bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning to Stratify Asymptomatic Alzheimer’s Disease Progression Risk with Cerebrospinal Fluid Biomarkers
Authors: Tandon Raghav , Watson Caroline M , Seyfried Nicholas T. , Mitchell Cassie S , Zhao Liping , Lah James J.
Published: December 2022

Background

Change in protein regulation begin years before Alzhiemer’s Disease (AD) functional symptom onset. The period where changes in proteins is detectable without overt cognitive dysfunction is often referred to as the asymptomatic AD stage. The ability to utilize biomarkers to determine who is most likely to transition to symptomatic AD is critical for potential future intervention development. Machine learning provides a means to stratify the asymptomatic AD population using measured biomarker levels.

Method

Seventy‐five peptides were measured in the cerebrospinal fluid (CSF) of subjects in the Emory Healthy Brain Study. Subjects labeled as symptomatic AD had a clinically confirmed AD diagnosis with cognitive deficit. Quantified total‐tau to amyloid beta ratio was used to label non‐symptomatic patients as either heathy control or asymptomatic AD. Recursive feature elimination (RFE) was used to identify a small set of predictive peptides best for classifying either symptomatic AD or healthy control AD. Asymptomatic AD subjects (n = 134) were clustered based on peptide levels using t stochastic nearest neighbor embedding (t‐SNE). Finally, the selected most predictive peptides and the k‐nearest neighbors (KNN) algorithm was utilized to calculate the proximity of asymptomatic AD subjects to healthy control or symptomatic AD. The calculated proximity represented the stratified AD progression.

Result

RFE successfully classified patient stage using <10 peptides (AUC > 95%, n =58 held out test subjects). Peptides mapped to the proteins NPTXR, YWHAZ, CHI3L1, VGF, APOE, SMOC1, and GAPDH were most discriminative. T‐SNE results revealed biomarker heterogeneity within the population, but cluster separation was sufficient to utilize KNN proximity as a stand‐in for approximated asymptomatic AD progression.

Conclusion

Machine learning of CSF biomarker levels successfully stratified asymptomatic subjects into AD‐like (more progressed) and control‐like (relatively less progressed) asymptomatic cases. Stratification of subjects based on biomarker levels could improve future clinical trial construction and assist in earlier intervention for higher risk subjects.
Role of polyelectrolytes in modulating membrane‐templated Aβ40 aggregation
Authors: Regmi Deepika , Du Deguo
Published: December 2022

Background

Amyloid fibril formation is associated with protein‐misfolding disorders and is a key pathway for the pathogenesis of Alzheimer’s disease (AD). The fibrillar structure of amyloid beta‐protein (Aβ) is the hallmark of amyloid plaques in the brains of patients with Alzheimer’s disease (AD). The interaction between the cell membrane and the Aβ40 peptide may induce membrane disruption and membrane leakage and may be related to the toxicity in Alzheimer’s disease (AD).

Method

In this regard, we evaluated the competitive effects of different polyelectrolytes such as chitosan (CHT), N‐trimethyl chitosan (TMC), heparin and dextran on peptide‐phospholipid membrane interactions and Aβ40 fibrillation. The impact of polyelectrolytes on AB aggregation at membrane interface and fibrillation of Aβ40 peptide was evaluated by utilizing biophysical techniques such as ThT binding assays and atomic force microscopy.

Result

The polyelectrolytes and lipid membranes co‐exist extensively in the cellular environment, we demonstrate that the interactions of polyelectrolytes and Aβ may substantially influence the role of the N‐terminal charged region of Aβ in initiating and guiding adsorption and aggregation of the peptide on the membrane surface.

Conclusion

Hence, there is a great deal of interest in polyelectrolytes that can bind to the Aβ40 peptide and interfere with the Aβ40 peptide‐membrane interactions and manipulate amyloid formation in Alzheimer’s disease (AD).
Optogenetic regulation of phosphatidylinositides in cellular and mouse models of Alzheimer’s disease
Authors: Costa Ana Paula , Acquarone Erica , Lazarian Artur , Herman Mathieu A , Arancio Ottavio , Hussaini S Abid , McIntire Laura Beth
Published: December 2022

Background

Major disappointments in late‐stage clinical trials have made it clear that additional therapeutic targets beyond amyloid β‐peptide (Aβ) and tau are urgently required for Alzheimer’s disease (AD). Phosphatidylinositol 4,5‐biphosphate [PI(4,5)P2] has previously been established as an important signaling lipid at the synapse and in a mouse model of Alzheimer’s disease. We hypothesize that the level of PI(4,5)P2 in the plasma membrane may be an early and critical determinant of AD associated molecular and behavioral deficits in cellular and mouse models of the disease.

Method

We tested the ability of a light‐inducible dimerization system to modify phosphoinositide content in vitro using a PC12 cell line overexpressing cryptochrome‐interacting basic‐helix‐loop‐helix (CIBN) fusion to a membrane targeted CAAX domain (CIBN‐CAAX), and blue‐light mediated binding of cryptochrome 2 (CRY2) fused with the catalytic domain of phosphatidylinositol 4‐phosphate 5‐kinase (CRY2‐PIP5K2A‐CD). We detected PI(4,5)P2 using the PI(4,5)P2 sensor plextrin homology domain of phospholipase C δ (PH‐PLCδ). Using virally mediated transduction of these constructs in mouse brain, we manipulated PI(4,5)P2 levels in hippocampus of a mouse model of AD, harboring the Amyloid Precursor Protein transgene (APP‐Tg). Behavioral deficits were assessed using novel object recognition (NOR). Brains were analyzed for detection of phosphoinositide using Imaging Mass Spectrometry.

