bluuebunny/crossref_metadata_2025 huggingface dataset:
Modular Synthesis of Cyclopropane‐Fused N‐Heterocycles Enabled by Underexplored Diazo Reagents
Authors: Richter Matthieu J. R. , Zécri Frédéric J. , Briner Karin , Schreiber Stuart L.
Published: April 2022

Cyclopropane‐fused N‐heterocycles are featured in various biologically active compounds and represent attractive scaffolds in medicinal chemistry. However, synthesis routes to access structurally and functionally diverse cyclopropane‐fused N‐heterocycles remain underexplored. Leveraging novel α‐diazo acylating agents, we report a general approach for the direct and modular synthesis of cyclopropane‐fused lactams from unsaturated amines. The operationally simple transformation, which proceeds through successive acylation, (3+2) cycloaddition and fragmentation, tolerates a broad range of functional groups and yields a wide spectrum of complex molecular scaffolds, including fused, bridged and spiro ring systems. We demonstrate the utility of this transformation in the concise syntheses of therapeutic agents milnaciprane and amitifadine.
Low temperature‐synthesized MgAl2O4:Eu3+ nanophosphors and their structural validations using density functional theory: photoluminescence, photocatalytic, and electrochemical properties for multifunctional applications
Authors: S. N. Manjula , M. Chandrasekhar , Naik Ramachandra , V. Revathi , H. Nagabhushana , C. R. Ravikumar , B. S. Surendra , A. Naveen kumar
Published: April 2022

A low temperature‐assisted and oxalyl dihydrazide fuel‐induced combustion synthesized series of uncalcined MgAl2O4:Eu3+ nanophosphors showed an average crystallite size of ~20 nm, and bandgap energy (Eg) of 4.50–5.15 eV, and were validated using density functional theory and found to match closely with the experimental values. The photoluminescence characteristic emission peaks of Eu3+ ions were recorded between 480 and 680 nm. The nanophosphors excited at 392 nm showed f–f transitions assigned as 5D0→7FJ (J = 0, 1, 2, and 3). The optimized MgAl2O4 phosphors had Commission Internationale de l'Eclairage coordinates in the red region, a correlated colour temperature of 2060 K, and a colour purity of 98.83%. The estimated luminescence quantum efficiency (
) was observed to be ~63% using Judd–Ofelt analysis. Electrochemical and photocatalytic performance were explored and indicated its multifunctional applications. Therefore, MgAl2O4:Eu3+ nanophosphors could be used for the fabrication of light‐emitting diodes, industrial dye degradation, and as electrodes for supercapacitor applications.
Metabonomics study on the hepatoprotective effect mechanism of polysaccharides from different processed products of Angelica sinensis on layer chickens based on UPLC–Q/TOF–MS/MS, multivariate statistical analysis and conjoint analysis
Authors: Wu Fan‐lin , Hu Yong‐hao , Ji Peng , Li Chen‐chen , He Jian
Published: April 2022

Chicken colibacillosis is one of the most severe diseases in the poultry industry. Ceftiofur sodium (CS) is often used to treat it in clinical practice and lipopolysaccharide (LPS) accumulates in the chicken's body. Previous experimental studies found that CS combined with LPS could induce liver injury in layer chickens, and polysaccharides from charred Angelica sinensis(CASP) had a better hepatoprotective effect than polysaccharides from unprocessed Angelica sinensis(UASP). However, the intervention mechanism was unclear. Thus, UPLC–Q/TOF–MS/MS‐based metabonomics and transcriptomics were used in this study to clarify the hepatoprotective effect mechanism of CASP and UASP in layer chickens. Transcriptomics and enzyme‐linked immunosorbent assay were used for biological verification of some critical mutual metabolic pathways screened with metabonomics. The comprehensive analysis results showed that in a layer chicken liver injury model built with LPS and CS, 12 critical metabolic pathways were disturbed, involving 10 important differential metabolites. The hepatoprotective effect mechanism of CASP is related to the arachidonic acid metabolism and mTOR signaling pathways, involving nine important differential metabolites. In contrast, the hepatoprotective effect mechanism of UASP is related to the arachidonic acid metabolism pathway, involving six important differential metabolites.
Revisiting the influence of corporate sustainability practices on corporate financial performance: An evidence from the global energy sector
Authors: Kumar Ajay , Gupta Jyotirani , Das Niladri
Published: April 2022

The purpose of this study is to theoretically and empirically extend the debate of the curvilinear linkage between corporate sustainability performance and its reporting practices (CSPR) and corporate financial performance (CFP) over its linearity assumption. The study focused on the financial and non‐financial metrics of the top global energy firms from 2006 to 2018 to accomplish this objective. It employed an estimated generalized least square method on the balanced panel of 3211 firm‐year observations. The findings assert the existence of a curvilinear relationship by spurning the linearity assumption. Further, results revealed a significant inverted U‐shaped relationship between CSPR and CFP. In addition to this, the investigation reveals that this relationship exists with the environmental and social attributes of CSPR. While the governance attribute was initially insignificant, however, it also exhibits a significant inverted‐U relationship after interacting with earnings. As a result, it adds to the existing literature by identifying earnings as a significant moderator in explaining the curvilinear relationship between CSPR and CFP. The inverted U‐shaped relationship may assist top management in developing a sustainable social and environmental policy based on a reactive strategy and help in formulating strategies to balance the value‐cost trade‐off for sustainable development.
Dihydroflavonoids as Bioactive Components of Penthorum chinense, a Miao Ethnomedicine, against NAFLD through Bile Acid Metabolism Pathway
Authors: Li Xiaoxi , Li Yatong , Zhao Wenwen , Yu Lan , Hu Xiaolu , Zhao Yimeng , Guo Qiang , Wang Xing , Wu Xia
Published: April 2022

