bluuebunny/crossref_metadata_2025 huggingface dataset:
Transfer of Axial Chirality to the Nanoscale Endows Carbon Nanodots with Circularly Polarized Luminescence
Authors: Di Noja Simone , Amato Francesco , Zinna Francesco , Di Bari Lorenzo , Ragazzon Giulio , Prato Maurizio
Published: April 2022

We report the synthesis, purification and characterization of chiral carbon nanodots starting from atropoisomeric precursors. The obtained atropoisomeric carbon nanodots are soluble in organic solvents and have good thermal stability, which are desirable features for technological applications. The synthetic protocol is robust, as it supports a number of variations in terms of molecular doping agents. Remarkably, the combination of axially chiral precursors and 1,4‐benzoquinone as doping agent results in green‐emissive carbon dots displaying circularly polarized luminescence. Dissymmetry factors of |3.5|×10−4 are obtained in solution, without the need of any additional element of chirality. Introducing axial chirality expands the strategies available to tailor the properties of carbon nanodots, paving the way for carbon nanoparticles that combine good processability in organic solvents with engineered advanced chiroptical properties.
Dye‐encapsulated nanocage‐based metal–organic frameworks as luminescent dual‐emitting sensors for selective detection of inorganic ions
Authors: Liu Mengfan , Yu Xin , Zhong Kaixuan , Chen Xiangyu , Feng Lijuan , Yao Shuo
Published: April 2022

A novel manganese‐based metal–organic framework (Mn‐MOF) with nanocage has been successfully synthesized by pore space partition (PSP) strategy. Benefiting from the ternary inorganic secondary building units (SBUs) of mononuclear, trinuclear, and rare tetranuclear bi‐paddlewheel, the material possesses good stability and abundant open metal sites (OMSs). As far as the organic SBU, the uncoordinated pyridine groups promote the formation of Lewis basic sites (LBSs). The multiple SBUs construct the overall framework with three types of cages which exhibits novel topology. Furthermore, the anionic framework provides the impetus to encapsulate cationic dyes, which facilitates the construction of dual‐emitting luminescent RhB@Mn‐MOF material with self‐calibrating sensing abilities. The composite material features prominent selective detection performance to Fe (III), which is obviously superior to the parent material. Additionally, a Zn‐MOF with similar structure to Mn‐MOF shows selective detection ability to Cu (II) and P2R@Zn‐MOF prepared by dye‐encapsulated has enhanced performance. However, the Mn‐based materials prepared by PSP provide appropriate cage and more active sites enable them obtain better detection ability. Therefore, the synergistic effect of PSP and dye‐encapsulated strategy is beneficial to improve the selective detection performance of the materials to inorganic ions.
Malarial PI4K inhibitor induced diaphragmatic hernias in rat: Potential link with mammalian kinase inhibition
Authors: Demarta‐Gatsi Claudia , Donini Cristina , Duffy James , Sadler Claire , Stewart Jane , Barber Jane A. , Tornesi Belen
Published: April 2022

Background

MMV390048 is an aminopyridine plasmodial PI4K inhibitor, selected as a Plasmodium blood‐stage schizonticide for a next generation of malaria treatments to overcome resistance to current therapies. MMV390048 showed an acceptable preclinical safety profile and progressed up to Phase 2a clinical trials. However, embryofetal studies revealed adverse developmental toxicity signals, including diaphragmatic hernias and cardiovascular malformations in rats but not rabbits.

Methods

In vivo exposures of free plasma concentrations of compound in rats were assessed in relation to in vitro human kinase inhibition by MMV390048, using the ADP‐Glo™ Kinase Assay.

Results

We demonstrate a potential link between the malformations seen in the embryofetal developmental (EFD) studies and inhibition of the mammalian PI4Kβ paralogue, as well as inhibition of the off‐target kinases MAP4K4 and MINK1. PI3Kγ may also play a role in the embryofetal toxicity as its in vitro inhibition is covered by in vivo exposure. The exposures in the rabbit embryofetal development studies did not reach concentrations likely to cause PI4K inhibition. Overall, we hypothesize that the in vivo malformations observed could be due to inhibition of the PI4K target in combination with the off‐targets, MAP4K4 and MINK1. However, these relationships are by association and not mechanistically proven.

Conclusions

Deciphering if the EFD effects are dependent on PI4K inhibition, and/or via inhibition of other off‐target kinases will require the generation of novel, more potent, and more specific PI4K inhibitors.
Micelle‐enhanced spectrofluorimetric method for the rapid determination of bronchodilator terbutaline and its prodrug bambuterol: application for content uniformity test
Authors: Nour‐Eldeen Deena A. , Omar Mahmoud A. , Mohamed Salwa Kh. , Mohamed Abobakr A.
Published: April 2022

A novel, simple and sensitive spectrofluorimetric approach for determination of terbutaline sulphate (TER) and its prodrug bambuterol (BAM) in their pure and pharmaceutical dosage forms was developed. The suggested approach depends on enhancing the native fluorescence of either TER or BAM at 315 and 297.2 nm after excitation at 277 and 259 nm, respectively, using sodium dodecyl sulphate (SDS) as a micellar medium. In the presence of 0.7% w/v SDS, ~1.38‐fold and 1.18‐fold enhancement is achieved in the relative fluorescence intensity (RFI) of TER and BAM, respectively. The fluorescence–concentration curves were rectilinear over the concentration range 0.8–16 μg ml−1, with detection limits (LOD) of 0.252 and 0.26 (μg ml−1), quantitation limits (LOQ) of 0.76 and 0.79 (μg ml−1), determination coefficients (r2) of 0.9981, and slopes of 45.92 and 10.44 for TER and BAM, respectively. The suggested approach was validated in accordance with International Council for Harmonisation criteria and was effectively applied in the analysis of the studied drugs in their commercial tablets. The high sensitivity of the proposed approach allows its application in evaluating the content uniformity testing of the studied drugs in their tablets through using the official United States Pharmacopeia criteria. Statistical analogies of the findings with that of the reported methods showed really good harmony and indicated no major differences in precision and accuracy.
Gulo gene locus, a new gene editing locus for mammalian cells
Authors: Habu Toshiyuki , Ishikawa Honoka , Kim Jiyeong
Published: April 2022

