bluuebunny/crossref_metadata_2025 huggingface dataset:
Anisotropicβ‐effect in the diffusive processes in the rotating magnetoconvection problems
Authors: Filippi Enrico , Brestenský Jozef
Published: December 2020

The influence of the anisotropicβ‐effect in the rotating magnetoconvection problems is studied. Several models of rotating magnetoconvection with different types of anisotropy are presented. A comparison among them is performed. We stress the difference, especially about the magnetoconvection models where there is anisotropy in the turbulent magnetic diffusivity. The influence on convection is thoroughly studied, and its physical meaning is discussed.
A Systematic Literature Review of Autism Research on Caregiver Talk
Authors: Bottema‐Beutel Kristen , Kim So Yoon
Published: December 2020

Describing how caregivers' talk to their autistic children, and how their talk may influence social and language outcomes, has important implications for developmental theory and intervention research. In this systematic literature review, we examine 294 caregiver talk variables extracted from 65 studies, provide a narrative overview of research findings, and link measurement approaches to various theories of language development. The majority of variables included only talk directed to children (90%), and specified the speech act being performed (57%). More than one‐third of variables measured talk that was responsive to children's attention, activities, or communication (38%), and slightly less than a third measured variables that elicited children's communication or engagement. Semantic aspects of talk were specified in 41% of variables, structural features were measured in 20% of variables, and suprasegmental features were measured in only 1% of variables. Talk quantity (without reference to other aspects of talk) was measured in 8% of variables. We found strong support that talk related to children's attention is implicated in autistic children's language development, but this construct has been measured inconsistently in terms of semantic, structural, and functional features. There is also evidence for bi‐directional relationships between caregiver's talk and autistic children's development on a variety of semantic and structural variables.

Lay Summary

In our review, we found many differences in how researchers measured caregiver's talk, but also some promising leads. Researchers should continue examining caregiver talk related to children's focus of attention to clarify how this type of language contributes to autistic children's development. We also found interesting research on how children influence caregiver's talk, and encourage researchers to continue to study how this occurs.
Isolation of cyanide‐degrading bacteria and molecular characterization of its cyanide‐degrading nitrilase
Authors: Terada Ayane , Komatsu Daisuke , Ogawa Takahiro , Flamandita Darin , Sahlan Muhamad , Nishimura Minoru , Yohda Masafumi
Published: December 2020

Hydrogen cyanide is an industrially important chemical, and its annual production is more than 1.5 million tons. Because of its toxicity, the cyanide‐containing effluents from industries have caused many environmental problems. Among various methods to treat the contaminated soils or water, the biological degradation is regarded to be promising. We isolated two cyanide‐degrading microorganisms, Pedobacter sp. EBE‐1 and Bacillus sp. EBE‐2, from soil contaminated with cyanide. Among these bacteria, Bacillus sp. EBE‐2 exhibited significantly a high cyanide‐degrading ability. Bacillus sp. EBE‐2 might be used for the remediation of cyanide contaminated water or soil. A nitrilase gene was cloned from Bacillus sp. EBE‐2. Bacillus nitrilase was expressed in Escherichia coli and purified. Bacillus nitrilase exhibited cyanide‐degrading activity as a large oligomer. Since formic acid formation from cyanide was observed, Bacillus nitrilase is likely to be a cyanide hydrolase. Although there exist various homologous enzymes annotated as carbon–nitrogen family hydrolases, this is the first report on the cyanide degrading activity. The structure and catalytic site of Bacillus nitrilase were studied by homology modeling and molecular docking simulation.
Fighting microbial pathogens by integrating host ecosystem interactions and evolution
Authors: Burmeister Alita R. , Hansen Elsa , Cunningham Jessica J. , Rego E. Hesper , Turner Paul E. , Weitz Joshua S. , Hochberg Michael E.
Published: December 2020

Successful therapies to combat microbial diseases and cancers require incorporating ecological and evolutionary principles. Drawing upon the fields of ecology and evolutionary biology, we present a systems‐based approach in which host and disease‐causing factors are considered as part of a complex network of interactions, analogous to studies of “classical” ecosystems. Centering this approach around empirical examples of disease treatment, we present evidence that successful therapies invariably engage multiple interactions with other components of the host ecosystem. Many of these factors interact nonlinearly to yield synergistic benefits and curative outcomes. We argue that these synergies and nonlinear feedbacks must be leveraged to improve the study of pathogenesis in situ and to develop more effective therapies. An eco‐evolutionary systems perspective has surprising and important consequences, and we use it to articulate areas of high research priority for improving treatment strategies.
Electronic Effects on the Depropargylation Process in the Reaction‐based Fluorescent Detection of Palladium Species: Benzocoumarin‐based Ratiometric Sensing Systems
Authors: Cho Seo Won , Reo Ye Jin , Sarkar Sourav , Ahn Kyo Han
Published: December 2020

The palladium catalyzed cross‐coupling reactions are indispensable in organic synthesis of pharmaceutical compounds, demanding convenient tools for the analysis of residual palladium contents. Propargyl aryl ether‐type fluorescent sensing systems that detect Pd(0)/Pd(II)/Pd(IV) species through depropargylation require no additives. We investigated a ratiometric sensing system based on a benzocoumarin dye; thus, three propargyl aryl ethers bearing electronically‐different self‐immolative linkers were synthesized and their relative response rate toward Pd(0) and Pd(II) were compared. We found that the response rate became faster when the self‐immolative linker became more electron‐deficient. The best‐performing system sensed Pd(0)/Pd(II) species selectively against various other metal species, which is also capable of fluorescent imaging of Pd(0)/Pd(II) species in cells. The work provides us a clue to accelerate the catalytic depropargylation step, which, when combined with a novel fluorophore, would enable us to develop out‐performing palladium sensing systems.
Effect of Cobalt Doping on Enhanced Lithium Storage Performance of Nanosilicon
Authors: Nulu Arunakumari , Nulu Venugopal , Sohn Keun Yong
Published: December 2020

