bluuebunny/crossref_metadata_2025 huggingface dataset:
Iron distribution in different tissues of homozygous Mask (msk/msk) mice and the effects of oral iron treatments
Authors: Asperti Michela , Brilli Elisa , Denardo Andrea , Gryzik Magdalena , Pagani Francesca , Busti Fabiana , Tarantino Germano , Arosio Paolo , Girelli Domenico , Poli Maura
Published: August 2021

Iron‐refractory iron deficiency anemia (IRIDA) is an autosomal recessive disorder caused by genetic mutations on TMPRSS6 gene which encodes Matriptase2 (MT2). An altered MT2 cannot appropriately suppress hepatic BMP6/SMAD signaling in case of low iron, hence hepcidin excess blocks dietary iron absorption, leading to a form of anemia resistant to oral iron supplementation. In this study, using the IRIDA mouse model Mask, we characterized homozygous (msk/msk) compared to asymptomatic heterozygous (msk/wt) mice, assessing the major parameters of iron status in different organs, at different ages in both sexes. The effect of carbonyl iron diet was analyzed as control iron supplementation being used for many studies in mice. It resulted effective in both anemic control and msk/msk mice, as expected, even if there is no information about its mechanism of absorption. Then, we mainly compared two forms of oral iron supplement, largely used for humans: ferrous sulfate and Sucrosomial iron. In anemic control mice, the two oral formulations corrected hemoglobin levels from 11.40 ± 0.60 to 15.38 ± 1.71 g/dl in 2–4 weeks. Interestingly, in msk/msk mice, ferrous sulfate did not increase hemoglobin likely due to ferroportin/hepcidin‐dependent absorption, whereas Sucrosomial iron increased it from 11.50 ± 0.60 to 13.53 ± 0.64 g/dl mainly in the first week followed by a minor increase at 4 weeks with a stable level of 13.30 ± 0.80 g/dl, probably because of alternative absorption. Thus, Sucrosomial iron, already used in other conditions of iron deficiency, may represent a promising option for oral iron supplementation in IRIDA patients.
Environmental and anthropogenic effects on the nesting patterns of Nigeria–Cameroon chimpanzees in North‐West Cameroon
Authors: Fotang Chefor , Bröring Udo , Roos Christian , Enoguanbhor Evidence C. , Dutton Paul , Tédonzong Luc R. D. , Willie Jacob , Yuh Yisa G. , Birkhofer Klaus
Published: August 2021

Environmental conditions and human activity influence the selection of nest sites by chimpanzees and may have serious conservation implications. We examined the characteristics of nesting trees preferred by chimpanzees, investigated the effect of vegetation composition and topography on nest site locations and seasonality on nesting heights of chimpanzees, and verified the effect of predator occurrence and human activity on the nesting behavior of the Nigeria–Cameroon chimpanzee (Pan troglodytes ellioti) in Kom‐Wum Forest Reserve (KWFR) and surrounding unprotected forest in Cameroon. We recorded 923 nests, 502 signs of human activity, and 646 nesting trees along line transects and recces (reconnaissance) for two seasons. We found that chimpanzees constructed more arboreal nests on tall primary trees with high lowest branch height and large diameter at breast height. Moreover, they oriented their nests within trees in the slope direction when the nesting trees were located on slopes. Additionally, the occurrence of chimpanzee nests was positively related to increasing elevation and slope and decreased with distance to primary forest. In contrast, the number of nests increased with distance to secondary forest, open land, and villages, and nesting height was not influenced by seasons. While we recorded no signs of large nocturnal chimpanzee predators at nesting trees, we found signs of hunting activity at nesting locations. Nesting high in trees is likely a way of avoiding hunting, while nest orientation within trees in slope direction shortens escape routes from human hunters. Our findings suggest that chimpanzees select safe trees (tall trees with high lowest branch height) located in nesting areas (primary forest, high elevation, and steep slopes) that are not easily accessible by humans. Therefore, conservation efforts should focus on protecting primary forests at high elevation and steep slopes and reducing human impact.
Direct Detection of Surface Species Formed on Iridium Electrocatalysts during the Oxygen Evolution Reaction
Authors: BalaKrishnan Arjun , Blanc Niclas , Hagemann Ulrich , Gemagami Parham , Wonner Kevin , Tschulik Kristina , Li Tong
Published: August 2021

The effect of surface orientations on the formation of iridium oxide species during the oxygen evolution reaction (OER) remains yet unknown. Herein, we use a needle‐shaped iridium atom probe specimen as a nanosized working electrode to ascertain the role of the surface orientations in the formation of oxide species during OER. At the beginning of electrolysis, the top 2–3 nm of (024), (026), (113), and (115) planes are covered by IrO−OH, which activates all surfaces towards OER. A thick subsurface oxide layer consisting of sub‐stoichiometric Ir−O species is formed on the open (024) planes as OER proceeds. Such metastable Ir−O species are thought to provide an additional contribution to the OER activity. Overall, this study sheds light on the importance of the morphological effects of iridium electrocatalysts for OER. It also provides an innovative approach that can directly reveal surface species on electrocatalysts at atomic scale.
Direct NO Reduction by a Biomimetic Iron(II) Pyrazolate MOF
Authors: Cai Zhongzheng , Tao Wenjie , Moore Curtis E. , Zhang Shiyu , Wade Casey R.
Published: August 2021

