bluuebunny/crossref_metadata_2025 huggingface dataset:
GM1‐gangliosidosis: The caregivers' assessments of symptom impact and most important symptoms to treat
Authors: Bingaman Amanda , Waggoner Christine , Andrews Sara M. , Pangonis Diana , Trad Marie , Giugliani Roberto , Giorgino Ruben , Jarnes Jeanine , Vakili Rojan , Ballard Victoria , Peay Holly L.
Published: December 2022

GM1‐gangliosidosis (GM1) is a rare neurodegenerative disorder leading to early mortality and causing progressive decline of physical skills and cerebral functioning. No approved treatment for GM1 exists. In this study—the first to explore priorities of parents of subjects with pediatric onset forms of GM1—we address a crucial gap by characterizing symptoms most critical to caregivers of children with GM1 to treat. Our two‐part, mixed‐methods approach began with focus groups, followed by interviews with a distinct set of parents. Interviews included a prioritization activity that used best‐worst scaling. Quantitative data were analyzed descriptively. Qualitative data were analyzed using thematic analysis and rapid analysis process. Parents prioritized the symptoms they believed would increase their child's lifespan and improve their perceived quality of life (QoL); these symptoms focused on communicating wants/needs, preventing pain/discomfort, getting around and moving one's body, and enhancing eating/feeding. Although lifespan was highly valued, almost all parents would not desire a longer lifespan without acceptable child QoL. Parents indicated high caregiver burden and progressive reduction in QoL for children with GM1. This novel study of caregiver priorities identified important symptoms for endpoints' selection in patient‐focused drug development in the context of high disease impact and unmet treatment needs.
Utility of dual‐energy computed tomography in the association of COVID‐19 pneumonia severity
Authors: Michishita Takahiro , Saji Ryo , Miyazaki Hiroshi , Mishima Sena , Shimada Kosuke , Minami Sakura , Okano Hiromu , Suzuki Naoya , Otsuka Tsuyoshi , Abe Takeru , Takeuchi Ichiro , Furuya Ryosuke
Published: December 2022

Aim

Coronavirus disease 2019 pneumonia differs from ordinary pneumonia in that it is associated with lesions that reduce pulmonary perfusion. Dual‐energy computed tomography is well suited to elucidate the etiology of coronavirus disease 2019 pneumonia, because it highlights changes in organ blood flow. In this study, we investigated whether dual‐energy computed tomography could be used to determine the severity of coronavirus disease 2019 pneumonia.

Methods

Patients who were diagnosed with coronavirus disease 2019 pneumonia, admitted to our hospital, and underwent dual‐energy computed tomography were included in this study. Dual‐energy computed tomography findings, plane computed tomography findings, disease severity, laboratory data, and clinical features were compared between two groups: a critical group (18 patients) and a non‐critical group (30 patients).

Results

The dual‐energy computed tomography results indicated that the percentage of flow loss was significantly higher in the critical group compared with the non‐critical group (P < 0.001). Additionally, our data demonstrated that thrombotic risk was associated with differences in clinical characteristics (P = 0.018). Receiver operating characteristic analysis revealed that the percentage of flow loss, evaluated using dual‐energy computed tomography, could predict severity in the critical group with 100% sensitivity and 77% specificity. However, there were no significant differences in the receiver operating characteristic values for dual‐energy computed tomography and plane computed tomography.

Conclusion

Dual‐energy computed tomography can be used to associate the severity of coronavirus disease 2019 pneumonia with high accuracy. Further studies are needed to draw definitive conclusions.
Spektroskopische Eigenschaften eines biologisch‐relevanten [Fe2(μ‐O)2] Diamond‐Core‐Motivs mit einem kurzen Eisen‐Eisen‐Abstand
Authors: Kass Dustin , Yao Shenglai , Krause Konstantin B. , Corona Teresa , Richter Liza , Braun Thomas , Mebs Stefan , Haumann Michael , Dau Holger , Lohmiller Thomas , Limberg Christian , Drieß Matthias , Ray Kallol
Published: December 2022

Dieisen‐Kofaktoren in Enzymen vollziehen diverse anspruchsvolle Transformationen. Die Strukturen hoch‐valenter Intermediate (Q in der löslichen Methanmonooxygenase und X in der Ribonukleotidreduktase) sind Gegenstand aktueller Diskussionen, seit Fe‐Fe‐Abstände von 2.1–3.4 Å eine Zuordnung zu geöffneten und geschlossen Kernen mit verbrückenden oder terminalen Oxido‐Gruppen in den aktiven Zentren ermöglichen. In dieser Studie berichten wir die kristallografische und spektroskopische Charakterisierung eines FeIII2(μ‐O)2‐Komplexes (2) mit tetraedrischen (4C) Zentren sowie einem geringen Fe‐Fe‐Abstand (2.52 Å), der in Lösungsmitteln beständig ist. 2 zeigt eine große Fe‐K‐Vorkanten‐Intensität. Diese resultiert aus der starken Asymmetrie an den TD‐FeIII‐Zentren bedingt durch die kurzen Fe‐μ‐O‐Bindungen. Während ein Fe‐Fe‐Abstand von ≈2.5 Å für sechsfach‐koordinierte Zentren in Q und X unwahrscheinlich ist, könnte ein Fe2(μ‐O)2‐Kern mit vierfacher (oder möglicherweise auch fünffacher) Koordination flexibel genug sein, um eine kurze Fe‐Fe‐Separierung mit großer Vorkanten‐Intensität zu ermöglichen. Diese Erkenntnis kann dazu beitragen, dass weitere Modelle für die Strukturen der hoch‐valenten Dieisen‐Intermediate, die sich im Zuge der biologischen O2‐Aktivierung bilden, in Betracht gezogen werden.
Monitoring Transformations of Catalytic Active States in Photocathodes Based on MoSx Layers on CuInS2 Using In Operando Raman Spectroscopy
Authors: Chae Sang Youn , Yoon Noyoung , Joo Oh shim , Park Eun Duck
Published: December 2022

