the European targets for mitigating climate change and reducing greenhouse gas emissions. The technical standard EN ISO 17225‐4 determines the woodchip quality classes based on different chemical–physical parameters. Among them, moisture content is one of the most important, and its real‐time monitoring could improve the product quality, increase combustion efficiency, and consequently provide a potential decrease of pollutant emissions. Although the lab procedure to determine moisture content is quite simple, it is too long compared to the real needs of power plant operators. A rapid and simple solution may be represented by near‐infrared spectroscopy coupled with chemometric techniques. In detail, two regression methods, that is, Partial Least Squares (PLS) and Rational function Ridge Regression (RRR), have been compared in order to develop a good model for the prediction of moisture content of woodchip samples as arrived at the lab or directly in the power plant. In addition, the prediction performance has been studied as a function of the number of the spectral measurements of the sample. The results showed that handheld instruments could give reliable results by taking enough replicated spectra. According to the estimated measurement uncertainty of moisture measurements, both methods suffer from lack of fit, and the performance could be better if all unknown sources of errors could be eliminated. In general, RRR performs significantly better than PLS, although, as with many nonlinear methods, the risk for outliers in predictions with RRR is higher than with PLS. This could be overpassed performing predictions with both methods, and in cases of big differences, PLS prediction could be chosen.
Experiments and simulation of liquid drainage in oscillating packed beds under roll and heave motions
Authors: Zhang Jian , Larachi Faïçal , Iliuta Ion , Taghavi Seyed M.
Published: February 2021

Replication in the laboratory of offshore sea/swell movements is an essential component in the study and design of unit operations commissioned for seagoing vessels. Whether these perturbations affect the internal fluid flow structure inside reactors on‐board ships is yet to be investigated. This study focuses on understanding the phenomenon of liquid drainage of a porous medium submitted to hexapod‐controlled column oscillations. Liquid saturation transients, drainage rate, and drainage velocity were monitored using wire‐mesh sensors in porous media, under forced tilting (roll) and non‐tilting (heave) oscillations. A 3D/transient Eulerian two‐fluid model was also solved in the robot moving reference frame to reproduce the accelerated liquid drainage measured in oscillating columns. Such acceleration was highlighted by unveiling the relationship between the roll amplitude, the wall‐region greater permeability, and the uneven crosswise liquid distribution. Finally, the moving‐frame fictitious acceleration forces stemming from column oscillations were found to be negligibly small compared with the gravity both under heave and roll excitations.
Thromboembolism, mortality, and bleeding in 2,435,541 atrial fibrillation patients with and without cancer: A nationwide cohort study
Authors: Pastori Daniele , Marang Amélie , Bisson Arnaud , Menichelli Danilo , Herbert Julien , Lip Gregory Y. H. , Fauchier Laurent
Published: February 2021

Background

The number of patients with atrial fibrillation (AF) and cancer is rapidly increasing in clinical practice. The impact of cancer on clinical outcomes in this patient population is unclear, as is the performance of the HAS‐BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol) and CHA2DS2‐VASc (Congestive Heart Failure, Hypertension, Age ≥ 75 years, Diabetes Mellitus, Stroke or Transient Ischemic Attack, Vascular Disease, Age 65 to 74 Years, Sex Category) scores.

Methods

This was an observational, retrospective cohort study including 2,435,541 adults hospitalized with AF. The authors investigated the incidence rates (IRs) of all‐cause and cardiovascular mortality, ischemic stroke, major bleeding, and intracranial hemorrhage (ICH) according to the presence of cancer and cancer types.

Results

Overall, 399,344 (16.4%) had cancer, with the most common cancers being metastatic, prostatic, colorectal, lung, breast, and bladder. During a mean follow‐up of 2.0 years, cancer increased all‐cause mortality (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.99‐2.01). The IR of ischemic stroke was higher with pancreatic cancer (2.8%/y), uterine cancer (2.6%/y), and breast cancer (2.6%/y), whereas it was lower with liver/lung cancer (1.9%/y) and leukemia/myeloma (2.0%/y), in comparison with noncancer patients (2.4%/y). Cancer increased the risk of major bleeding (HR, 1.27; 95% CI, 1.26‐1.28) and ICH (HR, 1.07; 95% CI, 1.05‐1.10). Leukemia, liver cancer, myeloma, and metastatic cancers showed the highest IRs for major bleeding/ICH. Major bleeding and ICH rates progressively increased with the HAS‐BLED score, which showed generally good predictivity with C indexes > 0.70 for all cancer types. The CHA2DS2‐VASc score's predictivity was slightly lower in AF patients with cancer.