Transgene technology is valuable and helpful in many fields, including basic medical and biological research, biotechnology, and therapy. Recent advances in targeting technology accelerate the production of transgenic plants and animals and the application for gene therapy. To develop the technology, we examine the utility as the new safe harbor locus, l‐gulono‐γ‐lactone oxidase (Gulo) locus in human and mice. We performed experiments in vitro and in vivo knockout and knockin mouse and cell lines to validate their applicability using these loci. The Gulo locus might be good candidates for safe harbor loci for transgenic research.
You have to give power to empower your team
Authors: Skipworth Stan
Published: April 2022

A familiar adage suggests that “You have to spend money to make money.” While there is a good amount of truth in this statement, the reality is that there are some who can have much simply given to them and yet they may not have the skills to augment their resources beyond that point. Spending money does not always lead to making money. Conversely, when it comes to power, we might see a purer form of the premise that using one's resources can create more.
Did court dismiss student's Title IX claim?
Authors: Lyerly Eric
Published: April 2022

Jane Doe was a member of Morgan State University's track and field team. In August 2017, another track athlete sexually assaulted Doe in her residence hall room. Doe's mother learned of the assault the following month and reported it to the university's athletics director.
Consider the benefits of informal, restorative solutions to allegations of harm
Authors: Sutton Halley
Published: April 2022

Your campus may already have measures in place to offer alternative resolution processes. But in case you're not familiar with alternative resolution processes (to be used in lieu of, or in conjunction with, disciplinary or punitive processes), you might consider the possibilities that such reflective and educational opportunities might offer your campus.
Report from Secret Service documents growing threats against women
Authors: Sutton Halley
Published: April 2022

A report released by the federal government outlines growing terrorism attacks against women by so‐called “anti‐feminists” or “involuntary celibates.” These are typically groups of men who commit acts of violence motivated at least in part by their inability to develop relationships with women.
Visible Light‐Driven Carboxylation of Olefins by Using 2D Metal‐Free Covalent Organic Framework as Intrinsic Photocatalyst: A Sustainable Approach for CO2 Utilization
Authors: Sarkar Priyanka , Das Anjan , Ghosh Swarbhanu , Manirul Islam Sk.
Published: April 2022

Photocatalytic metal‐free carboxylation of olefins offers an environment‐friendly approach for resolving the increasing energy issue as well as mitigating the dilemma caused by the greenhouse effect. Carboxylation of styrene and its derivatives by photocatalytic CO2 reduction reaction shows great potential for sustainable utilization of greenhouse gas CO2 into valuable chemicals. Herein, we have constructed a highly crystalline and thermally stable 2D porous covalent organic framework (COF) having very low band‐gap energy, 1.8 eV and it shows efficient photocatalytic activity towards the carboxylation of aryl‐alkenes in good yields in presence of p‐terphenyl as a co‐catalyst at ambient temperature under visible light irradiation and 1 atmospheric CO2 pressure which facilitates to overcome the current transition metal catalyzed approaches. In addition, TR‐OT COF is a proficient and highly selective catalyst with outstanding recyclability. This suggests that this COF material is a novel photocatalyst for CO2 reduction towards α, β‐carboxylation of styrene and its derivatives under 20 W light‐emitting diode (LED) light.
Materials Formed by Combining Inorganic Glasses and Metal‐Organic Frameworks
Authors: Chester Ashleigh M. , Castillo‐Blas Celia , Wondraczek Lothar , Keen David A. , Bennett Thomas D.
Published: April 2022

Here, we propose the combination of glassy or crystalline metal‐organic frameworks (MOFs) with inorganic glasses to create novel hybrid composites and blends.The motivation behind this new composite approach is to improve the processability issues and mechanical performance of MOFs, whilst maintaining their ubiquitous properties. Herein, the precepts of successful composite formation and pairing of MOF and glass MOFs with inorganic glasses are presented. Focus is also given to the synthetic routes to such materials and the challenges anticipated in both their production and characterisation. Depending on their chemical nature, materials are classified as crystalline MOF‐glass composites and blends. Additionally, the potential properties and applications of these two classes of materials are considered, the key aim being the retention of beneficial properties of both components, whilst circumventing their respective drawbacks.
A New Look at Molecular and Electronic Structure of Homoleptic Diiron(II,II) Complexes with N,N‐Bidentate Ligands: Combined Experimental and Theoretical Study
Authors: Korona Krzesimir , Terlecki Michał , Justyniak Iwona , Magott Michał , Żukrowski Jan , Kornowicz Arkadiusz , Pinkowicz Dawid , Kubas Adam , Lewiński Janusz
Published: April 2022

