bluuebunny/crossref_metadata_2025 huggingface dataset:
Solvent‐Activated Hafnium‐Containing Zeolites Enable Selective and Continuous Glucose–Fructose Isomerisation
Authors: Botti Luca , Kondrat Simon A. , Navar Ricardo , Padovan Daniele , Martinez‐Espin Juan S. , Meier Sebastian , Hammond Ceri
Published: July 2020

The isomerisation of glucose to fructose is a critical step towards manufacturing petroleum‐free chemicals from lignocellulosic biomass. Herein we show that Hf‐containing zeolites are unique catalysts for this reaction, enabling true thermodynamic equilibrium to be achieved in a single step during intensified continuous operation, which no chemical or biological catalyst has yet been able to achieve. Unprecedented single‐pass yields of 58 % are observed at a fructose selectivity of 94 %, and continuous operation for over 100 hours is demonstrated. The unexpected performance of the catalyst is realised following a period of activation within the reactor, during which time interaction with the solvent generates a state of activity that is absent in the synthesised catalyst. Mechanistic studies by X‐ray absorption spectroscopy, chemisorption FTIR, operando UV/Vis and 1H–13C HSQC NMR spectroscopy indicate that activity arises from isolated HfIV atoms with monofunctional acidic properties.
Preparation of novel biomass humate flame retardants and their flame retardancy in epoxy resin
Authors: Liu Guangya , Shi Huili , Kundu Chanchal Kumar , Li Zhiwei , Li Xiaohong , Zhang Zhijun
Published: July 2020

Humic acid (HA), a biomass material with plentiful oxygen‐containing functional groups, showed huge potential to be considered as a promising charring agent in flame retardancy. In this study, this HA was modified with four different metal ions like Fe2+, Mn2+, Al3+, and Cu2+ and finally, introduced into the epoxy resin (EP) to enhance the flame retardancy of the EP and the dispersion of these flame retardants into the EP matrix. When 10 wt% of HA‐Fe and HA‐Mn were incorporated into EP matrix, the limiting oxygen index (LOI) was increased from 21.2% for EP to 26.6 and 25.3% for the EP composites and the peak heat release rate (pHRR) was reduced by 36 and 35.5%, respectively. Such a significant improvement in flame retardancy was attributed to the catalytic charring of HA in the presence of metal ions, which ultimately increased the residual char formation and produced compact char layers during the combustion process to retard the transfer of heat and combustible gases between the EP composites and the flame zone. Finally, this kind of application provided a feasible way for the development of an environmentally friendly flame retardant with high efficiency, which improved the fire safety of EP matrix.
RNA interference of eclosion hormone gene reveals its roles in the control of ecdysis behavior in Heortia vitessoides Moore
Authors: Li Zhixing , Ye Qingya , Lyu Zihao , Lin Tong
Published: July 2020

Eclosion hormone (EH) is an important neuropeptide that regulates growth and development. This study predicted the EH gene (HvEH) of Heortia vitessoides Moore (Lepidoptera: Crambidae) from the transcriptome database and its expression patterns were determined using quantitative real‐time polymerase chain reaction. HvEH was expressed in all developmental stages and especially in the head area. RNA interference‐mediated silencing of HvEH (2 μg/individual) with double‐stranded HvEH RNA (dsHvEH) was achieved within 48 hr. Abnormal phenotypes appeared in the pupa and adult stages. dsHvEH injection suppressed pupation and eclosion rates. HvEH expression increased upon treatment with 20‐hydroxyecdysone but decreased at extreme temperatures. These results suggest that HvEH plays an essential role in ecdysis and wing formation in H. vitessoides.
Enhanced microbial corrosion of stainless steel by Acidithiobacillus ferrooxidans through the manipulation of substrate oxidation and overexpression of rus
Authors: Inaba Yuta , West Alan C. , Banta Scott
Published: July 2020

Acidithiobacillus ferrooxidans cells can oxidize iron and sulfur and are key members of the microbial biomining communities that are exploited in the large‐scale bioleaching of metal sulfide ores. Some minerals are recalcitrant to bioleaching due to the presence of other inhibitory materials in the ore bodies. Additives are intentionally included in processed metals to reduce environmental impacts and microbially influenced corrosion. We have previously reported a new aerobic corrosion mechanism where A. ferrooxidans cells combined with pyrite and chloride can oxidize low‐grade stainless steel (SS304) with a thiosulfate‐mediated mechanism. Here we explore process conditions and genetic engineering of the cells that enable corrosion of a higher grade steel (SS316). The addition of elemental sulfur and an increase in the cell loading resulted in a 74% increase in the corrosion of SS316 as compared to the initial sulfur‐ and cell‐free control experiments containing only pyrite. The overexpression of the endogenous rus gene, which is involved in the cellular iron oxidation pathway, led to a further 85% increase in the corrosion of the steel in addition to the improvements made by changes to the process conditions. Thus, the modification of the culturing conditions and the use of rus‐overexpressing cells led to a more than threefold increase in the corrosion of SS316 stainless steel, such that 15% of the metal coupons was dissolved in just 2 weeks. This study demonstrates how the engineering of cells and the optimization of their cultivation conditions can be used to discover conditions that lead to the corrosion of a complex metal target.
Computers, carbohydrates and cola: Designing an online lab experience for undergraduate health sciences and non‐majors in a pandemic paradigm
Authors: Mahaffey Angela L.
Published: July 2020