The electrochemical activation of CuInS2/MoSx for photoelectrochemical (PEC) H2 production was revealed for the first time through in operando Raman spectroscopy. During the activation process, the initial metallic MoSx phase was transformed to semiconducting MoSx, which facilitates charge carrier transfer between CuInS2 and MoSx. Ex situ X‐ray photoelectron spectroscopy and Raman spectroscopy suggest the existence of MoO3 after the activation process. However, apart from contradicting these results, in operando Raman spectroscopy revealed some of the intermediate steps of the activation process.
The Highly Controlled and Efficient Polymerization of Ethylene
Authors: Goller Alexander , Obenauf Johannes , Kretschmer Winfried P. , Kempe Rhett
Published: December 2022

The highly controlled and efficient polymerization of ethylene is a very attractive but challenging target. Herein we report on a Coordinative Chain Transfer Polymerization catalyst, which combines a high degree of control and very high activity in ethylene oligo‐ or polymerization with extremely high chain transfer agent (triethylaluminum) to catalyst ratios (catalyst economy). Our Zr catalyst is long living and temperature stable. The chain length of the polyethylene products increases over time under constant ethylene feed or until a certain volume of ethylene is completely consumed to reach the expected molecular weight. Very high activities are observed if the catalyst elongates 60 000 or more alkyl chains and the polydispersity of the strictly linear polyethylene materials obtained are very low. The key for the combination of high control and efficiency seems to be a catalyst stabilized by only one strongly bound monoanionic N‐ligand.
Impact of Mineralizing Agents on Aluminum Distribution and Acidity of ZSM‐5 Zeolites
Authors: Al‐Nahari Shadi , Dib Eddy , Cammarano Claudia , Saint‐Germes Etienne , Massiot Dominique , Sarou‐Kanian Vincent , Alonso Bruno
Published: December 2022

Intensive research on improving the catalytic properties of zeolites is focused on modulating their acidity and the distribution of associated Al sites. Herein, by studying a series of ZSM‐5 zeolites over a broad range of Al content, we demonstrate how the nature of the mineralizing agent (F− or OH−) used in hydrothermal syntheses directly impacts Al sites distribution. The proportions of Al sites, probed by 27Al NMR, depend on the Si/Al ratio for F−, but remain identical for OH− (from Si/Al=30 to 760). This leads to contrasting variations in weak and strong acidities. Such opposite effect of mineralizers is explained by the spatial location of negative charges and the resulting balance between short‐ and long‐range electrostatic interactions. This understanding paves the way for additional and simple opportunities to control zeolites’ acidity.
Expanded Conformations of Monomeric Tau Initiate Its Amyloidogenesis**
Authors: Fernández‐Ramírez María del Carmen , Ng Kevin Kan‐Shing , Menéndez Margarita , Laurents Douglas V. , Hervás Rubén , Carrión‐Vázquez Mariano
Published: December 2022

Understanding early amyloidogenesis is key to rationally develop therapeutic strategies. Tau protein forms well‐characterized pathological deposits but its aggregation mechanism is still poorly understood. Using single‐molecule force spectroscopy based on a mechanical protection strategy, we studied the conformational landscape of the monomeric tau repeat domain (tau‐RD244‐368). We found two sets of conformational states, whose frequency is influenced by mutations and the chemical context. While pathological mutations Δ280K and P301L and a pro‐amyloidogenic milieu favored expanded conformations and destabilized local structures, an anti‐amyloidogenic environment promoted a compact ensemble, including a conformer whose topology might mask two amyloidogenic segments. Our results reveal that to initiate aggregation, monomeric tau‐RD244‐368 decreases its polymorphism adopting expanded conformations. This could account for the distinct structures found in vitro and across tauopathies.
Visible light‐induced metal‐free atom transfer radical (co)polymerization of maleimides using commercial organocatalysts
Authors: Liao Daohong , Chen Ao , Pang Wenmin , Tan Chen , Bashir Muhammad Sohail
Published: December 2022

Metal‐free photocontrolled atom transfer radical polymerization (ATRP) has recently received increasing attention due to its ability to avoid heavy metal contamination. However, the polymerization of 1,2‐disubstituted olefin monomers by photocontrolled ATRP has rarely been reported. In this contribution, visible light‐induced metal free atom transfer radical (co)polymerization of maleimides (MI) by using several commercial organocatalysts was investigated in both batch and continuous flow processes. It was shown that the combination of the commercial dye eosin Y (EY) and cocatalyst N,N′,N′,N″,N″‐pentamethyldiethylenetriamine (PMDETA) can mediate controlled and selective ATRP of various N‐alkyl substituted MI monomers. The effect of polymerization time, initiators and catalysts are discussed. The results revealed that molecular weight (Mn) of the obtained polymers was increased by increase in monomers conversion with their narrow polydispersities (PDI ≤1.2). MIs alternating copolymerization with styrenes (St) under irradiation of visible light was also done which generated the polymaleimide resins with ultrahigh glass transition temperatures (Tg up to 259°C). Moreover, continuous flow process was also used for the co‐polymerization of MI and St by using a tubular reactor to get polymaleimide resins. Thus, this work provides an effective strategy to obtain copolymers of MI monomers and styrenes via both batch and continuous flow processes, enabling technical advantages for potential large‐scale applications.
Frequency analysis of random fatigue: Setup for an experimental study
Authors: Sgamma Michele , Chiocca Andrea , Bucchi Francesco , Frendo Francesco
Published: December 2022

