bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetically Programmable Fusion Cellular Vesicles for Cancer Immunotherapy
Authors: Meng Qian‐Fang , Zhao Yuyue , Dong Chunbo , Liu Lujie , Pan Yuanwei , Lai Jialin , Liu Zhida , Yu Guang‐Tao , Chen Xiaoyuan , Rao Lang
Published: October 2021

Herein, we report that genetically programmable fusion cellular vesicles (Fus‐CVs) displaying high‐affinity SIRPα variants and PD‐1 can activate potent antitumor immunity through both innate and adaptive immune effectors. Dual‐blockade of CD47 and PD‐L1 with Fus‐CVs significantly increases the phagocytosis of cancer cells by macrophages, promotes antigen presentation, and activates antitumor T‐cell immunity. Moreover, the bispecific targeting design of Fus‐CVs ensures better targeting on tumor cells, but less on other cells, which reduces systemic side effects and enhances therapeutic efficacies. In malignant melanoma and mammary carcinoma models, we demonstrate that Fus‐CVs significantly improve overall survival of model animals by inhibiting post‐surgery tumor recurrence and metastasis. The Fus‐CVs are suitable for protein display by genetic engineering. These advantages, integrated with other unique properties inherited from source cells, make Fus‐CVs an attractive platform for multi‐targeting immune checkpoint blockade therapy.
Unlocking the Stereoselectivity and Substrate Acceptance of Enzymes: Proline‐Induced Loop Engineering Test
Authors: Qu Ge , Bi Yuexin , Liu Beibei , Li Junkuan , Han Xu , Liu Weidong , Jiang Yingying , Qin Zongmin , Sun Zhoutong
Published: October 2021

Protein stability and evolvability influence each other. Although protein dynamics play essential roles in various catalytically important properties, their high flexibility and diversity makes it difficult to incorporate such properties into rational engineering. Therefore, how to unlock the potential evolvability in a user‐friendly rational design process remains a challenge. In this endeavor, we describe a method for engineering an enantioselective alcohol dehydrogenase. It enables synthetically important substrate acceptance for 4‐chlorophenyl pyridine‐2‐yl ketone, and perfect stereocontrol of both (S)‐ and (R)‐configured products. Thermodynamic analysis unveiled the subtle interaction between enzyme stability and evolvability, while computational studies provided insights into the origin of selectivity and substrate recognition. Preparative‐scale synthesis of the (S)‐product (73 % yield; >99 % ee) was performed on a gram‐scale. This proof‐of‐principle study demonstrates that interfaced proline residues can be rationally engineered to unlock evolvability and thus provide access to new biocatalysts with highly improved catalytic performance.
Transition‐Metal‐Catalyzed Monofluoroalkylation: Strategies for the Synthesis of Alkyl Fluorides by C−C Bond Formation
Authors: Butcher Trevor W. , Amberg Willi M. , Hartwig John F.
Published: October 2021

Alkyl fluorides modulate the conformation, lipophilicity, metabolic stability, and pKa of compounds containing aliphatic motifs and, therefore, have been valuable for medicinal chemistry. Despite significant research in organofluorine chemistry, the synthesis of alkyl fluorides, especially chiral alkyl fluorides, remains a challenge. Most commonly, alkyl fluorides are prepared by the formation of C−F bonds (fluorination), and numerous strategies for nucleophilic, electrophilic, and radical fluorination have been reported in recent years. Although strategies to access alkyl fluorides by C−C bond formation (monofluoroalkylation) are inherently convergent and complexity‐generating, they have been studied less than methods based on fluorination. This Review provides an overview of recent developments in the synthesis of chiral (enantioenriched or racemic) secondary and tertiary alkyl fluorides by monofluoroalkylation catalyzed by transition‐metal complexes. We expect this contribution will illuminate the potential of monofluoroalkylations to simplify the synthesis of complex alkyl fluorides and suggest further research directions in this growing field.
Single‐Cell Metabolomics by Mass Spectrometry: Opportunities and Challenges
Authors: Dolatmoradi Marjan , Samarah Laith Z. , Vertes Akos
Published: October 2021

Cellular heterogeneity is an inherent property of cell populations with a wide spectrum of biological manifestations, ranging from barely observable variations that enhance organismal adaptation, to life‐threatening differences. Single‐cell metabolomics can reveal molecular information and variations in metabolite concentrations between cells that are masked in cell‐population studies. These differences are quantitatively captured by the abundance distributions for the population and their statistical analysis can reveal the presence of latent subpopulations. In recent years, mass spectrometry (MS), combined with novel sampling and ionization techniques, has become an important tool for single‐cell metabolomics. These new techniques must contend with significant challenges in the form of small cell sizes and volumes, ultratrace metabolite amounts per cell, and potentially interfering high turnover rates and rapid diffusion. Owing to the ultrasmall sample volume, low abundance of some metabolites, and poor ionization efficiencies, metabolite detection, identification, and accurate quantitation remain a major challenge. The ability of some techniques to analyze tissue‐embedded cells opens the door for spatial metabolomics, potentially revealing cellular synergism in organ level metabolism. In this Concept article, we present a bird's eye view of these major themes in single cell metabolomics and some of the relevant MS‐based methods.
Identification of Novel Risk Loci for Behçet's Disease–Related Uveitis in a Chinese Population in a Genome‐Wide Association Study
Authors: Su Guannan , Zhong Zhenyu , Zhou Qingyun , Du Liping , Ye Zi , Li Fuzhen , Zhuang Wenjuan , Wang Chaokui , Liang Liang , Ji Yan , Cao Qingfeng , Wang Qingfeng , Chang Rui , Tan Handan , Yi Shenglan , Li Yujing , Feng Xiaojie , Liao Weiting , Zhang Wanyun , Shu Jia , Tan Shiyao , Xu Jing , Pan Su , Li Hongxi , Shi Jing , Chen Zhijun , Zhu Ying , Ye Xingsheng , Tan Xiao , Zhang Jun , Liu Zhangluxi , Huang Fanfan , Yuan Gangxiang , Pang Tingting , Liu Yizong , Ding Jiadong , Gao Yingnan , Zhang Meifen , Chi Wei , Liu Xiaoli , Wang Yuqin , Chen Ling , Meguro Akira , Takeuchi Masaki , Mizuki Nobuhisa , Ohno Shigeaki , Zuo Xianbo , Kijlstra Aize , Yang Peizeng
Published: October 2021

Objective

To explore susceptibility loci associated with uveitis in Behçet's disease (BD).