Conclusions

Cancer increased all‐cause mortality, major bleeding, and ICH risk in AF patients. The association between cancer and ischemic stroke differed among cancer types, and in some types, the risk of bleeding seemed to exceed the thromboembolic risk.
Review of the cytological features of olfactory neuroblastoma: A retrospective single‐center study
Authors: Okano Kimiaki , Ishida Mitsuaki , Sandoh Kaori , Ito Hiroko , Fujisawa Takuo , Iwai Hiroshi , Tsuta Koji
Published: February 2021

Olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor. Due to the rarity, there are scarce reports describing the cytological features of ONB. Thus, we aimed to analyze these cytological features and discuss their differences depending on the histological grading of ONB. Patients with a histopathological diagnosis of ONB who underwent fine‐needle aspiration cytology were enrolled in the study. The cytological features, including arrangement and shape of neoplastic cells, nuclear features, and presence of rosettes, were analyzed. Eight patients with ONB were enrolled; cytological specimens of seven patients were obtained from metastatic lesions and that of one patient were obtained from the nasal cavity tumor. The cytological specimens demonstrated variable‐sized clusters of neoplastic cells and single cells. Two‐cell pattern, composed of large‐sized viable neoplastic cells and small‐sized apoptotic cells, was noted in 3 of 4 high‐grade ONBs but in none of 4 low‐grade ONBs. This reflects that the presence of the two‐cell pattern may represent higher proliferation in neoplastic cells. The neoplastic cells had scant cytoplasm and round to oval nuclei containing fine to granular chromatin without conspicuous nucleoli. Rosettes and paranuclear blue bodies were observed in one patient. Most cytological specimens of ONB were obtained from metastatic lesions, especially from the cervical lymph node. Thus, ONB should be differentiated from malignant lymphoma and small cell neuroendocrine carcinoma. Recognition of these cytological features of ONB while considering patient history can aid in correctly diagnosing ONBs. Moreover, the presence of two‐cell pattern might reflect high‐grade histology of ONB.
Implementation of the International Academy of Cytology Yokohama standardized reporting for breast cytopathology: An 8‐year retrospective study
Authors: Wong Yin Ping , Vincent James Evelyna Prisha , Mohammad Azhar Mohammad Affieq Aiman , Krishnamoorthy Yogeswaran , Zainudin Nur Aqilah , Zamara Farhah , Tan Geok Chin , Shah Shamsul Azhar , Md Isa Nurismah , Baharoom Asmazila
Published: February 2021

Background

The International Academy of Cytology (IAC) Yokohama reporting system was recently proposed to serve as a standardized diagnostic platform for the cytological interpretation of breast fine needle aspiration biopsy (FNAB). Five cytological categories were suggested, linked to a certain risk of malignancy (ROM). The aim of this study was to assess the potency of this newly proposed reporting guideline, with a review of literatures.

Methods

This is a retrospective study over 8‐year duration in which all the breast FNABs performed in our institution were recategorized in accordance to the IAC Yokohama reporting system. Kappa coefficient was used to evaluate the agreement between the proposed cytological category and corresponding histological diagnosis, with the level of significance set at 5%. Cyto‐histopathological correlation and its diagnostic performance were also assessed.

Results

A total of 1136 breast FNABs were analyzed, including 31 repeat FNABs. Of these, 521 (47.1%) cases had matched histopathological results. Respective ROM for each category was: “insufficient” 13.6%, “benign” 0.4%, “atypical” 25.0%, “suspicious” 85.7%, and “malignant” 100%. There was substantial agreement (κ=0.757) between cytology and histopathological results. Our data revealed a high‐diagnostic specificity, sensitivity, positive and negative predictive value of 99.3% (95% CI: 97.6%‐99.9%), 94.2% (95% CI: 87.9%‐97.9%), 98.0% (95% CI: 92.5%‐99.5%), 98.0% (95% CI: 96.1%‐99.1%) respectively when both the “suspicious” and “malignant” cases were considered as positive tests, with area under the curve of 0.993.

Conclusions

The IAC Yokohama system is a reliable, evidence‐based, and standardized reporting system that helps to facilitate communication among cytopathologists, radiologists, and surgeons toward individualized patient management.
Evaluation of blood parameters by linear discriminant models for the detection of testosterone administration
Authors: Nair Vinod S. , Sharpe Ken , Husk Jacob , Miller Geoffrey D. , Van Eenoo Peter , Crouch Andre , Eichner Daniel
Published: February 2021

The steroidal module of the Athlete Biological Passport (ABP) has been used since 2014 for the longitudinal monitoring of urinary testosterone and its metabolites to identify samples suspicious for the use of synthetic forms of Endogenous Anabolic Androgenic Steroids (EAAS). Multiple recent studies have suggested that monitoring of blood parameters may provide enhanced detectability of exogenous testosterone administration. Transdermal and intramuscular testosterone administration studies were carried out in 15 subjects, and the effect on blood steroidal levels, hematological parameters, and gonadotropins was evaluated. Serum testosterone and dihydrotestosterone levels increased while gonadotropin levels were suppressed after administration. A modest increase in reticulocytes was also observed. The blood parameters that were responsive to the administrations were combined into several linear discriminant models targeting both administration (on) and washout (off) phases. The models were effective in detecting the large dose intramuscular administration but were less successful in the detection of the lower dose transdermal application. The blood profiling models may provide complementary value but do not appear to be substantially more advantageous than longitudinal urinary profiling.
Metabolism of 4F‐MDMB‐BICA in zebrafish by liquid chromatography–high resolution mass spectrometry
Authors: Yue Linna , Xiang Ping , Shen Baohua , Xu Duoqi , Song Fenyun , Yan Hui
Published: February 2021