Penthorum chinense Pursh. is a traditional herbal medicine of Miao, and its extracts (PCPE) have been used for treatment of liver diseases in the clinic including nonalcoholic fatty liver disease (NAFLD). However, the active components and pharmacological mechanisms of PCPE for treating NAFLD remain unclear. This study aimed to explore potential mechanisms of action through network pharmacology, molecular docking combined with experimental in vitro. A total of five dihydroflavonoids (1–5) with the same parent nucleus of pinocembrin (PCB) from PCPE, were selected as bioactive ingredients and 109 potential targets related to NAFLD were obtained from public databases and literature mining. The core targets related to the bile secretion signaling were selected based on PPI network and KEGG enrichment analysis for exploring the mechanism of PCPE against NAFLD. Molecular docking results showed good interaction between the core targets in bile secretion signaling pathway and the five compounds predicted to be bioactive. With the strong binding activity to retinoid X receptor‐alpha (RXRA) and farnesoid X receptor (FXR) protein, pinocembrin‐7‐O‐β‐D‐glucoside (PCBG, the highest content in PCPE) and its metabolite PCB, could significantly increase the expression of RXRA, FXR and bile salt export pump (BSEP) in L02 cells, and significantly decrease the expression of cholesterol 7α‐hydroxylase (CYP7A1) at mRNA and protein levels. This study provided favorable evidence for mechanism of the main dihydroflavonoids of PCPE against NAFLD, and presented a paradigm for the study of ethnomedicine.
Transcatheter implantation of covered stents serving as extravascular conduits—Proof of a CT‐based approach in three cases
Authors: Ewert Peter , Eicken Andreas , Tanase Daniel , Georgiev Stanimir , Will Albrecht , Pankalla Cornelia , Nagdyman Nicole , Meierhofer Christian , Hörer Jürgen
Published: April 2022

Background

Covered stents perform similar to surgically implanted conduits, although the stents work inside of vessels. We present a computed tomography (CT)‐based workflow for the implantation of covered stents as extravascular conduits.

Methods

We selected three different use cases: 1. Connecting a left‐sided partially anomalous drainage of a pulmonary vein to the left atrium. 2. Bypassing an outgrown Dacron conduit in aortic recoarctation. 3. Re‐directing hepatic venous blood to the left lung in a Fontan patient with heterotaxy, connecting the innominate vein to the right pulmonary artery like a right‐sided cavopulmonary connection. By postprocessing and analyzing CT scans for planning and by the use of long needles under biplane fluoroscopy for the realization of the procedure, we projected and performed the exit of a long needle out of a vessel, the re‐entering of a target vessel, and the bridging of the extravascular distance by implantation of covered stents.

Results

In all three cases, the covered stents were placed successfully, connecting vessels of 15–50 mm distance from each other with very good hemodynamic results. In one case, two stents were placed consecutively, overlapping each other to accomplish an exact fitting at the connection sites to the native vessels.
Pulmonary artery transection for resection of a middle mediastinal paraganglioma
Authors: Zhou Alice L. , Halub Meghan E. , Lotfalla Mira , Shou Benjamin L. , Kilic Ahmet
Published: April 2022

We report the case of a 65‐year‐old male patient who presented with chest pain and was found to have a mediastinal paraganglioma between the left atrium and main pulmonary artery. This is the first reported case of a mediastinal paraganglioma resection utilization transection of the main pulmonary artery.
A One‐Pot Approach for Bio‐Based Arylamines via a Combined Photooxidative Dearomatization‐Rearomatization Strategy
Authors: Afanasenko Anastasiia , Kavun Aleksei , Thomas Dylan , Li Chao‐Jun
Published: April 2022

The synthesis of arylamines from renewable resources under mild reaction conditions is highly desired for the sustainability of the chemical industry, where the production of hazardous waste is a prime concern. However, to date, there are very few tools in chemists’ toolboxes that are able to produce arylamines in a sustainable manner. Herein, a robust one‐pot approach for constructing bio‐based arylamines via a combined photooxidative dearomatization‐rearomatization strategy is presented. The developed methodology enables the synthesis of structurally complex amines in moderate‐to‐good isolated yields using biomass‐derived phenols, natural α‐amino acids, and naphthols under remarkably mild reaction conditions. For the photooxygenation of phenols, a novel chrysazine‐based catalyst system was introduced, demonstrating its efficiency for the synthesis of natural products – hallerone, rengyolone, and the pharmaceutically relevant prodrug DHED.
Dynamic Amino Acid Side‐Chains Grafting on Folded Peptide Backbone**
Authors: Zagiel Benjamin , Peker Taleen , Marquant Rodrigue , Cazals Guillaume , Webb Gabrielle , Miclet Emeric , Bich Claudia , Sachon Emmanuelle , Moumné Roba
Published: April 2022