Colleges and educational institutions throughout the globe have adapted a pseudo‐online educational model. This is also evident in health sciences courses designed for biochemical and chemical education. Biochemistry (along with general, organic and analytical) education is significant in the basic prerequisite education of undergraduate health sciences and non‐majors curriculum, including a selection of human physiology and nutrition courses. Providing practical and empirical experiences for students enrolled in chemistry for health professions course is essential, even in this time of uncertainty. Here an option for a simple and safe, comprehensive virtual learning experience on carbohydrates and chemistry topics in connection with healthcare was developed by complementing an existing virtual lab collection and implementing this approach in an undergraduate health sciences (non‐majors) course. Student responses to this online learning approach were recorded in a post‐lab survey.
A review of anatomy education during and after the COVID‐19 pandemic: Revisiting traditional and modern methods to achieve future innovation
Authors: Iwanaga Joe , Loukas Marios , Dumont Aaron S. , Tubbs R. Shane
Published: July 2020

The coronavirus disease 2019 (COVID‐19) pandemic has had enormous effects on anatomy education. During the pandemic, students have had no access to cadavers, which has been the principal way to learn anatomy since the 17th century. As it is difficult to predict future access to cadavers for students or in‐person classes, anatomy educators are encouraged to revisit all possible teaching methods in order to develop innovations. Here, we review anatomy education methods to apply to current and future education.
The effects of game‐based learning in the acquisition of “soft skills” on undergraduate software engineering courses: A systematic literature review
Authors: Garcia Ivan , Pacheco Carla , Méndez Francisco , Calvo‐Manzano Jose A.
Published: July 2020

The software industry is becoming an increasingly important part of the economy in countries that have realized that the education of future software engineers is crucial to having a vibrant software industry. However, software engineering education is still influenced by traditional teaching impeding the acquisition of soft skills. Game‐based learning (GBL) combines learning with different known resources, such as games, to support and improve the teaching/learning process and/or student evaluation through active learning. This study presents a systematic literature review on the use of GBL for teaching software engineering at the undergraduate level, from 2001 to 2020, by addressing four research questions: What kinds of games have been developed for software engineering education? Which software engineering areas have been addressed by these games? Which soft skills have been promoted by using these games? How have these skills been evaluated? The study found 96 studies to answer these four questions. The findings provided evidence on the development of digital games focused on teaching the fundamentals of software engineering defined by software engineering body of knowledge. Moreover, these games have been able to promote the acquisition of more than one soft skill which is beneficial for undergraduate students.
MAGI2‐AS3 suppresses MYC signaling to inhibit cell proliferation and migration in ovarian cancer through targeting miR‐525‐5p/MXD1 axis
Authors: Chang Hua , Zhang Xue , Li Baixue , Meng Xiangkai
Published: July 2020

Ovarian cancer (OV) is one of the most lethal gynecological malignance in females, and usually diagnosed at advanced stages. Long noncoding RNAs (lncRNAs) exhibit their crucial functions in modulatory mechanisms of cancers. Substantive studies have proven the anti‐tumor role of MAGI2‐AS3 in multiple cancers, but the physiological functions of MAGI2‐AS3 in OV need more detailed explanations. The current study corroborated that overexpression of MAGI2‐AS3 executed inhibitory activity in OV via hindering cell proliferation, cell cycle, migration as well as invasion while promoted apoptosis. Moreover MAGI2‐AS3 bound with miR‐525‐5p and negatively regulated the expression of miR‐525‐5p. Further studies testified that MXD1 was a downstream target of miR‐525‐5p and the competing relationship between MAGI2‐AS3 and MXD1 were confirmed by RNA pull down. Based on the combination between MAX and MYC, we analyzed the effects of MAGI2‐AS3 on MXD1 and MYC, unveiling the competing relationship between MXD1 and MYC for binding to MAX. Finally, we constructed rescue assays to certify that MAGI2‐AS3 suppressed the course of OV via enhancing MXD1 expression. In summary, MAGI2‐AS3 repressed the progression of OV by targeting miR‐525‐5p/MXD1 axis, offering a novel insight into understanding OV at the molecular level.
The benefit of complete revascularization after primary PCI for STEMI is attenuated by increasing age: Results from the DANAMI‐3‐PRIMULTI randomized study
Authors: Joshi Francis R. , Lønborg Jacob , Sadjadieh Golnaz , Helqvist Steffen , Holmvang Lene , Sørensen Rikke , Jørgensen Erik , Pedersen Frants , Tilsted Hans Henrik , Høfsten Dan , Køber Lars , Kelbæk Henning , Engstrøm Thomas
Published: July 2020

Objectives

To ascertain the effect of age on outcomes after culprit‐only and complete revascularization after Primary PCI (PPCI) for ST‐elevation myocardial infarction (STEMI).

Background

The numbers of older patients being treated with PPCI are increasing. The optimal management of nonculprit stenoses in such patients is unclear.

Methods

We conducted an analysis of patients aged ≥75 years randomized in the DANAMI‐3‐PRIMULTI study to either culprit‐only or complete FFR‐guided revascularization. The primary endpoint was a composite of all‐cause mortality, nonfatal reinfarction, and ischaemia‐driven revascularization of lesions in noninfarct‐related arteries after a median of 27 months of follow‐up.

Results

One hundred and ten of six hundred and twenty seven patients in the DANAMI‐3‐PRIMULTI trial were aged ≥75 years. These patients were more likely female (p < .001), hypertensive (p < .001), had lower hemoglobin levels (p < .001), and higher serum creatinine levels (p < .001) than the younger patients in the trial. Other than less use of drug‐eluting stents (96.6 versus 88.0%: p = .02), there were no significant differences in procedural technique and success between patients aged <75 years and those ≥75 years of age. There was no significant difference in the incidence of the primary endpoint in patients ≥75 years randomized to culprit‐only or FFR‐guided complete revascularization (HR 1.49 [95% CI 0.57–4.65]; log‐rank p = .19; p for interaction versus patients <75 years <.001). There was a significant interaction between age as a continuous variable, treatment assignment, and the primary outcome (p < .001); beyond the age of about 75 years, there may be no prognostic advantage to complete revascularization.