Result

In PC12 cells, initial results indicate that after optogenetic stimulation, cytosolic labeling by PH‐PLCδ was largely lost, and plasma membrane labeling was observed. In a mouse model of AD (APP‐Tg) after stimulation with blue light or control yellow light, behavioral paradigms including NOR were completed. NOR discrimination index was significantly reduced for Tg+/control compared to other groups (WT/control, WT/Opto) as expected. However, Tg+/Opto was not significantly different than WT/control or WT/Opto indicating amelioration of behavioral deficits in Tg+/Opto through optogenetic stimulation of PI(4,5)P2 production. Experimental groups did not show significant changes in motor function in the open field task. Our data indicate that optogenetic stimulation of PI(4,5)P2 accumulation in brain is able to rescue behavioral AD associated behavioral deficits.

Conclusion

Using sophisticated and specific optogenetic manipulation we have demonstrated that stimulation of PI(4,5)P2synthesis rescued behavioral deficits in a mouse model supporting the critical role of PI(4,5)P2 levels in AD.
Relationship between cytokines and β‐amyloid and Tau protein in the CSF of patients with Alzheimer's disease, amnestic mild cognitive impairment, and individuals without subjective cognitive impairment
Authors: Burgos Ivonne Carolina Bolaños , Hansen Erika de Oliveira , Romano‐Silva Marco Aurelo , Miranda Debora , Viana Bernardo de Mattos , Bicalho Maria Aparecida Camargos ,   Research group on aging and neurodegenerative diseases
Published: December 2022

Background

The neuroinflammation process is one of the main pathological features of Alzheimer's disease (AD). In the course of AD, the deposits of β‐amyloid plaques and neurofibrillary tangles lead to over‐activation of the microglia, resulting in increased production of pro‐inflammatory and anti‐inflammatory cytokines that may contribute to neuronal dysfunction and cell death. Currently, several efforts have been made to discover the role of cytokines in AD's pathogenesis and the relationship between these inflammatory factors and the presence of AD's main biological markers (1). The present study aimed to determine the quantitative correlation between cytokines, β‐amyloid, and Tau proteins and the cognitive status of the participants.

Method

CSF was collected by lumbar puncture from 80 older individuals with clinically defined AD (n=36), with amnestic mild cognitive impairment (aMCI) (n=24), and without objective cognitive impairment (n=20). CSF levels of β‐amyloid and p‐tau and t‐Tau and 27 cytokines were determined using the Luminex xMAP technique. Correlations were made between the cytokines, the β‐amyloid and Tau proteins levels, and the Mini‐Mental State test (MEEM).

Result

considering all individuals, there was a significant positive correlation between Aβ42, IL‐4 and IL‐8; p‐Tau positively correlated with G‐CSF and GM‐CSF and finally p‐Tau/Aβ42 negatively correlated with IL8. The MEEM was correlated negatively with Eotaxin, IL‐6 and IL‐15. Focusing only in the AD group, there was a positive correlation for Aβ42 with IL‐4, IL‐8 and negatively with IL‐17; t‐Tau correlated negatively with IL‐1ra and IL‐5; p‐Tau/Aβ42 positively correlated with IL‐17 and negatively with IL‐8 and IP10. The MEEM showed a positive correlation with IL‐4. In the control group, Aβ42 and VEGF had a negative correlation; p‐Tau negatively correlated with TNF‐α; p‐Tau/Aβ42 were correlated positively with GM‐CSF, IL‐1β and IL‐6. The MEEM did not present any correlation. Between the aMCI group, t‐Tau was correlated positively with PDGF‐BB, and the MEEM was correlated negatively with Eotaxin.

Conclusion

Changes in the neuroinflammatory profile are more prominent in AD patients compared to individuals without subjective cognitive impairment and those with aMCI.
Associations between performance on the Latin American Version of the Face‐Name and plasma Neurofilament Light Chain, NfL, in individuals with autosomal‐dominant Alzheimer’s disease: Preliminary findings from the Colombia‐Boston ‐COLBOS‐ remote study
Authors: Baena Ana Y.
Published: December 2022

Background

We previously reported that performance on the Latin American Spanish version of the Face‐Name Associative Memory Exam (LAS‐FNAME) differentiated between cognitively intact Presenilin1 (PSEN1) E280A mutation carriers from non‐carriers and that this performance was also associated with greater amyloid and tau burden in the entorhinal and inferior temporal cortices, when examining all carriers. Neurofilament light chain (NfL), a plasma‐based biomarker for neurodegeneration and a promising marker for early Alzheimer’s disease (AD) detection, is less invasive and expensive than PET imaging. Here, we examined whether levels of plasma NfL were associated with LAS‐FNAME performance in non‐demented PSEN1‐E280A carriers and non‐carriers.

Methods

A total of 51 PSEN1‐E280A carriers (mean age = 30.06 +/‐ 4.63), including 2 Mild Cognitive Impaired carriers and 50 age‐matched non‐carriers (mean age = 35.55 +/‐ 6.16) from the Colombia‐Boston (COLBOS) remote study were included. Participants underwent blood sampling and neuropsychological assessment, including the MMSE and LAS‐FNAME. Plasma NfL concentrations were measured with a single molecule array (Simoa) method. Mann‐Whitney and Spearman correlations were used to examine group differences and the relationships between LAS‐FNAME performance and NfL levels.

Results

There were no significant group differences in NfL levels or in the LAS‐FNAME Total Score, Immediate and Delayed Memory subscales (all p>0.05). However, mutation carriers (mean= 27.90) had lower MMSE scores than non‐carriers (mean= 28.47; p = 0.05). LAS‐FNAME Total Score was negatively associated with age (r=‐.37; p=0.007), and positively associated with MMSE scores (r=.54; p<0.001) in the carrier group. Among the entire sample, associations between NfL levels and age trended toward significance (p = 0.06). NfL levels were not associated with cognitive performance, including LAS‐FNAME or MMSE.