An efficient strategy for the synthesis of large libraries of conformationally defined peptides is reported, using dynamic combinatorial chemistry as a tool to graft amino acid side chains on a well‐ordered 3D (3‐dimension) peptide backbone. Combining rationally designed scaffolds with combinatorial side chains selection represents an alternative method to access peptide libraries for structures that are not genetically encodable. This method would allow a breakthrough for the discovery of protein mimetic for unconventional targets for which little is known.
Development of Fluorophosphoramidate as a Biocompatibly Transformable Functional Group and its Application as a Phosphate Prodrug for Nucleoside Analogs
Authors: Yoshida Yuki , Zheng Ti , Tanabe Wataru , Tomoike Fumiaki , Hashiya Fumitaka , Suzuki Tetsuro , Hirota Shuto , Saiki Yuriko , Horii Akira , Hirayama Akiyoshi , Soga Tomoyosi , Kimura Yasuaki , Abe Hiroshi
Published: April 2022

Synthetic phosphate‐derived functional groups are important for controlling the function of bioactive molecules in vivo. Herein we describe the development of a new type of biocompatible phosphate analog, a fluorophosphoramidate (FPA) functional group that has characteristic P−F and P−N bonds. We found that FPA with a primary amino group was relatively unstable in aqueous solution and was converted to a monophosphate, while FPA with a secondary amino group was stable. Furthermore, by improving the molecular design of FPA, we developed a reaction in which a secondary amino group is converted to a primary amino group in the intracellular environment and clarified that the FPA group functions as a phosphate prodrug of nucleoside. Various FPA‐gemcitabine derivatives were synthesized and their toxicity to cancer cells were evaluated. One of the FPA‐gemcitabine derivatives showed superior toxicity compared with gemcitabine and its ProTide prodrug, which methodology is widely used in various nucleoside analogs, including anti‐cancer and anti‐virus drugs.
Fine‐grain task‐parallel algorithms for matrix factorizations and inversion on many‐threaded CPUs
Authors: Catalán Sandra , Herrero José R. , Igual Francisco D. , Quintana‐Ortí Enrique S. , Rodríguez‐Sánchez Rafael
Published: April 2022

We extend a two‐level task partitioning previously applied to the inversion of dense matrices via Gauss–Jordan elimination to the more challenging QR factorization as well as the initial orthogonal reduction to band form found in the singular value decomposition. Our new task‐parallel algorithms leverage the tasking mechanism currently available in OpenMP to exploit “nested” task parallelism, with a first outer level that operates on matrix panels and a second inner level that processes the matrix either by ‐panels or by tiles, in order to expose a large number of independent tasks. We present a detailed performance analysis, including execution traces, which shows that the two‐level refinement into fine grain tasks allows for an improved load balancing and delivers high performance on current general‐purpose many‐core processors (CPUs) from Intel and AMD.
Enhanced Photocatalytic Hydrolysis Performance of Chiral Molecule Loaded Titanium Disulfide Nanosheets
Authors: Bai Xuesong , Cao Yang , Xu Yueshan , Huang Wei , Deng Peilin , Tian Xinlong , Liu Zhongxin , Wang Jieqiong , Tu Jinchun
Published: April 2022

The photoelectrochemical (PEC) water decomposition is a promising method to produce hydrogen from water. To improve the water decomposition efficiency of the PEC process, it is necessary to inhibit the generation of H2O2 byproducts and reduce the overpotential required by cheap catalysts and a high current density. Studies have shown that coating the electrode with chiral molecules or chiral films can increase the hydrogen production and reduce the generation of H2O2 byproducts. This is interpreted as the result of a chiral induced spin selectivity (CISS) effect, which induces a spin correlation between the electrons that are transferred to the anode. Here, we report the adsorption of chiral molecules onto titanium disulfide nanosheets. Firstly, titanium disulfide nanosheets were synthesized via thermal injection and then dispersed through ultrasonic crushing. This strategy combines the CISS with the plasma effect caused by the narrow bandgap of two‐dimensional sulfur compounds to promote the PEC water decomposition with a high current density.
Construction of Low‐Impedance and High‐Passivated Interphase for Nickel‐Rich Cathode by Low‐Cost Boron‐Containing Electrolyte Additive
Authors: Li Guanjie , Li Zifei , Cai Qinqin , Yan Chong , Xing Lidan , Li Weishan
Published: April 2022

The nickel‐rich cathode LiNi0.8Co0.1Mn0.1O2 (NCM811) possesses the advantages of high reversible specific capacity and low cost, thus regarded as a promising cathode material for lithium‐ion batteries (LIBs). However, the capacity of the NCM811 decays rapidly at high voltage due to the extremely unstable electrode/electrolyte interphase. The discharge capability at low temperature is also impaired because of the increasing interfacial impedance. Herein, a low‐cost film‐forming electrolyte additive with multi‐function, phenylboronic acid (PBA), was employed to modify the interphasial properties of the NCM811 cathode. Theoretical calculation and experimental results showed that PBA constructed a highly conductive and steady cathode electrolyte interphase (CEI) film through preferential oxidation decomposition, which greatly improved the interfacial properties of the NCM811 cathode at room (25 °C) and low temperature (−10 °C). Specifically, the capacity retention of NCM811/Li cell was increased from 68 % to 87 % after 200 cycles with PBA additive. Moreover, the NCM811/Li cell with PBA additive delivered higher discharge capacity under −10 °C at 0.5 C (173.7 mAh g−1 vs. 111.1 mAh g−1). Based on the improvement of NCM811 interphasial properties by additive PBA, the capacity retention of NCM811/graphite full‐cell was enhanced from 49 % to 65 % after 200 cycles.
Host preference of field‐derived Schistosoma mansoni is influenced by snail host compatibility and infection status
Authors: Laidemitt Martina R. , Gleichsner Alyssa M. , Ingram Christopher D. , Gay Steven D. , Reinhart Elizabeth M. , Mutuku Martin W. , O Oraro Polycup , Minchella Dennis J. , Mkoji Gerald M. , Loker Eric S. , Steinauer Michelle L.
Published: April 2022