Conclusions

In patients ≥75 years, after treatment of the culprit lesion in STEMI, there is no significant prognostic benefit to prophylactic complete revascularization of nonculprit stenoses. Pending further study, data would support a symptom‐guided approach to further invasive treatment.
Bicipitoradial bursitis: A diagnosis challenge!
Authors: Slouma Maroua , Rahmouni Safa , Dhahri Rim , Litaiem Noureddine , Gharsallah Imen , Metoui Leila , Louzir Bassem
Published: July 2020

Bicipitoradial bursitis should be considered in patients with antecubital mass and painful forearm pronation and supination movement. It can be due to several conditions such as calcium pyrophosphate dihydrate deposition, even in young patients. Ultrasound is useful to confirm the diagnosis, determine the etiology and to guide the treatment of bicipitoradial bursitis.
Adult‐onset epidermal nevus with epidermolytic hyperkeratotic pattern: Case report and dermoscopic findings
Authors: Mahshid Sadat Ansari , Maryam Nasimi , Kambiz Kamyab , Hamidreza Mahmoudi
Published: July 2020

EN is a hamartomatous proliferation of keratinocytes. The most common dermoscopic feature of EN is large brown circles in the absence of pigment network which is similar in different histopathological variants including epidermolytic hyperkeratotic.
Advances in the Electrochemical Treatment of Cancers and Tumors: Exploring the Current Trends, Advancements, and Mechanisms of Electrolytic Tumor Ablation
Authors: O'Brien Connor , Ignaszak Anna
Published: July 2020

Electrochemical therapy (EChT) is an evolving technique that allows for the minimally invasive ablation of tumors and cancers through the application of direct current (DC). The therapy boasts a low cost in comparison to many standardized procedures and could be made one of the most accessible forms of minimally invasive procedures for the targeting of tumors, owing to not only cost but also surgical simplicity. Furthermore, the treatment removes the need for oncospecific drugs and major surgical procedures, can be used when typical therapies are ill‐advised, and has shown clinical success in China, Brazil, Cuba, and Germany. Here, we will explore the new technologies, mathematical models, proposed mechanisms, and applications of EChT; as these develop, EChT may soon find itself at the forefront of the oncological world.
Variable selection in support vector regression using angular search algorithm and variance inflation factor
Authors: Folli Gabriely S. , Nascimento Márcia H.C. , de Paulo Ellisson H. , da Cunha Pedro H.P. , Romão Wanderson , Filgueiras Paulo R.
Published: July 2020

Here, we combine angular search algorithm and variance inflation factor (ASA‐VIF) with support vector regression (SVR) (ASA‐VIF‐SVR) to estimate total acid number (TAN), basic nitrogen content (BNC), and sulfur content (SC) in Brazilian crude oils. To prevent the interference of outliers, we further developed a strategy for outlier identification and applied it to nonlinear models based on RMSE (root mean square error). ASA‐VIF‐SVR was applied to near‐ and mid‐infrared spectroscopy (NIR and MIR) and hydrogen nuclear magnetic resonance (1H NMR) spectroscopy data available in a range of 93–194 samples. The models were evaluated for accuracy (root mean square error of calibration [RMSEC] and root mean square error of prediction [RMSEP]) and linearity (coefficient of determination, R2). The removal of outliers increased accuracy and linearity of our models. The ASA‐VIF model for TAN, BNC, and SC selected 0.37%, 0.93%, and 0.30% of variables from full NIR spectra; 0.21%, 0.27%, and 0.21% from full MIR; and 0.20%, 0.42%, and 0.15% from full 1H NMR. In most cases, the best results were obtained with variable selection compared with the full dataset. Also, 1H NMR generated more accurate and linear models with RMSEP and R2p of 0.0071 wt% and 0.86 for BNC and 0.0623 wt% and 0.79 for SC. TAN showed a better MIR result with RMSEP of 0.1426 mg KOH g–1 and R2p of 0.47. The most important region for 1H NMR and MIR was the one with the largest quantity of unpaired electrons (aromatic region).
Asymmetric Host Molecule Bearing Pyridine Core for Highly Efficient Blue Thermally Activated Delayed Fluorescence OLEDs
Authors: Yoon Jiwon , Kim Seong Keun , Kim Hyung Jong , Choi Suna , Jung Sang Won , Lee Hyuna , Kim Jun Yun , Yoon Dae‐Wi , Han Chang Wook , Chae Weon‐Sik , Kwon Jang Hyuk , Cho Min Ju , Choi Dong Hoon
Published: July 2020

In this study, two host materials, pCzBzbCz and pCzPybCz, are synthesized to achieve a high efficiency and long lifetime of blue thermally activated delayed fluorescence organic light‐emitting diodes (TADF‐OLEDs). The molecular design strategy involves the introduction of a pyridine group into the core structure of pCzPybCz as an electron‐withdrawing unit, and an electron‐donating phenyl group into the structure of pCzBzbCz. These host materials demonstrate good thermal stability and high triplet energy (T1=3.07 eV for pCzBzbCz and 3.06 eV for pCzPybCz) for the fabrication of blue TADF‐OLEDs. In particular, pCzPybCz‐based OLED devices demonstrate an external quantum efficiency (EQE) of 22.7 % and an operational lifetime of 24 h (LT90, time to attain 90 % of initial luminance) at an initial luminance of 1000 cd m−2. This superior lifetime could be explained by the C−N bond dissociation energy (BDE) in the host molecular structure. Furthermore, a mixed‐host system using the electron‐deficient 2,4‐bis(dibenzo[b,d]furan‐2‐yl)‐6‐phenyl‐1,3,5‐triazine (DDBFT) is proposed to inhibit the formation of the anion state of our host materials. In short, the device operational lifetime is further improved by applying DDBFT. The carbazole‐based asymmetric host molecule containing a pyridine core realizes a high‐efficiency blue TADF‐OLED showing a positive effect on the operating lifetime, and can provide useful strategies for designing new host materials.
Excitation Energy Transfer and Exchange‐Mediated Quartet State Formation in Porphyrin‐Trityl Systems
Authors: Nolden Oliver , Fleck Nico , Lorenzo Emmaline R. , Wasielewski Michael R. , Schiemann Olav , Gilch Peter , Richert Sabine
Published: July 2020