Methods

We conducted a 2‐stage study, consisting of a genome‐wide association study (GWAS) stage and a replication stage, in a Chinese population. The GWAS stage included 978 cases with BD‐related uveitis and 4,388 controls, and the replication stage included 953 cases with BD‐related uveitis and 2,129 controls. Luciferase reporter analysis and chromatin immunoprecipitation assay were performed to explore the functional role of susceptibility genetic variants near ZMIZ1.

Results

Three independent HLA alleles (HLA–B51 [3.75 × 10−190], HLA–A26 [1.50 × 10−18], and HLA–C0704 [3.44 × 10−16]) were identified as having a genome‐wide association with BD‐related uveitis. In the non‐HLA region, in addition to confirming 7 previously reported loci, we identified 22 novel susceptibility variants located in 16 loci. Meta‐analysis of the Chinese cohort consisting of 1,931 cases and 6,517 controls and a published Japanese cohort of 611 cases and 737 controls showed genome‐wide significant associations with ZMIZ1, RPS6KA4, IL10RA, SIPA1‐FIBP‐FOSL1, and VAMP1. Functional experiments demonstrated that genetic variants of ZMIZ1 were associated with enhanced transcription activity and increased expression of ZMIZ1.

Conclusion

This GWAS study identified a novel set of genetic variants that are associated with susceptibility to uveitis in BD. These findings enrich our understanding of the contribution of genetic factors to the disease.
Ammonia induces autophagy via circ‐IFNLR1/miR‐2188‐5p/RNF182 axis in tracheas of chickens
Authors: Zhang Tian‐yi , Chen Ting , Hu Wan‐ying , Li Ji‐chang , Guo Meng‐yao
Published: October 2021

Ammonia (NH3), an air pollutant in the living environment, has many toxic effects on various tissues and organs. However, the underlying mechanisms of NH3‐induced tracheal cell autophagy remains poorly understood. In present study, chickens and LMH cells were used as NH3 exposure models to investigate toxic effects. The change of tracheal tissues ultrastructure showed that NH3 exposure induced autolysosomes. The differential expression of 12 circularRNAs (circRNAs) was induced by NH3 exposure using circRNAs transcriptome analysis in broiler tracheas. We further found that circ‐IFNLR1 was down‐regulated, and miR‐2188‐5p was up‐regulated in tracheal tissues under NH3 exposure. Bioinformatics analysis and dual luciferase reporter system showed that circ‐IFNLR1 bound directly to miR‐2188‐5p and regulated each other, and miR‐2188‐5p regulated RNF182. Overexpression of miR‐2188‐5p caused autophagy and its inhibition partially reversed autophagy in LMH cells which were caused by ammonia stimulation or knockdown of circ‐IFNLR1. The expressions of three autophagy‐related genes (LC3, Beclin 1, and BNIP3) were observably up‐regulated. Our results indicated that NH3 exposure caused autophagy through circ‐IFNLR1/miR‐2188‐5p/RNF182. These results provided new insights for the study of ammonia on environmental toxicology on ceRNA and circRNAs in vivo and vitro.
Compliance with mass marketing solicitation: The role of verbatim and gist processing
Authors: Nolte Julia , Hanoch Yaniv , Wood Stacey A. , Reyna Valerie F.
Published: October 2021

Introduction

Mass marketing scams threaten financial and personal well‐being. Grounded in fuzzy‐trace theory, we examined whether verbatim and gist‐based risk processing predicts susceptibility to scams and whether such processing can be altered.

Methods

Seven hundred and one participants read a solicitation letter online and indicated willingness to call an “activation number” to claim an alleged $500,000 sweepstakes prize. Participants focused on the solicitation's verbatim details (hypothesized to increase risk‐taking) or its broad gist (hypothesized to decrease risk‐taking).

Results

As expected, measures of verbatim‐based processing positively predicted contact intentions, whereas measures of gist‐based processing negatively predicted contact intentions. Contrary to hypotheses, experimental conditions did not influence intentions (43% across conditions). Contact intentions were associated with perceptions of low risk, high benefit, and the offer's apparent genuineness, as well as self‐reported decision regret, subjective vulnerability to scams, and prior experience falling for scams.

Conclusions

Overall, message perceptions and prior susceptibility, rather than experimental manipulations, mattered in predicting scam susceptibility.
The transcription factor interferon regulatory factor‐1 is an endogenous mediator of myocardial ischemia reperfusion injury
Authors: Jiang Wenlong , Chen Guoxiong , Pu Jun
Published: October 2021