Schistosome parasites cause a chronic inflammatory disease in humans, and recent studies have emphasized the importance of control programs for understanding the aquatic phases of schistosomiasis transmission. The host‐seeking behavior of larval schistosomes (miracidia) for their snail intermediate hosts plays a critical role in parasite transmission. Using field‐derived strains of Kenyan snails and parasites, we tested two main hypotheses: (1) Parasites prefer the most compatible host, and (2) parasites avoid hosts that are already infected. We tested preference to three Biomphalaria host snail taxa (B. pfeifferi, B. sudanica, and B. choanomphala), using allopatric and sympatric Schistosoma mansoni isolates and two different nonhost snail species that co‐occur with Biomphalaria, Bulinus globosus, and Physa acuta. We also tested whether schistosomes avoid snail hosts that are already infected by another trematode species and whether competitive dominance played a role in their behavior. Preference was assessed using two‐way choice chambers and by visually counting parasites that moved toward competing stimuli. In pairwise comparisons, we found that S. mansoni did not always prefer the more compatible snail taxon, but never favored an incompatible host over a compatible host. While parasites preferred B. pfeifferi to the nonhost species B. globosus, they did not significantly prefer B. pfeifferi versus P. acuta, an introduced species in Kenya. Finally, we demonstrated that parasites avoid infected snails if the resident parasite was competitively dominant (Patagifer sp.), and preferred snails infected with subordinates (xiphidiocercariae) to uninfected snails. These results provide evidence of “fine tuning” in the ability of schistosome miracidia to detect hosts; however, they did not always select hosts that would maximize fitness. Appreciating such discriminatory abilities could lead to a better understanding of how ecosystem host and parasite diversity influences disease transmission and could provide novel control mechanisms to improve human health.
Drivers of flea abundance in wild rodents across local and regional scales in the Chihuahuan Desert, northwestern Mexico
Authors: Pontifes Paulina A. , Fernández‐González Adriana , García‐Peña Gabriel E. , Roche Benjamin , Suzán Gerardo
Published: April 2022

The broad distribution of macroparasites and their thriving populations are matters of health and economic concern. Macroparasites cause damage both directly through their feeding habits, which impact host fitness, and indirectly through the transmission of various infectious diseases of relevance to human and domestic animal health and wildlife conservation. Because the impacts of macroparasites on host health and the risk of disease transmission are directly related to their abundance, understanding the drivers of macroparasite burden is of relevance. Various host traits and environmental factors have been associated with differences in macroparasite abundance. In addition to these variables, spatial scale is increasingly incorporated to understand how these drivers vary across space. However, variation in the relative importance of host traits and environmental factors as predictors of abundance at different scales is not well understood. To further clarify the relationship between scale and drivers of macroparasite abundance, we investigated the effects of host traits and environmental factors on flea abundance in rodents of the Chihuahuan Desert in northwestern Mexico on three levels: within a single site, between sampling sites with different vegetation types, and across the region. This partitioning allowed us to compare drivers at both local and regional scales. Fleas provide a natural model to assess the interplay between host and environmental variables across scales because their life cycles alternate between on‐host and off‐host environments and their hosts have varying ranges of distribution. We sampled 1311 fleas from 674 rodent individuals of 14 different species across 40 sampling plots between 2012 and 2013. Using generalized linear mixed models, we found that flea abundance was associated with different combinations of host traits such as size and sex. The specific combination of predictive variables differed across species, while the effects on flea abundance showed context and scale dependency, although this could only be tested at the full level of analysis on the most abundant species,Dipodomys merriami. Sampling season was the only variable consistently significant across scales, reflecting the far‐reaching effects of large‐scale, interannual environmental fluctuations. These results emphasize that integrating spatial scale can strengthen study design for monitoring macroparasite burden.
A technological quality control system for rice supply chain
Authors: Tao Qi , Cai Zhenyu , Cui Xiaohui
Published: April 2022

Rice quality affects social stability, consumer health, and corporate brand benefit. The traditional supply chain traceability management system is centralized, monopolized, asymmetric, and opaque. It is the main factor leading to frequent food safety incidents. This paper proposes a technological quality control system for rice supply chain to protect rice products quality and safety. Firstly, it adopts risk assessment and traceability mechanism to prevent the hazard factors in the production and processing. Then, to prevent spoiled food from endangering the consumers’ health and reduce food waste, it explores a shelf life model of rice products to predict the remaining shelf life of products. Finally, this paper constructs a decentralized traceability management system based on blockchain and IoT, which enables consumers to access the real information of rice products and helps supervisors to monitor the quality of products in the supply chain.
Nanoscale molybdenum oxide improves plant growth and increases nitrate utilisation in rice (Oryza sativa L.)
Authors: Zhang Haipeng , Wang Rui , Chen Zhiqing , Pu Jialing , Wang Juanjuan , Zhang Hongcheng , Yang Yanju
Published: April 2022