High‐capacity silicon anodes are attracting more attention, owing to their high theoretical capacities and low working potentials. However, massive volume changes and low intrinsic electric conductivity remain substantial challenges that limit the practical applications of these anodes in lithium‐ion batteries (LIBs). In this study, cobalt‐doped silicon nanoparticles with different Co concentrations (0.1 %, 0.3 %, and 0.5 %) are prepared by using a simple low‐temperature annealing process and are studied as anodes for LIBs. Compared to pure silicon, the obtained 0.5 % cobalt‐doped silicon anode can serve as a promising anode and shows a high discharge capacity of 3409 mAh g−1 (97.2 % capacity retention vs. first reversible capacity) with 98.1 % coulombic efficiency after 40 cycles, at 200 mA g−1. After a long 320 cycles, the electrode delivered 3029 mAh g−1 with 86.4 % capacity retention. This cobalt‐doped silicon anode also exhibits superior rate capability and a highly stable long cycle life at higher current densities as well as high mass loading. These remarkable enhancements in electrochemical properties indicate that cobalt doping yields increased conductivity, mitigates volume expansion, and provides shorter lithium transportation lengths across the silicon nanoparticles.
Mono‐Doped Carbon Nanofiber Aerogel as a High‐Performance Electrode Material for Rechargeable Zinc‐Air Batteries
Authors: Li Yiming , Chen Meihua , Chu Mingming , Wang Xue , Wang Yixuan , Lin Xiangsong , Cao Xuebo
Published: December 2020

Nitrogen‐doped porous carbon (NPC) materials have attracted increased attention for zinc‐air battery (ZAB) applications because of their comparable electrocatalytic activity to precious metals. However, few metal‐free NPC catalysts exhibit an oxygen reduction reaction performance better than Pt catalysts, together with high oxygen evolution reaction catalytic activity. Herein, an efficient oxygen electrocatalyst based on highly integrated carbon nanofiber (CNF) and NPC aerogels, with CNF as the core and NPC as the shell, is demonstrated. The NPC@CNF aerogels are prepared through a large‐scale, direct pyrolysis of metal‐organic frameworks and bacterial cellulose hybrids. This mono‐doped carbon material with nitrogen heteroatoms displays outstanding bifunctional performance compared to the individual counterparts, which demonstrates the effectiveness of morphological and structural engineering. Density functional theory calculations reveal that the active sites with the participation of multi‐electrons weaken the O−O bond and facilitate the four‐electron oxygen reduction in the dissociation pathway. The ZAB based on the NPC@CNF air electrode exhibits a peak density of 96 mW cm−2 and a stable charge–discharge durability of over 420 cycles with an overpotential increase of only 0.10 V, indicating that the mono‐doped NPC@CNF performs as one of the best bifunctional catalysts among those recently reported metal‐based and metal‐free catalysts.
Synthesis of Co3O4/Carbon Heteroaerogels with Ultrahigh Capacitance via Polyethyleneimine Intercalation of Co2BIM4 Nanosheets
Authors: Liu Chuanyao , Yue Wenzhe , Li Yanhong , Huang Aisheng
Published: December 2020

The development of metal–organic frameworks (MOFs)‐based supercapacitors have attracted intense concentration in recent years due to their regularly arranged porous and tunable pore sizes. However, the performance of the MOFs‐derived supercapacitors is also low because of their poor electrical conductivity and rarely accessible active sites. In the present work, we developed a Co‐MOF (namely Co2BIM4, BIM=benzimidazole) nanosheets derived Co3O4/nitrogen‐doped carbon (Co2BIM4‐Co3O4/NC) heteroaerogel as a novel supercapacitor electrode. The 3D Co2BIM4‐Co3O4/NC heteroaerogels were obtained by directly intercalating polyethyleneimine (PEI) into the interlayers of Co2BIM4 nanosheets and following by carbonizing the resulting Co2BIM4/PEI composite. The Co2BIM4‐Co3O4/NC electrode possessed 3D conductive framework with an overlapped hetero‐interface and expanded interlayers, leading to fast and stable charge transfer/diffusion and an enhanced pseudocapacitance performance. Therefore, the Co2BIM4‐Co3O4/NC electrode showed ultrahigh capacitance of 2568 F g−1 at 1 A g−1, 1747 F g−1 at 10 A g−1, and excellent long cycling time with a capacitance preservation of 92.7 % following 10000 cycles at 10 A g−1, which is very promising for applications in supercapacitors and other energy storage devices.
Ruthenium‐Catalyzed Coupling Reactions of CO2 with C2H4 and Hydrosilanes towards Silyl Esters
Authors: Kunihiro Kana , Heyte Svetlana , Paul Sébastien , Roisnel Thierry , Carpentier Jean‐François , Kirillov Evgueni
Published: December 2020

A series of in situ‐prepared catalytic systems incorporating RuII precursors and bidentate phosphine ligands has been probed in the reductive carboxylation of ethylene in the presence of triethylsilane as reductant. The catalytic production of propionate and acrylate silyl esters was evidenced by high‐throughput screening (HTS) and implemented in batch reactor techniques. The most promising catalyst systems identified were made of Ru(H)(Cl)(CO)(PPh3)3 and 1,4‐bis(dicyclohexylphosphino)butane (DCPB) or 1,1’‐ferrocene‐diyl‐bis(cyclohexylphosphine) (DCPF). A marked influence of water on the acrylate/propionate selectivity was noted. Turnover numbers [mol mol(Ru)−1] up to 16 for acrylate and up to 68 for propionate were reached under relatively mild conditions (20 bar, 100 °C, 0.5 mol % Ru, 40 mol % H2O vs. HSiEt3). Possible mechanisms are discussed.
Evidence for Atropisomerism in Polycyclic γ‐Butenolides: Synthesis, Scope, and Spectroscopic Studies
Authors: Roy Debayan , Baire Beeraiah
Published: December 2020