Myocardial ischemia reperfusion (MIR) injury negatively affects the prognosis of acute myocardial infarction (AMI), while effective suppression of MIR injury remains a largely unmet clinical need. Interferon regulatory factors (IRF) are key players in chronic cardiac disorders such as cardiac remodeling. However, their roles in acute MIR injury remain largely unknown. In the current study, microarray data indicated that IRF1 expression was consistently changed in the human ischemic heart and ischemic reperfused mouse heart. Western blot analysis confirmed the expression alterations of IRF1 in ischemic reperfused mouse heart. Cardiac‐specific IRF1 knockdown significantly decreased infarct size, improved cardiac function, and suppressed myocardial apoptosis after MIR injury. Conversely, cardiac‐specific IRF1 overexpression significantly promoted MIR injury. Further investigation revealed that IRF1 transcriptionally regulated the expression of inducible nitric oxide synthase (iNOS), and augmented oxidative stress. Taken together, we presented the first direct evidence that IRF1 served as a mediator of MIR injury, and IRF1 may represent a potential therapeutic target for alleviating MIR injury.
Long noncoding RNA HAGLR sponges miR‐338‐3p to promote 5‐Fu resistance in gastric cancer through targeting the LDHA‐glycolysis pathway
Authors: Hu Jing , Huang Lujie , Ding Qi , Lv Jiaming , Chen Zhe
Published: October 2021

Gastric cancer (GC) is one of the most common human malignancies due to its invasiveness and metastasis. 5‐Fu is a widely applied chemotherapeutic agent against GC. Although 5‐Fu therapy has achieved improvements in GC treatment, a large fraction of patients developed drug resistance which significantly limited its clinical applications. Recent studies revealed the pivotal roles of long noncoding RNAs (lncRNAs) in tumorigenesis and progressions of various tumors, including GC. However, the biological roles and molecular mechanisms of lncRNA HAGLR in GC remain unclear. Here, we report HAGLR was upregulated in both GC tissues and cell lines. In addition, HAGLR was associated with a poorly survival rate of GC patients. Blocking HAGLR inhibited GC cells proliferation and sensitized GC cells to 5‐Fu. Bioinformatical analysis and luciferase assay demonstrated that HAGLR sponged microRNA (miR)‐338‐3p, which functions as a tumor suppressor in GC to downregulate its expressions. Moreover, from the established 5‐Fu resistant GC cell line (HGC27 5‐Fu R), we detected significantly elevated HAGLR, downregulated miR‐338‐3p, and glucose metabolism compared with parental HGC27 cells. We identified lactate dehydrogenase‐A (LDHA), a glucose metabolism key enzyme, was the direct target of miR‐338‐3p in GC cells. Rescue experiments demonstrated that restoration of miR‐338‐3p in HAGLR‐overexpressing HGC27 5‐Fu R cells successfully overrode the HAGLR‐promoted 5‐Fu resistance through targeting LDHA. Taken together, this study revealed essential roles and molecular mechanisms for the HAGLR‐mediated 5‐Fu resistance in GC, contributing to the development of new noncoding RNA‐based therapeutic strategies against chemoresistant GC.
Activation of Molecular O2 on CoFe2O4 (001) Surfaces: An Embedded Cluster Study
Authors: Rushiti Arjeta , Hättig Christof
Published: October 2021

Dioxygen activation pathways on the (001) surfaces of cobalt ferrite, CoFe2O4, were investigated computationally using density functional theory and the hybrid Perdew‐Burke‐Ernzerhof exchange‐correlation functional (PBE0) within the periodic electrostatic embedded cluster model. We considered two terminations: the A‐layer exposing Fe2+ and Co2+ metal sites in tetrahedral and octahedral positions, respectively, and the B‐layer exposing octahedrally coordinated Co3+. On the A‐layer, molecular oxygen is chemisorbed as a superoxide on the Fe monocenter or bridging a Fe−Co cation pair, whereas on the B‐layer it is adsorbed at the most stable anionic vacancy. Activation is promoted by transfer of electrons provided by the d metal centers onto the adsorbed oxygen. The subsequent dissociation of dioxygen into monoatomic species and surface reoxidation have been identified as the most critical steps that may limit the rate of the oxidation processes. Of the reactive metal‐O species, [FeIII−O]2+ is thermodynamically most stable, while the oxygen of the Co−O species may easily migrate across the A‐layer with barriers smaller than the associative desorption.
Azimuthal Dipolar Rotor Arrays on Surfaces
Authors: Hamer Sebastian , von Glasenapp Jan‐Simon , Röhricht Fynn , Li Chao , Berndt Richard , Herges Rainer
Published: October 2021

A set of dipolar molecular rotor compounds was designed, synthesized and adsorbed as self‐assembled 2D arrays on Ag(111) surfaces. The title molecules are constructed from three building blocks: (a) 4,8,12‐trioxatriangulene (TOTA) platforms that are known to physisorb on metal surfaces such as Au(111) and Ag(111), (b) phenyl groups attached to the central carbon atom that function as pivot joints to reduce the barrier to rotation, (c) pyridine and pyridazine units as small dipolar units on top. Theoretical calculations and scanning tunneling microscopy (STM) investigations hint at the fact that the dipoles of neighboring rotors interact through space through pairs of energetically favorable head‐to‐tail arrangements.
Putting Anion‐π Interactions at Work for Catalysis
Authors: Luo Na , Ao Yu‐Fei , Wang De‐Xian , Wang Qi‐Qiang
Published: October 2021

Since its discovery two decades ago, anion‐π interaction has been increasingly recognized as an important driving force. Extensive theoretical and experimental efforts on the ground‐state anion‐π binding and recognition have laid the bases for exploring its relevance in catalysis. Accordingly, the concept of “anion‐π catalysis” that employing an electron‐deficient π surface (π‐acidic surface) for anionic reaction intermediate and transition state stabilization has emerged. This article shortly reviews the emergence and development of this concept, aiming to provide an emphasis on the general concept and key progress in this exciting area. To highlight the essential contribution of anion‐π interactions, the contents are organized according to their role engaged in catalytic process, for example from both ground‐state and transition‐state stabilization to solely transition‐state stabilization, mainly by a single π‐face, and to cooperative π‐face activation. A concluding remark and outlook on future development of this field is also given.
Coordinatively Unsaturated Amidotitanocene Cations with Inverted σ and π Bond Strengths: Controlled Release of Aminyl Radicals and Hydrogenation/Dehydrogenation Catalysis
Authors: Bonnin Quentin , Edlová Tereza , Sosa Carrizo E. Daiann , Fleurat‐Lessard Paul , Brandès Stéphane , Cattey Hélène , Richard Philippe , Le Gendre Pierre , Normand Adrien T.
Published: October 2021