Conclusions

Preliminary findings suggest that LAS‐FNAME may be a useful tool to track disease progression in those at increased risk for dementia. Further, our findings suggest that NfL levels may not be associated with performance on associate memory tasks, such as LAS‐FNAME, in prodromal stages of ADAD. Future work with a larger sample of carriers, across the preclinical/prodromal spectrum will allow for a more comprehensive examination of these associations.
Synergistic Porosity and Charge Effects in a Supramolecular Porphyrin Cage Promote Efficient Photocatalytic CO2Reduction**
Authors: An Lun , De La Torre Patricia , Smith Peter T. , Narouz Mina R. , Chang Christopher J.
Published: December 2022

We present a supramolecular approach to catalyzing photochemical CO2reduction through second‐sphere porosity and charge effects. An iron porphyrin box (PB) bearing 24 cationic groups,FePB‐2(P), was made via post‐synthetic modification of an alkyne‐functionalized supramolecular synthon.FePB‐2(P)promotes the photochemical CO2reduction reaction (CO2RR) with 97 % selectivity for CO product, achieving turnover numbers (TON) exceeding 7000 and initial turnover frequencies (TOFmax) reaching 1400 min−1. The cooperativity between porosity and charge results in a 41‐fold increase in activity relative to the parent Fe tetraphenylporphyrin (FeTPP) catalyst, which is far greater than analogs that augment catalysis through porosity (FePB‐3(N), 4‐fold increase) or charge (Fep‐tetramethylanilinium porphyrin (Fe‐p‐TMA), 6‐fold increase) alone. This work establishes that synergistic pendants in the secondary coordination sphere can be leveraged as a design element to augment catalysis at primary active sites within confined spaces.
Computergesteuerte Entwicklung von Ylid‐funktionalisierten Phosphinen für Palladium‐katalysierte Hiyama‐Kupplungen
Authors: Goebel Jonas F. , Löffler Julian , Zeng Zhongyi , Handelmann Jens , Hermann Albert , Rodstein Ilja , Gensch Tobias , Gessner Viktoria H. , Gooßen Lukas J.
Published: December 2022

Palladium‐katalysierte Kupplungen von Silicium‐Enolaten mit Arylelektrophilen sind von großem synthetischem Nutzen, aber oft auf teure Bromid‐Substrate beschränkt. Eine vergleichende experimentelle Studie bestätigte, dass keines der etablierten Ligandensysteme die Kupplung kostengünstiger Arylchloride mit α‐Trimethylsilylalkylnitrilen ermöglicht. Im Gegensatz dazu führten ylid‐funktionalisierte Phosphine (YPhos) zu vielversprechenden Ergebnissen. Mit Hilfe eines statistischen Modells wurden die Reaktionsausbeuten mit strukturellen Eigenschaften der Liganden korreliert und hocheffiziente Katalysatorstrukturen vorhergesagt. Mit Hilfe dieses chemieinformatischen Ansatzes wurden neue YPhos‐Liganden speziell auf die Anforderungen von Hiyama‐Kupplungen zugeschnitten. Diese Liganden brechen Aktivitätrekorde und ermöglichten die Kupplung von Arylchloriden mit α‐Trimethylsilylalkylnitrilen. Der präparative Nutzen des Katalysatorsystems wurde durch die Synthese von pharmazeutisch bedeutsamen α‐Arylalkylnitrilen, α‐Arylcarbonylen und Biarylen aufgezeigt.
Wurtzite CuGaS2 with an In‐Situ‐Formed CuO Layer Photocatalyzes CO2 Conversion to Ethylene with High Selectivity
Authors: Chakraborty Subhajit , Das Risov , Riyaz Mohd , Das Kousik , Singh Ashutosh Kumar , Bagchi Debabrata , Vinod Chathakudath P. , Peter Sebastian C.
Published: December 2022

We present surface reconstruction‐induced C−C coupling whereby CO2 is converted into ethylene. The wurtzite phase of CuGaS2. undergoes in situ surface reconstruction, leading to the formation of a thin CuO layer over the pristine catalyst, which facilitates selective conversion of CO2 to ethylene (C2H4). Upon illumination, the catalyst efficiently converts CO2 to C2H4 with 75.1 % selectivity (92.7 % selectivity in terms of Relectron) and a 20.6 μmol g−1 h−1 evolution rate. Subsequent spectroscopic and microscopic studies supported by theoretical analysis revealed operando‐generated Cu2+, with the assistance of existing Cu+, functioning as an anchor for the generated *CO and thereby facilitating C−C coupling. This study demonstrates strain‐induced in situ surface reconstruction leading to heterojunction formation, which finetunes the oxidation state of Cu and modulates the CO2 reduction reaction pathway to selective formation of ethylene.
Enhanced Activity of Enzyme Immobilized on Hydrophobic ZIF‐8 Modified by Ni2+ Ions
Authors: Yang Xiao‐Gang , Zhang Ji‐Rui , Tian Xu‐Ke , Qin Jian‐Hua , Zhang Xin‐Ya , Ma Lu‐Fang
Published: December 2022

The development of efficient enzyme immobilization to promote their recyclability and activity is highly desirable. Zeolitic imidazolate framework‐8 (ZIF‐8) has been proved to be an effective platform for enzyme immobilization due to its easy preparation and biocompatibility. However, the intrinsic hydrophobic characteristic hinders its further development in this filed. Herein, a facile synthesis approach was developed to immobilize pepsin (PEP) on the ZIF‐8 carrier by using Ni2+ ions as anchor (ZIF‐8@PEP‐Ni). By contrast, the direct coating of PEP on the surface of ZIF‐8 (ZIF‐8@PEP) generated significant conformational changes. Electrochemical oxygen evolution reaction (OER) was employed to study the catalytic activity of immobilized PEP. The ZIF‐8@PEP‐Ni composite attains remarkable OER performance with an ultralow overpotential of only 127 mV at 10 mA cm−2, which is much lower than the 690 and 919 mV overpotential values of ZIF‐8@PEP and PEP, respectively.
The Asymmetric Buchwald–Hartwig Amination Reaction
Authors: Lu Chuan‐Jun , Xu Qi , Feng Jia , Liu Ren‐Rong
Published: December 2022