The frequency‐domain approach to fatigue life estimation in random loading has been largely investigated due to its computational advantages, and several methods for the frequency translation of the most common time‐domain methods have been proposed. Between the most known frequency methods, there are Bendat's method, valid for narrow‐band signals, and Dirlik's formula, which ifis considered the best result for wide‐band signals. However, a great part of the frequency methods takes the rainflow count as a reference time‐domain method and uses the rainflow damage computation as the exact value to emulate. Therefore, very few experimental data for the fatigue life of mechanical components subject to random loads are available in the literature. This work presents the setup for a series of experimental tests for specimens subjected to random loads, aiming at achieving experimental data to compare with the results provided by frequency methods. After a brief description of the materials used for the setup, the two‐step test concept is described: first, the specimen will be subjected to random loads obtained by a certain power spectral density for an amount of time which should nominally cause a 30% of damage; then, the fatigue test will be ended on a resonance testing machine to compute the actual residual fatigue life of the specimen; this two‐step testing also allows to reduce the time requested for the tests. The test bench developed for the experimental investigation is described in the paper, together with the results of some preliminary tests, aimed at verifying the feasibility of the conceived procedure.
Sequential Methods for Di‐ and Tetrahydro‐Pyranone Synthesis Enable Concise Access to Tuscolid δ‐Lactone
Authors: Gao Xin , Menche Dirk
Published: December 2022

Two novel tandem sequences for stereoselective synthesis of elaborate hydropyranones are reported. The first one relies on an aldol‐lactonization procedure of a chiral enolate with an unprotected aldehyde, while the second one is based on a challenging dienolate ketone addition with concomitant cyclization and substrate controlled reduction. Both approaches proceed with high efficiency and stereoselectivity and enable very short accesses to the authentic pyranone subunit of the complex polyketide tuscolid and will be important to develop a first total synthesis of this structurally unique macrolide and to evaluate the tuscolid‐tuscoron rearrangement.
Analysis of polymeric nanoparticle properties for siRNA/DNA delivery in a tumor xenograft tissue slice air–liquid interface model
Authors: Karimov Michael , Scherer Marlene , Franke Heike , Ewe Alexander , Aigner Achim
Published: December 2022

Background

Classical two‐dimensional (2D) cell culture as a drug or nanoparticle test system only poorly recapitulates in vivo conditions. Animal studies are costly, ethically controversial, and preclude large‐scale testing.

Methods and Results

We established a three‐dimensional (3D) tissue slice air–liquid interface (ALI) culture model for nanoparticle testing. We developed an optimized procedure for the reproducible generation of large sets of tissue slices from tumor xenografts that retain their tissue architecture. When used for the analysis of nanoparticles based on chemically modified polyethylenimines (PEIs) to deliver siRNA or DNA, differences in transfection efficacy and cytotoxicity between nanoparticles were observed more clearly than in 2D cell culture. While nanoparticle efficacies between cell culture and the tissue slice model overall correlated, the tissue slice model also identified particularly suitable candidates whose efficacy was underestimated in 2D cell culture and had already been shown in previous in vivo studies.

Conclusion

The ex vivo 3D tissue slice ALI culture model is a powerful system that allows the effective evaluation of biological nanoparticle efficacy and biocompatibility in an intact tissue environment. It is comparably inexpensive, time‐saving, and follows the 3R principle, while allowing the identification of critical nanoparticle properties and optimal candidates for in vivo applications.
A dialysis medium refreshment cell culture set‐up for an osteoblast‐osteoclast coculture
Authors: Vis Michelle Anna Maria , de Wildt Bregje Wilhelmina Maria , Ito Keita , Hofmann Sandra
Published: December 2022

Culture medium exchange leads to loss of valuable auto‐ and paracrine factors produced by the cells. However, frequent renewal of culture medium is necessary for nutrient supply and to prevent waste product accumulation. Thus it remains the gold standard in cell culture applications. The use of dialysis as a medium refreshment method could provide a solution as low molecular weight molecules such as nutrients and waste products could easily be exchanged, while high molecular weight components such as growth factors, used in cell interactions, could be maintained in the cell culture compartment. This study investigates a dialysis culture approach for an in vitro bone remodeling model. In this model, both the differentiation of human mesenchymal stromal cells (MSCs) into osteoblasts and monocytes (MCs) into osteoclasts is studied. A custom‐made simple dialysis culture system with a commercially available cellulose dialysis insert was developed. The data reported here revealed increased osteoblastic and osteoclastic activity in the dialysis groups compared to the standard nondialysis groups, mainly shown by significantly higher alkaline phosphatase (ALP) and tartrate‐resistant acid phosphatase (TRAP) activity, respectively. This simple culture system has the potential to create a more efficient microenvironment allowing for cell interactions via secreted factors in mono‐ and cocultures and could be applied for many other tissues.
Addressing multilevel barriers to clinical trial participation among Black and White men with prostate cancer through the PACCT study
Authors: Eggly Susan , Senft Nicole , Kim Seongho , Heath Elisabeth I. , Jang Hyejeong , Moore Tanina F. , Baidoun Fatmeh , Manning Mark A. , Penner Louis A. , Albrecht Terrance L. , Carducci Michael A. , Lansey Dina , Hamel Lauren M.
Published: December 2022

Background

Cancer clinical trial participation is low and inequitable. Partnering Around Cancer Clinical Trials (PACCT) addressed systemic and interpersonal barriers through an observational study of eligibility and an intervention to improve patient–physician communication and trial invitation rates.