Cationic amidotitanocene complexes [Cp2Ti(NPhAr)][B(C6F5)4] (Cp=η5‐C5H5; Ar=phenyl (1 a), p‐tolyl (1 b), p‐anisyl (1 c)) were isolated. The bonding situation was studied by DFT (Density Functional Theory) using EDA‐NOCV (Energy Decomposition Analysis with Natural Orbitals for Chemical Valence). The polar Ti−N bond in 1 a–c features an unusual inversion of σ and π bond strengths responsible for the balance between stability and reactivity in these coordinatively unsaturated species. In solution, 1 a–c undergo photolytic Ti−N cleavage to release Ti(III) species and aminyl radicals ⋅NPhAr. Reaction of 1 b with H3BNHMe2 results in fast homolytic Ti−N cleavage to give [Cp2Ti(H3BNHMe2)][B(C6F5)4] (3). 1 a–c are highly active precatalysts in olefin hydrogenation and silanes/amines cross‐dehydrogenative coupling, whilst 3 efficiently catalyzes amine‐borane dehydrogenation. The mechanism of olefin hydrogenation was studied by DFT and the cooperative H2 activation key step was disclosed using the Activation Strain Model (ASM).
Spatiotemporal imaging and analysis of mouse and human liver bud morphogenesis
Authors: Ogoke Ogechi , Guiggey Daniel , Mon Tala , Shamul Claire , Ross Shatoni , Rao Saroja , Parashurama Natesh
Published: October 2021

Background

The process of liver organogenesis has served as a paradigm for organ formation. However, there remains a lack of understanding regarding early mouse and human liver bud morphogenesis and early liver volumetric growth. Elucidating dynamic changes in liver volumes is critical for understanding organ development, implementing toxicological studies, and for modeling hPSC‐derived liver organoid growth. New visualization, analysis, and experimental techniques are desperately needed.

Results

Here, we combine observational data with digital resources, new 3D imaging approaches, retrospective analysis of liver volume data, mathematical modeling, and experiments with hPSC‐derived liver organoids. Mouse and human liver organogenesis, characterized by exponential growth, demonstrate distinct spatial features and growth curves over time, which we mathematically modeled using Gompertz models. Visualization of liver‐epithelial and septum transversum mesenchyme (STM) interactions suggests extended interactions, which together with new spatial features may be responsible for extensive exponential growth. These STM interactions are modeled with a novel in vitro human pluripotent stem cell (hPSC)‐derived hepatic organoid system that exhibits cell migration.

Conclusions

Our methods enhance our understanding of liver organogenesis, with new 3D visualization, analysis, mathematical modeling, and in vitro models with hPSCs. Our approach highlights mouse and human differences and provides potential hypothesis for further investigation in vitro and in vivo.
Optical Properties in Heteronuclear Gold(I)/Silver(I) Complexes of Aliphatic Mixed‐Donor Macrocycles Featuring Metallophilic Interactions
Authors: Donamaría Rocío , Lippolis Vito , López‐de‐Luzuriaga José M. , Monge Miguel , Nieddu Mattia , Olmos M. Elena
Published: October 2021

The reaction of the polymeric heterometallic compound [{Au(C6Cl5)2}Ag]n with the macrocyclic ligands 1‐aza‐4,7,10‐trithiacyclododecane (L1), 1,7‐diaza‐4,11‐dithiacyclododecane (L2), 1‐aza‐4,10‐dithia‐7‐oxacyclododecane (L3) in tetrahydrofuran (THF) and 1 : 1 reaction molar ratio affords the new Au(I)/Ag(I) complexes [{Au(C6Cl5)2}{Ag(L1)}] (1), [{Au(C6Cl5)2}{Ag(L2)}] (2), [{Au(C6Cl5)2}{Ag(L3)}] (3) and [{Au(C6Cl5)2}{Ag(L3)}]2 (4) that have been structurally characterized. Despite 1–3 show the same nature of binuclear complexes, only 3 changes its luminescence properties upon grinding as a consequence of partial amorphization.
Application of Sugar Amino Acids: Flow Chemistry Used for α/β‐Chimera Synthesis
Authors: Goldschmidt Gőz Viktória , Duong Kim Hoang Yen , Horváth Dániel , Ferentzi Kristóf , Farkas Viktor , Perczel András
Published: October 2021

Two ring size β‐Sugar Amino Acids, βSAAs, Fmoc‐RibAFU(ip)‐OH and Fmoc‐GlcAPU(Me,Bn)‐OH, as Lego‐elements are introduced to make α/β‐chimera peptides by flow‐based solid phase peptide synthesis (SPPS). Their synthesis alongside selected α‐amino acids, αAA, is fine‐tuned. The recently published 50 % TFA cleavage protocol of tBu protected shorter (Ser, Asp) and larger aromatic (Tyr, Trp), with bulky side chain protected Arg(Pbf) and Gln(Trt) residues was probed. We found that this milder condition is sufficient to successfully remove both the 1,2‐O‐isopropylidene from RibAFU(ip) and tBu, Pbf and Trt from the other αAA residues, but to preserve the 2,3‐di‐O‐benzyl protection of GlcAPU(Me,Bn). Note that O‐benzyl groups can be subsequently cleaved by HF or catalytic hydrogenation. Tuned protocols allow the efficient synthesis of 16‐mer penetratin analogues via continuous flow conditions incorporating either RibAFU(ip) or GlcAPU(Me,Bn) βSAAs. Both acid concentration (50 %/95 %) and type (TFA/HF) allow a versatile protecting group removal and thus, to fine‐tune the hydrophilicity and aromaticity of the above building blocks in chimera constructs.
Further Investigation of the 2‐Azido‐phenylselenylation of Glycals
Authors: Fomitskaya Polina A. , Argunov Dmitry A. , Tsvetkov Yury E. , Lalov Andrey V. , Ustyuzhanina Nadezhda E. , Nifantiev Nikolay E.
Published: October 2021