Over the past few decades, the Buchwald–Hartwig reaction has emerged as a powerful tool for forging C−N bonds, and has been vital to the pharmaceuticals, materials, and catalysis fields. However, asymmetric Buchwald–Hartwig amination reactions for constructing centered chirality, planar chirality, and axial chirality remain in their infancy owing to limited substrate scope and laggard ligand design. The recent surge in interest in the synthesis of C−N/N−N atropisomers, has witnessed a renaissance in asymmetric Buchwald–Hartwig amination chemistry as the first practical protocol for the preparation of C−N atropisomers. This review highlights reported asymmetric Buchwald–Hartwig amination protocols and provides a brief overview of their chemical practicality.
Color‐Tunable Dual‐Mode Organic Afterglow from Classical Aggregation‐Caused Quenching Compounds for White‐Light‐Manipulated Anti‐Counterfeiting
Authors: Liang Yaohui , Xu Chao , Zhang Huaqing , Wu Shiying , Li Jian‐An , Yang Yifan , Mao Zhu , Luo Suilian , Liu Cong , Shi Guang , Sun Fengqiang , Chi Zhenguo , Xu Bingjia
Published: December 2022

Color‐tunable dual‐mode organic afterglow excited by ultraviolet (UV) and white light was achieved from classical aggregation‐caused quenching compounds for the first time. Specifically, two luminescent systems, which could produce significant organic afterglow composed of persistent thermally activated delayed fluorescence and ultralong organic phosphorescence under ambient conditions, were constructed by doping fluorescein sodium and calcein sodium into aluminum sulfate. Their lifetimes surpassed 600 ms, and the dopant concentrations were as low as 5×10−6 wt %. Moreover, the persistent luminescence colors of the materials could be tuned from blue to green and then to yellow by simply varying the concentrations of guest compounds or the temperature in the range of 260–340 K. Inspired by these exciting results, the afterglow materials were used for UV‐ and white‐light‐manipulated anti‐counterfeiting and preparation of elastomers with different colors of persistent luminescence.
Computer‐Driven Development of Ylide Functionalized Phosphines for Palladium‐Catalyzed Hiyama Couplings
Authors: Goebel Jonas F. , Löffler Julian , Zeng Zhongyi , Handelmann Jens , Hermann Albert , Rodstein Ilja , Gensch Tobias , Gessner Viktoria H. , Gooßen Lukas J.
Published: December 2022

Palladium‐catalyzed couplings of silicon enolates with aryl electrophiles are of great synthetic utility, but often limited to expensive bromide substrates. A comparative experimental study confirmed that none of the established ligand systems allows to couple inexpensive aryl chlorides with α‐trimethylsilyl alkylnitriles. In contrast, ylide functionalized phosphines (YPhos) led to encouraging results. A statistical model was developed that correlates the reaction yields with ligand features. It was employed to predict catalyst structures with superior performance. With this cheminformatics approach, YPhos ligands were tailored specifically to the demands of Hiyama couplings. The newly synthesized ligands displayed record‐setting activities, enabling the elusive coupling of aryl chlorides with α‐trimethylsilyl alkyl nitriles. The preparative utility of the catalyst system was demonstrated by the synthesis of pharmaceutically meaningful α‐aryl alkylnitriles, α‐arylcarbonyls and biaryls.
A study of bubble size/shape evolution in microbubble countercurrent contacting flotation column
Authors: Han Jikang , Li Yanfeng , Chen Peng
Published: December 2022

Cationic collectors are widely used in the flotation of iron ore, silicate, oxides, and so forth. At this stage, so much research has been carried out on flotation column cells, but more attention needs to be paid to the hydrodynamic properties in the presence of cationic collectors in cells. In order to study foaming performance and hydrodynamic characteristics in the presence of GE609, the bubble characteristics are studied in an experimental scale flotation column. A high‐speed camera recorder is used to take bubbles' images, and the bubble size and shape under different conditions is measured by image analysis. This paper aims to explore the effect of dispersed gas and continuous liquid velocities on the bubble size and aspect ratio at different axial heights in a countercurrent flotation column in the presence and absence of GE609. In the systems, the bubble size distributions and shapes at different axial positions were obtained by using high‐speed camera technology in the superficial gas velocity (Ug) ranges of 0.0021–0.0106 m/s and superficial liquid velocity (UL) ranges of 0.00123–0.00209 m/s. Through the comparison with relevant papers and studying the experiment data, the relationship between the Sauter mean diameter and Ug, UL and axial heights have been analyzed by using multiple linear regression and dimensional analysis. The experimental data have been adopted to establish the correlation between the bubble diameter and the dimensionless array, which have been compared with other literature. And the predicted values/results of Weber and Morton number correlation in this work are relatively close to the experimental values.
Investigation of combinedN2‐ andKMnO4‐pretreatment to reduce stabilization time of polyacrylonitrile‐based carbon fibers
Authors: Liu Ziwen , Hanning Srimali , Su Yuchen , Bouhrara Mohamed , Gries Thomas
Published: December 2022

Lightweight materials are continuously gaining importance due to their potential in the reduction of energy consumption. Carbon fibers and fiber reinforced composites exert impeccable mechanical properties while maintaining a low density. However, carbon fibers and their composites have significantly high production costs, which limit their application areas. Currently they are used in areas such as the aerospace and wind energy sectors where mechanical properties maintain a supremacy above the costs. In order to expand the application opportunities of carbon fibers, it is necessary to reduce the process time during their thermal conversion and thus ultimately reduce production costs. In the present article, an innovative approach is pursued in which the residence time during stabilization is reduced by 20% using a combination of an aqueous KMnO4‐ and an atmospheric N2‐treatment of the polyacrylonitrile precursor material. After validation on a continuous production scale, the results show that it is possible to accelerate desired stabilization reactions using a combined application of KMnO4and N2. Not only can partial stabilization steps be skipped, but the activation temperature of the stabilization reactions can also be reduced, so that stabilization could proceed at lower temperatures, ultimately leading to energy and cost reductions.
Gel Electrolytes for Electrochemical Actuators and Sensors Applications
Authors: Deng Zhenzhen , Liu Yaoda , Dai Zhengfei
Published: December 2022