Photogenerated multi‐spin systems hold great promise for a range of technological applications in various fields, including molecular spintronics and artificial photosynthesis. However, the further development of these applications, via targeted design of materials with specific magnetic properties, currently still suffers from a lack of understanding of the factors influencing the underlying excited state dynamics and mechanisms on a molecular level. In particular, systematic studies, making use of different techniques to obtain complementary information, are largely missing. This work investigates the photophysics and magnetic properties of a series of three covalently‐linked porphyrin‐trityl compounds, bridged by a phenyl spacer. By combining the results from femtosecond transient absorption and electron paramagnetic resonance spectroscopies, we determine the efficiencies of the competing excited state reaction pathways and characterise the magnetic properties of the individual spin states, formed by the interaction between the chromophore triplet and the stable radical. The differences observed for the three investigated compounds are rationalised in the context of available theoretical models and the implications of the results of this study for the design of a molecular system with an improved intersystem crossing efficiency are discussed.
Photocatalytic Reductive Radical‐Polar Crossover for a Base‐Free Corey–Seebach Reaction
Authors: Donabauer Karsten , Murugesan Kathiravan , Rozman Urša , Crespi Stefano , König Burkhard
Published: July 2020

A metal‐free generation of carbanion nucleophiles is of prime importance in organic synthesis. Herein we report a photocatalytic approach to the Corey–Seebach reaction. The presented method operates under mild redox‐neutral and base‐free conditions giving the desired product with high functional group tolerance. The reaction is enabled by the combination of photo‐ and hydrogen atom transfer (HAT) catalysis. This catalytic merger allows a C−H to carbanion activation by the abstraction of a hydrogen atom followed by radical reduction. The generated nucleophilic intermediate is then capable of adding to carbonyl electrophiles. The obtained dithiane can be easily converted to the valuable α‐hydroxy carbonyl in a subsequent step. The proposed reaction mechanism is supported by emission quenching, radical–radical homocoupling and deuterium labeling studies as well as by calculated redox‐potentials and bond strengths.
P450 CYP17A1 Variant with a Disordered Proton Shuttle Assembly Retains Peroxo‐Mediated Lyase Efficiency
Authors: Liu Yilin , Denisov Ilia G. , Grinkova Yelena V. , Sligar Stephen G. , Kincaid James R.
Published: July 2020

Human cytochrome P450 CYP17A1 first catalyzes hydroxylation at the C17 position of either pregnenolone (PREG) or progesterone (PROG), and a subsequent C17−C20 bond scission to produce dehydroepiandrosterone (DHEA) or androstenedione (AD). In the T306A mutant, replacement of the Threonine 306 alcohol functionality, essential for efficient proton delivery in the hydroxylase reaction, has only a small effect on the lyase activity. In this work, resonance Raman spectroscopy is employed to provide crucial structural insight, confirming that this mutant, with its disordered proton shuttle, fails to generate essential hydroxylase pathway intermediates, accounting for the loss in hydroxylase efficiency. Significantly, a corresponding spectroscopic study with the susceptible lyase substrate, 17‐OH PREG, not only reveals an initially trapped peroxo‐iron intermediate experiencing an H‐bond interaction of the 17‐OH group with the proximal oxygen of the Fe‐Op‐Ot fragment, facilitating peroxo‐ attack on the C20 carbon, but also unequivocally shows the presence of the subsequent hemiketal intermediate of the lyase reaction.
S‐Trifluoroethyl Benzenesulfonothioate: A Bench‐Stable Reagent for Electrophilic Trifluoroethylthiolation†
Authors: Huang Shuai , Xia Ziheng , Lu Kui , Lu Haifeng , Tung Chen‐Ho , Xu Zhenghu
Published: July 2020

Summary of main observation and conclusion

We report herein a practical approach for synthesis of an electrophilic trifluoroethylthiolation reagent PhSO2SCH2CF3 (1) from easily available materials. The reaction proceeded through a protonation and nucleophilic substitution cascade of the in situ formed trifluorodiazoethane. This bench‐stable reagent could easily be applied to introduce trifluoroethylthio group into small organic molecules.
The Origins of Toroidal Micelles from a Liquid–Crystalline Triblock Copolymer†
Authors: Jin Bixin , Liu Guojun , Li Xiaoyu
Published: July 2020

Summary of main observation and conclusion

In this paper, we reported a systematic study on the formation mechanism of bent toroidal micelles from a triblock copolymer poly(acrylic acid)‐block‐(2‐cinnamoyloxylethyl methacrylate)‐block‐poly(perfluorooctylethyl methacrylate) (PAA‐b‐PCEMA‐b‐ PFMA) in the binary solvent mixture of methanol and α,α,α‐trifluorotoluene (MeOH/TFT) through a heating‐cooling procedure. It was found that the formation process of toroids was predominantly kinetic‐controlled, and can be influenced by the preparation protocol, solvent composition and stirring rate of the solutions. The toroids were formed via a complicated morphological transition process. At high temperature, the polymer formed bilayered vesicles with bumpy surface, while upon cooling, the vesicles broke and unfolded into bumpy platelet micelles, which subsequently perforated into toroidal and cylindrical micelles upon further cooling. Besides the distinct and unique bumpy vesicle and platelet structures, the transformation mechanisms from vesicular to platelet, and toroidal micelles are also very intriguing, and may provide new insights into the interconversion of micellar morphologies.
Metal‐Free Decarboxylation of α,β‐Unsaturated Carboxylic Acids for Carbon–Carbon and Carbon–Heteroatom Coupling Reactions
Authors: Xu Xianjun , Van der Eycken Erik V. , Feng Huangdi
Published: July 2020