Derivatives of 2‐azido‐2‐deoxysugars are widely applied as precursor of 2‐amino‐2‐deoxysugars in the synthesis of various oligosaccharides of bacterial, fungal and mammalian origin. Heterogeneous or homogeneous azidophenylselenylation (APS) of glycals, i. e., reaction of glycals with Ph2Se2, PhI(OAc)2 and NaN3 or TMSN3 as azide radical donors, is a straightforward way to phenyl 2‐azido‐2‐deoxy‐1‐selenoglycosides that can be directly used as glycosyl donors. However, heterogeneous APS is characterized by insufficient reproducibility and scalability. We have studied the effect of reaction conditions on the product distribution in heterogeneous APS of 3,4,6‐tri‐O‐acetyl‐d‐galactal and found the conditions that enabled reliable preparation of crystalline phenyl 2‐azido‐2‐deoxy‐1‐seleno‐α‐d‐galactopyranoside triacetate in yield of 58 % on the 3.7 mmol scale. APS of 3,4,6‐tri‐O‐acetyl‐d‐glucal under those conditions produced a ∼1 : 1 mixture of phenyl 2‐azido‐2‐deoxy‐1‐seleno‐α‐d‐gluco‐ and mannopyranosides in total yield of 78 %. Acetoxyphenylselenylation of differently protected galactals and 3,4,6‐tri‐O‐acetyl‐d‐glucal under the action of Ph2Se2 and PhI(OAc)2 has been shown to be a convenient method for the synthesis of 1‐O‐acetyl‐2‐seleno‐2‐deoxy derivatives, valuable intermediates in chemistry of 2‐deoxysugars. 2‐Seleno‐2‐deoxy sugars were characterized in detail by NMR data including 77Se chemical shifts and nJSe−H coupling constant values.
Visible Light Activated Benzimidazolequinone Alkoxyamines of 1,1,3,3‐Tetramethylisoindolin‐2‐yloxyl (TMIO)
Authors: Kielty Patrick , Chalmers Benjamin A. , Farràs Pau , Smith Dennis A. , Aldabbagh Fawaz
Published: October 2021

1,1,3,3‐Tetramethylisoindolin‐2‐yloxyl (TMIO) is a well‐known stable 2,3‐dihydroisoindoline aminoxyl radical, which is thermally generated (at >100 °C) from literature alkoxyamine derivatives. Herein is the synthesis of visible light activated benzimidazolequinone alkoxyamines of TMIO using oxidative methods and the first room temperature nitroxide‐exchange experiments with 2,2,6,6‐tetramethylpiperidine‐1‐oxyl (TEMPO) analogues. For the alkoxyamine TMIO‐Vis dissociation rate constants are provided using TEMPO and oxygen as radical traps.
Groundwater Potential Zone Mapping Using Analytical Hierarchy Process and GIS in Muga Watershed, Abay Basin, Ethiopia
Authors: Melese Tadele , Belay Tatek
Published: October 2021

Groundwater is an important resource that contributes significantly to the total annual water supply. The purpose of the present study is to assess and delineate the groundwater recharge zone using geospatial technology through an analytical hierarchal process (AHP) method in to the Muga watershed, Abay Basin. Remote sensing satellite images and the corresponding data are used for the preparation of thematic layers, viz., geology, rainfall, slope, soil, curvature, topography wetness index, elevation, drainage density, land use land cover, and lineament density of the study watershed. All thematic layers are integrated with a multicriteria evaluation technique. Weighted overlay index analysis is carried out to give rank for each parameter. The weight is assigned for each thematic layer depending on the AHP technique. The reliability of the output is checked by the calculated consistency index and consistency ratio which is reasonably acceptable (0.044 < 0.1). Verification is done by considering the groundwater well locations in the validation datasets. The receiver operating characteristic curve and area under curve (=82.9%) are used to explore the prediction accuracy.
Effects of hydrologic variability and remedial actions on first flush and metal loading from streams draining the Silverton caldera, 1992–2014
Authors: Petach Tanya N. , Runkel Robert L. , Cowie Rory M. , McKnight Diane M.
Published: October 2021

This study examined water quality in the upper Animas River watershed, a mined watershed that gained notoriety following the 2015 Gold King mine release of acid mine drainage to downstream communities. Water‐quality data were used to evaluate trends in metal concentrations and loads over a two‐decade period. Selected sites included three sites on tributary streams and one main‐stem site on the Animas River downstream from the tributary confluences. During the study period, metal concentrations and loads varied seasonally and annually because of hydrologic variability and remedial actions designed to ameliorate the effects of acid mine drainage. Water‐quality data were divided into two periods based on the timing of remedial activities in the watershed. The first period includes active water treatment, surface reclamation and installation of bulkheads in adits; the second period includes the decade following these activities. Water‐quality data were used to estimate annual and monthly zinc loads using the Adjusted Maximum Likelihood Method (using LOADEST software) and U.S. Geological Survey streamflow data. This study presents one of the first applications of LOADEST focused on metal loads. Monthly flow‐weighted concentrations were analysed using a Mann‐Kendall trend test to determine the direction, magnitude, and significance of temporal trends in zinc loading in any given month and using t‐test comparisons between the two periods. Zinc loads estimated for the Animas River below the tributaries indicate decreased zinc loading during the rising limb of the hydrograph in the second period, perhaps reflecting a reduction of snowmelt‐derived zinc load following surface reclamation activities. In contrast, base‐flow zinc loading increased at the main‐stem site, perhaps because of the cessation of water treatment in tributary streams. Flow weighting of monthly load estimates yielded increased statistical significance and enabled more nuanced differentiation between the effects of hydrologic variability and remedial activities on zinc loading.
Oral and gastric microbiome in relation to gastric intestinal metaplasia
Authors: Wu Fen , Yang Liying , Hao Yuhan , Zhou Boyan , Hu Jiyuan , Yang Yaohua , Bedi Sukhleen , Sanichar Navin Ganesh , Cheng Charley , Perez‐Perez Guillermo , Tseng Wenche , Tseng Wenzhi , Tseng Mengkao , Francois Fritz , Khan Abraham R. , Li Yihong , Blaser Martin J. , Shu Xiao‐ou , Long Jirong , Li Huilin , Pei Zhiheng , Chen Yu
Published: October 2021