Paddlewheel‐type binuclear complexes featuring metal−metal bonding have been the subject of widespread interest due to fundamental concern in their electronic structures and potential applications. Here, we explore the molecular and electronic structures of diiron(II,II) complexes with N,N’‐diarylformamidinate ligands. While a paddlewheel‐type diiron(II,II) complex with N,N’‐diphenylformamidinate ligands (DPhF) exhibits the centrosymmetric [Fe2(μ‐DPhF)4] structure, a minor alteration in the ligand system, i. e., switching from phenyl to p‐tolyl N‐substituted formamidinate ligand (DTolF), resulted in the isolation of an unprecedented non‐centrosymmetric [Fe(μ‐DTolF)3Fe(κ2‐DTolF)] complex. Both complexes were characterized using single‐crystal X‐ray diffraction, magnetic measurements, 57Fe Mössbauer spectroscopy, and cyclic voltammetry along with high‐level ab‐initio calculations. The results provide a new view on a range of factors controlling the ground‐state electronic configuration and structural diversity of homoleptic diiron(II,II) complexes. Model calculations determined that the Mayer bond orders for Fe−Fe interactions are significantly lower than 1 and equal to 0.15 and 0.28 for [Fe2(μ‐DPhF)4] and [Fe(μ‐DTolF)3Fe(κ2‐DTolF)], respectively.
PROTOCOL: Occupational health and safety regulatory interventions to improve the work environment: An evidence and gap map of effectiveness studies
Authors: Bondebjerg Anja , Filges Trine , Pejtersen Jan H. , Viinholt Bjørn C. A. , Burr Hermann , Hasle Peter , Tompa Emile , Birkefoss Kirsten , Bengtsen Elizabeth
Published: April 2022

This is the protocol for a Campbell systematic review. The objectives are as follows: provide an overview of the existing evidence base by identifying available systematic reviews and primary effectiveness studies, identify clusters of evidence suitable for a systematic review and identify gaps in evidence where primary research is needed.
PROTOCOL: Systematic review of methods to reduce risk of bias in knowledge translation interventional studies in health‐related issues
Authors: Ahmadi Ayat , Yazdizadeh Bahareh , Doshmangir Leila , Majdzadeh Reza , Asghari Shabnam
Published: April 2022

Background

Review studies have reported on the low quality of study methodologies and poor reporting of knowledge translation (KT) interventional studies. This flaw cause the result of such studies to become misleading.

Objectives

The present review is designed to evaluate the effect of methodological factors on the results of interventional studies that aimed to evaluate KT strategies at the policy level.

Search Methods

Bibliographic databases and grey literature databases will be searched. The retrieved studies will be recorded in Covidence. After screening titles and abstracts, the full texts of selected studies will be assessed against the inclusion criteria. Disagreements will be resolved through discussion or by consultation with a third author.

Selection Criteria

Primary studies are studies that aimed to estimate the efficacy of KT strategies to improve evidence‐informed policymaking. Study participants include policymakers and the intervention is a KT strategy. The main outcome is the desired changes in policy‐makers towards evidence‐informed decision‐making.

Data Collection and Analysis

The main effect sizes will be expressed as standard mean difference and its variance for the main efficacy outcome of KT strategies in primary studies. Forest plot meta‐analysis will be used to synthesize the effect of each group of KT strategies. The contribution of ROB to the efficacy of KT interventions will be assessed via Meta‐epidemiology analysis. The overall estimate will be calculated using inverse‐variance random‐effects meta‐analysis with a 95% confidence interval for the estimate.
Monosubstitution of 1H‐Imidazo[4,5‐f][1,10]phenanthroline Ligands Yields Maximum Luminescence Quantum Yield in Ruthenium Polypyridyl Complexes
Authors: Lämmle Martin , Bagemihl Benedikt , Nauroozi Djawed , Petermann Lydia , Pannwitz Andrea , Rau Sven
Published: April 2022

Six different monoarylated N‐aryl‐1H‐imidazo[4,5‐f][1,10]phenanthroline (Rip) ligands and their corresponding ruthenium complexes [(tbbpy)2Ru(Rip)]2+ Ru(Rip) have been synthesized bearing different aryl substituents on the imidazole unit including electron donating and accepting groups. N,N’‐disubstitution on the imidazole unit yielded five new 1‐aryl‐3‐benzyl‐1H‐imidazo[4,5‐f][1,10]phenanthrolinium bromide (RR'ip)+ ligands and the corresponding ruthenium complexes [(tbbpy)2Ru(RR'ip)]3+ Ru(RR'ip). All complexes were characterized in terms of their structural, photophysical, photochemical and electrochemical properties. The photophysical data revealed a high luminescence quantum yield (21.6–22.8 %) for monoarylated Ru(Rip) complexes compared to [Ru(bpy)3]2+ (9.5 %) under inert conditions. Generating the imidazolium unit, yielding Ru(RR'ip)‐complexes lead to notable loss of quantum yields. Furthermore, we observed an enhanced photostability of Ru(RR'ip) complexes in the case of ortho substituted aryl groups.
Shikonin attenuates kidney tubular epithelial cells apoptosis, oxidative stress, and inflammatory response through nicotinamide adenine dinucleotide phosphate oxidase 4/PTEN pathway in acute kidney injury of sepsis model
Authors: Peng Yanqin , Li Yuan , Li Hao , Yu Junhua
Published: April 2022