Nanoscale molybdenum oxide (nano‐MoO3) is widely used in industrial and environmental fields and its release to the environment is increasing. However, the potential effect of nano‐MoO3 on rice (Oryza sativa L.) seedling growth is unclear. Herein, the different impacts of vaired concentrations (0, 50, 100, 200 and 300 μg Mo L–1) of Na2MoO4 and nano‐MoO3 on the growth and nitrate (NO3–) utilisation of rice were investigated using hydroponics. The Mo concentration in roots and shoots, N metabolism enzyme activity, root morphology, root redox ability and root exudates were then analysed to understand the potential mechanisms of the growth impacts. Results showed that the Mo concentration in rice roots increased incrementally as the amount of Mo application increased, whereas different Mo sources did not affect the Mo concentration in shoots. Both Na2MoO4 and nano‐MoO3 promoted the growth and NO3– utilisation of rice. The promotion effects of higher nano‐MoO3 dosages were better than those of Na2MoO4. Nano‐MoO3 application significantly affected the activity of nitrate reductase (NR), glutamine synthetase (GS) and glutamate synthase (NADH‐GOGAT), which in turn promoted NO3– assimilation. Additionally, rice seedlings treated with nano‐MoO3 had a relatively high rice root volume, surface area, total absorption area, active absorption area, low‐molecular‐weight organic acids, root oxidation and reduction capacities. Based on these results, it is proposed that nano‐MoO3 facilitates rice growth and NO3– assimilation via the enhancement of nitrogen metabolism enzyme activity and the promotion of good root morphological and physiological characters with high root secretion concentration and redox ability. This study provides insights regarding the further application of nano‐MoO3 in agriculture enhancing N use efficiency and rice productivity.
Combination studies of operating cell, inlet‐line, and humidification temperatures on performance of proton exchange membrane fuel cell
Authors: Thiyagarajan Prem Kumar , Jeganathan Kanchana , Kumar P Manoj
Published: April 2022

The combined influence of factors, that is, operating cell temperature, humidification temperature (HT) (indirectly relative humidity), and reactant gas inlet‐line temperature on the performance of proton exchange membrane fuel cell was experimentally and statistically studied. A catalyst‐coated membrane, membrane electrode assembly, of 6.25 cm2 active area and 0.29 mgpt cm–2 catalyst loading was used in the study. Experimentally, the effect of individual factors and their combinations on cell performance was studied. Statistical analyses were carried out to find the main and interaction effects of different factors. Analysis of variance (ANOVA, 5% significance level, 95% confidence level) analysis, which was validated for homoscedasticity, was used to evaluate the significance of the main and interaction effects of factors. From the study, it was observed that the HT had a significant main effect (988 W m–2). Both interaction plots and ANOVA results revealed that the combination of operating cell and HT was the most significant. The study showed a very interesting observation that the statistical interaction effect (545 W m–2) was half of the experimental deviation value (1090 W m–2) between the summation of independent effects and the combined effect.
Thickness determination of laminate core layers from microscopy images
Authors: Hartmann Stefan , Dileep Pranav Kumar , Harhash Mohamed , Palkowski Heinz
Published: April 2022

In sandwich laminates made of metal–polymer–metal (MPM) layers under forming conditions, the thickness changes along the thin‐layered specimens are of particular interest. To measure this distribution, it is common to take microscopic images and determine manually the thicknesses at particular discrete points. We compare and provide several methods determining the thickness distribution from microscopic images. First, an interpolation scheme is chosen to obtain a continuous function of the interfaces between the layers instead of the discrete pixel data. Afterwards, the methods—ruled surface approach, orthogonal projection, embedded circle scheme, and a dull but simple method—are applied and compared with each other. For very smooth data, most of the schemes show equivalent results. However, the “brute force”—called the dull approach—turns out to be the most robust scheme, particularly, if noisy data is studied. The Gaussian error propagation concept is applied to study the uncertainties resulting from noisy pixel data. The schemes are adapted to finite element simulation results as well so that a direct comparison of experimental and numerical data would be possible.
A review of the mutagenic potential of N‐ethyl‐N‐nitrosourea (ENU) to induce hematological malignancies
Authors: Nath Priyatosh , Maiti Debasish
Published: April 2022

This review is intended to summarize the existing literature on the mutagenicity of N‐ethyl‐N‐nitrosourea (ENU) in inducing hematological malignancies, including acute myeloid leukemia (AML) in mice. Blood or hematological malignancies are the most common malignant disorders seen in people of all age groups. Driven by a number of genetic alterations, leukemia rule out the normal proliferation and differentiation of hematopoietic stem cells (HSCs) and their progenitors in the bone marrow (BM) and severely affects blood functions. Out of all hematological malignancies, AML is the most aggressive type, with a high incidence and mortality rate. AML is found as either de novo or secondary therapeutic AML (t‐AML). t‐AML is a serious adverse consequence of alkylator chemotherapy to the cancer patient and alone constitutes about 10%−20% of all reported AML cases. Cancer patients who received alkylator chemotherapy are at an elevated risk of developing t‐AML. ENU has a long history of use as a potent carcinogen that induces blood malignancies in mice and rats that are pathologically similar to human AML and t‐AML. ENU, once entered into the body, circulates all over the body tissues and reaches BM. It creates an overall state of suppression within the BM by damaging the marrow cells, alkylating the DNA, and forming DNA adducts within the early and late hematopoietic stem and progenitor cells. The BM holds a weak DNA repair mechanism due to low alkyltransferase, and poly [ADP‐ribose] polymerase (PARP) enzyme content often fails to obliterate those adducts, acting as a catalyst to bring genetic abnormalities, including point gene mutations as well as chromosomal alterations, for example, translocation and inversion. Taking advantage of ENU‐induced immune‐suppressed state and weak immune surveillance, these mutations remain viable and slowly give rise to transformed HSCs. This review also highlights the carcinogenic nature of ENU and the complex relation between the ENU's overall toxicity in the induction of hematological malignancies.
The Pfizer Crystal Structure Database: An essential tool for structure‐based design at Pfizer
Authors: Gehlhaar Daniel K. , Luty Brock A. , Cheung Philip P. , Litman Andy H. , Owen Robert M. , Rose Peter W.
Published: April 2022