Design and development of a domino cyclative approach for the synthesis of new polycyclic γ‐butenolides from β‐aryl‐Z‐enoate propargylic alcohols, through the interception of an intermediate of the Z‐enoate‐assisted Meyer–Schuster rearrangement, has been reported. A systematic NMR analysis of various derivatives of this class revealed and supported the potential atropisomerism associated with them. These molecules represent first examples of butenolide ring‐based atropisomeric compounds in organic chemistry. The synthetic process involves a synchronous construction of both rings with concurrent creation of the potential stereogenic rotational axis.
Tumor mutational burden on cytological samples: A pilot study
Authors: Pepe Francesco , Pisapia Pasquale , Gristina Valerio , Rocco Danilo , Micheli Mariacarolina , Micheli Pietro , Iaccarino Antonino , Tufano Rossella , Gragnano Gianluca , Russo Gianluca , De Luca Caterina , Sgariglia Roberta , Nacchio Mariantonia , Girolami Ilaria , Eccher Albino , Russo Antonio , Troncone Giancarlo , Malapelle Umberto
Published: December 2020

Background

Immune‐checkpoint inhibitors (ICIs) represent an important treatment option for patients who have advanced stage non–small cell lung cancer (NSCLC). Currently, evaluation of the expression level of programmed death‐ligand 1 (PD‐L1) has proven highly successful as a positive predictive biomarker for ICIs. In addition to PD‐L1, other promising predictive biomarkers are emerging, including high tumor mutational burden (TMB‐H). However, measuring TMB‐H remains challenging for several reasons, among which is the difficulty in obtaining adequate tissue material from NSCLC patients. There are no data in the current literature regarding the possibility of adopting cell blocks (CBs) for TMB evaluation; therefore, our goal was to evaluate the feasibility of analyzing TMB on CBs.

Methods

For evaluation of differences in run metric parameters, 8 pairs of histological and CB samples from patients with NSCLC were analyzed using the Oncomine Tumor Mutational Load Assay on Ion Torrent S5 GS next‐generation sequencing (NGS) platform.

Results

Most CBs (6/8, 75.0%) were successfully analyzed by adopting the broad NGS panel approach. CBs provided results similar to those obtained on histological matched specimens in terms of median total reads (7207048.80 vs 7558817.80), median mapped reads (7075753.83 vs 7513822.00), median read lengths (115.50 vs. 113.00), median percentage of reads on‐target (97.49% vs. 98.45%), median average reads per amplicon (454.67 vs 476.14), and median uniformity of amplicon coverage (83.52% vs 84.13%).

Conclusion

In this pilot study, we demonstrated the technical feasibility of assessing TMB on CBs.
The Science Library: Curation and visualization of a science gateway repository
Authors: Braines Dave , Stockdill‐Mander Jane , Lee Eunjin
Published: December 2020

Scientific publications from a group or consortium often form a coherent larger body of work with underlying threads and relationships. Rich social, structural, and topical networks between authors and organizations can be identified, and to convey these we have created the publicly available “Science Library” as a user‐centric, interactive portal. A key consideration in this endeavor is rapid and efficient curation of the corpus of publications, both in terms of assuring quality, as well minimizing the effort required. For this to be sustainable it must offer substantial benefits to the community and avoid excessive operational cost through cumbersome or complex processes. We describe the agility of the Science Library implementation as a controlled natural language (CNL) semantic knowledge graph and describe the different roles within the community to ensure efficient curation, validation, and provenance of the content. By describing the process of curation and validation, alongside the CNL‐based definition of the model we show how relatively non‐technical users are able to interact with, and contribute to the Science Library. This provides an extensible approach, initially based around digital library and virtual community capabilities, that can be applied more broadly to support other desired capabilities of Science Gateways.
Prognostic impacts of serum uric acid levels in patients with chronic heart failure: insights from the CHART‐2 study
Authors: Fujihashi Takahide , Sakata Yasuhiko , Nochioka Kotaro , Miura Masanobu , Abe Ruri , Kasahara Shintaro , Sato Masayuki , Aoyanagi Hajime , Yamanaka Shinsuke , Hayashi Hideka , Shiroto Takashi , Sugimura Koichiro , Takahashi Jun , Miyata Satoshi , Shimokawa Hiroaki ,   CHART‐2 Investigators
Published: December 2020

Aims

Prognostic impacts of serum uric acid (UA) levels in patients with chronic heart failure (CHF) remain inconclusive, especially for the whole range of serum UA levels.