Natural compounds were used in the treatment of acute kidney injury (AKI) caused by sepsis. This study investigated the function of shikonin from the roots of Arnebia purpurea in sepsis‐induced AKI model. The target genes of shikonin were predicted by traditional Chinese medicine integrative database (TCMID). The markers of kidney injury, oxidative stress, and inflammatory factors were measured by enzyme‐linked immunosorbent assay (ELISA). The pathological changes of kidney tubules were assessed by Hematoxylin and Eosin staining. Apoptosis of kidney tubular epithelial cells (KTECs) was detected by the terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling. Protein expression was measured by western blot. Shikonin significantly improved kidney injury induced by cecal ligation and perforation (CLP). Besides, shikonin reduced KTECs apoptosis, malondialdehyde (MDA), reactive oxygen species (ROS), interleukin‐1β (IL‐1β), IL‐6, and tumor necrosis factor‐α (TNF‐α) levels, while augmented SOD and IL‐10 levels. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase4 (NOX4) was predicted a target gene of shikonin. The expression of NOX4 was significantly inhibited in shikonin‐treated group and the levels of phosphatidylinositol 3,4,5‐trisphosphate 3‐phosphate and dual specificity protein phosphate (PTEN) and p‐p65 were decreased, while level of p‐Akt was elevated. In vitro experiments, shikonin inhibited cell apoptosis, inflammatory, and ROS in human HK‐2 cells and rat TECs. Shikonin downregulated expression of NOX4, PTEN and p‐p65, and upregulated p‐AKT and Bcl‐2 expression in HK2 cells treated with lipopolysaccharide (LPS). Moreover, overexpression of NOX4 enhanced the effect of LPS on the expression level of PTEN, p‐p65, p‐AKT, and Bcl‐2, which was reversed by the addition of shikonin. Taken together, shikonin could improve sepsis‐induced AKI in rats, and attenuate the LPS induced KTECs apoptosis, oxidative stress, and inflammatory reaction via modulating NOX4/PTEN/AKT pathway.
Easy and convenient millimole‐scale synthesis of new, potential biomarkers for gamma‐hydroxybutyric acid (GHB) intake: Feasible for analytical laboratories
Authors: Steuer Christian , Quattrini Dario , Raeber Justine , Waser Philipp , Steuer Andrea E.
Published: April 2022

New biomarkers indicating the abuse of drugs and alcohol are still of major interest for clinical and forensic sciences. The endogenous neurotransmitter and approved drug, gamma‐hydroxybutyric acid (GHB), is often illegally used for drug‐facilitated crimes by spiking GHB into alcoholic beverages. Analytical detection windows of only 6 h in blood and 12 h in urine are often too short to provide reliable proof of GHB ingestion. Therefore, new biomarkers are needed to prove exogenous GHB administration. Previously, amino acid GHB conjugates were discovered in an untargeted metabolomics screening and fatty acid esters with GHB were recently discussed as promising biomarkers to enlarge the analytical detection time windows. However, the development of analytical methods is still slowed down since reference compounds for targeted screenings are still missing. In this paper, we describe simple procedures for the rapid synthesis and purification of amino acid GHB conjugates as well as fatty acid esters, which can be adopted in analytical and clinical/forensic laboratories. Structural characterization data, together with IR, 1H‐nuclear magnetic resonance (NMR), 13C‐NMR, high‐resolution mass spectra (MS), and MS/MS spectra in positive and negative ionization mode are reported for all obtained GHB conjugates and GHB conjugate precursors.
Food deprivation exposes sex‐specific trade‐offs between stress tolerance and life span in the copepod Tigriopus californicus
Authors: Li Ning , Flanagan Ben A. , Edmands Suzanne
Published: April 2022

Long life is standardly assumed to be associated with high stress tolerance. Previous work shows that the copepod Tigriopus californicus breaks this rule, with longer life span under benign conditions found in males, the sex with lower stress tolerance. Here, we extended this previous work, raising animals from the same families in food‐replete conditions until adulthood and then transferring them to food‐limited conditions until all animals perished. As in previous work, survivorship under food‐replete conditions favored males. However, under food deprivation life span strongly favored females in all crosses. Compared to benign conditions, average life span under nutritional stress was reduced by 47% in males but only 32% in females. Further, the sex‐specific mitonuclear effects previously found under benign conditions were erased under food limited conditions. Results thus demonstrate that sex‐specific life span, including mitonuclear interactions, are highly dependent on nutritional environment.
Divergence in gut bacterial community between females and males in the wolf spider Pardosa astrigera
Authors: Gao Ying , Wu Pengfeng , Cui Shuyan , Ali Abid , Zheng Guo
Published: April 2022

Sex is one of the important factors affecting gut microbiota. As key predators in agroforestry ecosystem, many spider species show dramatically different activity habits and nutritional requirements between females and males. However, how sex affects gut microbiota of spiders remains unclear. Here, we compared the composition and diversity of gut bacteria between female and male Pardosa astrigera based on bacterial 16S rRNA gene sequencing. Results showed that the richness of bacterial microbiota in female spiders was significantly lower than in male spiders (p < .05). Besides, β‐diversity showed a significant difference between female and male spiders (p = .0270). The relative abundance of Actinobacteriota and Rhodococcus (belongs to Actinobacteriota) was significantly higher in female than in male spiders (p < .05), whereas the relative abundance of Firmicutes and Acinetobacter (belongs to Proteobacteria) and Ruminococcus and Fusicatenibacter (all belong to Firmicutes) was significantly higher in male than in female spiders (p < .05). The results also showed that amino acid and lipid metabolisms were significantly higher in female than in male spiders (p < .05), whereas glycan biosynthesis and metabolism were significantly higher in male than in female spiders (p < .05). Our results imply that sexual variation is a crucial factor in shaping gut bacterial community in P. astrigera spiders, while the distinct differences of bacterial composition are mainly due to their different nutritional and energy requirements.
Predicting distributions of Wolbachia strains through host ecological contact—Who's manipulating whom?
Authors: Darwell Clive T. , Souto‐Vilarós Daniel , Michalek Jan , Boutsi Sotiria , Isua Brus , Sisol Mentap , Kuyaiva Thomas , Weiblen George , Křivan Vlastimil , Novotny Vojtech , Segar Simon T.
Published: April 2022