Advanced functional materials, especially gel electrolytes, play a very important role in the preparation of electrochemical actuators and sensors, and have received extensive attention. In this review, a general classification of gel electrolytes is firstly introduced according to the type of medium. Then, the research progress of gel electrolytes with different types used to fabricate electrochemical actuators is summarized. Next, the current research progress of gel electrolytes used in different types of electrochemical sensors, including strain sensors, stress sensors, and gas sensors is introduced. Finally, the future challenges and development prospects of electrochemical actuators and sensors based on gel electrolytes are discussed. The huge application prospects of gel electrolyte are worthy of further focusing by researchers, which will have an indispensable impact on human life and development.
Patterns of care and outcome of CIC‐rearranged sarcoma patients: A nationwide study of the French sarcoma group
Authors: Brahmi Mehdi , Gaspar Nathalie , Gantzer Justine , Toulmonde Maud , Boudou‐Rouquette Pascaline , Bompas emmanuelle , Firmin Nelly , Valentin Thibaud , Cancel Mathilde , Duffaud Florence , Bertucci Francois , Perrin Christophe , Dufresne Armelle , Marec‐Bérard Perrine , Jean‐Denis Myriam , Ray‐Coquard Isabelle , Le Loarer Francois , Pierron Gaille , Tirode Franck , Blay Jean‐Yves , Watson Sarah
Published: December 2022

Background

CIC‐rearranged sarcomas (CIC‐RS) represent the most frequent subset of “Ewing‐like” undifferentiated small round cell sarcomas. These tumors tend to be more aggressive than Ewing sarcomas. Moreover, treatment strategy can differ according to teams. The primary aim of this retrospective study was to describe the characteristics, treatments, and outcome for patients with CIC‐RS included in the French NETSARC+ database.

Methods

Pediatric and adult patients from 13 French centers with a diagnosis of CIC‐RS were registered from October 2008 to March 2021. Patients and tumors characteristics were collected from the national network NETSARC+ database (http://netsarc.sarcomabcb.org). CIC‐RS diagnosis was pathologically and molecularly confirmed with a central review by expert pathologists. Two groups of patients were studied: those treated as classical Ewing sarcomas (cohort EwS) and those treated as high‐grade soft tissue sarcomas (cohort STS) according to ESMO and/or EpSSG guidelines. Survival was calculated using the Kaplan–Meier method and the log‐rank test was used to compare survival.

Results

Among 79 patients, the male/female sex ratio was 0.7 and the median age at diagnosis was 27 years (range 2–87). With a median follow‐up of 37 months, 39 patients died of the disease. Median overall survival from diagnosis was 18 months, with no significant difference between both cohorts (p = 0.9). Nevertheless, when focusing on patients with metastatic disease at diagnosis (N = 21), all patients from cohort STS died of disease while some patients from cohort EwS were still alive and in complete remission.

Conclusion

FSG experience confirms the aggressive clinical course of CDS patients regardless of chemotherapy regimen.
Molecular Docking Studies and the Effect of Fluorophenylthiourea Derivatives on Glutathione‐Dependent Enzymes
Authors: Demir Yeliz , Türkeş Cüneyt , Küfrevioğlu Ömer İrfan , Beydemir Şükrü
Published: December 2022

Cancer is a serious problem affecting the health of all human societies. Chemotherapy refers to the use of drugs to kill cancer or the origin of cancer. In the past three decades, researchers have studied about proteins and their roles in the production of cancer cells. Glutathione S‐transferases (GSTs) are a superfamily of enzymes that play a key role in cellular detoxification, protecting against reactive electrophiles attacks, including chemotherapeutic agents. Glutathione reductase (GR) is an important antioxidant enzyme involved in protecting the cell against oxidative stress. In this current study, GST and GR enzymes were purified from human erythrocytes using affinity chromatography. GR was obtained with a specific activity of 5.95 EU/mg protein and a 52.38 % yield. GST was obtained with a specific activity of 4.88 EU/mg protein and a 74.88 % yield. The effect of fluorophenylthiourea derivatives on the purified enzymes was investigated. Afterward, KI values were found to range from 23.04±4.37 μM–59.97±13.45 μM for GR and 7.22±1.64 μM–41.24±2.55 μM for GST. 1‐(2,6‐difluorophenyl)thiourea was showed the best inhibition effect for both GST and GR enzymes. The relationships of inhibitors with 3D structures of GST and GR were explained by molecular docking studies.
Novel Chalcone‐Phenazine Hybrids Induced Ferroptosis in U87‐MG Cells through Activating Ferritinophagy
Authors: Zhang Chunhua , Ding Qifan , Xia Zhuolu , Wang Hengyu , Jiang Feng , Lu Yuanyuan
Published: December 2022

Thirty‐seven novel chalcone‐phenazine hybrid molecules (C1∼C13 and F1∼F24) with 1,2,3‐triazole or ethyl group as linkers were designed and synthesized in this study. Some compounds exhibited selective cytotoxicity against U87‐MG cancer cell lines in vitro, in which compound C4 were found to have the best antiproliferative activity. SAR study indicated 1,2,3‐triazole group may be crucial for enhancing compounds’ cytotoxicity. C4 was verified to induce ferroptosis in U87‐MG cells by transcription, lipid peroxidation, lipid ROS assays. Furthermore, C4 was up‐regulated LC3‐II, degradated FTH1, and then increasing iron resulted in the down‐regulation of NCOA4. Together, all above evidences highlighted the potential of compound C4 that triggered ferroptosis by activating ferritinophagy against U87‐MG cells.
The Cyanobacterial “Nutraceutical” Phycocyanobilin Inhibits Cysteine Protease Legumain
Authors: Wilkinson Isabel V. L. , Castro‐Falcón Gabriel , Roda‐Serrat Maria C. , Purdy Trevor N. , Straetener Jan , Brauny Melanie M. , Maier Lisa , Brötz‐Oesterhelt Heike , Christensen Lars P. , Sieber Stephan A. , Hughes Chambers C.
Published: December 2022