A novel metal‐organic framework (MOF) containing one‐dimensional, Fe2+ chains bridged by dipyrazolate linkers and N,N‐dimethylformamide (DMF) ligands has been synthesized. The unusual chain‐type metal nodes feature accessible coordination sites on adjacent metal centers, resulting in motifs that are reminiscent of the active sites in non‐heme diiron enzymes. The MOF facilitates direct reduction of nitric oxide (NO), producing nearly quantitative yields of nitrous oxide (N2O) and emulating the reactivity of flavodiiron nitric oxide reductases (FNORs). The ferrous form of the MOF can be regenerated via a synthetic cycle involving reduction with cobaltocene (CoCp2) followed by reaction with trimethylsilyl triflate (TMSOTf).
Mild Intermolecular Synthesis of a Cyclopropane‐Containing Tricyclic Skeleton: Unusual Reactivity of Isobenzopyryliums
Authors: Liu Shuxuan , Qian Hui , Zhang Tianyu , Xie Hongling , Han Zhengyu , Guo Wengang , Huang Hai , Sun Jianwei
Published: August 2021

Cyclopropanes embedded in a polycyclic bridged architecture are a versatile structural motif, but such complex frameworks often impose substantial synthetic challenges. Herein we introduce a new approach for the expedient access to such spring‐loaded strained systems via an exceptionally mild intermolecular convergent process between the readily available isobenzopyryliums and vinyl boronic acids. Different from the typical conventional approaches, our protocol does not involve the highly active carbenoid intermediates or strong conditions in order to overcome the disfavored kinetic and thermodynamic problems. Instead, the key cyclopropane ring was formed between the well‐positioned nucleophile and electrophile in the adduct from the regioselective [4+2] cycloaddition. Thus, this unusual process also represents a new reactivity of the versatile isobenzopyryliums. The choice of a Brønsted acid catalyst with proper acidity is crucial to the high efficiency and selectivity for this multiple bond‐forming process. The strained products are precursors to other useful synthetic building blocks.
Four‐Selective Pyridine Alkylation via Wittig Olefination of Dearomatized Pyridylphosphonium Ylides
Authors: Fricke Patrick J. , Dolewski Ryan D. , McNally Andrew
Published: August 2021

Methods to synthesize alkylated pyridines are valuable because these structures are prevalent in pharmaceuticals and agrochemicals. We have developed a distinct approach to construct 4‐alkylpyridines using dearomatized pyridylphosphonium ylide intermediates in a Wittig olefination‐rearomatization sequence. Pyridine N‐activation is key to this strategy, and N‐triazinylpyridinium salts enable coupling between a wide variety of substituted pyridines and aldehydes. The alkylation protocol is viable for late‐stage functionalization, including methylation of pyridine‐containing drugs. This approach represents an alternative to metal‐catalyzed sp2‐sp3 cross‐coupling reactions and Minisci‐type processes.
Sono‐Fenton Chemistry Converts Phenol and Phenyl Derivatives into Polyphenols for Engineering Surface Coatings
Authors: Mei Hanxiao , Gao Zhiliang , Zhao Kaijie , Li Mengqi , Ashokkumar Muthupandian , Song Aixin , Cui Jiwei , Caruso Frank , Hao Jingcheng
Published: August 2021

We report a sono‐Fenton strategy to mediate the supramolecular assembly of metal–phenolic networks (MPNs) as substrate‐independent coatings using phenol and phenyl derivatives as building blocks. The assembly process is initiated from the generation of hydroxyl radicals (.OH) using high‐frequency ultrasound (412 kHz), while the metal ions synergistically participate in the production of additional .OH for hydroxylation/phenolation of phenol and phenyl derivatives via the Fenton reaction and also coordinate with the phenolic compounds for film formation. The coating strategy is applicable to various phenol and phenyl derivatives and different metal ions including FeII, FeIII, CuII, and CoII. In addition, the sono‐Fenton strategy allows real‐time control over the assembly process by turning the high‐frequency ultrasound on or off. The properties of the building blocks are maintained in the formed films. This work provides an environmentally friendly and controllable method to expand the application of phenolic coatings for surface engineering.
Preparation and properties of PBAT/PLA composites modified by PVA and cellulose nanocrystals
Authors: Liu Hailu , Chen Ruilian , Sun Xiaoyan , Li Fayong , Shen Huayan , Wang Ke , Wang Qing , Li Yuan , Xie Dong , Chen Junjia
Published: August 2021

Cellulose nanocrystal (CNC) was prepared through the hydrolysis of concentrated sulfuric acid using commercial bagasse pulp as a raw material. The performance of the developed CNC was tested through the atomic force microscope, particle size measurement, and zeta potential analysis. The melt blending method was adopted to prepare thermoplastic polyvinyl alcohol (TPVA) and CNC‐TPVA using the glycerol (GI)‐dicondensed triethylene glycol (TEG) complex. The TPVA and CNC‐TPVA were blended with poly(butylene adipate‐coterephthalate) and polylactic acid composite material (COM) through melt extrusion granulation and blown film, and then explored the effect of CNC on the UV aging properties of materials. The complex plasticizer could effectively break the PVA hydrogen bond and reduce its melting point. It had been observed that CNC had good interface compatibility with PVA, and CNC did not affect the crystallinity of PVA, but it could weaken the hydrogen bond between GI, TEG, and PVA, thereby reduce the plasticizing effect of PVA. Compared TPVA‐COM with CNC‐TPVA‐COM, detailed information of crystallization, the thermal stability of materials and mechanical properties was presented in the UV aging process, it was found that the cross‐section of CNC‐TPVA‐COM was rough, and its unevenness formed a striped structure, and its hydrogen bond strength, diffraction peak strength and anti‐aging performance were all improved.
Visible‐Light‐Driven Sulfonylation/Cyclization to Access Sulfonylated Benzo[4,5]imidazo[2,1‐a]isoquinolin‐6(5H)‐ones
Authors: Wang Chen , Sun Guoquan , Huang Hong‐Li , Liu Jing , Tang Hua , Li Yinghua , Hu Honggang , He Shipeng , Gao Fei
Published: August 2021