Reproductive isolation in response to divergent selection is often mediated via third‐party interactions. Under these conditions, speciation is inextricably linked to ecological context. We present a novel framework for understanding arthropod speciation as mediated by Wolbachia, a microbial endosymbiont capable of causing host cytoplasmic incompatibility (CI). We predict that sympatric host sister‐species harbor paraphyletic Wolbachia strains that provide CI, while well‐defined congeners in ecological contact and recently diverged noninteracting congeners are uninfected due to Wolbachia redundancy. We argue that Wolbachia provides an adaptive advantage when coupled with reduced hybrid fitness, facilitating assortative mating between co‐occurring divergent phenotypes—the contact contingency hypothesis. To test this, we applied a predictive algorithm to empirical pollinating fig wasp data, achieving up to 91.60% accuracy. We further postulate that observed temporal decay of Wolbachia incidence results from adaptive host purging—adaptive decay hypothesis—but implementation failed to predict systematic patterns. We then account for post‐zygotic offspring mortality during CI mating, modeling fitness clines across developmental resources—the fecundity trade‐off hypothesis. This model regularly favored CI despite fecundity losses. We demonstrate that a rules‐based algorithm accurately predicts Wolbachia infection status. This has implications among other systems where closely related sympatric species encounter adaptive disadvantage through hybridization.
Hybrid Ni2P/CoP Nanosheets as Efficient and Robust Electrocatalysts for Domestic Wastewater Splitting
Authors: Tan Yeshu , Feng Jianrui , Kang Liqun , Liu Longxiang , Zhao Fangjia , Zhao Siyu , Brett Dan J.L. , Shearing Paul R. , He Guanjie , Parkin Ivan P.
Published: April 2022

The development of low‐cost, robust and efficient non‐noble metal electrocatalysts is still a pursuit for the hydrogen evolution reaction (HER). Herein, a self‐standing electrocatalyst, Ni2P/CoP nanosheet, was fabricated directly on three‐dimensional Ni foams by two facile steps, which illustrated both high activity and stability for HER in different electrolytes. Benefiting from the porous structures of nanosheets with large specific surface area and the hybrid Ni2P/CoP, the as‐prepared electrocatalyst presented remarkable HER with overpotentials of 65.2 and 87.8 mV to reach a current density of −10 mA cm−2 in neutral and alkaline media, respectively. Density function theory calculations revealed a lower activation energy of water dissociation and efficient HER steps of hybrid Ni2P/CoP nanosheets compared with mono CoP. The self‐standing electrocatalyst maintained excellent chemical stability. Additionally, the HER process in domestic wastewater was realized with more impressive performance by using Ni2P/CoP nanosheets compared with commercial Pt/C. Hydrogen was continuously generated for 20 h in mildly alkaline dishwashing wastewater. This work provides a feasible way to fabricate non‐noble metal and self‐standing hybrid bimetallic phosphides for HER in neutral and alkaline media, showing great potential for efficient hydrogen production by re‐utilizing wastewater resources.
The EPICTER score: a bedside and easy tool to predict mortality at 6 months in acute heart failure
Authors: Romero‐Correa Miriam , Salamanca‐Bautista Prado , Bilbao‐González Amaia , Quirós‐López Raul , Nieto‐Martín Maria Dolores , Martín‐Jiménez María Luisa , Morales‐Rull José Luis , Quiles‐García Dolores , Gómez‐Gigirey Adriana , Formiga Francesc , Aramburu‐Bodas Óscar , Arias‐Jiménez José Luis ,   the EPICTER Investigators group
Published: April 2022

Aims

Estimating the prognosis in heart failure (HF) is important to decide when to refer to palliative care (PC). Our objective was to develop a tool to identify the probability of death within 6 months in patients admitted with acute HF.

Methods and results

A total of 2848 patients admitted with HF in 74 Spanish hospitals were prospectively included and followed for 6 months. Each factor independently associated with death in the derivation cohort (60% of the sample) was assigned a prognostic weight, and a risk score was calculated. The accuracy of the score was verified in the validation cohort. The characteristics of the population were as follows: advanced age (mean 78 years), equal representation of men and women, significant comorbidity, and predominance of HF with preserved ejection fraction. During follow‐up, 753 patients (26%) died. Seven independent predictors of mortality were identified: age, chronic obstructive pulmonary disease, cognitive impairment, New York Heart Association class III–IV, chronic kidney disease, estimated survival of the patient less than 6 months, and acceptance of a palliative approach by the family or the patient. The area under the ROC curve for 6 month death was 0.74 for the derivation and 0.68 for the validation cohort. The model showed good calibration (Hosmer and Lemeshow test, P value 0.11). The 6 month death rates in the score groups ranged from 6% (low risk) to 54% (very high risk).