Pfizer's Crystal Structure Database (CSDB) is a key enabling technology that allows scientists on structure‐based projects rapid access to Pfizer's vast library of in‐house crystal structures, as well as a significant number of structures imported from the Protein Data Bank. In addition to capturing basic information such as the asymmetric unit coordinates, reflection data, and the like, CSDB employs a variety of automated methods to first ensure a standard level of annotations and error checking, and then to add significant value for design teams by processing the structures through a sequence of algorithms that prepares the structures for use in modeling. The structures are made available, both as the original asymmetric unit as submitted, as well as the final prepared structures, through REST‐based web services that are consumed by several client desktop applications. The structures can be searched by keyword, sequence, submission date, ligand substructure and similarity search, and other common queries.
Electrolysis of glycerol to value‐added chemicals in alkaline media
Authors: Shubair Asma , Houache Mohamed SE , Mousavi M S Shayan , Botton Gianluigi A , Baranova Elena A.
Published: April 2022

BACKGROUND

Glycerol, a by‐product of biodiesel production, is produced in large quantities, exceeding its demand. The saturation of glycerol resulted in a sharp reduction in its market value and the surplus waste may pose a risk to the environment. By means of electrochemical technologies, glycerol could be oxidized into value‐added products such as glycerate, tartronate and lactate. In the present work, carbon‐supported NiBi catalysts with different atomic ratios (NixBi1−x/C, wherex = 100, 95, 90 and 50 at%) were fabricated and utilized in a 25 cm2 electrolysis cell.

RESULTS

The as‐fabricated catalysts were characterized and analyzed by various physicochemical and electrochemical characterizations. Using a three‐electrode electrochemical cell, Ni95Bi5/C showed the highest current density of 104 mA cm−2, with an onset potential of 1.32 V versus a reversible hydrogen electrode. Long‐term chronoamperometry was performed in a glycerol electrolysis cell accompanied by the product analysis using high‐performance liquid chromatography. It was found that Ni95Bi5/C had higher selectivity to glycerate C3 product compared to Ni/C. Additionally, optimizing experimental conditions (applied potential, residence time and temperature) to achieve higher selectivity to C3 products was thoroughly studied. The selectivity to C3 value‐added products was enhanced by adjusting the operating conditions.

CONCLUSION

Small addition of bismuth to Ni/C enhanced both catalytic activity and selectivity to C3 products. The main products formed on NixBi1−x/C were formate and glycerate, while the secondary products were glycolate, tartronate, oxalate and lactate. By running electrolysis under optimal conditions, the selectivity to C3 products was significantly enhanced. © 2022 Society of Chemical Industry (SCI).
Comprehensive determination of the processing level of rhizome of Polygonatum sibiricum by macroscopic, micromorphological, and microscopic characterizations
Authors: Cheng Xile , Ji Hongyuan , Cheng Cheng , Sun Yongfang , Cheng Haitao , Wang Dongmei , Pan Yingni , Liu Xiaoqiu
Published: April 2022

The rhizome of Polygonatum sibiricum Red. (PR, Huangjing in Chinese) has served as traditional medicine and foodstuff in China for over 2000 years. However, due to its irritating effect on the throat, Huangjing must be processed before clinical use. People have been exploring to determine the processing level of traditional Chinese medicine in an accurate tool. The evaluation of PR processing levels based on macroscopic and microscopic characteristics has not yet been performed. This study aimed to provide a convenient method to determine the level of PR processing by monitoring the changes in color and crystal inclusion. According to the Chinese Pharmacopeia (2020 edition), macroscopic, micromorphological, and microscopic observations were performed with a polarized light microscope. Color quantization based on the CIE L*a*b* color system using a CM‐2300d colorimeter. Color parameters h°, L*, and ΔE* had a significant influence on the differentiation ability. The inner transverse section of PR samples gradually turned into moist black with specular luster, which was consistent with the traditional identification of “brightness like oil and color like black lacquer.” The change rate of the needle crystal morphology increased with the processing level, and the change rate of the needle crystal of the fifth product was over 90%. Combined with the correlation analysis, needle‐like crystals were related to color parameters and could be used as an alternative marker to discriminate PR samples from different processing levels. The results confirmed the potential applicability of macroscopic and microscopic features for the classification of PR samples with different processing levels.

Research Highlights

Color parameters h°, L*, and ΔE* had a significant influence on the differentiation ability.

Micromorphological results were consistent with the traditional identification.

High correlations were found between color parameters and needle‐like crystals.
An international multicenter propensity‐score matched and coarsened‐exact matched analysis comparing robotic versus laparoscopic partial liver resections of the anterolateral segments
Authors: Kadam Prashant , Sutcliffe Robert P , Scatton Olivier , Sucandy Iswanto , Kingham T. Peter , Liu Rong , Choi Gi Hong , Syn Nicholas L. , Gastaca Mikel , Choi Sung‐Hoon , Chiow Adrian K. H. , Marino Marco V. , Efanov Mikhail , Lee Jae‐Hoon , Chong Charing C. , Tang Chung‐Ngai , Cheung Tan‐To , Pratschke Johann , Wang Xiaoying , Campos Ricardo Robless , Ivanecz Arpad , Park James O. , Rotellar Fernando , Fuks David , D'Hondt Mathieu , Han Ho‐Seong , Troisi Roberto I. , Goh Brian K. P. ,   International Robotic and Laparoscopic Liver Resection Study Group Investigators
Published: April 2022

Background

Robotic liver resections (RLR) may have the ability to address some of the drawbacks of laparoscopic liver resections (LLR) but few studies have done a head‐to‐head comparison of the outcomes after anterolateral segment resections by the two techniques.