Visible‐light‐driven sulfonylation/cyclization of N‐methacryloyl‐2‐phenylbenzoimidazoles has been successfully developed. Using commercially available sulfonyl chloride as sulfonylation reagent, a wide range of sulfonylated benzo[4,5]imidazo[2,1‐a]isoquinolin‐6(5H)‐ones with potential antitumor activity were provided in acceptable to excellent yields. This method has the advantages of mild reaction conditions and outstanding functional group tolerance, and provides a new strategy for the development of potential antitumor lead compounds.
The parallel treatments design: A systematic review
Authors: Frampton Sarah E. , Guinness Kendra E. , Axe Judah B.
Published: August 2021

The identification of interventions that are both effective and efficient is an ongoing need for the practice of applied behavior analysis. The parallel treatments design (PTD) has been described as powerful tool for comparing interventions in applied settings. The PTD combines elements of the multiple probe design and the adapted alternating treatments design. Execution of a PTD requires adherence to experimental tactics related to both designs, as well as adherence to specific features of the PTD outlined by the original authors (Gast & Wolery, 1988). The purpose of this systematic literature review was to evaluate (a) publication trends with the PTD, (b) applications of the PTD across behaviors and interventions, and (c) the extent to which articles that named the PTD as the design adhered to its defining features. Outcomes are discussed with respect to the utility of the PTD, limitations of the PTD, and potential refinements of the definition of the PTD.
Industry 4.0, innovation, and sustainable development: A systematic review and a roadmap to sustainable innovation
Authors: Ghobakhloo Morteza , Iranmanesh Mohammad , Grybauskas Andrius , Vilkas Mantas , Petraitė Monika
Published: August 2021

Despite the recent interest in the Industry 4.0 applications for sustainability, little is known on the processes through which digital transformation and Industry 4.0 technologies enable sustainable innovation in manufacturing. The present study addresses this knowledge gap by developing a strategic roadmap that explains how businesses can leverage Industry 4.0 technologies to introduce sustainability into innovative practices. For this purpose, the study conducts a systematic review of extant literature to identify Industry 4.0 functions for sustainable innovation and applies interpretive structural modeling to devise the promised roadmap. The results offer interesting insights into Industry 4.0 applications for sustainable innovation. The strategic roadmap developed reveals that Industry 4.0 enables sustainable innovation through 11 functions. Industry 4.0 and the underlying digital technologies and principles allow businesses to improve interfunctional collaboration and better integrate with internal and external stakeholders. Industry 4.0 further improves the knowledge base and advanced manufacturing competency and promotes organizational capabilities valuable to sustainable innovation such as green absorptive capacity, sustainable partnership, and sustainable innovation orientation. Through these functions, Industry 4.0 subsequently enhances green process innovation capacity and the ability to develop or reintroduce eco‐friendly products economically and competitively. Overall, the roadmap explains the complex precedence relationships among the 11 sustainable innovation functions of Industry 4.0, offering important implications for businesses that seek to leverage Industry 4.0 sustainability implications and manage sustainable development.
Stenting as a treatment for cranio‐cervical artery dissection: Improved major adverse cardiovascular event‐free survival
Authors: Vezzetti Alexandra , Rosati Lauren M. , Lowe Forrest J. , Graham C. Blease , Moftakhar Roham , Mangubat Erwin , Sen Souvik
Published: August 2021

Introduction

Cranio‐cervical artery dissection (CeAD) is a common cause of cerebrovascular events in young subjects with no clear treatment strategy established. We evaluated the incidence of major adverse cardiovascular events (MACE) in CeAD patients treated with and without stent placement.

Methods

COMParative effectiveness of treatment options in cervical Artery diSSection (COMPASS) is a single high‐volume center observational, retrospective longitudinal registry that enrolled consecutive CeAD patients over a 2‐year period. Patients were ≥ 18 years of age with confirmed extra‐ or intracranial CeAD on imaging. Enrolled participants were followed for 1 year evaluating MACE as the primary endpoint.

Results

One‐hundred ten patients were enrolled (age 53 ± 15.9, 56% Caucasian, and 50% male, BMI 28.9 ± 9.2). Grade I, II, III, and IV blunt vascular injury was noted in 16%, 33%, 19%, and 32%, respectively. Predisposing factors were noted in the majority (78%), including sneezing, carrying heavy load, chiropractic manipulation. Stent was placed in 10 (10%) subjects (extracranial carotid n = 9; intracranial carotid n = 1; extracranial vertebral n = 1) at the physician's discretion along with medical management. Reasons for stent placement were early development of high‐grade stenosis or expanding pseudoaneurysm. Stented patients experienced no procedural or in‐hospital complications and no MACE between discharge and 1 year follow up. CeAD patients treated with medical management only had 14% MACE at 1 year.

Conclusion

In this single high‐volume center cohort of CeAD patients, stenting was found to be beneficial, particularly with development of high‐grade stenosis or expanding pseudoaneurysm. These results warrant confirmation by a randomized clinical trial.
Incidence of acquired ventricular septal defect after transcatheter aortic valve replacement: A large single center experience
Authors: Nona Paul , Mahmood Shazil , Lemor Alejandro , Qintar Mohammed , O'Neill Brian , Lee James , Frisoli Tiberio , Wang Dee Dee , Eng Marvin , O'Neill William W. , Villablanca Pedro A.
Published: August 2021

Objective

To determine the rate and clinical outcomes of post‐TAVR VSD.