Conclusions

The EPICTER score, developed from a prospective and unselected cohort, is a bedside and easy‐to‐use tool that could help to identify high‐risk patients requiring PC.
A neuroimaging study of interpersonal distance in identical and fraternal twins
Authors: Rosén Jörgen , Kastrati Granit , Kuja‐Halkola Ralf , Larsson Henrik , Åhs Fredrik
Published: April 2022

Keeping appropriate interpersonal distance is an evolutionary conserved behavior that can be adapted based on learning. Detailed knowledge on how interpersonal space is represented in the brain and whether such representation is genetically influenced is lacking. We measured brain function using functional magnetic resonance imaging in 294 twins (71 monozygotic, 76 dizygotic pairs) performing a distance task where neural responses to human figures were compared to cylindrical blocks. Proximal viewing distance of human figures was compared to cylinders facilitated responses in the occipital face area (OFA) and the superficial part of the amygdala, which is consistent with these areas playing a role in monitoring interpersonal distance. Using the classic twin method, we observed a genetic influence on interpersonal distance related activation in the OFA, but not in the amygdala. Results suggest that genetic factors may influence interpersonal distance monitoring via the OFA whereas the amygdala may play a role in experience‐dependent adjustments of interpersonal distance.
LncRNA FIRRE stimulates PTBP1‐induced Smurf2 decay, stabilizes B‐cell receptor, and promotes the development of diffuse large B‐cell lymphoma
Authors: Liu Qin‐Hua , Dai Guan‐Rong , Wu Yi , Wang Xiao‐Nan , Song Ming‐Yue , Li Xiao‐Dan , Wu Zhengsheng , Xia Rui‐Xiang
Published: April 2022

Sustained expression of B‐cell receptor (BCR) critically contributes to the development of diffuse large B‐cell lymphoma (DLBCL). However, little is known on the mechanism regulating BCR expression. In the present study, we explored the biological significance of functional intergenic repeating RNA element (FIRRE) in DLBCL and its regulation on BCR. Functional impacts of FIRRE on cell viability, transformation, and apoptosis were examined by MTT, colony formation, and flow cytometry, respectively. The interaction between FIRRE and polypyrimidine tract binding protein 1 (PTBP1) was identified by RNA pull‐down and verified using RNA immunoprecipitation (RIP) assays. The effects of FIRRE and PTBP1 on Smurf2 mRNA were examined by RIP, RNA pull‐down, and mRNA stability assays. Smurf2‐mediated BCR ubiquitination was investigated using co‐immunoprecipitation, ubiquitination, and protein stability assays. In vivo, xenograft models were used to assess the impacts of targeting FIRRE on DLBCL growth. FIRRE was specifically up‐regulated in and essentially maintained multiple malignant behaviors of BCR‐dependent DLBCL cells. Through the interaction with PTBP1, FIRRE promoted the mRNA decay of Smurf2, a ubiquitin ligase for the degradation BCR protein. Targeting FIRRE was sufficient to regulat Smurf2 and BCR expressions and inhibit DLBCL malignancy both in vivo and in vitro. FIRRE‐PTBP1 interaction, by simulating Smurf2 mRNA decay and stabilizing BCR, promotes the development of DLBCL. Consequently, targeting this signaling mechanism may provide therapeutic benefits for DLBCL.
The cardioprotective effects of perindopril in a model of polymicrobial sepsis: The role of radical oxygen species and the inflammation pathway
Authors: Topcu Atilla , Kostakoglu Ugur , Mercantepe Tolga , Yilmaz Hulya K. , Tumkaya Levent , Uydu Huseyin A.
Published: April 2022

Mortality rates associated with myocardial dysfunction due to sepsis and septic shock are generally high across the world. The present study focused on the antioxidant and anti‐inflammatory effects of perindopril (PER) for the purpose of preventing the adverse effects of sepsis on the myocardium and developing new alternatives in treatment. The control group received only saline solution via the oral route for 4 days. The second group underwent cecal ligation puncture (CLP), and the third underwent CLP and received PER (2 mg/kg). Rats in the third group received 2 mg/kg PER per oral (p.o.) from 4 days before induction of sepsis. Thiobarbituric acid reactive species (TBARS), total thiol (‐SH), interleukin‐1 beta (IL‐1β), IL‐6, 8‐hydroxy‐2′‐deoxyguanosine (8‐OHdG), and nuclear factor kappa B (NF‐κB/p65) levels increased in the CLP groups. In contrast, PER (2 mg/kg) decreased the levels of biochemical parameters other than total‐SH and decreased 8‐OHdG, NF‐κB/p65 immunopositivity in rat heart tissues. The data from this study show that impairment of the oxidant/antioxidant balance and inflammatory cytokine levels in favor of inflammation in heart tissue under septic conditions results in severe tissue damage. PER administration before sepsis was shown to exhibit antioxidant and anti‐inflammatory properties by reducing these effects. This in turn increased the importance of PER as new evidence of its protective effects in heart tissue.
Impairment of transcription factor Gcr1p binding motif perturbs OPI3 transcription in Saccharomyces cerevisiae
Authors: Chidambaram Ravi , Ramachandran Gowsalya , Rajasekharan Ram , Nachiappan Vasanthi
Published: April 2022

In Saccharomyces cerevisiae, the transcription factor GCR1 plays a vital role in carbohydrate metabolism and in the current study we tried to elucidate its role in lipid metabolism. In silico analysis revealed the upstream activation sequence (UAS) in the promoter region of OPI3 possessed six conserved recognition sequences for Gcr1p and the ChIP assay confirmed the binding of Gcr1p on the OPI3 promoter region. The real‐time quantitative polymerase chain reaction and promoter–reporter activity revealed a substantial reduction in OPI3 expression and was supported with decreased phosphatidylcholine (PC) level that is rescued with exogenous choline supplementation in gcr1∆ cells. Simultaneously, there was an increase in triacylglycerol level, accompanied with increased number and size of lipid droplets in gcr1∆ cells. The expression of pT1, pT2 truncations in opi3∆ cells revealed the −1 to −500 bp in the promoter region is essential for the activation of OPI3 transcription. The mutation specifically at UASCT box (−265) in the OPI3 promoter region displayed a reduction in the PC level and the additional mutation at UASINO (−165) further reduced the PC level. Collectively, our data suggest that the GCR1 transcription factor also regulates the OPI3 expression and has an impact on lipid homeostasis.
The impact of psychological hardiness on intolerance of uncertainty in university students during the COVID‐19 pandemic
Authors: Oral Meltem , Karakurt Nurgül
Published: April 2022