Methods

Physicians at two comprehensive cancer centers and Black and White men with prostate cancer participated. Patients were followed for 2 years to determine whether they became potentially eligible for an available therapeutic trial. Potentially eligible patients were randomized to receive a trials‐focused Question Prompt List or usual care. Patient–physician interactions were video‐recorded. Outcomes included communication quality and trial invitation rates. Descriptive analyses assessed associations between sociodemographic characteristics and eligibility and effects of the intervention on outcomes.

Results

Only 44 (22.1%) of participating patients (n = 199) became potentially eligible for an available clinical trial. Patients with higher incomes were more often eligible (>$80,000 vs. <$40,000, adjusted OR = 6.06 [SD, 1.97]; $40,000–$79,000 vs. <$40,000, adjusted OR = 4.40 [SD, 1.81]). Among eligible patients randomized to the intervention (n = 19) or usual care (n = 25), Black patients randomized to the intervention reported participating more actively than usual care patients, while White intervention patients reported participating less actively (difference, 0.41 vs. −0.34). Intervention patients received more trial invitations than usual care patients (73.7% vs. 60.0%); this effect was greater for Black (80.0% vs. 30.0%) than White patients (80.0% vs. 66.7%).

Conclusions

Findings suggest the greatest enrollment barrier is eligibility for an available trial, but a communication intervention can improve communication quality and trial invitation rates, especially for eligible Black patients.
2‐Arylpropylamines from 1‐Propenylbenzenes in a New One‐Pot Metathesis–Hydroaminomethylation Protocol
Authors: Avendaño‐Villarreal Jesus A. , Delolo Fábio G. , Granato Artur V. , Gusevskaya Elena V. , dos Santos Eduardo N.
Published: December 2022

2‐Arylpropylamines are useful as active pharmaceutical ingredients (APIs) and as synthetic building blocks in fine chemistry. Herein we report a new and efficient methodology to transform naturally occurring 1‐propenylbenzenes into 2‐arylpropylamines employing a one‐pot ethenolysis/hydroaminomethylation protocol. Four consecutive reactions must occur in the same reaction vessel and the careful selection of the reaction conditions was critical to obtain the desired products in high yields. The negative interference between the ethenolysis and the hydroaminomethylation (HAM) catalysts was circumvented by the appropriate adjustment on the molar ratio of the catalysts. As a result, nine 2‐arylpropylamines were obtained in yields ranging in 75–93 %.
Strain‐Sensitive On‐Surface Ladderization by Non‐Dehydrogenative Heterocyclization
Authors: Ma Yujing , Sugawara Kazuma , Ishigaki Yusuke , Sun Kewei , Suzuki Takanori , Kawai Shigeki
Published: December 2022

On‐surface cyclodehydrogenation recently became an important reaction to planarize π‐conjugated molecules and oligomers. However, the high‐activation barrier to cleave the C−H bond often requires high‐temperature annealing, consequently restricting structures of precursor molecules and/or leading to random fusion at their edges. Here, we present a synthesis of pyrrolopyrrole‐bridged ladder oligomers from 11,11,12,12‐tetrabromo‐1,4,5,8‐tetraaza‐9,10‐anthraquinodimethane molecules on Ag(111) with bond‐resolved scanning tunnelling microscopy. This non‐dehydrogenative cyclization between pyrazine and ethynylene/cumulene groups has a low‐activation barrier for forming intermediary dimeric oligomer containing dipyrazinopyrrolopyrrolopyrazine units, thus giving new insight into the strain‐sensitive in ladder‐oligomer formation.
Azatriseptanes: Strained Framework Analogs of [7,7,7]Circulenes
Authors: Zhang Kai , Hope Philip A. , El Bitar Nehme Mélissa , Linden Anthony , Spingler Bernhard , Rickhaus Michel
Published: December 2022

The synthesis and characterization of heptagon‐embedded polycyclic aromatic compounds are essential for understanding the effect of negative curvature on carbon allotropes such as fullerenes and graphenes that have applications in functional organic materials. However, owing to the synthetic difficulties in functionalizing and embedding seven‐membered rings, these strain‐challenged structures are relatively unexplored. We report here the synthesis, characterization, and properties of a triarylamine core bridged with ethano chains at the 2,2’‐positions. In doing so, we provide access to the first heterocycle containing three fused heptagon rings with a nitrogen at its core (BATA‐NHAc). X‐ray crystallographic analysis and DFT calculations revealed a remarkably strained structure wherein two of the bridged aryl units approach coplanarity, while the third ring is twisted out of plane at 70°. UV‐vis and emission spectroscopies identify red‐shifted absorption and concentration‐dependent emission profiles, respectively, as a result of the unique conformation and self‐assembly properties of BATA‐NHAc. Furthermore, cyclic voltammetry shows a decrease in the oxidation potential for BATA‐NHAc in comparison to the non‐bridged analog. This study opens new avenues in understanding the structure–property relationships of curved π‐aromatics and the construction of π‐frameworks of increasing complexity.
Bendamustine in the treatment of patients with indolent non‐Hodgkin lymphoma refractory or relapse to rituximab treatment: An open‐label, single‐agent, multicenter study in China
Authors: Gao Yan , Liu Yizhen , Wang Yafei , Zhang Qingyuan , Wu Depei , Ye Xu , Wu Jianqiu , Xu Wei , Zhou Jianfeng , Yang Yu , Cen Hong , Zhang Feng , Xiang Ying , Tang Xiaoqiong , Ding Kaiyang , Lin JinYing , Ma Lei , Wang Shunqing , Yu Hao , Zhao Yang , Song Bin , Lv Fangfang , Huang Huiqiang
Published: December 2022