Evidence suggests that Helicobacter pylori plays a role in gastric cancer (GC) initiation. However, epidemiologic studies on the specific role of other bacteria in the development of GC are lacking. We conducted a case‐control study of 89 cases with gastric intestinal metaplasia (IM) and 89 matched controls who underwent upper gastrointestinal endoscopy at three sites affiliated with NYU Langone Health. We performed shotgun metagenomic sequencing using oral wash samples from 89 case‐control pairs and antral mucosal brushing samples from 55 case‐control pairs. We examined the associations of relative abundances of bacterial taxa and functional pathways with IM using conditional logistic regression with and without elastic‐net penalty. Compared with controls, oral species Peptostreptococcus stomatis, Johnsonella ignava, Neisseria elongata and Neisseria flavescens were enriched in cases (odds ratios [ORs] = 1.29‐1.50, P = .004‐.01) while Lactobacillus gasseri, Streptococcus mutans, S parasanguinis and S sanguinis were under‐represented (ORs = 0.66‐0.76, P = .006‐.042) in cases. Species J ignava and Filifactor alocis in the gastric microbiota were enriched (ORs = 3.27 and 1.43, P = .005 and .035, respectively), while S mutans, S parasanguinis and S sanguinis were under‐represented (ORs = 0.61‐0.75, P = .024‐.046), in cases compared with controls. The lipopolysaccharide and ubiquinol biosynthesis pathways were more abundant in IM, while the sugar degradation pathways were under‐represented in IM. The findings suggest potential roles of certain oral and gastric microbiota, which are correlated with regulation of pathways associated with inflammation, in the development of gastric precancerous lesions.
In vivo sensing of cutaneous edema: A comparative study of diffuse reflectance, Raman spectroscopy and multispectral imaging
Authors: Budylin Gleb S. , Davydov Denis A. , Zlobina Nadezhda V. , Baev Alexey V. , Artyushenko Vyacheslav G. , Yakimov Boris P. , Shirshin Evgeny A.
Published: October 2021

Quantitative noninvasive assessment of water content in tissues is important for biomedicine. Optical spectroscopy is potentially capable of solving this problem; however, its applicability for clinical diagnostics remains questionable. The presented study compares diffuse reflectance spectroscopy, Raman spectroscopy and multispectral imaging in the characterization of cutaneous edema. The source‐detector geometries for each method are selected based on Monte Carlo simulations results to detect the signal from the dermis. Then, the kinetics of the edema development is studied for two models. All methods demonstrate synchronous trends for histamine‐induced edema: The water content reaches a maximum of 1 hour after histamine application and then gradually decreases. For the venous occlusion, a 51% increase in water content is observed with Raman spectroscopy. The differences in water content estimation by three methods are explained based on the light propagation model. The obtained results are essential for introducing quantitative optical water measurement technology to the clinics.
Rapid and sensitive detection of L‐FABP for prediction and diagnosis of acute kidney injury in critically ill patients by chemiluminescent immunoassay
Authors: Sun Tao , Qu Shufang , Huang Tiancha , Ping Ying , Lin Qinyan , Cao Ying , Liu Weiwei , Wang Danhua , Kong Piaoping , Tao Zhihua
Published: October 2021

Background

Acute kidney injury (AKI) was a common clinical complication among critically ill patients in Intensive Care Unit with high morbidity and mortality. Human liver fatty acid‐binding protein (L‐FABP) as a renal tubular injury biomarker was considered a predictor of AKI; however, high‐throughput and sensitive detection methods were still urgently needed. We constructed a sensitive and rapid detection method for detecting L‐FABP and for exploring the clinical application of L‐FABP as a predictor for AKI.

Methods

We developed an automated detection method of chemiluminescent immunoassay to measure L‐FABP and evaluated the analytical performance of the new methodology including analytical selectivity, analytical sensitivity, linear range, the minimum limit of detection (LOD), repeatability, and accuracy. One hundred patients were enrolled in this study to explore the predictive and diagnostic ability for AKI.

Results

The chemiluminescent immune‐based L‐FABP assay had outstanding analytical sensitivity including the detection limit of 0.88 ng/ml, and a wide linear range of 2 ng/ml to 160 ng/ml. It also exhibited excellent repeatability with intra‐analysis CVs of 8.73%, 4.72%, and 3.79%, respectively, and the inter‐analysis CVs of 13.47%, 7.28%, and 5.94%, respectively. The recovery rate assay exhibited a good accuracy with three L‐FABP concentration of 99.76%, 102.27%, and 96.92%, respectively. The reference interval of L‐FABP was between 0.88 ng/ml and 5.98 ng/ml. The evaluation of predictive and diagnostic performance showed that higher concentration of L‐FABP indicated higher risk of AKI occurrence and disease progression.