Methods and results

In the Chronic Heart Failure Registry and Analysis in the Tohoku District‐2 (CHART‐2) study, we enrolled 4652 consecutive patients with CHF and classified them into four groups based on baseline serum UA levels by the Classification and Regression Tree: G1 (<3.8 mg/dL, N = 313), G2 (3.8–7.1 mg/dL, N = 3070), G3 (7.2–9.2 mg/dL, N = 1018), and G4 (>9.2 mg/dL, N = 251). Mean age was 71 ± 12, 69 ± 12, 68 ± 13, and 69 ± 15 years in G1, G2, G3, and G4, respectively (P < 0.001). During the median follow‐up of 6.3 years, in G1, G2, G3, and G4, 111 (35%), 905 (29%), 370 (36%), and 139 (55%) patients died and 79 (25%), 729 (24%), 300 (29%), and 115 (46%) experienced heart failure hospitalization, respectively (both P < 0.001). G1 was characterized by a significantly high prevalence of women as compared with G2, G3, and G4 (59%, 32%, 24%, and 23%, respectively). Serum creatinine levels (0.8 ± 0.4, 0.9 ± 0.4, 1.2 ± 0.6, and 1.4 ± 0.8 mg/dL, respectively), prevalence of atrial fibrillation (34%, 39%, 45%, and 50%, respectively), and diuretics use (36%, 45%, 67%, and 89%, respectively) increased from G1, G2, G3 to G4 (all P < 0.001), while left ventricular ejection fraction decreased from G1, G2, G3 to G4 (59 ± 15, 58 ± 15, 54 ± 15, and 52 ± 17%, respectively, P < 0.001). Multivariable Cox proportional hazards models showed that, as compared with G2, both G1 and G4 had increased incidence of all‐cause death [adjusted hazard ratio (aHR) 1.34, 95% confidence interval (CI) 1.08–1.67, P = 0.009; aHR 1.28, 95% CI 1.02–1.61, P = 0.037, respectively] and heart failure admission (aHR 1.39, 95% CI 1.09–1.78, P = 0.008 and aHR 1.35, 95% CI, 1.06–1.71, P = 0.014, respectively). This U‐shaped relationship was evident in the elderly patients. Furthermore, abnormal transitions to either higher or lower levels of serum UA from G2 were associated with increased mortality (aHR 1.29, 95% CI 1.06–1.57, P = 0.012; aHR 1.57, 95% CI 1.12–2.20, P = 0.009).

Conclusions

These results demonstrate that serum UA levels have the U‐shaped prognostic effects and abnormal transitions to either higher or lower levels are associated with poor prognosis in the elderly patients with CHF.
Nickel‐ and Palladium‐Catalyzed Cross‐Coupling of Aryl Fluorosulfonates and Phosphites: Synthesis of Aryl Phosphonates
Authors: Zhang Guofu , Wang Jing , Guan Chenfei , Zhao Yiyong , Ding Chengrong
Published: December 2020

The synthesis of aryl phosphonates via nickel and palladium‐catalyzed cross‐coupling of aryl fluorosulfonates and phosphites is described. The products were obtained in good to excellent yields under mild conditions with broad functional group compatibility, employing either Pd(OAc)2 and DPEPhos or the readily available NiCl2(dme) and Xantphos as catalytic systems. Noteworthily, the present C(sp2)−P bond formation method could be applied to the direct conversion of phenols to the corresponding aryl phosphonates in one pot via reaction of phenols with SO2F2 and subsequent palladium‐catalyzed cross‐coupling.
“On‐Resin” Disulfide Peptide Synthesis with Methyl 3‐Nitro‐2‐pyridinesulfenate
Authors: Kobayashi Kiyotaka , Taguchi Akihiro , Cui Yan , Shida Hayate , Muguruma Kyohei , Takayama Kentaro , Taniguchi Atsuhiko , Hayashi Yoshio
Published: December 2020

New methodologies for the construction of full peptide structures with all disulfide bonds on the resin are attractive for the development of solid phase peptide synthesis. Detailed reaction conditions for the on‐resin disulfide bond formation have been investigated using a mild and chemically stable oxidizing reagent, methyl 3‐nitro‐2‐pyridinesulfenate (Npys‐OMe). Monocyclic oxytocin, MCH and bicyclic α‐conotoxin ImI were synthesized in both semi‐automated and full‐automated protocols. It was found that on‐resin intramolecular disulfide bond formation with Npys‐OMe proceeds with the minimal formation of peptide oligomers by adopting a solvent system with 0.4 M LiCl/DMF. Crude peptides with complete disulfide bond patterns can be obtained in high purity using both protocols. This minimized the RP‐HPLC purification step and the desired peptides were obtained with better yields. To our knowledge, this is the first fully automated construction of a bicyclic disulfide peptide on resin with more than 50 % purity in Fmoc‐based SPPS. These results suggest that Npys‐OMe is a useful reagent for the disulfide bond formation in automated protocols.
EurJOC Going Virtual: Finding New Ways to Collaborate and Exchange Research!
Authors: Nijs Anne
Published: December 2020

Editor Anne Nijs summarizes the unusual year of 2020 and highlights the newly launched virtual symposia that were held, as well as the special issues and collections that were published by the European Journal of Organic Chemistry in the last year. The entire editorial team thanks all our authors, reviewers, and readers for their continued trust and support.
Emotional traumatic experiences significantly contribute to identify a maltreated ecophenotype sub‐group in eating disorders: Experimental evidence
Authors: Monteleone Alessio Maria , Cascino Giammarco , Ruzzi Valeria , Pellegrino Francesca , Patriciello Giuseppina , Barone Eugenia , Carfagno Marco , Monteleone Palmiero , Maj Mario
Published: December 2020

Objective

Eating disorders (EDs) are associated with a high prevalence of childhood maltreatment (CM). We aimed to experimentally assess if people with EDs and history of CM show altered biological, emotional and behavioural responses to the Trier Social Stress Test (TSST).

Methods

According to Childhood Trauma Questionnaire cut‐off scores, 29 participants (14 with anorexia nervosa [AN] and 15 with bulimia nervosa [BN]) were classified as maltreated (Mal) ED participants while 19 participants (11 with AN and eight with BN) without CM were identified as no maltreated (noMal) ED participants. Cortisol, anxiety and hunger responses to TSST and post‐stress body dissatisfaction were measured.

Results

Mal ED people showed heightened emotional reactivity, lower levels of hunger and more severe post‐stress body dissatisfaction in comparison with noMal ones. Higher cortisol production was observed in people with AN, regardless of CM history, and in those with BN and emotional CM. Emotional trauma was the main CM type contributing to the experimental differences observed in Mal ED people.