Background

Transcatheter aortic valve replacement (TAVR) is a safe and established procedure for patients with severe symptomatic aortic stenosis. Ventricular septal defect (VSD) is a rare complication of TAVR. The rate of post‐TAVR VSD and patient outcomes are not well known.

Methods

A retrospective record review of VSD cases occurring after all TAVRs performed between January 2012 and September 2020 at one urban US tertiary hospital. VSD rate and early‐ and long‐term outcomes were analyzed. Computed tomography images taken before TAVR and transthoracic echocardiograms done before and after each procedure were analyzed.

Results

Of the 1908 patients who underwent TAVR in the study period, 7 patients (0.37%) had post‐procedure VSD. The average patient age was 77 ± 11 years with average society of thoracic surgeons short‐term risk score of 6%. All 7 implanted valves were balloon‐expandable. Of the 7 TAVR procedures, 5 were performed on a native tricuspid valve, 1 was performed on a native bicuspid valve, and 1 was done as a “valve‐in‐valve” procedure on a prior surgical bioprosthetic valve. All VSDs were small and restrictive in nature. Right heart failure in a patient with preexisting right ventricular dysfunction occurred in 1 (13%) patient who died. The remaining 6 patients (86%) were discharged. All 6 patients (86%) were alive and stable at 1 year follow‐up, reporting improvement in symptoms (NYHA class I‐II), with no evidence of right ventricular dysfunction.

Conclusion

VSD is a rare complication of TAVR. Hemodynamic and clinical sequelae in majority of the patients in this study did not result in mortality. Proper imaging techniques and appropriate pre‐procedure planning are needed to decrease the incidence of VSD formation post‐TAVR.
Catalytic Formation of Cyclic Carbonates using Gallium Aminotrisphenolate Compounds and Comparison to their Aluminium Congeners: A Combined Experimental and Computational Study
Authors: Álvarez‐Miguel Lucía , Burgoa Jesús Damián , Mosquera Marta E. G. , Hamilton Alex , Whiteoak Christopher J.
Published: August 2021

This work reports on the use of gallium aminotrisphenolate compounds as catalysts for the synthesis of cyclic carbonates from epoxides and CO2. The results show that they are highly active, and more so than the corresponding aluminium congeners. The catalyst system is applicable at low and elevated temperatures across a wide substrate scope including terminal, internal, multiple and fully deuterated epoxides. Applying low catalyst loadings has allowed for a TON of 344,000 to be obtained, highlighting their stability. A DFT investigation has confirmed that the gallium catalysts have lower energetic profiles compared to the aluminium congeners. Measurement of the Lewis acidity of both the gallium and aluminium aminotrisphenolate compounds using the Gutmann‐Beckett method provides the experimental proof that the gallium compounds are more Lewis acidic than their aluminium congeners. Finally, Ab‐Initio Molecular Dynamic (AIMD) simulations have investigated and quantified the dynamic behaviour of the catalytic systems, highlighting an important increase in fluxionality in some cases which helps to explain the increase in catalytic activity.
Mechanisms of Si Nanoparticle Formation by Molten Salt Magnesiothermic Reduction of Silica for Lithium‐ion Battery Anodes
Authors: Ansari Hamedani Ali , Ow‐Yang Cleva W. , Hayat Soytas Serap
Published: August 2021

Molten salt methods enable the synthesis of Si nanostructures by moderating the thermal energy evolved in highly exothermic magnesiothermic reduction reactions (MRR) of silica. Due to their cost‐effectiveness and scalability, these techniques are well suited for producing nanoscale Si for a number of applications, including energy storage. To control the microstructure morphology and particle size, it is necessary to understand the formation mechanism of the Si produced. By evaluating the time‐resolved phase evolution, when NaCl moderates the thermal energy generated by MRR of SiO2, we elucidate 3 parallel interfacial reaction mechanisms yielding Si nanoparticles – via Mg vapor, Mg‐rich eutectic liquid, and Mg ions dissolved in molten NaCl. These individual Si nanoparticles offer a striking contrast to the typical by‐product of MRR of SiO2 with and without NaCl, which yields a 3‐dimensional (3‐D) porous network of sintered Si nanoparticles. Lithium‐ion battery half‐cells with electrodes composed of individual Si nanoparticles showed a greater first‐cycle irreversible discharge capacity and faster capacity loss over the first 5 cycles at a current density of 200 mA g−1 compared to half‐cells with electrodes of a porous 3‐D Si network–indicative due to thicker solid electrolyte interphase (SEI) formation on individual particles. At a higher current rate of 400 mA g−1, once SEI formation and activation of Si are established, both cells exhibit a similar capacity retention rate over 100 cycles.
Illuminating Protein Phase Separation: Reviewing Aggregation‐Induced Emission, Fluorescent Molecular Rotor and Solvatochromic Fluorophore Based Probes
Authors: Bai Yulong , Liu Yu
Published: August 2021