Background

The optimal treatment strategy for refractory or relapse (R/R) indolent non‐Hodgkin lymphoma (iNHL) has not been fully identified. This study aims to investigate the efficacy and tolerance of bendamustine hydrochloride developed in native Chinese corporation in the treatment of patients with R/R iNHL.

Methods

A total of 101 patients from 19 centers were enrolled in this study from July 2016 to February 2019. Bendamustine hydrochloride (120 mg/m2) was given on days 1 and 2 of each 21‐day treatment cycle for six planned cycles or up to eight cycles if tolerated. Parameters of efficacy and safety were analyzed.

Results

The median age of the patients was 53.44 (range, 24.4–74.6) years old. A total of 56 (55.44%) patients completed at least six treatment cycles, and the relative dose intensity was 93.78%. The overall response rate was 72.28%, and the median duration of response was 15.84 months (95% confidence interval [CI], 13.77–27.48 months). Median progression‐free survival was 16.52 months (95% CI, 14.72–23.41 months), and the median overall survival was not reached. Grade 3 or 4 hematologic toxicities included neutropenia (77.22%), thrombocytopenia (29.70%), and anemia (15.84%). The most frequent nonhematologic adverse events (any grade) included nausea, vomiting, fatigue, fever, decreased appetite, and weight loss. Seven patients died during the trial, and four cases may be related to the investigational drug.

Conclusions

This study reveals that bendamustine hydrochloride is a feasible treatment option for the indolent B‐cell non‐Hodgkin lymphoma patient who has not remitted or relapsed after treatment with rituximab. All adverse events were predictable and manageable.
CRISPR‐Suppressor Scanning for Systematic Discovery of Drug‐Resistance Mutations
Authors: Ngan Kevin C. , Lue Nicholas Z. , Lee Ceejay , Liau Brian B.
Published: December 2022

CRISPR‐Cas9 genome editing technologies have enabled complex genetic manipulations in situ, including large‐scale, pooled screening approaches to probe and uncover mechanistic insights across various biological processes. The RNA‐programmable nature of CRISPR‐Cas9 greatly empowers tiling mutagenesis approaches to elucidate molecular details of protein function, in particular the interrogation of mechanisms of resistance to small molecules, an approach termed CRISPR‐suppressor scanning. In a typical CRISPR‐suppressor scanning experiment, a pooled library of single‐guide RNAs is designed to target across the coding sequence(s) of one or more genes, enabling the Cas9 nuclease to systematically mutate the targeted proteins and generate large numbers of diverse protein variants in situ. This cellular pool of protein variants is then challenged with drug treatment to identify mutations conferring a fitness advantage. Drug‐resistance mutations identified with this approach can not only elucidate drug mechanism of action but also reveal deeper mechanistic insights into protein structure‐function relationships. In this article, we outline the framework for a standard CRISPR‐suppressor scanning experiment. Specifically, we provide instructions for the design and construction of a pooled sgRNA library, execution of a CRISPR‐suppressor scanning screen, and basic computational analysis of the resulting data. © 2022 Wiley Periodicals LLC.

Basic Protocol 1: Design and generation of a pooled sgRNA library

Support Protocol 1: sgRNA library design using command‐line CRISPOR

Support Protocol 2: Production and titering of pooled sgRNA library lentivirus

Basic Protocol 2: Execution and analysis of a CRISPR‐suppressor scanning experiment
Therapeutic role of Artemether in the prevention of hepatic steatosis through miR‐34a‐5p/PPARα pathway
Authors: Chen Li , Yu Shuang , Hong Shubing , Lin Xia , Zhu Xiaonan , Cao Xiaopei , Li Yanbing , Xiao Haipeng
Published: December 2022

Artemether (ATM) is a natural antimalarial drug that can also regulate glucose and lipid metabolism. However, little is known regarding its pharmacological action in metabolic dysfunction‐associated fatty liver disease (MAFLD), and the underlying mechanisms remain undetermined. The aim of this study was to explore the therapeutic effects of ATM against hepatic steatosis and the possible mechanisms. ATM significantly decreased blood glucose levels, improved glucose tolerance, reduced inflammatory response, and alleviated hepatic steatosis in the ob/ob mouse model as well as the high‐fat diet‐fed mice. ATM also inhibited lipid accumulation in murine hepatocytes in vitro. Using RNA sequencing, miR‐34a‐5p and peroxisome proliferator‐activated receptor‐α (PPARα) were identified as important regulators during ATM treatment. ATM administration downregulated miR‐34a‐5p expression and miR‐34a‐5p abrogated the inhibitory effects of ATM on PO (palmitate + oleate)‐induced lipid accumulation as well as triglycerides levels in murine hepatocytes. Furthermore, the expression of PPARα, a target gene of miR‐34a‐5p, was upregulated by ATM and PPARα inhibitor MK‐886 abolished the positive effect of ATM. Consequently, PPARα agonist fenofibrate reversed the decreased mitochondrial fatty acid β‐oxidation induced by miR‐34a‐5p mimics after ATM treatment, thereby leading to attenuation of intracellular lipid accumulation. Taken together, ATM is a promising therapeutic agent against MAFLD that reduces lipid deposition by suppressing miR‐34a‐5p and upregulating PPARα.
Synthetic Studies towards Pheromones by Cyanide‐Catalyzed Ring Transformation of α‐Hydroxy‐β‐oxoesters to δ‐Valerolactones
Authors: Speldrich Jean‐Marico , Schmidtmann Marc , Christoffers Jens
Published: December 2022