Methods

A retrospective study was conducted of 3202 patients who underwent minimally invasive LR of the anterolateral liver segments at 26 international centres from 2005 to 2020. Two thousand six hundred and six cases met study criteria of which there were 358 RLR and 1868 LLR cases. Perioperative outcomes were compared between the two groups using a 1:3 Propensity Score Matched (PSM) and 1:1 Coarsened Exact Matched (CEM) analysis.

Results

Patients matched after 1:3 PSM (261 RLR vs 783 LLR) and 1:1 CEM (296 RLR vs 296 LLR) revealed no significant differences in length of stay, readmission rates, morbidity, mortality, and involvement of or close oncological margins. RLR surgeries were associated with significantly less blood loss (50 mL vs 100 ml, P < .001) and lower rates of open conversion on both PSM (1.5% vs 6.8%, P = .003) and CEM (1.4% vs 6.4%, P = .004) compared to LLR. Though PSM analysis showed RLR to have a longer operating time than LLR (170 minutes vs 160 minutes, P = .036), this difference proved to be insignificant on CEM (167 minutes vs 163 minutes, P = .575).

Conclusion

This multicentre international combined PSM and CEM study showed that both RLR and LLR have equivalent perioperative outcomes when performed in selected patients at high‐volume centres. The robotic approach was associated with significantly lower blood loss and allowed more surgeries to be completed in a minimally invasive fashion.
Activating transcription factor 2 promotes the progression of hepatocellular carcinoma by inducing the activation of the WHSC1‐mediated TOP2A/PI3K/AKT axis
Authors: Bao Zhong‐Ming , Yao Dan , Qian Xu , Zhang Hua‐Guo , Yang Ming , Guo Yun‐Hu , Qin Lei
Published: April 2022

Activating transcription factor 2 (ATF2) is a tumor driver gene implicated in several human malignancies. This study aimed to determine the roles of ATF2 and its related molecules in the tumorigenesis of hepatocellular carcinoma (HCC). According to the Pan‐cancer bioinformatics system, ATF2 is highly expressed in HCC. An increase in the expression of ATF2 was identified in clinically collected tumor tissues and procured HCC cells. The silencing of ATF2 reduced the viability, colony formation, invasion, and death resistance of HepG2 and SNU‐398 cells in vitro. ATF2 promoted the transcription of Wolf‐Hirschhorn syndrome candidate 1 (WHSC1) by binding to its promoter. WHSC1 further increased the expression of DNA topoisomerase II alpha (TOP2A) in HCC by inducing the dimethylation of histone H3 lysine 36 (H3K36me2) in the TOP2A promoter region. TOP2A activated the oncogenic PI3K/AKT signaling pathway. Further overexpression of WHSC1 activated the TOP2A/PI3K/AKT axis and restored the malignant behaviors of HCC cells suppressed by ATF2 silencing in vitro. In summary, this study demonstrated that, depending on WHSC1, ATF2 can activate the TOP2A/PI3K/AKT signaling cascade to promote the tumorigenesis of HCC. ATF2, WHSC1, and TOP2A may serve as potential targets in managing HCC.
Associations of emotion recognition, loneliness, and social functioning in euthymic patients with bipolar disorder
Authors: Lee Chia Ning , Huang Yu‐Lien , Chang Hui Hua , Kuo Che Yu , Lu Tsung‐Hua , Hsieh Yi‐Ting , Chang Wei Hung , Yang Yen Kuang , Chen Po See , Tseng Huai‐Hsuan
Published: April 2022

Emotion recognition deficit is related to impaired community functioning. Loneliness is also associated with impaired social performance. However, the way in which emotion recognition and loneliness may contribute to social functioning remains unclear in euthymic patients with bipolar disorder. We aimed to examine emotion recognition ability in Han Chinese euBD patients relative to healthy controls (HCs) and to investigate the associations between emotion recognition, loneliness, and social functioning. Thirty‐nine HCs and 46 euthymic BD patients completed an emotion recognition task and nonsocial cognitive measures related to executive function and attention. The UCLA loneliness scale and Social Performance Scale were administered to evaluate psychological loneliness and social functioning, respectively. We observed lower emotion recognition accuracy, higher loneliness, and poorer social functioning in the BD patients after adjustment for demographic data. Loneliness was negatively associated with global social functioning in both the BD and HC groups. Higher loneliness and lower emotion recognition accuracy were associated with poorer social functioning in euthymic BD in different subdomains. Our study confirmed a subtle impairment of emotion recognition ability in euthymic BD. Loneliness impacts globally on social functioning, while emotion recognition ability may affect specific subdomains of social functioning in euthymic BD. Alleviation of loneliness and enhancement of social cognition might improve social functioning in BD patients.
Predictable shifts in diversity and ecosystem function in phytoplankton communities along coastal salinity continua
Authors: Olli Kalle , Tamminen Timo , Ptacnik Robert
Published: April 2022