Protein phase separation process involving protein unfolding, misfolding, condensation and aggregation etc. has been associated with numerous human degenerative diseases. The complexity in protein conformational transitions results in multi‐step and multi‐species biochemical pathways upon protein phase separation. Recent progresses in designing novel fluorescent probes have unraveled the enriched details of phase separated proteins and provided mechanistic insights towards disease pathology. In this review, we summarized the design and characterizations of fluorescent probes that selectively illuminated proteins at different phase separated states with a focus on aggregation‐induced emission probes, fluorescent molecular rotors, and solvatochromic fluorophores. Inspired by these pioneering works, a design blueprint was proposed to further develop fluorescent probes that can potentially shed light on the unresolved protein phase separated states in the future.
Cu Decorated Rh/TiO2 Catalyst for Selective Hydrogenation of Phenylacetylene to Styrene
Authors: Liu Yang , Zhao Yong , Zhao Yulong , Jiang Peng
Published: August 2021

Phenylacetylene as an impurity in styrene is poisonous to catalysts for styrene polymerization in the production of polystyrene plastics. The selective hydrogenation of phenylacetylene to styrene is an industrially promising route to overcome this challenge yet lacks cost‐effective catalysts to prevent the overhydrogenation of styrene to ethylbenzene. In this work, we report an efficient and robust copper‐decorated Rh/TiO2 catalyst for the selective hydrogenation of phenylacetylene to styrene. By optimizing the copper coverage on TiO2 supported Rh nanoparticles, we achieved a selectivity of 83% towards styrene formation at a phenylacetylene conversion of 93%. The appropriate Cu coverage is found to modulate the electronic states of surface Rh atoms and changes the Rh exposed active sites, weakening the binding strength of alkene and hydrogen intermediates on Rh and thus mitigating the overhydrogenation and enhancing the selectivity for styrene generation. This work offers insights on the rational design of efficient Rh‐based bimetallic catalysts for selective hydrogenation of phenylacetylene to styrene.
Drug Interactions Involving 17α‐Ethinylestradiol: Considerations Beyond Cytochrome P450 3A Induction and Inhibition
Authors: Rodrigues A. David
Published: August 2021

It is widely acknowledged that drug‐drug interactions (DDIs) involving estrogen (17α‐ethinylestradiol (EE))‐containing oral contraceptives (OCs) are important. Consequently, sponsors of new molecular entities (NMEs) often conduct clinical studies with priority given to OCs as victims of cytochrome P450 (CYP) 3A (CYP3A) induction and inhibition. Such scenarios are reflected in the US Food and Drug Administration‐issued guidance documentation related to OC DDI studies. Although CYP3A is important, OCs such as EE are metabolized by sulfotransferase 1E1 and UDP‐glucuronosyltransferase (UGT) 1A1, expressed in the gut and liver, and so both can also serve as loci of victim OC DDI. Therefore, for any NME, one should carefully consider its induction and inhibition profile involving CYP3A4/5, UGT1A1, and SULT1E1. As DDI perpetrators, available clinical DDI data indicate that EE‐containing OCs can induce (e.g., UGT1A4 and CYP2A6) and inhibit (CYP1A2 ≥ CYP2C19 > CYP3A4/5 > CYP2C8, CYP2B6, CYP2D6, and CYP2C9) various CYP forms. Although available in vitro CYP inhibition data do not explain such a graded inhibitory effect in vivo, it is hypothesized that EE differentially modulates CYP expression via potent agonism of the estrogen receptor expressed in the gut and liver. From the standpoint of the NME as potential OC DDI victim, therefore, it is important to assess its projected (pre‐phase I) or known therapeutic index and pharmacokinetic profile (fraction absorbed, absolute oral bioavailability, clearance/extraction class, fraction metabolized by CYP1A2, CYP2C19, CYP2A6, and UGT1A4). Such information can enable the prioritization, design, and interpretation of NME‐OC DDI studies.
Vacancy Engineering in Transition Metal Sulfide and Oxide Catalysts for Hydrodeoxygenation of Lignin‐Derived Oxygenates
Authors: Jiang Sinan , Ji Na , Diao Xinyong , Li Hanyang , Rong Yue , Lei Yaxuan , Yu Zhihao
Published: August 2021

The catalytic hydrodeoxygenation (HDO) of lignin has long been a hot research topic and vacancy engineering is a new means to develop more efficient catalysts for this process. Oxygen vacancies and sulfur vacancies are both widely used in HDO. Based on the current research status of vacancies in the field of lignin‐derived oxygenates, this Minireview discusses in detail design methods for vacancy engineering, including surface activation, synergistic modification, and morphology control. Moreover, it is clarified that in the HDO reaction, vacancies can act as acidic sites, promote substrate adsorption, and regulate product distribution, whereas for the catalysts, vacancies can enhance stability and reducibility, improve metal dispersion, and improve redox capacity. Finally, the characterization of vacancies is summarized and strategies are proposed to address the current deficiencies in this field.
Pyroptosis, metabolism, and tumor immune microenvironment
Authors: Du Tiantian , Gao Jie , Li Peilong , Wang Yunshan , Qi Qiuchen , Liu Xiaoyan , Li Juan , Wang Chuanxin , Du Lutao
Published: August 2021

In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues.
Multiplexed detection of agents affecting erythropoiesis (AAEs) and overall strategy for optimizing initial testing procedure
Authors: Martin Laurent , Ericsson Magnus , Marchand Alexandre
Published: August 2021