In this study, in vivo metabolic studies of the synthetic cannabinoid 4F‐MDMB‐BICA were investigated using zebrafish models. The metabolites were identified and structurally illustrated by liquid chromatography‐high resolution mass spectrometry. Fourteen phase‐I metabolites and four phase‐II metabolites were generated from zebrafish. The main metabolic pathways of the phase‐I metabolism included N‐dealkylation, N‐dealkylation combined with hydroxylation, amide hydrolysis, oxidative defluorination, oxidative defluorination to butyric acid, acetic acid formation at the indole side chain, hydroxylation, ester hydrolysis followed by hydroxylation, dehydrogenation, dehydrogenation, and N‐dealkylation, and oxidative defluorination subsequently combined with dehydrogenation. The main biotransformations of the phase‐II metabolism were glucuronidation and sulfation. Two phase‐I metabolites (A1 and A11) and four phase‐II metabolites (A2, A3, A4, and A12) were reported for the first time. A14, which was confirmed in human biological samples, was detected only in zebrafish samples but not found in human liver microsome incubation study. The current study indicates that the zebrafish model is a promising tool for elucidating the metabolism of NPS in the future.
From glacial refugia to hydrological microrefugia: Factors and processes driving the persistence of the climate relict tree Zelkova sicula
Authors: Garfì Giuseppe , Carimi Francesco , Fazan Laurence , Gristina Alessandro Silvestre , Kozlowski Gregor , Livreri Console Salvatore , Motisi Antonio , Pasta Salvatore
Published: February 2021

With only two tiny populations, the climate relict Zelkova sicula (Sicily, Italy) is one of the rarest trees in the world. It also represents the most marginal member of genus Zelkova that was widespread in the broadleaved forests thriving in warm–temperate climates throughout Eurasia until the Last Glacial Age. Occurring at the westernmost range of the genus under typical Mediterranean climate, the micro‐topographic settings have always appeared crucial for the survival of this relict. However, the factors and processes actually involved in its persistence in the current refugia, as well as the response of similar relict trees in arid environments, are poorly understood worldwide. In the aim to elucidate these aspects, in the two sites hosting Z. sicula analyses of topographical attributes were combined with investigations on soil moisture dynamics. Additionally, plants’ growth and spatial distribution patterns were analyzed to detect fine‐scale differences between populations and assess the possible ecological amplitude of the species. Results revealed that convergent topographies are basic determinants of microrefugia in arid environments. Within the investigated sites, underground moisture never decreases below 25%, buffering seasonal rainfall fluctuations. Therefore, hydrological microrefugia play a key role in decoupling from regional climate, supporting the target species in coping with an unsuitable climatic envelope. Additionally, the inter‐population variability of biometric attributes showed that individual growth is site‐dependent and the species retains a relative ecological plasticity, whereas the strongly clumped spatial patterns confirmed the common clonal growth. On one hand, deeply incised landforms have acted as effective hydrologic microrefugia, on the other clonality coupled with triploidy supposedly improved the resistance of Z. sicula to harsh environments, though entailing inability to reproduce sexually. Most likely, sterility and environmental/physical barriers that have existed for millennia have prevented this relict from leaving the last suitable microrefugia, resulting in the two current rear edge populations.
Natural seedling recruitment and regeneration in deforested and sand‐filled Mangrove forest at Eagle Island, Niger Delta, Nigeria
Authors: Numbere Aroloye O.
Published: February 2021

Seed recruitment is a major driver of mangrove restoration globally. It is hypothesized that soil condition and channel hydrology can accelerate seedling recruitment and regeneration after a major disturbance. Species abundance, diversity indices, microbial and chemical concentrations in sand‐filled mangrove forest was studied. Eight plots measuring 487.77 m2 each were established with ten transects in each plot in a random block design to investigate the effect of soil conditions on seedling growth. A total of 1,886 seedlings were counted. Seedling abundance was significantly different between red (Rizophora racemosa), white (Laguncularia racemosa), and black (Avicennia germinans) mangroves, and nypa palm (nypa fruticans). The most dominant species was black mangrove, and the least dominant species was nypa palm. Muddy soils had the most abundant species (n = 994) followed by sandy (n = 457) and semi‐muddy (435) soils. Furthermore, sandy soils had the highest species diversity (H = 0.896) followed by semi‐muddy (H = 0.876) and muddy (H = 0.583) soils. The soil metal concentration has no correlation with seed abundance and occur in the order Iron > Nitrate > Copper > Cadmium. Soil with high species diversity had high soil microbial population; however, seedling abundance was correlated with soil nutrients and not heavy metals. Small seeds are easily recruited while good soil condition plus existing hydrological connection facilitated natural seedling regeneration in the disturbed mangrove forest.