Salinity is a major environmental predictor of phytoplankton species richness and composition. We hypothesize that the variation in phytoplankton richness along coastal salinity gradients is reflected in essential ecosystem functions like resource use efficiency (RUE)—the proportion of limiting resource that is converted into biomass. To test the hypothesis, we analyzed time series of phytoplankton and environmental variables from the Chesapeake Bay and the Baltic Sea. We analyzed the relationship among salinity, diversity, and RUE in bivariate and interaction association, and in structural equation model (SEM)—a form of path analysis to resolve multivariate relationships among interrelated variables. We concluded that the intrusion of marine water will lead to rapid change in species diversity on the fresh side. Despite diversity drop, individual community functions, like RUE, remain relatively resilient, reflecting functional redundancy. We propose that the salinity gradient also reflects trophic complexity, allowing stable resource use at reduced diversity.
Facile Preparation of Cost‐Effective Triphenylamine‐Based Nanoporous Organic Polymers for CO2, I2, and Organic Solvents Capture
Authors: Yan Jun , Guo Yide , Xie Siyu , Wang Qilin , Leng Zesong , Li Dan , Qi Kangru , Sun Haiyu
Published: April 2022

Seeking cost‐effective construction of nanoporous organic polymers for CO2 and I2 capture and organic solvents adsorption remains challenging. Two triphenylamine‐based nanoporous organic polymers, ANOP‐1 and ANOP‐2, have been prepared successfully by Friedel–Crafts (F–C) hydroxyalkylation from low‐cost triphenylamine (TPA) with commercial terephthalaldehyde and isophthalaldehyde, respectively. The effect of isomers of phenyl dialdehydes on the structure of porous architecture is investigated. The as‐prepared ANOPs exhibit a moderate uptake of CO2, I2, and organic solvents because of the electron‐rich TPA unit and nanometer‐scale pore size of <2 nm. These findings demonstrate that F–C hydroxyalkylation is a cost‐effective strategy for producing large amounts of triphenylamine‐enriched, high specific BET surface area materials to develop commercial organic materials for industrial use.
Epidermis‐Like High Performance Wearable Strain Sensor for Full‐Range Monitoring of the Human Activities
Authors: Madhavan R.
Published: April 2022

Stretchable strain sensors with outstanding performance are in critical demand with substantial progress in wearable electronic systems. In this work, a graphite conductive network‐based active sensor material encapsulated within Ecoflex (sandwich structured Ecoflex/graphite/Ecoflex) is employed for strain and wearable monitoring applications. The typical active sensor material is successfully deposited onto the skin‐like Ecoflex stretchable supporting material utilizing a spray coating technique to obtain a highly conductive brittle graphite nanoflake film. As a result, the Ecoflex/graphite/Ecoflex sandwich structured strain sensors exhibit high performance with a large strain sensitivity. Owing to the brittle–stretchable conductive network, the spray‐coated strain sensor exhibited high gauge factors of 132 and 32 in the 0–20% and 20–40% strain ranges, respectively. Moreover, this strain sensor demonstrated a quick response speed (150 ms), prominent linearity (R2 > 0.99 in the strain range of 5–20%), and high durability (>1000 stretch–release cycles at a large‐scale strain of 30%) making it attractive for monitoring entire‐range of human bodily motions including facial expressions (frowning, eye blinking, and cheek movement), vocal cord vibrations, and human articular joint motions (bending process of a finger, wrist, elbow, and knee ), thereby indicating enormous application prospects in healthcare devices, intelligent robotics, and human–computer interfaces.
Investigation of the Potential of Bile Acid Methyl Esters as Inhibitors of Aldo‐keto Reductase 1C2: Insight from Molecular Docking, Virtual Screening, Experimental Assays and Molecular Dynamics
Authors: Marinović Maja A. , Petri Edward T. , Grbović Ljubica M. , Vasiljević Bojana R. , Jovanović‐Šanta Suzana S. , Bekić Sofija S. , Ćelić Andjelka S.
Published: April 2022

Human aldo‐keto reductase 1C isoforms (AKR1C1‐C4) catalyze reduction of endogenous and exogenous compounds, including therapeutic drugs, and are associated with chemotherapy resistance. AKR1C2 is involved in metastatic processes and is a target for the treatment of various cancers. Here we used molecular docking to explore the potential of a series of eleven bile acid methyl esters as AKR1C2 inhibitors. Autodock 4.2 ranked 10 of the 11 test compounds above a decoy set generated based on ursodeoxycholic acid, a known AKR1C2 inhibitor, while 5 of these 10 ranked above 94 % of decoys in Autodock Vina. Seven inactives reported in the literature not to inhibit AKR1C2 ranked below the decoy threshold: 5 of these are specific inhibitors of AKR1C3, a related isoform. Using the same parameters, Autodock Vina identified steroidal analogs of AKR1C substrates, bile acids, and AKR1C inhibitors in the top 5 % of a virtual screen of a natural product library. In experimental assays, 6 out of 11 of the tested bile acid methyl esters inhibited >50 % of AKR1C2 activity, while 2 compounds were strong AKR1C3 inhibitors. Potential off‐target interactions with the glucocorticoid receptor were measured using a yeast‐based fluorescence assay, where results suggest that the methyl ester could interfere with binding. The top ranking compound based on docking and experimental results showed dose‐dependent inhibition of AKR1C2 with an IC50 of ∼3.6 μM. Molecular dynamics simulations (20 ns) were used to explore potential interactions between a bile acid methyl ester and residues in the AKR1C2 active site. Our molecular docking results identify AKR1C2 as a target for bile acid methyl esters, which combined with virtual screening results could provide new directions for researchers interested in synthesis of AKR1C inhibitors.