Erythropoietin receptor agonists (ERAs) are drugs acting on the early erythropoietic stages developed to treat anemia and other erythropoiesis disease and are prohibited by the World Anti‐Doping Agency (WADA). As an alternative to ERAs, a new drug, belonging to the transforming growth factor‐b inhibitors family, was recently developed to treat diseases linked to ineffective erythropoiesis. This drug, named as Luspatercept (Reblozyl®), is acting on the later stages of erythropoiesis to promote erythrocytes. This drug might be used by cheating athletes either independently or in combination with ERAs. Indeed, it was shown that Luspatercept and recombinant erythropoietin (rEPO) can act synergistically to increase red blood cells production, potentially allowing the use of lower doses for an efficient effect. Our aim was to find a way to combine the detection of ERAs and Luspatercept without impacting the sensitivity and specificity of ERAs detection from the current techniques implemented in antidoping laboratories and to reduce the time of analysis and total sample volume needed. Magnetic beads coated with antibodies were preferred for IP of samples for its potential multiplexing. Then, the following steps of the method were selected considering that SAR/SDS‐PAGE are the electrophoretic methods authorized for initial testing procedure by WADA and that biotinylated primary antibodies used for the immunodetection results in the best sensitivity and specificity and is time saving. The method developed in this work for the combined detection of agents affecting erythropoiesis (AAEs) showed specificity, sensitivity, and robustness and is easily and quickly implementable to all antidoping laboratories.
Optimizing the discovery and assessment of therapeutic targets in heart failure with preserved ejection fraction
Authors: Fusco‐Allison Gabrielle , Li Desmond K. , Hunter Benjamin , Jackson Dan , Bannon Paul G. , Lal Sean , O'Sullivan John F.
Published: August 2021

There is an urgent need for models that faithfully replicate heart failure with preserved ejection fraction (HFpEF), now recognized as the most common form of heart failure in the world. In vitro approaches have several shortcomings, most notably the immature nature of stem cell‐derived human cardiomyocytes [induced pluripotent stem cells (iPSC)] and the relatively short lifespan of primary cardiomyocytes. Three‐dimensional ‘organoids’ incorporating mature iPSCs with other cell types such as endothelial cells and fibroblasts are a significant advance, but lack the complexity of true myocardium. Animal models can replicate many features of human HFpEF, and rodent models are the most common, and recent attempts to incorporate haemodynamic, metabolic, and ageing contributions are encouraging. Differences relating to species, physiology, heart rate, and heart size are major limitations for rodent models. Porcine models mitigate many of these shortcomings and approximate human physiology more closely, but cost and time considerations limit their potential for widespread use. Ex vivo analysis of failing hearts from animal models offer intriguing possibilities regarding cardiac substrate utilisation, but are ultimately subject to the same constrains as the animal models from which the hearts are obtained. Ex vivo approaches using human myocardial biopsies can uncover new insights into pathobiology leveraging myocardial energetics, substrate turnover, molecular changes, and systolic/diastolic function. In collaboration with a skilled cardiothoracic surgeon, left ventricular endomyocardial biopsies can be obtained at the time of valvular surgery in HFpEF patients. Critically, these tissues maintain their disease phenotype, preserving inter‐relationship of myocardial cells and extracellular matrix. This review highlights a novel approach, where ultra‐thin myocardial tissue slices from human HFpEF hearts can be used to assess changes in myocardial structure and function. We discuss current approaches to modelling HFpEF, describe in detail the novel tissue slice model, expand on exciting opportunities this model provides, and outline ways to improve this model further.
Enhanced Performance of All‐Solution Processed Multilayer OLEDs by Photoluminescence Lifetime Reduction of Cu(I) Complex Emitters Containing Chalcogenolate‐Diimine Ligands
Authors: Salla Cristian A. M. , Farias Giliandro , Pereira Alessandra , Cremona Marco , Quirino Welber G. , Legnani Cristiano , de Souza Bernardo , Bechtold Ivan H.
Published: August 2021

Luminescent and solution‐processable copper(I) complexes offer the perspective of obtaining devices that combine efficiency and stability at low production costs. Here, we investigate Cu(I) complexes with phosphine and 1,10‐phenanthroline‐derived ligands, which show thermally activated delayed fluorescence (TADF) and phosphorescence applied to all‐solution processed multilayer OLEDs. Unsubstituted, thiadiazole‐substituted and selenodiazole‐substituted phenanthroline ligands were compared to evaluate the potential of the incorporation of sulfur and selenium atoms to enhance the device performance. A shortening of the photoluminescence lifetime of the selenium‐containing emitter was found to compensate this emitter's lower emission yield, leading to devices of comparable performance to devices based on the more efficiently emitting unsubstituted phenanthroline complex. The results indicate that the emission lifetime reduction is a promising approach to improve OLEDs based on solution‐processable Cu(I) complexes.
Toxicity Identification Evaluation of Sediments from the Xihe River
Authors: Ke Xin , Feng Shuna , Luan Jingde , Zhang Feijie , Zhou Yan
Published: August 2021

In the present study, chinonomus riparius larvae were selected as a model organism, and 11 sediment samples from the Xihe River in Shenyang underwent toxicity identification evaluation (TIE) to identify sediment toxic pollutants. Heavy metals and organic pollutants were the main toxic pollutants through toxicity screening and characterization. The results of toxicity identification showed that the pollution level from Cd was most serious and that phenol and P-methyl phenol were the major organic pollutants. Moreover, a spiking test of Cd was conducted, which indicated that Cd was the main toxic pollutant of sediments at sites 4, 6, 7, 8, and 10. We confirm that TIE is the most effective method to determine the relationship between toxic effects and toxic pollutants. Environ Toxicol Chem 2021;40:3103–3110. © 2021 SETAC
Evaluation of a personalized functional nearinfra‐redoptical tomography workflow using maximum entropy on the mean
Authors: Cai Zhengchen , Uji Makoto , Aydin Ümit , Pellegrino Giovanni , Spilkin Amanda , Delaire Édouard , Abdallah Chifaou , Lina Jean‐Marc , Grova Christophe
Published: August 2021