The blue biliprotein phycocyanin, produced by photo‐autotrophic cyanobacteria including spirulina (Arthrospira) and marketed as a natural food supplement or “nutraceutical,” is reported to have anti‐inflammatory, antioxidant, immunomodulatory, and anticancer activity. These diverse biological activities have been specifically attributed to the phycocyanin chromophore, phycocyanobilin (PCB). However, the mechanism of action of PCB and the molecular targets responsible for the beneficial properties of PCB are not well understood. We have developed a procedure to rapidly cleave the PCB pigment from phycocyanin by ethanolysis and then characterized it as an electrophilic natural product that interacts covalently with thiol nucleophiles but lacks any appreciable cytotoxicity or antibacterial activity against common pathogens and gut microbes. We then designed alkyne‐bearing PCB probes for use in chemical proteomics target deconvolution studies. Target identification and validation revealed the cysteine protease legumain (also known as asparaginyl endopeptidase, AEP) to be a target of PCB. Inhibition of this target may account for PCB's diverse reported biological activities.
Identification of quantitative trait loci for γ‐oryzanol concentration using a cross between cultivars with extremely high and low γ‐oryzanol levels
Authors: Nakano Hiroshi , Takai Toshiyuki , Kondo Motohiko
Published: December 2022

Background and Objective

Aside from its various biomedical effects, γ‐oryzanol is a biomarker for heat stress in rice (Oryza sativa L.). Recently, we found that a japonica cultivar Momiroman had the highest γ‐oryzanol among 92 cultivars. In the present study, we aimed to detect the quantitative trait locus (QTLs) for the concentrations of cycloartenyl ferulate (1), 24‐methylenecycloartanyl ferulate (2), and total γ‐oryzanol in the populations from a cross between Momiroman and an indica cultivar Takanari.

Findings

We detected the QTLs for the concentrations of 1, 2, and/or total γ‐oryzanol on chromosomes 4, 5, 9, and 11. The Momiroman alleles at the QTLs on chromosomes 4, 5, and 11 increased the concentrations of 1, 2, and/or total γ‐oryzanol, whereas the Takanari alleles at the QTLs on chromosome 9 increased.

Conclusion

Considering the literature data, the japonica alleles at the QTLs on chromosomes 4, 5, and 11 may increase the concentrations of 1, 2, and/or total γ‐oryzanol in the indica genetic background.

Significance and Novelty

This study revealed the QTLs for the concentrations of 1, 2, and/or total γ‐oryzanol on chromosomes 4, 5, 9, and 11, providing essential information for the development of cultivars with specific biomedical properties or heat stress resistance.
Ciprofloxacin induced toxic epidermal necrolysis with cholestatic hepatitis: A case report with literature review and revisit to the Naranjo adverse drug reaction probability scale
Authors: Dhakal Bishal , Dawadi Sagun , Khadka Laxman , Bohara Sujan , Neupane Shashank , Ale Magar Priajan , Pathak Bishnu Deep , Upadhaya Regmi Binit
Published: December 2022

Ciprofloxacin, among the many Fluoroquinolones, has been widely used as a broad‐spectrum antibiotic due to its wide range of action and relatively safe adverse effect profile. However, among the cutaneous adverse drug reactions due to Ciprofloxacin, toxic epidermal necrolysis occurring along with cholestatic hepatitis is a rare one. Here, we present a case of a 22‐year‐old male patient who was diagnosed with toxic epidermal necrolysis with cholestatic hepatitis secondary to Ciprofloxacin. Naranjo adverse drug reaction probability scale was used for the causal association.
A case of pericarditis in a middle‐aged woman with COVID‐19
Authors: Kushima Hisako , Shimizu Sayaka , Koide Yohei , Kawamura Akira , Ishii Hiroshi
Published: December 2022

The frequency of pericarditis as a complication in COVID‐19 patients without underlying disease is not well known. We report a case of COVID‐19 presenting with pericarditis without myocarditis or severe respiratory symptoms in a middle‐aged woman, who had neither underlying disease nor previous diagnosis of COVID‐19.
Childhood Guillain–Barre syndrome in the SARS‐CoV‐2 era: Is there any causative relation?
Authors: Pourbakhtyaran Elham , Heidari Morteza , Akbari Masood Ghahvechi , Mohammadi Mahmoud , Badv Reza Shervin , Zamani Gholamreza , Tavasoli Ali Reza , Rezaei Zahra , Mamishi Setareh , Haji Esmaeil Memar Elmira , Hosseiny Seyyed Mohammad Mahdi , Ghabeli Homa , Haghighi Roya , Ashrafi Mahmoud Reza
Published: December 2022

We reported an association between SARS‐CoV‐2 infection and Guillain–Barre syndrome (GBS). From 37 patients with GBS, previous SARS‐CoV‐2 clinical clues, including fever, cough, and diarrhea, were recorded in 18 patients. Among them, SARS‐CoV‐2 IgG was detected in seven patients, considered confirmed as cases. SARS‐CoV‐2 PCR was positive in just one patient. Although we found no increase in patient recruitment during the pandemic compared to previous years, our study indicated that SARS‐CoV‐2 is associated with poorer outcomes regarding GBS disability scale and hospital stay.
MOx@VOx‐Pd‐type Nanorods and Nanotubes as Catalysts for Selective Reduction of NO
Authors: Warmuth Lucas , Lott Patrick , Deutschmann Olaf , Feldmann Claus
Published: December 2022