Conclusions

This is the first study providing experimental and multi‐level support to the maltreated ecophenoptype hypothesis in people with EDs. These findings may promote new insights into the biological bases of EDs and provide novel therapeutic implications.
Machinelearning‐basedmultimodal prediction of language outcomes in chronic aphasia
Authors: Kristinsson Sigfus , Zhang Wanfang , Rorden Chris , Newman‐Norlund Roger , Basilakos Alexandra , Bonilha Leonardo , Yourganov Grigori , Xiao Feifei , Hillis Argye , Fridriksson Julius
Published: December 2020

Recent studies have combined multiple neuroimaging modalities to gain further understanding of the neurobiological substrates of aphasia. Following this line of work, the current study uses machine learning approaches to predict aphasia severity and specific language measures based on a multimodal neuroimaging dataset. A total of 116 individuals with chronic left‐hemisphere stroke were included in the study. Neuroimaging data included task‐based functional magnetic resonance imaging (fMRI), diffusion‐based fractional anisotropy (FA)‐values, cerebral blood flow (CBF), and lesion‐load data. The Western Aphasia Battery was used to measure aphasia severity and specific language functions. As a primary analysis, we constructed support vector regression (SVR) models predicting language measures based on (i) each neuroimaging modality separately, (ii) lesion volume alone, and (iii) a combination of all modalities. Prediction accuracy across models was subsequently statistically compared. Prediction accuracy across modalities and language measures varied substantially (predicted vs. empirical correlation range:r= .00–.67). The multimodal prediction model yielded the most accurate prediction in all cases (r= .53–.67). Statistical superiority in favor of the multimodal model was achieved in 28/30 model comparisons (p‐value range: <.001–.046). Our results indicate that different neuroimaging modalities carry complementary information that can be integrated to more accurately depict how brain damage and remaining functionality of intact brain tissue translate into language function in aphasia.
Identification and initial characterization of a potent inhibitor of ferroptosis
Authors: Kuganesan Nishanth , Dlamini Samkeliso , McDaniel Jade , Tillekeratne Viranga L. M. , Taylor William R.
Published: December 2020

Ferroptosis is a form of iron‐dependent cell death characterized by elevated lipid peroxides and reactive oxygen species (ROS). Glutathione (GSH) plays an essential role in scavenging ROS to maintain cell viability and acts as a cofactor of GSH peroxidase 4 (GPX4) that protects lipids from oxidation. We have previously described a novel class of small molecules that induce ferroptosis in certain types of cancer cells. These compounds induce ferroptosis by blocking the uptake of cystine required for GSH synthesis. Even though ferroptosis is a well‐established form of cell death, signaling pathways that modulate this process are not known. Therefore, we used a panel of growth factors/kinase inhibitors to test effects on ferroptosis induced by our lead compound. We discovered that BMS536924, a dual inhibitor of insulin‐like growth and insulin receptors, is a potent inhibitor of ferroptosis. Further investigation indicated that the anti‐ferroptotic activity of BMS536924 does not lie in its ability to inhibit insulin signal transduction. Instead, we provide evidence that BMS536924 binds iron, an essential cofactor in ferroptosis. Our results suggest caution in interpreting the effects of BMS536924 in investigations of insulin signaling and uncover a novel ferroptosis inhibitor.
Catalyst free sequential one‐pot reaction for the synthesis of 3‐indole propanoates/propanoic acid/propanamides as antituberculosis agents
Authors: Rajeev Narasimhamurthy , Sharath Kumar Kothanahally S. , Bommegowda Yadaganahalli K. , Rangappa Kanchugarakoppal S. , Sadashiva Marilinganadoddi P.
Published: December 2020

A highly efficient catalyst free one pot four component synthesis of highly functionalized three‐substituted indole derivatives has been reported. Thus, sequential catalyst free condensation of readily available aldehydes with Meldrum's acid followed by Michael addition of indole resulting three carbon component condensed product and concurrent decarboxylation by the nucleophilic attack of ethanol/water/amines affords three‐indole propanoates/propanoic acid/propanamides in affordable yields. Further, synthesized compounds and standard drugs were evaluated against Mycobacterium tuberculosis H37Rv strain by Alamar blue assay method. Majority of the compounds exhibited the superior activity and specifically compound 4d has MIC 1.6 μg/ml, which is better than the reference drugs used.
Comparison of seven different reagents of peroxidase method for small and dense low density lipoprotein cholesterol (sdLDL‐C) measurement
Authors: Xuesong Fan , Enshi Wang , Jianxun He , Lei Zhang , Xiaoli Zeng , Hui Yuan
Published: December 2020

Background

We validated the performance of seven different reagents of peroxidase method for sdLDL‐C in two automatic analyzers that are common in Chinese laboratories.

Methods

Seven commercially available sdLDL‐C assays were analyzed with the Beckman AU5400 and Mindray BS2000 automatic analyzers. A total of 336 blood samples were collected and the reference interval was also validated in 298 apparently healthy individuals. Serum samples were used for method comparison of precision, recovery, lower limit of detection, comparison and concurrence analysis, as well as reference interval for the Mindray reagent.

Results

The repeatability CV% of the seven sdLDL‐C assays were 0.81%~3.66% for Mindray BS2000 and 0.76%~3.91% for Beckman AU5400, while Total CVs for Mindray BS2000 sdLDL‐C assay were 1.34%~4.81%, and that of Beckman AU5400 were 2.25%~10.33%. The measured recovery rates of sdLDL‐C assays were within the allowable ±10% deviation range. There was no obvious difference between the reagents in the lower limit detection. There was a difference between the validation results of the reference range and the manufacturer's.BSBE, Mindray, and Dongou had a high degree of association with DENKA SEIKEN on Mindray BS2000, while BSBE, Mindray, Dongou and Merit Choice had a high degree of association with DENKA SEIKEN on Beckman AU5400. Passing–Bablok regression showed excellent linear correlation between BSBE and Mindray and DENKA SEIKEN and on Beckman AU5400.