Metal‐free decarboxylative coupling reactions represent an alternative paradigm for carbon–carbon or carbon–heteroatom bond formation that complement more traditional metal catalysis approaches. In this review, recent advances in metal‐free decarboxylation reactions of α,β‐unsaturated carboxylic acids are highlighted. Two major reaction classes are covered: 1) generation of C–C, C–N, C–S, C–X bonds using propiolic acids; 2) transformations of alkenyl acids for C–C, C–P, C–N, C–S, C–X bond‐forming. Some cases involving electrochemistry and photochemistry represent a frontier area for carbon–carbon and carbon–heteroatom coupling processes. Additionally, the proposed mechanisms for both types of reactions are discussed.
Identification of a Suitable Peptidic Molecular Platform for the Development of NPY(Y1)R‐Specific Imaging Agents
Authors: Krieger Korbinian , Wängler Björn , Schirrmacher Ralf , Wängler Carmen
Published: July 2020

NPY(Y1)R (neuropeptide Y receptor subtype 1) is an important target structure for tumor‐specific imaging and therapy as this receptor subtype is overexpressed in very high density and incidence especially in human breast cancer. Targeting this receptor with radiolabeled truncated analogues of the endogenous ligand NPY (neuropeptide Y) has, however, not yet resulted in satisfactory imaging results when using positron emission tomography (PET). This can be attributed to the limited stability of these PET imaging agents caused by their fast proteolytic degradation. Although highly promising NPY analogues were developed, their stability has only been investigated in very few cases. In this systematical work, we comparatively determined the stability of the five most promising truncated analogues of NPY that were developed over the last years, showing the highest receptor affinities and subtype selectivities. The stability of the peptides was assessed in human serum as well as in a human liver microsomal stability assay; these gave complementary results, thus demonstrating the necessity to perform both assays and not just conventional serum stability testing. Of the tested peptides, only [Lys(lauroyl)27,Pro30,Lys(DOTA)31,Bip32,Leu34]NPY27‐36 showed high stability against peptidase degradation; thus this is the best‐suited truncated NPY analogue for the development of NPY(Y1)R‐specific imaging agents.
Ligand‐Free Yolk‐Shell Nanoparticles: Synthesis and Catalytic Applications
Authors: Shaik Firdoz
Published: July 2020

Ligand‐Free yolk‐shell nanoparticles (LFYSNs) consist of ligand‐free core (nanoparticle) enclosed in a hollow nanocavity of a porous shell have been attracted great interest owing to their unique nanoarchitecture features, enchanting physicochemical properties and extensive potential applications. LFYSNs are considered as a unique category of conventional yolk‐shell nanoparticles (YSNs). YSNs are usually consist of organic‐capped core (nanoparticle) and the presence of capping ligands on the surface of metal core may show deleterious effects in catalytic applications. Here, a comprehensive overview on the recent progress of LFYSNs synthetic strategies and catalytic applications are discussed. The fabrication methods for LFYSNs are mainly focused on a ‘‘ship‐in‐a‐bottle/pre‐shell’’ approach and sub‐divided into three categories, including volume confined, photochemical and seedless/colloidal methods. The catalytic applications of LFYSNs including chemical and photo catalysis, and electrocatalysis are discussed in detail. Moreover, the superlative catalytic activity of LFYSNs is highlighted. Finally, perspectives on future research direction and development of LFYSNs are discussed briefly.
Model‐Informed Drug Development of the Masked Anti‑PD‑L1 Antibody CX‐072
Authors: Stroh Mark , Green Michelle , Millard Bjorn L. , Apgar Joshua F. , Burke John M. , Garner Will , Lu Hong , Lyman Susan K. , Desnoyers Luc R. , Richardson Jennifer , Hannah Alison , Kavanaugh W. Michael
Published: July 2020

CX‑072 is an anti‑PD‑L1 (programmed death ligand 1) Probody therapeutic (Pb‐Tx) designed to be preferentially activated by proteases in the tumor microenvironment and not in healthy tissue. Here, we report the model‐informed drug development of CX‐072. A quantitative systems pharmacology (QSP) model that captured known mechanisms of Pb‐Tx activation, biodistribution, elimination, and target engagement was used to inform clinical translation. The QSP model predicted that a trough level of masked CX‐072 (intact CX‐072) of 13–99 nM would correspond to a targeted, 95% receptor occupancy in the tumor. The QSP model predictions appeared consistent with preliminary human single‑dose pharmacokinetic (PK) data following CX‐072 0.03–30.0 mg/kg as monotherapy: CX‑072 circulated predominantly as intact CX‐072 with minimal evidence of target‐mediated drug disposition. A preliminary population PK (POPPK) analysis based upon 130 subjects receiving 0.03–30.0 mg/kg as monotherapy included a provision for a putative time‐dependent and dose‐dependent antidrug antibody (ADA) effect on clearance (CL) with a mixture model. Preliminary POPPK estimates for intact CX‐072 time‐invariant CL and volume of distribution were 0.306 L/day and 4.84 L, respectively. Exposure–response analyses did not identify statistically significant relationships with best change from baseline sum of measurements and either adverse events of grade ≥ 3 or of special interest. Simulations suggested that > 95% of patients receiving CX‐072 10 mg/kg every two weeks would exceed the targeted trough level regardless of ADA, and that dose adjustment by body weight was not necessary, supporting a fixed 800 mg dose for evaluation in phase II.
Exposure–Response Analyses of Anaplastic Lymphoma Kinase Inhibitors Crizotinib and Alectinib in Non‐Small Cell Lung Cancer Patients
Authors: Groenland Stefanie L. , Geel Dieuwertje R. , Janssen Julie M. , de Vries Niels , Rosing Hilde , Beijnen Jos H. , Burgers Jacobus A. , Smit Egbert F. , Huitema Alwin D.R. , Steeghs Neeltje
Published: July 2020