Conclusions

The clinical application of rapid and sensitive detection method of L‐FABP based on the newly developed chemiluminescent immunoassay could offer benefits for patients. L‐FABP was a potentially predictive and diagnostic biomarker for AKI.
Internet addiction and nonsuicidal self‐injury in adolescence: Associations with offline and online social support
Authors: Liu Sihan , Lin Min‐Pei , Lee Yueh‐Ting , Wu Jo Yung‐Wei , Hu Wei‐Hsuan , You Jianing
Published: October 2021

Objectives

Both nonsuicidal self‐injury (NSSI) and Internet addiction (IA) are important health issues for adolescents, and social support has been extensively examined as a protective factor for both. This study aims to compare the effect of offline and online social support on IA, and that on NSSI as well.

Method

A total of 1911 Chinese adolescents (53.27% females, Mage = 16.83 ± 0.37) completed self‐report questionnaires assessing offline social support, online social support, IA, and NSSI.

Results

The structural equation modeling analysis showed that offline social support was negatively associated with IA and NSSI, while online social support was positively associated with IA and NSSI; IA was positively associated with NSSI. Furthermore, implications for preventions and interventions of IA and NSSI were discussed. The indirect model explained a relatively small variance of NSSI, indicating the possibility of additional factors in the development of NSSI that should be further investigated.

Conclusion

This study indicated the differences between offline and online social support, and their different associations with IA and NSSI.
Children's resilience during Covid‐19 confinement. A child's perspective–Which general and media coping strategies are useful?
Authors: Cauberghe Verolien , De Jans Steffi , Hudders Liselot , Vanwesenbeeck Ini
Published: October 2021

This study explored how children (9–13 years old) coped with the uncertain situation during the first Covid‐19 confinement period (Spring 2020) and whether media helped them handle the situation. Based on a survey among 667 West‐European (Belgian) children, we concluded that children used various strategies to cope with the situation. Seeking social support via social media and searching for distraction was applied by most children. Creating a comforting atmosphere was used by many, although not evaluated as an effective strategy. Whereas older children searched for Covid‐19‐related information, younger children indicated to avoid news media to regulate their emotions. The Covid‐19 anxiety of parents in the confinement period impacted upon the general level of concerns of their children. The results offer policy recommendations on how to support children in handling the tensive Covid‐19 situation, especially during lockdown periods.
Hazard function effects on promoting self‐control in variable interval time‐based interventions in rats
Authors: Bailey Carrie , Panfil Kelsey , Kirkpatrick Kimberly
Published: October 2021

The present experiments investigated properties of time‐based interventions used to increase self‐control. Rats received impulsive‐choice assessments before and after interventions that consisted of different distributions of delays to reinforcement. In Experiment 1, rats received an intervention with an increasing hazard function where delays were more evenly distributed, a decreasing hazard function where delays were mostly short, or a constant hazard function where delays were exponentially distributed. Surprisingly, rats that received the decreasing hazard function made the most self‐controlled choices. Response rates during intervention trials showed that rats anticipated reinforcement based on the shape of the distributions they received. In Experiment 2, rats received an intervention with a decreasing hazard function with a steep slope or a shallow slope. Both time‐based interventions increased self‐control and produced similar response‐rate patterns, indicating that the slope of the decreasing hazard function may not play a strong role in intervention efficacy. While this research aligns with previous literature showing that time‐based interventions improved self‐control, exposure to short delays produced the biggest improvements. Ultimately, exposure to short delays may increase the subjective value of the larger–later choice while occasional long delays may promote the ability to wait, which may have important implications for translational applications.
A Comparison of 3 T and 7 T MRI for the Clinical Evaluation of Uveal Melanoma
Authors: Tang Michael C.Y. , Jaarsma‐Coes Myriam G. , Ferreira Teresa A. , Zwirs ‐ Grech Fonk Lorna , Marinkovic Marina , Luyten Gregorius P.M. , Beenakker Jan‐Willem M.
Published: October 2021

Background

Magnetic resonance imaging (MRI) is increasingly being used in the diagnosis and treatment planning of uveal melanoma (UM), the most common primary intraocular tumor. Initially, 7 T MRI was primarily used, but more recently these techniques have been translated to 3 T, as it is more commonly available.

Purpose

Compare the diagnostic performance of 3 T and 7 T MRI of UM.

Study Type

Prospective.

Population

Twenty‐seven UM patients (19% female).

Field Strength/Sequence

3 T: T1‐ and T2‐weighted three‐dimensional (3D) spin echo (SE) and multi‐slice (MS) SE, 7 T: T1‐weighted 3D gradient echo (GE), T2‐weighted 3D SE and MS SE, 3 T and 7 T GE dynamic contrast‐enhanced. T1 weighted images: acquired before and after Gadolinium (Gd) administration.

Assessment

For all sequences, scan and diagnostic quality was quantified using a 5‐point Likert scale. Signal intensities on T1 and T2 relative to choroid and eye muscle respectively were assessed as well as the tumor prominence. Finally, the perfusion time‐intensity curves (TICs) were classified as plateau, progressive, or wash‐out.

Statistical Tests

Image quality scores were compared between both field strengths using Wilcoxon signed‐rank and McNemar tests. Paired t‐tests and Bland–Altman were used for comparing tumor prominences. P < 0.05 was considered statistically significant.

Results

Image quality was comparable between 3 T and 7 T, for 3DT1, 3DT2, 3DT1Gd (P = 0.86; P = 0.34; P = 0.78, respectively) and measuring tumor dimensions (P = 0.40). 2DT1 and 2DT2 image quality were rated better on 3 T compared to 7 T. Most UM had the same relative signal intensities at 3 T and 7 T on T1 (17/21) and T2 (13/17), and 16/18 diagnostic TICs received the same classification. Tumor prominence measurements were similar between field strengths (95% confidence interval: −0.37 mm to 0.03 mm, P = 0.097).