The cyanide‐catalyzed ring‐transformation of α‐hydroxy‐β‐oxoesters to δ‐lactones with exocyclic ester moiety is the key transformation for the preparation of racemic 5‐hexadecanolide (15 % over nine steps) and 6‐acetoxy‐5‐hexadecanolide (22 % over eight steps), two insect pheromones. The benzyloxycarbonyl moiety is transformed via the acid chloride to the undecanoyl side chain. After reduction of the ketone to the secondary alcohol, this functional group was either reduced via the chloro compound to furnish the 5‐hexadecanolide. On the other hand, stereoselective reduction of the ketone gave secondary alcohol with the wrong relative configuration, which was established by X‐ray single‐crystal structure. Inversion was achieved by reaction of the methanesulfonate with cesium acetate yielding (R*,S*)‐6‐acetoxy‐5‐hexadecanolide with the relative configuration also present in the natural product.
Synthesis of Synergistic Ni(OH)2@ZnO Core–Shell Nanostructured Electrodes by a Hydrothermal Method and Atomic Layer Deposition for High‐Performance Supercapacitors
Authors: Lee Woo-Jae , Kim Kwang Ho , Choi Young Joong , Wan Zhixin , Kwon Se-Hun
Published: December 2022

A novel nanoporous Ni(OH)2@ZnO core–shell architecture is successfully synthesized via a hydrothermal reaction and atomic layer deposition (ALD). This hybrid material exhibited a well‐defined core–shell nanostructure with high purity and good crystallinity. The conductivity of the electrodes is obviously enhanced by the ALD ZnO thin film. Compared to the conventional Ni(OH)2, the Ni(OH)2 coated with 10 nm of ZnO exhibited significantly enhanced performance, with a maximum specific capacitance value of ≈1,400 F g−1 at a current density of 1 A g−1, which is attributed to the improved charge‐transfer resistance. The asymmetric Ni(OH)2@ZnO//graphene supercapacitor exhibited a good capacitance retention rate and an energy density of 32 Wh kg−1 at a power density of 480 W kg−1, which are higher than those of pure nanostructured Ni(OH)2 and ZnO‐based asymmetric supercapacitors. The remarkable electrochemical performance is contributed to the synergetic presence of the core–shell nanostructure with a high surface area and the highly conductive ZnO films with optimized thickness, which achieve appropriate mass ratio control of the active material. The design of the core–shell architectures demonstrated in this work is expected to be a new and promising approach to ALD for the development of hybrid electrode materials for high‐performance supercapacitor applications.
Design of Inorganic–Organic Hydrophobic Coating on Zn Anode Realizes Highly Reversible and Dendrite‐Free Zn‐Ion Batteries
Authors: Wang Yuan-Yi , Tian Chen-Yang , Zhang Dong-Ting , Zhao Bei , Wang Ya-Qin , Liu Mao-Cheng
Published: December 2022

The zinc‐ion battery (ZIB) has attracted wide attention due to its environmental protection, abundant reserves, and desirable theoretical capacity. However, the application of ZIBs is limited by the dendrite growth and side reactions on the Zn anode. Herein, a boron microparticles and polyvinylidene fluoride (PVDF) composite modified layer (B‐PVDF) is constructed on the surface of a Zn anode, and a Zn anode with hydrophobic coating is obtained (B‐PVDF@Zn). The hydrophobic PVDF modified layer prevents the direct contact between H2O molecules and Zn anode, while boron microparticles guide the flux of Zn2+; thus, dendrite growth and side reactions are concurrently inhibited. And B‐PVDF@Zn//B‐PVDF@Zn symmetric battery maintains a stable overpotential (<45 mV) after 1050 h at a current density of 1 mA cm−2with a planting capacity of 1 mAh cm−2. The capacity retention rate of B‐PVDF@Zn//V2O5is 62.1% after 400 cycles, which shows improved cycle stability. The research proves the feasibility of the hydrophobic modified layer for the stable Zn anode; it supplies a new research idea for the diversity of Zn anode surface design.
Design concepts for avoiding story mechanisms in steel MRFs under seismic loading
Authors: Kim Jeongjoo , Sause Richard
Published: December 2022