In the present study, we proposed and evaluated a workflow of personalized near infra‐red optical tomography (NIROT) using functional near‐infrared spectroscopy (fNIRS) for spatiotemporal imaging of cortical hemodynamic fluctuations. The proposed workflow from fNIRS data acquisition to local 3D reconstruction consists of: (a) the personalized optimal montage maximizing fNIRS channel sensitivity to a predefined targeted brain region; (b) the optimized fNIRS data acquisition involving installation of optodes and digitalization of their positions using a neuronavigation system; and (c) the 3D local reconstruction using maximum entropy on the mean (MEM) to accurately estimate the location and spatial extent of fNIRS hemodynamic fluctuations along the cortical surface. The workflow was evaluated on finger‐tapping fNIRS data acquired from 10 healthy subjects for whom we estimated the reconstructed NIROT spatiotemporal images and compared with functional magnetic resonance imaging (fMRI) results from the same individuals. Using the fMRI activation maps as our reference, we quantitatively compared the performance of two NIROT approaches, the MEM framework and the conventional minimum norm estimation (MNE) method. Quantitative comparisons were performed at both single subject and group‐level. Overall, our results suggested that MEM provided better spatial accuracy than MNE, while both methods offered similar temporal accuracy when reconstructing oxygenated (HbO) and deoxygenated hemoglobin (HbR) concentration changes evoked by finger‐tapping. Our proposed complete workflow was made available in the brainstorm fNIRS processing plugin—NIRSTORM, thus providing the opportunity for other researchers to further apply it to other tasks and on larger populations.
Outcome of treatment with carfilzomib before and after treatment with daratumumab in relapsed or refractory multiple myeloma patients
Authors: Højholt Karen Louise , Gregersen Henrik , Szabo Agoston Gyula , Klausen Tobias Wirenfeldt , Levring Mette Bøegh , Preiss Birgitte , Helleberg Carsten , Breinholt Marie Fredslund , Hermansen Emil , Rahbek Gjerdrum Lise Mette , Bønløkke Søren Thorgaard , Nielsen Katrine , Kjeldsen Eigil , Iversen Katrine Fladeland , Teodorescu Elena Manuela , Kurt Eva , Strandholdt Casper , Andersen Mette Klarskov , Vangsted Annette Juul
Published: August 2021

Real world evidence is important since most patients cannot be included in randomized clinical trials (RCTs). In a nationwide, cohort of relapsed/refractory multiple myeloma patients treated with daratumumab (N = 635), we retrospective studied patients treated with carfilzomib (N = 251). Data were collected by audit of medical records. We compared characteristics of patients treated with carfilzomib before daratumumab (Car‐Da; N = 150) and after daratumumab (Da‐Car; N = 101) with those not treated with carfilzomib (N = 384). Furthermore, we examined effectiveness and safety of carfilzomib. The group of patients treated with carfilzomib differed from patients not treated with carfilzomib in the following parameters: They were younger, more were treated up‐front with high dose melphalan and autologous stem cell transplantation (HDM‐ASCT)and had relapse within 18 months thereafter, and more had high‐risk cytogenetic abnormalities (CA) and amplification 1q (amp1q). In patients treated with Car‐Da, 30.3% had high‐risk CA and 30.1% had amp1q and in Da‐Car it was 43.3% and 41%, respectively. In the Car‐Da cohort, 34.4% experienced early relapse after HDM‐ASCT versus 47.4% in the Da‐Car cohort. The percentage of patients with very good partial remission was higher in patients treated with Car‐Da compared to Da‐Car (31.7% vs. 17.4%). The median duration of treatment and time to next treatment (TNT) of Car‐Da/Da‐Car were 4.6/4.3 months and 7.1/4.3 months and only a trend toward superior TNT for Car‐Da was found (p = 0.06). Toxicity of carfilzomib was the same as reported in RCT. A similar poor TNT of daratumumab was found when used before (5.6 months) or after carfilzomib (4.9 months). In this cohort of patients with sequential treatment with carfilzomib and daratumumab or vice versa, a high percentage of patients were high‐risk by CA, amp1q, and early relapse after HDM‐ASCT. Outcome of Car‐DA and outcome of Da‐Car were equally poor. These patients should be considered for new promising treatment strategies.
Energy transference in time‐dependent Cattaneo–Christov double diffusion of second‐grade fluid with variable thermal conductivity
Authors: Haider Ali , Ayub Assad , Madassar Naeem , Ali Rao K. , Sabir Zulqurnain , Shah Syed Z. H. , Kazmi Syed H.
Published: August 2021

The current investigation communicates the characteristics of upper‐convected second grade nanofluid thin film flow over a time‐dependent stretching sheet with variable thermal conductivity and Cattaneo–Christov double diffusion theory. The mathematical model generates a system of nonlinear partial differential equations (PDEs) for heat, momentum, and mass transfer phenomena. Similarity variables converted the PDEs into nonlinear ordinary differential equations (ODEs). Furthermore, received ODEs are numerically rescued with the built‐in program Bvp4c in MATLAB. The impact of physical parameters like second‐grade fluid , unsteadiness parameter , Prandtl number , Schmidt number , variable thermal conductivity , variable diffusivity , the square of dimensionless film thickness , relaxation time , and retardation time are scrutinized. Tables revealed numerical exposure and graphs depict the geometrical aspect of the current study. The velocity field is improved by heightening the λ, magnification in temperature is found for greater conductivity parameter Greater in the temperature profile goes smaller. The rate of mass transfer diminishes by uplifting the estimations in relaxation time parameter
Pterostilbene suppresses oxidative stress and allergic airway inflammation through AMPK/Sirt1 and Nrf2/HO‐1 pathways
Authors: Xu Chang , Song Yilan , Wang Zhiguang , Jiang Jingzhi , Piao Yihua , Li Li , Jin Shan , Li Liangchang , Zhu Lianhua , Yan Guanghai
Published: August 2021