Crizotinib and alectinib are anaplastic lymphoma kinase (ALK)‐inhibitors indicated for the treatment of ALK‐positive metastatic non‐small cell lung cancer (NSCLC). At the currently used fixed doses, interindividual variability in exposure is high. The aim of this study was to investigate whether minimum plasma concentrations (Cmin) of crizotinib and alectinib are related to efficacy and toxicity. An observational study was performed, in which ALK‐positive NSCLC patients who were treated with crizotinib and alectinib and from whom pharmacokinetic samples were collected in routine care, were included in the study. Exposure–response analyses were explored using previously proposed Cmin thresholds of 235 ng/mL for crizotinib and 435 ng/mL for alectinib. Forty‐eight crizotinib and 52 alectinib patients were included. For crizotinib, median progression‐free survival (mPFS) was 5.7 vs. 17.4 months for patients with Cmin < 235 ng/mL (48%) and ≥ 235 ng/mL, respectively (P = 0.08). In multivariable analysis, Cmin < 235 ng/mL resulted in a hazard ratio (HR) of 1.79 (95% confidence interval (CI), 0.90–3.59, P = 0.100). In a pooled analysis of all crizotinib patients (not only ALK‐positive, n = 79), the HR was 2.15 (95% CI, 1.21–3.84, P = 0.009). For alectinib, mPFS was 12.6 months vs. not estimable (95% CI, 19.8–not estimable) for patients with Cmin < 435 ng/mL (37%) and ≥ 435 ng/mL, respectively (P = 0.04). Multivariable analysis resulted in an HR of 4.29 (95% CI, 1.33–13.90, P = 0.015). In conclusion, PFS of crizotinib and alectinib treated NSCLC patients is prolonged in patients with Cmin ≥ 235 ng/mL and 435 ng/mL, respectively. Therefore, therapeutic drug monitoring should be part of routine clinical management for these agents.
The moderating role of personal value orientation on the links between perceived corporate social performance and purchase intentions
Authors: Alniacik Esra , Moumen Charefeddine , Alniacik Umit
Published: July 2020

This study examines how personal values affect the impact of perceived CSR aspects on purchase intentions by investigating the differences between two groups of customers, which are customers with more self‐centered values (self‐enhancement value orientation) and customers with more altruistic values (self‐transcendent value orientation). The research sample consisted of 356 customers of six banks in Algiers, capital city of Algeria. Research hypotheses were tested by structural equation modeling (SEM). Data analyses revealed that personal values can change the strength and the direction of the relationship between the perceived economic and philanthropic aspects of CSR on purchase intentions. However, no such effect is detected on the links between perceived legal and ethical aspect of CSR and purchase intentions. Customers with self‐enhancement values are more interested in economic and legal aspects of CSR, whereas customers with self‐transcendence values are mainly interested in philanthropic aspect of CSR. Research and managerial implications of the findings are discussed.
Volatile molecules for COVID‐19: A possible pharmacological strategy?
Authors: Colalto Cristiano
Published: July 2020

COVID‐19 is a novel coronavirus disease with a higher incidence of bilateral pneumonia and pleural effusion. The high pulmonary tropism and contagiousness of the virus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have stimulated new approaches to combat its widespread diffusion. In developing new pharmacological strategies, the chemical characteristic of volatility can add therapeutic value to the hypothetical drug candidate. Volatile molecules are characterized by a high vapor pressure and are consequently easily exhaled by the lungs after ingestion. This feature could be exploited from a pharmacological point of view, reaching the site of action in an uncommon way but allowing for drug delivery. In this way, a hypothetical molecule for COVID‐19 should have a balance between its lung exhalation characteristics and both antiviral and anti‐inflammatory pharmacological action. Here, the feasibility, advantages, and disadvantages of a therapy based on oral administration of possible volatile drugs for COVID‐19 will be discussed. Both aerosolized antiviral therapy and oral intake of volatile molecules are briefly reviewed, and an evaluation of 1,8‐cineole is provided in view of a possible clinical use and also for asymptomatic COVID‐19.
Room without a view—Den excavation in relation to body size in brown bears
Authors: Shiratsuru Shotaro , Friebe Andrea , Swenson Jon E. , Zedrosser Andreas
Published: July 2020