Vanadium oxide (VOx‐Pd) nanotubes as well as VOx‐coated ZnO nanorods (ZnO@VOx‐Pd) and VOx‐coated, layered‐titania nanotubes (l‐TiO2@VOx‐Pd) are decorated with Pd nanoparticles and evaluated for selective catalytic reduction with hydrogen (H2‐SCR) for the first time. The nanostructures exhibit lengths of 300 to 700 nm, diameters of 20–100 nm and, in the case of the nanotubes, an inner tube diameter of about 10 nm. Pd nanoparticles (14±5 nm) are well‐dispersed over the respective nanorod/nanotube nanostructure. Structure and composition are characterized by SEM, TEM, EDXS with element mapping, XPS, FT‐IR, XRD, and sorption analysis. Thermal analysis indicates the nanostructures to be thermally stabile up to 350 °C (VOx), and 500 °C (ZnO@VOx, l‐TiO2@VOx). All catalysts are tested for their activity in regard of the selective catalytic reduction of NO with H2, revealing a significant impact of the catalyst support on both activity and selectivity. Specifically, l‐TiO2@VOx nanotubes show promising properties with an activity up to 70 % and a selectivity up to 80 % N2.
Bimetallic Catalysts for Sustainable Chemistry: Surface Redox Reactions For Tuning The Catalytic Surface Composition
Authors: Especel Catherine , Lafaye Gwendoline , Epron Florence
Published: December 2022

The development of a bimetallic catalyst for a given reaction requires not only the selection of the appropriate metals M1 and M2 but also the control as far as possible of the distribution of the two metals together and at the support surface in the case of supported catalysts. Preparation methods using redox reactions specifically enable the deposition of a second metal M2 at the surface of monometallic M1 nanoparticles, leading in most cases to core‐shell nanoparticles with strong metal‐metal interactions. Various methods are possible depending on the electrochemical potentials of the species involved: either a direct redox reaction, also named galvanic replacement, or the reduction of an intermediate reducing agent activated at the surface of M1. In this minireview, the fundamental bases of the preparation of bimetallic catalysts by both types of redox reactions and the recent advances in that domain are described.
Four‐Step Synthesis of (−)‐4‐epi‐Presilphiperfolan‐8α‐ol by Intramolecular Iron Hydride Atom Transfer‐Mediated Ketone‐Alkene Coupling and Studies to Accesstrans‐Hydrindanols with a Botryane Scaffold
Authors: Saladrigas Mar , Gómez‐Bengoa Enrique , Bonjoch Josep , Bradshaw Ben
Published: December 2022

From an (R)‐(+)‐pulegone‐derived building block that incorporates the stereo‐defined tertiary carbon bearing a methyl group, as found in the targeted sesquiterpenoid, a four‐step synthesis of (−)‐4‐epi‐presilphiperfolan‐8‐α‐ol was achieved. The key processes involved are a ring‐closing metathesis leading to a bridged alkene‐tethered ketone and its subsequent FeIII‐mediated metal‐hydride atom transfer (MHAT) transannular cyclization. This synthetic method, implying an irreversible addition of a carbon‐centered radical upon a ketone by means of a hydrogen atom transfer upon the alkoxy radical intermediate, was also applied in the synthesis oftrans‐fused hydrindanols structurally related to botrydial compounds.
Vibrational Sum Frequency Generation Spectra of Water‐Vapor Interfaces Covered by Alcohols: Effects of Surface Coverage and Coupling between Oscillators
Authors: Das Banshi , Chandra Amalendu
Published: December 2022

The present study deals with the effects of varying coverage of water surface by alcohols on the vibrational sum frequency generation (VSFG) spectrum of interfacial water. We have considered two different alcohols: Tertiary butyl alcohol (TBA) whose alkyl part is fully branched and stearyl alcohol (STA) which has a long linear alkyl chain with larger hydrophobic surface area than that of TBA. With increase of the alcohol concentration, the hydrogen bonded OH stretch region of the VSFG spectrum is found to change following a regular trend for the STA‐water system, whereas non‐monotonic variation of the VSFG spectrum is observed for the TBA‐water system which can be correlated with the presence of very different interactions of TBA molecules at different concentrations. On increasing the concentration of TBA, the hydrophobic groups get more tilted towards the water phase and significant hydrophobic interactions are introduced at higher concentrations. Whereas, for STA, there is a gradual increase in the hydrophilic interaction. Because of stacking interactions between the long chain alkyl groups, the hydrophobic parts stay outward from the water phase at higher concentrations and a regular change in the VSFG spectrum is observed. We have also presented a computationally efficient scheme to calculate the VSFG spectrum of interfacial systems for coupled oscillators which is expected to be beneficial for the treatment of coupling where the interfacial system size is inherently large.
An ecosystems perspective on the reconversion of offshore platforms: Towards a multi‐level governance
Authors: Basile Vincenzo , Loia Francesca , Capobianco Nunzia , Vona Roberto
Published: December 2022

The decommissioning of offshore platforms has been increasingly discussed due to its economic, social, and environmental impacts. The high complexity of this multilevel context pushes for the adoption of a service ecosystem view to explore the value propositions and actors' relations involved in resource exchanges. This study follows a mixed‐method approach based on semistructured interviews conducted with oil and gas stakeholders and content analysis of the secondary data collected. The results highlight the ecosystem elements and identify the main drivers for sustainable growth in the process of the reconversion of oil and gas assets. A “meta” level is theorized to investigate how the actors' purposes can be harmonized with an ecosystem's goal to encourage the diffusion of a sustainable‐oriented culture in the context of offshore decommissioning. In this sense, the study provides several insights for researchers and professionals in both the local and national governance field and the oil and gas industry.
Synergistic Combination of Fermi Level Equilibrium and Plasmonic Effect for Formic Acid Dehydrogenation
Authors: Zhu Jiannan , Huang Jing , Dai Jiawei , Jiang Lipei , Xu You , Chen Rong , Li Longhua , Fu Xiaoqi , Wang Zhengyun , Liu Hongfang , Li Guangfang
Published: December 2022