This paper proposes alternative seismic design approaches for steel moment‐resisting frames (MRFs) that improve their performance and reduce the number of undesirable one‐story and two‐story yield mechanisms that form under seismic loading, compared to MRFs designed using the conventional strong‐column‐weak‐beam (SCWB) design approach. The alternative design approaches are capacity‐design approaches that directly compare story shear force demands from nonlinear time‐history analyses (NTHA) with corresponding shear force capacities in design iterations to avoid one‐story and two‐story mechanisms. To implement the capacity‐design approach, the NTHA use special capacity‐controlled numerical models for design, in which the one‐story and two‐story shear force design demands are limited by the intended yield mechanisms of the MRF. Unlike the SCWB approach, the alternative design approaches directly address the cause of undesirable one‐story and two‐story mechanisms. The paper presents NTHA results for a set of MRFs, where some were designed using a conventional approach (including SCWB) and some were designed using the alternative approaches. The increases in nominal steel weight of the MRFs designed using the alternative approaches are relatively small compared to the weight of the MRF designed using the conventional SCWB approach. Compared to the MRF designed using the SCWB approach, the MRFs designed using the alternative design approaches have improved seismic performance with reduced tendency to form one‐story and two‐story mechanisms, more uniform story drifts, reduced maximum story drift, and improved collapse performance.
Comparison of Two Estrogen Chemically Activated Luciferase Expression Cell Bioassays to Liquid Chromatography–Mass Spectrometry for Quantifying Estrone in Water Samples
Authors: Brennan Jennifer , Henke Abigail , Gale Robert , Nicks Diane , Tillitt Donald
Published: December 2022

Chemically activated luciferase expression (CALUX) cell bioassays are popular tools for assessing endocrine activity of chemicals such as certain environmental contaminants. Although activity equivalents can be obtained from CALUX analysis, directly comparing these equivalents to those obtained from analytical chemistry methods can be problematic because of the complexity of endocrine active pathways. We explored the suitability of two estrogen CALUX bioassays (the Organisation for Economic Co-operation and Development–approved VM7Luc4E2 cell bioassay and the VM7LucERβc9 cell bioassay) for quantitation of estrogen. Quadrupole-time of flight ultraperformance liquid chromatography–mass spectrometry (LC/MS) was selected as a comparative method. Regression analysis of measured estrone (E1) calibration samples showed all three methods to be highly predictive of nominal concentrations (p ≤ 7.5 × 10–51). Extracts of water sampled from laboratory dilutor tanks containing E1 at 0, 20, and 200 ng/L alone and in combination with atrazine were selected to test the quantitative capabilities of the CALUX assays. Process controls (0 and 100 ng E1/L) and a separate E1 standard (10 ng/ml, used to prepare the E1 process control) were also tested. Levels of E1 determined by LC/MS analysis and bioanalytical equivalents (ng E1/L) determined by CALUX analyses were comparable except in certain instances where the samples required dilution prior to CALUX analyses (e.g., the E1 process control and E1 standard). In those instances, measurements by CALUX were slightly but significantly decreased relative to LC/MS. Atrazine had no effect on the ability of either LC/MS or the CALUX bioassays to quantify E1. The present study illustrates the CALUX bioassays as successful in quantifying an estrogen in simple water samples and further characterizes their utility for screening. Environ Toxicol Chem 2023;42:333–339. Published 2022. This article is a U.S. Government work and is in the public domain in the USA.

Abstract

Both quadrupole-time of flight ultraperformance liquid chromatography–mass spectrometry and estrogen chemically activated luciferase expression bioassays are highly predictive of nominal concentrations. QTOF-LC/MS = quadrupole-time of flight ultraperformance liquid chromatography–mass spectrometry; E1 = estrone.
1H-Nuclear Magnetic Resonance Metabolomics Analysis of Arabidopsis thaliana Exposed to Perfluorooctanoic Acid and Perfluoroctanesulfonic Acid
Authors: O'Hara Liam , Longstaffe James G.
Published: December 2022

Perfluorinated alkyl substances (PFAS) are ubiquitous environmental contaminants that are widely used in consumer products and fire suppression foams. The presence of PFAS in ground and surface water can create a route for PFAS to enter the soil, exposing ecosystems (including agroecosystems), where they will move through the food web via biomagnification. The toxicity of PFAS to plants, particularly in agricultural ecosystems, is of emerging concern due to the application of biosolids that are often contaminated with PFAS. Nevertheless, due to the low concentrations of PFAS in most agricultural soils, the direct impact of PFAS on plant health is not well understood. We used 1H-nuclear magnetic resonance (NMR) metabolomics to explore the effects of exposure of two key PFAS, perfluorooctanoic acid and perfluorooctanesulfonic acid, on Arabidopsis thaliana, a model organism. We found that Arabidopsis exhibited an accumulation of multiple metabolites, including soluble sugars (glucose and sucrose), multiple amino acids, and tri-carboxylic acid (TCA) cycle intermediates, suggesting that PFAS exposure impacts the metabolism of plants by causing an accumulation of stress-related amino acids and soluble sugars that drives increased activity of the TCA cycle. The present study shows that 1H-NMR metabolomics is a viable tool for investigating changes in the metabolic profile of plants exposed to PFAS and can be used to illuminate the stress response of plants in a high-throughput, nonbiased manner. Environ Toxicol Chem 2023;42:663–672. © 2022 SETAC
Effect of packaging and encapsulation on the oxidative and sensory stability of omega‐3 supplements
Authors: Yenipazar Hande , Şahin‐Yeşilçubuk Neşe
Published: December 2022