The purpose of the study was to measure the impact of psychological hardiness on the intolerance of uncertainty (IOU) among university students during the coronavirus disease 2019 (COVID‐19) pandemic. A cross‐sectional correlational research design was used in the study, where participants were selected by convenience sampling. The data was collected from 1217 undergraduate students from a university in Turkey through web‐based questionnaires. The Intolerance of Uncertainty Scale assessed data, including intolerance of uncertainty. In addition, the Personal Views Survey III‐R was used to measure students' psychological hardiness. The results indicated that Turkish undergraduate students overall had high IOU and above‐average psychological hardiness. Psychological hardiness was negatively correlated with IOU. Students losing a loved one because of COVID‐19 had increased intolerance to uncertainty and lower psychological hardiness. Psychological hardiness was a powerful predictor of IOU. These findings show the need to implement hardiness‐training programs for undergraduate students to increase their tolerance to uncertainty and reduce the effect of grief.
Mixotrophic flagellate ingestion boosts microplastic accumulation in ascidians
Authors: Pennati Roberta , Castelletti Chiara , Parolini Marco , Scarì Giorgio , Mercurio Silvia
Published: April 2022

Microplastics are contaminants of global environmental concern. They can be ingested by a variety of organisms when they enter the food web. Several studies have reported trophic transfer of microplastics from low trophic levels to higher ones. Bioaccumulation has been suggested to occur but few studies have demonstrated it for marine environments. In this article, in controlled laboratory conditions, we exposed filter‐feeder ascidian juveniles to microplastics in the presence or in absence of mixotrophic cryptomonad flagellates. Cryptomonads can efficiently ingest microbeads, and their presence significantly increased the concentration of microplastics in the digestive tract of the ascidians. Our results demonstrate the occurrence of microplastic bioaccumulation in the lower levels of the marine trophic chain and suggest that unicellular organisms can be key actors in microplastic trophic transfer at the microscale level.
Rapid and quantitative evaluation of vaccinia virus‐induced host shutoff using newly generated cell lines stably expressing secreted Gaussia luciferase
Authors: Molina Joshua A. , Yang Zhilong
Published: April 2022

Host shutoff, characterized by a global decline of cellular protein synthesis, is commonly observed in many viral infections, including vaccinia virus (VACV). Classic methods measuring host shutoff include the use of radioactive or nonradioactive probes to label newly synthesized proteins followed by radioautography or sodium dodecyl‐sulfate polyacrylamide gel electrophoresis to resolve the proteins for follow‐up detection. Although these are highly reliable methods, they are time‐ and labor‐consuming. Here, we generated two cell lines stably expressing secreted Gaussia luciferase. These reporter cells allow rapid, quantitative, and consecutive monitoring of host shutoff from a single infection sample. We evaluated host shutoff induced by wild‐type and various mutant VACVs using the reporter cell lines. The results validated the utilities of the reporter cells and quantitatively characterized VACV‐induced host shutoff at different stages of replication. Notably, the results also indicated additional major unidentified VACV shutoff factors. Our study provides new tools to study host shutoff. The reporter cells are also suitable for high throughput settings and rapid testing of clinically isolated viruses. In combination with classical methods, these tools will greatly facilitate understanding of virus‐induced host shutoff, and protein synthesis shutoff caused by other physiologically relevant stresses.
Development of an effective and safe system for bioavailability of vitamin E supplements in the stomach
Authors: Kouchi Mandana Moradi , Amani Hossein , Naseri Ali , Kariminezhad Hasan
Published: April 2022

Vitamin E deficiency has caused many problems for humans, especially patients who have difficulty absorbing this substance in their meals. Vitamin E supplements are commonly suggested to patients to solve these problems. Thus, improving the bioavailability of vitamin E in O/W microemulsions is one of the challenges for researchers. Another challenge is the safe production of these materials which must be considered. Using biosurfactants instead of surfactants is a move towards green and safe production and consumption of these materials. This paper discusses method of preparing vitamin E microemulsions by using a crude biosurfactant from Yarrowia lipolytica IMUFRJ50628. In this work, maximal crude biosurfactant concentration 3.3 g/L was attained after 130 h of cultivation and the crude biosurfactant was characterized by FTIR analysis. Phase diagram of bio‐ based microemulstions (water/vitamin E/soy bean oil/lecithin/biosurfactant) was compared with chemical‐based microemulstions (water/vitamin E/soy bean oil/lecithin/Tween 80). The results showed that the crude biosurfactant is a good alternative to the Tween 80 for green production consideration. Dynamic light scattering measurements for the both systems showed they were stable under human stomach conditions such as 37°C and pH = 2 for 7 days. Our successful method for preparing a bio‐ based O/W microemulsion confirmed that biosurfactants can be used instead of surfactants from chemical synthesis and it is thought that the incorporation of biosurfactants may be widely used in the future as a vehicle for vitamin E in the pharmaceutical and food industries.
High‐resolution water‐quality and ecosystem‐metabolism modeling in lowland rivers
Authors: Pathak Devanshi , Hutchins Michael , Brown Lee E. , Loewenthal Matthew , Scarlett Peter , Armstrong Linda , Nicholls David , Bowes Mike , Edwards François , Old Gareth
Published: April 2022