Conclusions

Our results indicate that the basic performance can meet the testing requirements, but the comparability between them is still insufficient.
Cell dynamics in Hertwig's epithelial root sheath are regulated by β‐catenin activity during tooth root development
Authors: Yang Siqin , Choi Hwajung , Kim Tak‐Heun , Jeong Ju‐Kyung , Liu Yudong , Harada Hidemitsu , Cho Eui‐Sic
Published: December 2020

β‐catenin, a key mediator of Wnt signaling, plays multiple roles in tooth development. However, the role of β‐catenin in Hertwig's epithelial root sheath (HERS) during root formation remains unclear. In this study, we generated inducible tissue‐specific β‐catenin conditional knockout mice (Ctnnb1i∆shh) to investigate how β‐catenin in HERS affects tooth root development. The inactivation of β‐catenin in HERS led to interrupted root elongation due to premature disruption of HERS. This phenotype was accompanied by reduced cell‐cell adhesion and decreased expression of junctional proteins, as well as increased epithelial‐to‐mesenchymal transition of HERS cells upon β‐catenin depletion. Accordingly, stabilization of β‐catenin in HERS (Catnbi∆shh) led to the formation of unfragmented HERS and resulted in the failure of HERS dissociation, with increased expression of junctional proteins. Our results suggest that fine control of β‐catenin is important for HERS to guide root formation through regulating its structural integrity.
Lean regional muscle volume estimates using explanatory bioelectrical models in healthy subjects and patients with muscle wasting
Authors: Bachasson Damien , Ayaz Alper Carras , Mosso Jessie , Canal Aurélie , Boisserie Jean‐Marc , Araujo Ericky C.A. , Benveniste Olivier , Reyngoudt Harmen , Marty Benjamin , Carlier Pierre G. , Hogrel Jean‐Yves
Published: December 2020

Background

The availability of non‐invasive, accessible, and reliable methods for estimating regional skeletal muscle volume is paramount in conditions involving primary and/or secondary muscle wasting. This work aimed at (i) optimizing serial bioelectrical impedance analysis (SBIA) by computing a conductivity constant based on quantitative magnetic resonance imaging (MRI) data and (ii) investigating the potential of SBIA for estimating lean regional thigh muscle volume in patients with severe muscle disorders.

Methods

Twenty healthy participants with variable body mass index and 20 patients with idiopathic inflammatory myopathies underwent quantitative MRI. Anatomical images and fat fraction maps were acquired in thighs. After manual muscle segmentation, lean thigh muscle volume (lVMRI) was computed. Subsequently, multifrequency (50 to 350 kHz) serial resistance profiles were acquired between current skin electrodes (i.e. ankle and hand) and voltage electrodes placed on the anterior thigh. In vivo values of the muscle electrical conductivity constant were computed using data from SBIA and MRI gathered in the right thigh of 10 healthy participants. Lean muscle volume (lVBIA) was derived from SBIA measurements using this newly computed constant. Between‐day reproducibility of lVBIA was studied in six healthy participants.

Results

Electrical conductivity constant values ranged from 0.82 S/m at 50 kHz to 1.16 S/m at 350 kHz. The absolute percentage difference between lVBIA and lVMRI was greater at frequencies >270 kHz (P < 0.0001). The standard error of measurement and the intra‐class correlation coefficient for lVBIA computed from measurements performed at 155 kHz (i.e. frequency with minimal difference) against lVMRI were 6.1% and 0.95 in healthy participants and 9.4% and 0.93 in patients, respectively. Between‐day reproducibility of lVBIA was as follows: standard error of measurement = 4.6% (95% confidence interval [3.2, 7.8] %), intra‐class correlation coefficient = 0.98 (95% confidence interval [0.95, 0.99]).

Conclusions

These findings demonstrate a strong agreement of lean muscle volume estimated using SBIA against quantitative MRI in humans, including in patients with severe muscle wasting and fatty degeneration. SBIA shows promises for non‐invasive, fast, and accessible estimation and follow‐up of lean regional skeletal muscle volume for transversal and longitudinal studies.
Immune function changes of the IDPN‐induced Tourette syndrome rat model
Authors: Liu Xiumei , Wang Xueming , Cao Aihua , Zhang Xiaoling
Published: December 2020

There may be immunologic alternations during Tourette syndrome (TS) development. This study aimed to determine the immune function changes in different aspects (spleen or thymus index, plasma cytokines, and T cell) in an 3,3′‐iminodipropionitrile (IDPN)‐induced rat model of TS. Male Sprague‐Dawley rats were assigned to control and TS groups. The control group received intraperitoneal infections of normal saline (5 ml kg−1 day−1), and the TS rats were injected with IDPN (150 mg kg−1 day−1). The spleen and thymus indices were calculated. The expression of anti‐inflammatory cytokines and inflammatory cytokines TNF‐α, in peripheral blood were measured by ELISA and Western blotting. The proportion of CD3+, CD4+, CD8+, Treg, Th1, and Th2 cells were determined by fluorescence‐activated cell sorting analysis. After 1 week of IDPN treatment, TS rats had decreased spleen and thymus weights versus control. The plasma levels of IL‐4, IL‐10, IL‐12, IFN‐γ, and TNF‐α were significantly increased, while no significant difference in TGF‐β was found. Flow cytometry analysis demonstrated that TS rats had significantly reduced CD3+ and CD4+ cells in spleen, without any change in the proportion of CD8+ cells. Furthermore, the ratio of Treg cells (CD4+/CD25+/FoxP3+) was decreased in TS rats; simultaneously, Th1 cells (CD4+/IFN‐γ+) and Th2 cells (CD4+/IL4+) were dramatically increased. Together, IDPN can trigger immune dysfunction through impairment of matured Th cells, in particular for the Treg subset.
Synthesis of azide congeners of preQ1 as potential substrates for tRNA guanine transglycosylase
Authors: Brooks Allen F. , Garcia George A. , Showalter Hollis D.
Published: December 2020