Data Conclusion

Diagnostic performance of the evaluated 3 T protocol proved to be as capable as 7 T, with the addition of 3 T being superior in assessing tumor growth into nearby anatomical structures compared to 7 T.

Level of Evidence

2

Technical Efficacy

Stage 3
Detection of Saint Louis encephalitis virus in two Brazilian states
Authors: Moraes Marília M. , Kubiszeski Janaina Rigotti , Vieira Carla J. da Silva Pessoa , Gusmao Arianne Fagotti , Pratis Taina Silva , Colombo Tatiana E. , Thies Sirlei Franck , do Carmo Araujo Fabiana , Zanelli Cleslei F. , Milhim Bruno Henrique Gonçalves de Aguiar , da Silva Gislaine C. D. , Nogueira Maurício L. , Pacca Carolina C. , Bronzoni Roberta V. de Morais , Mondini Adriano
Published: October 2021

We describe the circulation of Saint Louis encephalitis virus (SLEV) in two Brazilian States during outbreaks of Dengue and Zika viruses. We detected the virus in a patient from Araraquara, State of São Paulo, and in patients and in a mosquito pool of Culex quinquefasciatus from Sinop, State of Mato Grosso. Phylogenetic analysis grouped samples from this study within genotype V, which are closely related to other strains that previously circulated in other parts of the country. Genotype V seems to have established circulation in Brazil.
Bladder preserving robotic pelvic exenteration for locally advanced rectal cancer‐technique and short‐term outcomes
Authors: Jaganmurugan Ramamurthy , Kazi Mufaddal , Sukumar Vivek , Gori Jayesh , Prakash Gagan , Pal Mahendra , Bakshi Ganesh , de Souza Ashwin , Saklani Avanish
Published: October 2021

Aim

In selected patients with advanced rectal cancers involving the prostate or seminal vesicles, the bladder can be preserved to avoid the complications associated with an ileal conduit. The study was aimed at reviewing the technique and short‐term outcomes of patients that underwent bladder sparing robotic pelvic exenteration with suprapubic cystostomy (SPC).

Methods

Case series of bladder preserving exenteration from a single tertiary care center. Technique for en‐bloc prostatectomy with abdominoperineal resection is described.

Results

Five patients underwent bladder sparing robotic pelvic exenteration with SPC, all had R0 resections. Four patients had prostatic invasion and one patient had prostatic adenocarcinoma. Postoperative complications were seen in three patients of which two were re‐explored. At a median follow‐up of 10 months, two patients developed systemic relapses. There were no local recurrences.

Conclusion

Robotic bladder sparing exenteration is technically feasible, provides acceptable short‐term outcomes, and avoids complications of ileal conduit.
The inadequate use of the determination coefficient in analytical calibrations: How other parameters can assess the goodness‐of‐fit more adequately
Authors: Sanchez Juan M.
Published: October 2021

Simple linear regression using ordinary least‐squares is the most common function applied in laboratories for analytical calibrations. The determination and/or the correlation coefficients are usually the parameters applied for assessing the goodness‐of‐fit of a simple linear calibration. However, these parameters are unable to detect the highly biased results at low calibration levels that are obtained with ordinary least‐squares. In this study, the use of other parameters based on the relative standard errors of the calculated contents is evaluated. It has been found that these alternative parameters can detect the biased results obtained at low calibration levels with ordinary least‐squares, being the relative standard error the one that seems to provide the most adequate results. Ordinary least‐squares should only be applied if the lower limit of quantification is set to at least five times above the conventional limit of quantification. For trace analysis, where the lowest possible limit of quantification is required, weighted least‐squares should be applied to obtain accurate estimates, especially at low concentrations. One of the greatest advantages of the relative standard error is that this parameter can be determined for all types of regression functions and is not limited to calibrations with linear relationships between the variables.
Specialized Feeding Patterns and Marine Resource Use by Nonnative Catfishes in a Coastal River Ecosystem Revealed by Dietary and Stable Isotopic Analyses
Authors: Belkoski David J. , Drzewicki Maya , Scharf Frederick S.
Published: October 2021

Two large predatory catfishes, the Flathead Catfish Pylodictis olivaris and Blue Catfish Ictalurus furcatus, have been introduced into multiple U.S. Atlantic slope drainages in recent decades, with concomitant reductions in native fish abundance and changes in faunal community composition. Here, we report on a study of the trophic ecology of sympatric Flathead Catfish and Blue Catfish in the lower Cape Fear River, North Carolina, to estimate trophic positions and identify possible impacts on marine and estuarine prey resources. We applied both dietary and stable isotope analysis to quantify species-specific foraging patterns, as well as the extent of variation among tributaries, seasonal periods, and ontogeny. Both catfish species displayed limited dietary breadth and specialized feeding patterns focused on prey resources within a restricted range of trophic levels. Dietary overlap between Blue Catfish and Flathead Catfish was low, and the species were separated by more than one trophic position. Flathead Catfish relied heavily on fish prey throughout ontogeny, with macroinvertebrates (crustaceans) as a consistent secondary prey resource, and showed increased reliance on potential anadromous prey resources at the largest sizes. Blue Catfish diets were dominated by the invasive Asian clam Corbicula fluminea, with contributions from fish prey only increasing for the largest individuals. Catfish trophic ecology varied among tributaries, and to a greater extent for Flathead Catfish, in terms of both the fish fauna eaten and the relative contribution of different invertebrate prey. Isotopic signatures for Flathead Catfish aligned with stomach contents to indicate a greater contribution of marine prey resources, including anadromous fishes, in the main-stem Cape Fear River compared with the Black and Northeast Cape Fear rivers. Our findings indicate that the predatory impacts of catfishes introduced to coastal river ecosystems will differ considerably between catfish species and may also vary within systems across fine spatial scales.