Hibernation is an adaptive strategy to survive harsh winter conditions and food shortage. The use of well‐insulated winter dens helps animals minimize energy loss during hibernation. Brown bears (Ursus arctos) commonly use excavated dens for hibernation. Physical attributes of excavated dens are expected to impact the bear's heat retention and energy conservation. The objective of this study was to examine the determinants of cavity size of excavated dens and the impact of physical attributes of excavated dens on energy conservation in hibernating bears, hypothesizing that bears excavate dens in a way to minimize heat loss and optimize energy conservation during hibernation. We predicted that den cavity size would be determined by the bear's body size and that older bears would excavate better‐fitting cavities to minimize heat loss, due to their previous experience. We further predicted that physical attributes of excavated dens would affect the bears’ posthibernation body condition. Our results revealed that bears excavated a den cavity in relation to their body size, regardless of sex, and that older bears tended to excavate better‐fitting den cavities compared to young bears, as we expected. Older bears excavated better‐fitting den cavities, suggesting a potentially experience‐based shift with age in den‐excavation behavior and an optimum cavity size relative to a bear's body size. Our key finding is that insulation of excavated dens provided by wall/rood thickness and bedding materials had a significant positive effect on bears’ posthibernation body condition. We believe that our study provides new insight into how not only the quality of denning habitat, but also the quality of dens may affect hibernating animals, by presenting a potential adaptive aspect of den preparation (age effect on efficiency in den excavation) and effect of den attributes on the posthibernation body condition of brown bears.
Direct effects of nitrogen addition on seed germination of eight semi‐arid grassland species
Authors: Zhang Tong , Liu Mengzhou , Huang Xudong , Hu Wei , Qiao Ning , Song Hongquan , Zhang Bing , Zhang Rui , Yang Zhongling , Liu Yinzhan , Miao Yuan , Han Shijie , Wang Dong
Published: July 2020

Seed germination plays an important role in mediating plant species composition of grassland communities under nitrogen (N) enrichment. Shifts of plant community structure with N‐enhanced deposition in terrestrial ecosystems have occurred globally. Despite numerous studies about the effects of enhanced N deposition on mature plant communities, few studies have focused on seed germination. Using a laboratory experiment, we report the effects of five N concentrations, including 0, 5, 10, 20, and 40 mM N (NH4NO3) on seed germination of eight semi‐arid grassland species. Results showed that low N concentrations (5‐ and 20‐mM N) promoted mean final germination proportion of all eight species by 4.4% and 6.4%, but high concentrations (40 mM N) had no effect. The mean germination rate was decreased 2.1% and 5.1% by higher N concentration (20‐ and 40‐mM N) levels, but germination start time showed the opposite trend, delayed by 0.7, 0.9, and 1.8 d for the 10, 20, and 40 mM N treatments. Final germination proportion, mean germination rate, and germination start time were significantly different among species in response to N concentration treatments. The final germination proportion of Allium tenuissimum and Chenopodium glaucum were suppressed by increased N concentration, whereas it increased for Potentilla bifurca, Plantago asiatica, and Setaria viridis. Our findings provide novel insights into N deposition‐induced species loss based on seed germination factors in semi‐arid grassland communities.
Nocturnal thoracic volume overload and post‐discharge outcomes in patients hospitalized for acute heart failure
Authors: Chang Hao‐Chih , Huang Chi‐Jung , Cheng Hao‐Min , Yu Wen‐Chung , Chiang Chern‐En , Sung Shih‐Hsien , Chen Chen‐Huan
Published: July 2020

Aims

Volume overload and perturbations of pulsatile haemodynamics may precipitate acute heart failure (AHF). Nocturnal thoracic volume overload due to rostral fluid shift during recumbency undetected by daytime measures may impact nighttime haemodynamics and post‐discharge outcomes.

Methods and results

A total of 63 patients (median 60 years, 79.4% men, and left ventricular ejection fraction 29.4%) hospitalized for AHF were enrolled. Once clinical euvolaemia was achieved, noninvasive pulsatile haemodynamics were assessed during daytime followed by circadian monitoring (6 p.m. to 5 a.m.) of thoracic fluid content and thoracic fluid content index (TFCi) using impedance cardiography, normalized electromechanical activation time ratio (EMAT%) using acoustic cardiography, and mean blood pressure using ambulatory blood pressure monitoring before discharge. The primary endpoints were composited of the first hospitalization for heart failure and death from any cause. Patients were also followed for the repeated heart failure hospitalizations. During a median follow‐up duration of 16 months, 33 patients encountered primary composite endpoints (52.4%), and there were 42 hospitalizations developed among 25 patients. An overnight increase in TFCi along with persistently prolonged EMAT% and low mean blood pressure was observed in the eventful group. Overnight increase in TFCi (ΔTFCi, the difference between the measures at 4 a.m. and 6 p.m.) was an independent predictor of primary composite events (hazard ratio and 95% confidence interval: 1.58, 1.07–2.33; P = 0.022) and recurrent composite events (2.22, 1.51–3.26; P < 0.001), after adjusting for potential confounding factors. A high ΔTFCi (≥0.5/kΩ/m2) significantly correlated with higher post‐discharge events (hazard ratio 6.25; 95% confidence interval 2.30–16.96; P < 0.001) in comparison with a low ΔTFCi (<0.5/kΩ/m2). ΔTFCi was significantly associated with EMAT%, estimated glomerular filtration rate, and left ventricular ejection fraction, but not with parameters of pulsatile haemodynamics.

Conclusions

Nocturnal thoracic volume overload in AHF before discharge, indicating the presence of residual volume overload unidentified by daytime measures, may predict post‐discharge outcomes.
Circulating sST2 and catestatin levels in patients with acute worsening of heart failure: a report from the CATSTAT‐HF study
Authors: Borovac Josip A. , Glavas Duska , Susilovic Grabovac Zora , Supe Domic Daniela , Stanisic Lada , D'Amario Domenico , Kwok Chun S. , Bozic Josko
Published: July 2020

Aims

Soluble suppression of tumourigenicity 2 (sST2) and catestatin (CST) reflect myocardial fibrosis and sympathetic overactivity during the acute worsening of heart failure (AWHF). We aimed to determine serum levels and associations of sST2 and CST with in‐hospital death as well as the association between sST2 and CST among AWHF patients.