PreQ1 (2) is a precursor of queuine (1) that in eubacteria is incorporated into transfer RNA (tRNA) by tRNA guanine transglycosylase (TGT) before being further elaborated into queuine. The queuine modification is unusual and occurs across all eukaryotes and eubacteria with few exceptions, but its function remains unclear. As the modified nucleotide occurs through incorporation of a specially synthesized nucleotide instead of via modification of a genetically encoded base, a study of the sites of modification by prepared probes is possible. We report the synthesis of two novel azide congeners (3,4) of preQ1 for this purpose. The evaluation of their interaction with TGT shows that both probes act as weak competitive inhibitors of guanine exchange of guanine(34) tRNATyr with a Ki of ~70 μM. However, we could not show that these are substrates for TGT‐catalyzed incorporation into tRNA. We believe the reason for this is a marked loss of binding due to the azide functionality of 3 and 4 abrogating the possibility of two hydrogen bonds to the carbonyl group of Leu231 and Met260 of TGT, previously observed for the terminal methylene amine of preQ1 by x‐ray crystallography.
Dominant modes of interannual variability in precipitation over the Hengduan Mountains during rainy seasons
Authors: Tao Weichen , Huang Gang , Dong Danhong , Wang Pengfei , Yu Ting , Gong Hainan
Published: December 2020

Present study investigates the dominant modes of interannual variability in precipitation over the Hengduan Mountains (HM) during rainy seasons. The leading two empirical orthogonal function (EOF) modes of HM precipitation explain 28.4 and 13.9% of the total variance, respectively. Positive EOF1 phase features enhanced precipitation anomalies over the southern HM, and a dipole structure with wet anomalies occupying large areas from the YunGui plateau to Tibetan Plateau is observed in positive EOF2 phase. Analysis of moisture budget and omega equation indicate the importance of leading EOF modes related circulation anomalies, which bring the horizontal warm advection to the HM, favouring the anomalous upward motions and precipitation increase there. For EOF1, the HM is controlled by an anomalous quasi‐barotropic cyclone. This cyclone is one part of a zonally oriented barotropic wave‐like pattern highly resembling the Silk Road pattern. Besides, the SST anomalies over the Indo‐Pacific sector are similar to the decaying phase of La Niña, which induces the wet anomalies and further triggers the anomalous lower‐level cyclone as a Rossby wave response. For EOF2, an anomalous cyclone appears over the Northeast Asia from lower to upper levels, and southerly wind anomalies prevail over the HM. The North Atlantic Oscillation and its coupled tripole SST pattern trigger a zonal wave‐like pattern at middle and high latitudes emanating from the Central Europe, across Mongolia to Northeast Asia. Moreover, the SST anomalies over the Indo‐Pacific sector resemble the developing phase of El Niño, which induces the meridional Pacific‐Japan/East Asia‐Pacific teleconnection from tropical NWP to Northeast Asia.
Two types of warm blobs in the Northeast Pacific and their potential effect on the El Niño
Authors: Chen Ziyan , Shi Jian , Li Chun
Published: December 2020

In recent years, the predominant marine heatwaves in Northeast Pacific, the so‐called warm blobs, have exerted substantial environmental and socioeconomic influences on North America and its coastal waters. We select the historical warm blob events from 1951 to 2018 and divide them into double‐peak and single‐peak categories by their seasonal evolutions. The heat budget analyses attribute the leading contributor of double‐peak warm blobs to the surface heat flux at the first wintertime maximum while the vertical entrainment and diffusion take responsibility for the second peak 5 months later. The positive net heat flux anomalies indicate less heat loss from ocean to the atmosphere due to an exceptionally anomalous high as the northern lobe of the North Pacific Oscillation and intensive easterly anomalies, which counteract with the climatological westerlies. For the single‐peak category, the vertical entrainment and diffusion primarily trigger the warm blob and also lead to its termination. Moreover, the single‐peak warm blob induces positive sea surface temperature (SST) anomalies near the Baja California and establishes the Pacific Meridional Mode as the oceanic bridge to convey its influence onto the tropics and trigger the following El Niño around 10 months after the peak. In addition, the subsurface processes, such as the trade wind charging mechanism, also play an essential part by bringing warmer water upwards to the surface and hence cause the positive SST anomalies in equatorial central‐eastern Pacific. However, the interim connection between the double‐peak warm blob and El Niño is not very clear although their intensities appear to be stronger.
Emerging electron microscopy and 3D methodologies to interrogate Staphylococcus aureus osteomyelitis in murine models
Authors: de Mesy Bentley Karen L. , Galloway Chad A. , Muthukrishnan Gowrishankar , Echternacht Scott R. , Masters Elysia A. , Zeiter Stephan , Schwarz Edward M. , Leckenby Jonathan I.
Published: December 2020