High‐resolution monitoring of water quality and ecosystem functioning over large spatial scales in expansive lowland river catchments is challenging. Therefore, we need modeling tools to predict these processes at locations where observations are absent. Here, we present a new approach to estimate ecosystem metabolism underpinned by a high‐resolution, process‐based model of in‐stream flows and water quality. The model overcomes the current challenges in metabolism modeling by accounting for oxygen transport under varying flows and oxygen transformations due to biogeochemical processes. We implement the model in a 62‐km‐long stretch of the River Thames, England, using observations spanning 2 yr. Model outputs suggest that the river is primarily autotrophic from mid‐spring to mid‐summer due to high biomass during low‐flow periods, and is heterotrophic during the rest of the year. Ecosystem respiration in upstream reaches is driven mainly by biochemical oxygen demand, autotrophic respiration, and nitrification processes, whereas downstream sites also show a control of benthic oxygen demand in addition to the aforementioned processes. Using empirical modeling, we analyze the sensitivity of our estimated metabolism rates to multiple environmental stressors. Results demonstrate that empirical models could be useful for rapid river health assessments, but need improvements to reproduce peak metabolism rates. The process‐based model, although more complex than existing in situ approaches to metabolism quantification, allows inference when gaps in continuous observations are present. The model offers additional benefits for predicting metabolism rates under future scenarios of environmental change incorporating multiple stressor effects.
Concomitant knockout of target and transporter genes in filamentous fungi by genome co‐editing
Authors: Tamano Koichi
Published: April 2022

In most countries, genetically modified microorganisms are not approved for use for fermentation in the food industry. Therefore, random mutagenesis and subsequent screening are performed to improve the productivities of valuable metabolites and enzymes as well as other specific functions in an industrial microbial strain. In addition, targeted gene knockout is performed by genetic recombination using its enzyme genes as selectable markers to maintain self‐cloning status. However, random mutagenesis has a drawback as it does not guarantee improvement of the targeted function. Conversely, self‐cloning is rarely used to breed an industrial microbial strain. This is probably because a self‐cloning strain is similar to a genetically modified strain, as both undergo homologous recombination, although exogenous genes are not introduced. In this article, I discuss the usefulness of genome editing technology as a substitute for conventional techniques to breed filamentous fungal strains. This article particularly focusses on “genome co‐editing,” a genome editing technology used for knocking out two genes concomitantly, as reported in Magnaporthe grisea and Aspergillus oryzae. Especially, when genome co‐editing is applied to a target gene and a membrane transporter gene that aid the entry of toxic compounds into cells, the resulting clone can be categorized as an autotrophic and non‐genetically modified clone. Such a clone should easily apply to industrial fermentation without being restricted by a genetically modified status. Genome co‐editing will also be used to construct mutant strains with multiple target gene knockouts by eliminating multiple membrane transporter genes. This could substantially improve the productivities of valuable metabolites and enzymes in a stepwise manner. Thus, genome co‐editing is considered a potentially powerful method to knock out single or multiple target genes that can contribute to the breeding of filamentous fungal strains in the food industry.
Epidermal growth factor receptor signaling in precancerous keratinocytes promotes neighboring head and neck cancer squamous cell carcinoma cancer stem cell‐like properties and phosphoinositide 3‐kinase inhibitor insensitivity
Authors: Nguyen Khoa A. , Keith Madison J. , Keysar Stephen B. , Hall Spencer C. , Bimali Anamol , Jimeno Antonio , Wang Xiao‐Jing , Young Christian D.
Published: April 2022

Head and neck squamous cell carcinoma (HNSCC) is commonly associated with tobacco and alcohol consumption that induce a “precancerous field,” with phosphoinositide 3‐kinase (PI3K) signaling being a common driver. However, the preclinical effectiveness of PI3K inhibitors has not necessarily translated to remarkable benefit in HNSCC patients. Thus, we sought to determine how precancerous keratinocytes influence HNSCC proliferation, cancer stem cell (CSC) maintenance, and response to PI3K inhibitors. We used the NOK keratinocyte cell line as a model of preneoplastic keratinocytes because it harbors two frequent genetic events in HNSCC, CDKN2A promoter methylation and TP53 mutation, but does not form tumors. NOK cell coculture or NOK cell‐conditioned media promoted HNSCC proliferation, PI3K inhibitor resistance, and CSC phenotypes. SOMAscan‐targeted proteomics determined the relative levels of >1300 analytes in the media conditioned by NOK cells and HNSCC cells ± PI3K inhibitor. These results demonstrated that NOK cells release abundant levels of ligands that activate epidermal growth factor receptor (EGFR) and fibroblast growth factor receptor (FGFR), two receptor tyrosine kinases with oncogenic activity. Inhibition of EGFR, but not FGFR, blunted PI3K inhibitor resistance and CSC phenotypes induced by NOK cells. Our results demonstrate that precancerous keratinocytes can directly support neighboring HNSCC by activating EGFR. Importantly, PI3K inhibitor sensitivity was not necessarily a cancer cell‐intrinsic property, and the tumor microenvironment impacts therapeutic response and supports CSCs. Additionally, combined inhibition of EGFR with PI3K inhibitor diminished EGFR activation induced by PI3K inhibitor and potently inhibited cancer cell proliferation and CSC maintenance.