Methods and results

A total of 96 AWHF patients were consecutively enrolled, while levels of sST2 and CST were determined and compared between non‐survivors and survivors. Predictive values of sST2 and CST for in‐hospital death were determined by the penalized multivariable Firth logistic regression. The diagnostic ability of sST2 and CST for in‐hospital death was assessed by the receiver operating characteristic analysis and examined with respect to the N‐terminal pro‐brain natriuretic peptide (NT‐proBNP), high‐sensitivity cardiac troponin I, and C‐reactive protein. The in‐hospital death rate was 6.25%. Serum sST2 and CST levels were significantly higher among non‐survivors than survivors [146.6 (inter‐quartile range, IQR 65.9–156.2) vs. 35.3 (IQR 20.6–64.4) ng/mL, P < 0.001, and 19.8 (IQR 9.9–28.0) vs. 5.6 (IQR 3.4–9.8) ng/mL, P < 0.001, respectively]. Both sST2 and CST were independent predictors of in‐hospital death [Firth coefficient (FC) 6.00, 95% confidence interval (CI), 1.48–15.20, P = 0.005, and FC 6.58, 95% CI 1.66–21.78, P = 0.003, respectively], while NT‐proBNP was not a significant predictor (FC 1.57, 95% CI 0.51–3.99, P = 0.142). In classifying non‐survivors from survivors, sST2 provided area under the curve (AUC) of 0.917 (95% CI 0.819–1.000, P < 0.001) followed by CST (AUC 0.905, 95% CI 0.792–1.000, P < 0.001), while NT‐proBNP yielded AUC of 0.735 (95% CI 0.516–0.954, P = 0.036). High‐sensitivity cardiac troponin I and C‐reactive protein were not found as significant classifiers of in‐hospital death (AUC 0.719, 95% CI 0.509–0.930, P = 0.075, and AUC 0.682, 95% CI 0.541–0.822, P = 0.164, respectively). Among survivors, those with sST2 serum levels ≥35 ng/mL had significantly higher CST levels, compared with those with sST2 < 35 ng/mL (9.05 ± 5.17 vs. 5.06 ± 2.76 ng/mL, P < 0.001). Serum sST2 levels positively and independently correlated with CST levels in the whole patient cohort (β = 0.437, P < 0.001).

Conclusions

Elevated sST2 and CST levels, reflecting two distinct pathophysiological pathways in heart failure, might indicate impending clinical deterioration among AWHF patients during hospitalization and facilitate prognosis beyond traditional biomarkers regarding the risk of in‐hospital death (CATSTAT‐HF ClinicalTrials.gov Number NCT03389386).
In Situ Growth of Co4N Nanoparticles–Embedded Nitrogen‐Doped Carbon Nanotubes on Metal–Organic Framework–Derived Carbon Composite as Highly Efficient Electrocatalyst for Oxygen Reduction and Evolution Reactions
Authors: Kone Issa , Ahmad Zubair , Xie Ao , Tang Yang , Sun Yanzhi , Chen Yongmei , Yang Xiaojin , Wan Pingyu
Published: July 2020

Highly efficient and low‐cost bifunctional electrocatalysts for oxygen reduction and evolution reactions (ORR/OER) are central to new generation rechargeable metal–air batteries. Herein, hierarchical microspheres assembled by in situ generated Co4N nanoparticles (Co4N Nps)‐embedded nitrogen‐doped carbon nanotubes (Co4N@NCNTs) are constructed by a facile urea acid (UA)‐assisted pyrolysis of zeolitic imidazole framework (ZIF)‐67. In this strategy, the UA sharply decomposes at 440 °C to carbonaceous gases, which facilitate the nucleation of Co4N Nps for the catalytic growth of the NCNT microspheres structure from the intermediate ZIF‐67 polyhedrons. The as‐prepared Co4N@NCNTs exhibit high N content, abundant Co4N active species, high electron conductivity, and large specific area on a hierarchical micro‐mesoporous structure. Therefore, the Co4N@NCNTs not only exceed Pt/C in terms of ORR half wave potential (0.85 vs 0.83 V) and limiting current density (5.50 vs 5.20 mA cm−2), but also manifest comparable OER activity with Ru/C. In the rechargeable zinc–air battery test, the bifunctional Co4N@NCNTs show excellent performance with high discharge and low charge potentials and relatively stable voltage gap as long as 500 cycles, which greatly outperform those of commercial Pt–Ru/C.
Acoustic and fractal analyses of the mechanical properties and fracture modes of bedding‐containing shale under different seepage pressures
Authors: Wu Zhonghu , Lou Yili , Yin Shuai , Wang Anli , Liu Hao , Sun Wenjibin , Zuo Yujun , Chen Bin
Published: July 2020

The mechanical properties and failure modes of shale that contains bedding were analyzed under coupled seepage pressure and stress. In the numerical model, seven sets of shale samples with different dip‐bedding values were considered, and a seepage‐stress coupling numerical simulation was carried out. The results showed that the compressive strength of shale exhibited obvious anisotropy with increase in the bedding angle, and the compressive strength decreased with an increase in the osmotic pressure. The elastic modulus of shale showed an increasing trend with increase in the bedding angle, while the osmotic pressure had little effect on the elastic modulus of shale. The results also showed that weak bedding had a significant impact on the shale failure mode. When the osmotic pressure was 4 MPa, the shale fracture mode showed five failure modes. When the osmotic pressure was 8 MPa, the shale fracture mode exhibited four failure modes. When the osmotic pressure was 12 MPa, the shale fracture mode showed four failure modes. As the osmotic pressure increased, the osmotic pressure played a leading role in the shale rupture process. The spatial distribution of the acoustic emission demonstrated some self‐similarity patterns, and its fractal characteristics were analyzed. It was found that the fractal dimension better reflects the rupture damage to the shale. The larger the fractal dimension is, the more severe the rupture of shale.