Introduction

Pterostilbene (Pts) may be used for allergic asthma treatment. The AMPK/Sirt1 and Nrf2/HO‐1 pathways are potential targets for asthma treatement. However, the relationship between Pts and AMPK/Sirt1 and Nrf2/HO‐1 pathways in asthma is unclear. Herein, we aim to explore the pharmacological effects of Pts on oxidative stress and allergic inflammatory response as well as the mechanism involving AMPK/Sirt1 and Nrf2/HO‐1 pathways.

Methods

Asthma model was established in mice with ovalbumin (OVA). The model mice were treated by different concentrations of Pts. Lung pathological changes were observed through histological staining. In vitro, lipopolysaccharide (LPS)‐stimulated 16HBE cells were treated with Pts. The siAMPKα2, siSirt1 and siNrf2 knockdown, and treatment with compound C, EX‐527 or ML385 were also performed in 16HBE cells. Enzyme‐linked immunosorbent assay was used to detect interleukin‐4 (IL‐4), IL‐13, IL‐5, total and OVA specific immunoglobulin E (IgE), and interferon γ (IFN‐γ). Pneumonography was used to measure the airway hyperreactivity (AHR). Superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA) levels were also detected. Immunohistochemistry, Western blot and immunofluorescence were used to measure protein levels.

Results

Pts significantly attenuated lung inflammatory cell infiltration and goblet cell proliferation. Meanwhile, Pts treatment could reduce IL‐4, IL‐13, IL‐5, and IgE (total and OVA specific) levels in the asthma model mice. However, IFN‐γ in bronchoalveolar lavage fluid was elevated. In addition, Pts reduced AHR. We also found that Pts treatment promoted serum SOD and CAT, and reduced MDA. In vitro results showed that Pts treatment promoted iNOS, TNF‐α, COX‐2, IL‐1β, and IL‐6 expressions in 16HBE cells, prolonged G0/G1 phase of the cell cycle, and resulted in a shortened G2M phase. Moreover, we found that Pts promoted the phosphorylation of AMPK in 16HBE, and meanwhile inhibited the increase of ROS induced by LPS. Additionally, Pts treatment inhibited p‐AMPK, Sirt1, Nrf2 and HO‐1, which in turn leads to the alleviation of AMPK/Sirt1 and Nrf2/HO‐1 pathways.

Conclusion

Pts alleviated oxidative stress and allergic airway inflammation via regulation of AMPK/Sirt1and Nrf2/HO‐1 signaling pathways.
Commodity prices and inflation risk
Authors: Garratt Anthony , Petrella Ivan
Published: August 2021

This paper investigates the role of commodity price information when evaluating inflation risk. Using a model averaging approach, we provide strong evidence of in‐sample and out‐of‐sample predictive ability from commodity prices and convenience yields to inflation, establishing clear point and density forecast performance gains when incorporating disaggregated commodities price information. The resulting forecast densities are used to calculate the (ex‐ante) risk of inflation breaching defined thresholds that broadly characterize periods of high and low inflation. We find that information in commodity prices significantly enhances our ability to pick out tail inflation events and to characterize the level of risks associated with periods of high volatility in commodity prices.
The deposits channel revisited
Authors: Schaffer Matthew , Segev Nimrod
Published: August 2021

Drechsler et al. (2017) present a novel reformulation of the bank lending channel of monetary transmission based on market power in local deposits markets, which they term the deposits channel. In this paper, we first perform a successful narrow replication of their key empirical results. We then revisit their results on lending in two ways. First, recent studies have pointed out the unique dynamics of credit card loans in Community Reinvestment Act loan origination data. When accounting for this heterogeneity, we find key results are sensitive to the inclusion of credit card banks that raise funds outside of local deposit markets. Second, we show that inconsistencies with related empirical studies can be explained by differences in market power measure, sample period, and the inclusion of alternative control variables. The results highlight that market power on opposing sides of bank balance sheets can impact monetary transmission through alternative channels. Overall, this paper suggests the mechanisms underlying the response of lending to monetary policy remains an important open question.
Aggregate consumption and wealth in the long run: The impact of financial liberalization
Authors: Gardberg Malin , Pozzi Lorenzo
Published: August 2021

This paper investigates the impact of financial liberalization on the relationship between consumption and total wealth (i.e., the sum of asset wealth and human wealth). Financial liberalization is persistent and may signal changes in expected future consumption growth rates and/or in rates of return on wealth that, through the intertemporal budget constraint, affect the current consumption–wealth ratio. We estimate the long‐run relationship between consumption, total wealth, and financial liberalization by state space methods using quarterly US data. The results show that the trend in the consumption–wealth ratio is well‐captured by our baseline liberalization indicator. We find that the increase in this indicator over the sample period has increased the consumption–wealth ratio with about 10%. Investigating the responsible channel, additional estimates show that financial liberalization has predictive power for aggregate consumption growth rather than for returns, a result that supports an incomplete markets interpretation of the link between liberalization and the consumption–wealth ratio.