Recent breakthroughs in our understanding of orthopaedic infections have come from advances in transmission electron microscopy (TEM) imaging of murine models of bone infection, most notably Staphylococcus aureus invasion and colonization of osteocyte‐lacuno canalicular networks of live cortical bone during the establishment of chronic osteomyelitis. To further elucidate this microbial pathogenesis and evaluate the mechanism of action of novel interventions, additional advances in TEM imaging are needed. Here we present detailed protocols for fixation, decalcification, and epoxy embedment of bone tissue for standard TEM imaging studies, as well as the application of immunoelectron microscopy to confirm S. aureus occupation within sub‐micron canaliculi. We also describe the first application of the novel Automated‐Tape‐UltraMicrotome system with three‐dimensional reconstruction and volumetric analyses to quantify S. aureus occupation within the osteocyte‐lacuno canalicular networks. Reconstruction of the three‐dimensional volume broadened our perspective of S. aureus colonization of the canalicular network and, surprisingly, revealed adjacent noninfected canaliculi. This observation has led us to hypothesize that viable osteocytes of the osteocyte‐lacuno canalicular networks respond and resist infection, opening future research directions to explain the paradox of adjacent uninfected canaliculi and life‐long deep bone infection in patients with chronic osteomyelitis.
A Pilot Study of a Moral Injury Group Intervention Co‐Facilitated by a Chaplain and Psychologist
Authors: Cenkner David P. , Yeomans Peter D. , Antal Chris J. , Scott J. Cobb
Published: December 2020

Moral injury, an experience of betrayal or transgression of moral values, continues to receive attention because of its associations with psychiatric disorders, including posttraumatic stress disorder and suicidality. There is growing recognition that moral injury may require novel interventions that involve religious or spiritual paradigms. This pilot study presents feasibility data and exploratory outcomes for 40 veteran participants across seven cohorts who participated in a novel 12‐week moral injury group (MIG) over 35 months. The MIG was cofacilitated by a Veterans Affairs chaplain and psychologist and designed to reduce distress and improve functioning in individuals with histories of morally injurious experiences from military service. The intervention included a ceremony in which participants shared testimonies of their moral injury with the general public. Recruitment feasibility and retention were high, with participants completing an average of 9.45 (SD = 2.82) sessions of the 12‐week group, and 32 participants (80.0%) attending nine or more sessions and the community healing ceremony. Exploratory analyses revealed medium effect sizes, ω2 = 0.05–0.08, for reductions in depressive symptoms, improvements in psychological functioning, and self‐compassion after the intervention, with small effect sizes, ω2 = 0.03, in anticipated directions for personal growth and spiritual struggles. The results were not impacted by participant engagement in concurrent psychological treatments. Taken together, these findings support the feasibility of the MIG, the potential merit of an interdisciplinary approach to addressing moral injury, and justification for further research into the efficacy of this approach.
Sampling pore water at a centimeter resolution in sandy permeable sediments of lakes, streams, and coastal zones
Authors: Anschutz Pierre , Charbonnier Céline
Published: December 2020

Concentration gradients in the solid fraction and pore water of modern sediments allow to identify benthic biogeochemical processes and the associated fluxes. Gradients are often obtained from layers sampled below the sediment–water interface from sediment cores. Numerous examples in the literature show results from cores collected in impermeable porous sediments, but very few from permeable sediment cores. Indeed, the acquisition of vertical profiles in sandy permeable sediments with a spatiotemporal resolution equivalent to that of muddy sediments is a challenge. We present here a simple protocol that allows sampling of sandy sediments and their interstitial waters with a vertical resolution of 1 cm. This method is suitable for shallow environments, such as intertidal zones, lakes, lagoons, and stream beds. The method is based on rapid conditioning of hand‐collected cores. The cores are pre‐cut lengthwise. Immediately after recovery, they are laid horizontally, opened, and sliced. Interstitial water is collected by centrifugation on site shortly after cutting the core with tubes equipped with a 0.2μm membrane. Optimally, 30 min is sufficient between core collection and conditioning of 12 sections of a 20‐cm long core. The examples shown indicate that the method is reproducible. Reduced dissolved compounds such as Fe(II), Mn(II), and NH4+show profiles without significant oxidation. At the time of core cutting, small volumes of pore water are seeping out of the core, but for sediments with a permeability of up to 10−10m2, this seepage does not disturb the shape of the pore‐water profiles.
Overexpression of chemokine receptor lymphotactin receptor 1 has prognostic value in clear cell renal cell carcinoma
Authors: Chang Xian , Cao Ya , Fu Wan‐Lei , Tang Xue‐Feng , Wang Ya‐Li , Lv Yang‐Fan , Guo Qiao‐Nan
Published: December 2020

Background

Clear cell renal cell carcinoma (ccRCC) is an aggressive subtype of renal cell carcinoma. X‐C motif chemokine receptor 1 (XCR1) exerts important roles in tumor progression; however, its role in ccRCC is unclear.

Methods

We utilized publicly available data from The Cancer Genome Atlas (TCGA) to assess the role of XCR1 in ccRCC and validated the results in 36 samples from patients with ccRCC who underwent curative resection in Xinqiao Hospital Chongqing. XCR1 overexpression was identified in ccRCC, which was confirmed by qRT‐PCR assay and immunohistochemical staining of ccRCC samples.

Results

For the TCGA and clinical data, Kaplan–Meier survival analysis revealed that higher XCR1 expression in ccRCC was related to longer overall survival. Cox regression analysis suggested that XCR1 is an independent risk factor for ccRCC. GSEA analysis suggested that XCR1 is associated with the JAK/STAT signaling pathway. XCR1 knockdown by small interfering RNA (siRNA) significantly increased ccRCC cell proliferation and migration, and decreased cell apoptosis.

Conclusion

We found higher XCR1 expression in ccRCC compared with that in normal tissues is related to longer overall survival in patients with ccRCC. XCR1 knockdown significantly increased RCC cells proliferation and migration, and decreased apoptosis. XCR1 might be used as a prognostic biomarker in ccRCC in the future.