Developing an efficient catalyst for formic acid (FA) dehydrogenation is a promising strategy for safe hydrogen storage and transportation. Herein, we successfully developed trimetallic NiAuPd heterogeneous catalysts through a galvanic replacement reaction and a subsequent chemical reduction process to boost hydrogen generation from FA decomposition at room temperature by coupling Fermi level engineering with plasmonic effect. We demonstrated that Ni worked as an electron reservoir to donate electrons to Au and Pd driven by Fermi level equilibrium whereas plasmonic Au served as an optical absorber to generate energetic hot electrons and a charge‐redistribution mediator. Ni and Au worked cooperatively to promote the charge heterogeneity of surface‐active Pd sites, leading to enhanced chemisorption of formate‐related intermediates and eventually outstanding activity (342 mmol g−1 h−1) compared with bimetallic counterpart. This work offers excellent insight into the rational design of efficient catalysts for practical hydrogen energy exploitation.
Differences in the intrinsic chondrogenic potential of human mesenchymal stromal cells and iPSC‐derived multipotent cells
Authors: Xiang Shiqi , Lin Zixuan , Makarcyzk Meagan J. , Riewruja Kanyakorn , Zhang Yiqian , Zhang Xiurui , Li Zhong , Clark Karen L. , Li Eileen , Liu Silvia , Hao Tingjun , Fritch Madalyn R. , Alexander Peter G. , Lin Hang
Published: December 2022

Background

Human multipotent progenitor cells (hiMPCs) created from induced pluripotent stem cells (iPSCs) represent a new cell source for cartilage regeneration. In most studies, bone morphogenetic proteins (BMPs) are needed to enhance transforming growth factor‐β (TGFβ)‐induced hiMPC chondrogenesis. In contrast, TGFβ alone is sufficient to result in robust chondrogenesis of human primary mesenchymal stromal cells (hMSCs). Currently, the mechanism underlying this difference between hiMPCs and hMSCs has not been fully understood.

Methods

In this study, we first tested different growth factors alone or in combination in stimulating hiMPC chondrogenesis, with a special focus on chondrocytic hypertrophy. The reparative capacity of hiMPCs‐derived cartilage was assessed in an osteochondral defect model created in rats. hMSCs isolated from bone marrow were included in all studies as the control. Lastly, a mechanistic study was conducted to understand why hiMPCs and hMSCs behave differently in responding to TGFβ.

Results

Chondrogenic medium supplemented with TGFβ3 and BMP6 led to robust in vitro cartilage formation from hiMPCs with minimal hypertrophy. Cartilage tissue generated from this new method was resistant to osteogenic transition upon subcutaneous implantation and resulted in a hyaline cartilage‐like regeneration in osteochondral defects in rats. Interestingly, TGFβ3 induced phosphorylation of both Smad2/3 and Smad1/5 in hMSCs, but only activated Smad2/3 in hiMPCs. Supplementing BMP6 activated Smad1/5 and significantly enhanced TGFβ’s compacity in inducing hiMPC chondrogenesis. The chondro‐promoting function of BMP6 was abolished by the treatment of a BMP pathway inhibitor.

Conclusions

This study describes a robust method to generate chondrocytes from hiMPCs with low hypertrophy for hyaline cartilage repair, as well as elucidates the difference between hMSCs and hiMPCs in response to TGFβ. Our results also indicated the importance of activating both Smad2/3 and Smad1/5 in the initiation of chondrogenesis.
Loss of G0/G1 switch gene 2 (G0S2) promotes disease progression and drug resistance in chronic myeloid leukaemia (CML) by disrupting glycerophospholipid metabolism
Authors: Gonzalez Mayra A. , Olivas Idaly M. , Bencomo‐Alvarez Alfonso E. , Rubio Andres J. , Barreto‐Vargas Christian , Lopez Jose L. , Dang Sara K. , Solecki Jonathan P. , McCall Emily , Astudillo Gonzalo , Velazquez Vanessa V. , Schenkel Katherine , Reffell Kelaiah , Perkins Mariah , Nguyen Nhu , Apaflo Jehu N. , Alvidrez Efren , Young James E. , Lara Joshua J. , Yan Dongqing , Senina Anna , Ahmann Jonathan , Varley Katherine E. , Mason Clinton C. , Eide Christopher A. , Druker Brian J. , Nurunnabi Md , Padilla Osvaldo , Bajpeyi Sudip , Eiring Anna M.
Published: December 2022

Tyrosine kinase inhibitors (TKIs) targeting BCR::ABL1 have turned chronic myeloid leukaemia (CML) from a fatal disease into a manageable condition for most patients. Despite improved survival, targeting drug‐resistant leukaemia stem cells (LSCs) remains a challenge for curative CML therapy. Aberrant lipid metabolism can have a large impact on membrane dynamics, cell survival and therapeutic responses in cancer. While ceramide and sphingolipid levels were previously correlated with TKI response in CML, the role of lipid metabolism in TKI resistance is not well understood. We have identified downregulation of a critical regulator of lipid metabolism, G0/G1 switch gene 2 (G0S2), in multiple scenarios of TKI resistance, including (1) BCR::ABL1 kinase‐independent TKI resistance, (2) progression of CML from the chronic to the blast phase of the disease, and (3) in CML versus normal myeloid progenitors. Accordingly, CML patients with low G0S2 expression levels had a worse overall survival. G0S2 downregulation in CML was not a result of promoter hypermethylation or BCR::ABL1 kinase activity, but was rather due to transcriptional repression by MYC. Using CML cell lines, patient samples and G0s2 knockout (G0s2−/−) mice, we demonstrate a tumour suppressor role for G0S2 in CML and TKI resistance. Our data suggest that reduced G0S2 protein expression in CML disrupts glycerophospholipid metabolism, correlating with a block of differentiation that renders CML cells resistant to therapy. Altogether, our data unravel a new role for G0S2 in regulating myeloid differentiation and TKI response in CML, and suggest that restoring G0S2 may have clinical utility.