Omega‐3 fatty acid consumption is getting more common due to its positive impacts on human health. Since consumers cannot get their omega‐3 needs from natural sources, omega‐3‐rich products play an essential part in the diet. However, they are highly susceptible to oxidation; thus, storage conditions affect their quality. Product form is also another critical factor for stability. In this study, fatty acid composition, oxidative stability, and sensory properties of different omega‐3 products having varied packaging types were investigated. Moreover, the effect of consumer behavior regarding the recommended usage was assessed during storage. Syrup forms (maximum values at the end of the storage: PV = 44.6 meq/kg oil for S32, p‐AV = 16.87 for S22, and TOTOX = 96.94 for S11) are more susceptible to oxidation than capsule (maximum values at the end of the storage: PV = 7.62 meq/kg oil for C31, p‐AV = 19.58 for C12, and TOTOX = 30.44 for C12) and chewable forms (maximum values at the end of the storage: PV = 26.14 meq/kg oil for G12, p‐AV = 13.47 for G12, and TOTOX = 65.76 for G12). In addition, capsules complied more with limit values during storage and were better protected according to the sensory scores. The aroma and taste of the omega‐3 products generally changed in a negative manner during storage. Capsulated samples were better protected according to the sensory evaluation scores at the end of the storage period. Fish oil samples belonging to the same company but provided from different stores showed significant differences, which is an indicator of nonstandard raw material, ingredient, or processing.
Combination of gamma irradiation and storage condition for improving mechanical and physical postharvest characteristics of fresh garlic cloves
Authors: Yoosefian Seyedeh Hoda , Ahmadi Ebrahim , Mohammad‐Razdari Ayat
Published: December 2022

The aim of this study was the discrimination and optimization of irradiation effect under physical and mechanical experiments on garlic. The samples were irradiated with 0, 75, and 150 Gy doses and stored at 4 and 18°C for 5 months. Physical, mechanical, and color properties were measured in the period of storage. Based on the results, all irradiated garlic samples had less quality variation than control samples. Response surface methodology (RSM) optimized dose, storage time, and temperature of the stored garlic which was 75 Gy, 2 months, and 17°C, respectively. In addition, after finding the optimal dose, time, and temperature, the most effective factor as weight loss was obtained and the data were classified by the principal component analysis (PCA) approach. The results showed that the PCA method had a high ability to classify and separate the data obtained from measuring the physicochemical properties of garlic and cover 99% variance of data. Moreover, partial least square (PLS) was applied for predicting weight loss data with R2 0.9999. As well, a mechanical test was investigated for finding the best situation and duration of storage condition. Finally, irradiation prevented the destruction of garlic and saved garlic in the best quality as compared with control or nonirradiated samples. After all this, it can be decided to keep garlic in warehouses and transfer this product with minimum damage.
Catalyst degradation under different test and poisoning conditions – Comparison parameters definition to map the effects on proton exchange membrane fuel cell voltage
Authors: Gadducci Eleonora , Reboli Tommaso , Rivarolo Massimo , Magistri Loredana
Published: December 2022

Proton exchange membrane fuel cells (PEMFCs) are considered among the most promising technologies for hydrogen utilization in both stationary and transport applications. Nevertheless, the cost of its components – especially the catalyst and the membrane – is still consistent and far from the cost predicted by the US Department of Energy. It is therefore essential to predict the effect of contaminants on PEMFC materials and to estimate their useful life. The literature on this topic is consistent, but the absence of standards for the experimental tests under contaminated flows makes it difficult to extrapolate the generic degradation trends and compare the results of different publications. This work aims to collect and interpret the results of the recent studies on catalyst contamination: the voltage degradation rate and reduction effect are defined via a data modeling work to understand and compare the effects of different contaminants, their concentrations, exposure times, and current densities. Thanks to the results of the present study, some conclusions are drawn regarding the impact of the different pollutants on cell voltage decay, with attention dedicated to establishing a correlation that takes into account also the different operating conditions.
Pricing multiasset time‐varying double‐barrier options with time‐dependent parameters
Authors: Lyuu Yuh‐Dauh , Zhang Yu‐Quan
Published: December 2022

This paper proposes the first lattice to price multiasset double‐barrier options when barriers, volatilities, correlations, and interest rates are all time varying. The nodes are strategically placed to both match the volatilities and align with the two barriers per asset for fast convergence. The branching probabilities are provably valid. The size of our lattice is , where is the number of time steps and is the number of assets, and is only for continuously monitored double‐barrier knock‐out options.
miRNA‐124 alleviated memory impairment induced by d‐galactose rapidly in male rats via microglia polarization
Authors: Huang Jinghao , Chen Dengchao , Lin Xinyi , Yang Chengxia , Lin Xianzhong
Published: December 2022

MiRNA‐124 has been considered to play a significant role in the formation of memory and a variety of neurodegenerative diseases. In this study, the aim is to verify whether miRNA‐124 is involved in memory impairment induced by d‐galactose, and explore the underlying neuroprotective mechanism. The results revealed that rapid administration of d‐galactose (1000 mg/kg subcutaneously) in mice caused memory impairments, as determined by Novel Object Recognition test, Morris Water Maze test, and histological assessments. MiRNA‐124 agomir is stereotactic injected into hippocampus, thus alleviated memory impairment induced by d‐galactose and reversed the neural damage and neuroinflammation. Furthermore, the results of molecular biological analysis and immunohistochemistry revealed that miRNA‐124 markedly reduced neuroinflammation induced by d‐galactose through polarization of microglia as determined by detection of ionized calcium binding adapter molecule 1 (Iba‐1), inducible nitric oxide synthase (iNOS) and arginase‐1(Arg‐1), which also downregulated inflammatory mediators, including interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α), and upregulated IL‐4 and IL‐10. Hence, taken together, the results of the present study suggested that miRNA‐124 showed a significant negative correlation with memory impairment and neuroinflammation induced by d‐galactose rapidly, possibly via polarization of microglia from M1 to M2. It is possible that miRNA‐124 can be used as a new target for the pathogenesis of memory impairment, including age‐associated neurodegenerative diseases such as Alzheimer's disease.