bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing Apoe with divalent‐siRNAs improves amyloid burden and activates immune response pathways in Alzheimer's disease
Authors: Ferguson Chantal M. , Hildebrand Samuel , Godinho Bruno M. D. C. , Buchwald Julianna , Echeverria Dimas , Coles Andrew , Grigorenko Anastasia , Vangjeli Lorenc , Sousa Jacquelyn , McHugh Nicholas , Hassler Matthew , Santarelli Francesco , Heneka Michael T. , Rogaev Evgeny , Khvorova Anastasia 
Published: February 2024

AbstractINTRODUCTIONThe most significant genetic risk factor for late‐onset Alzheimer's disease (AD) is APOE4, with evidence for gain‐ and loss‐of‐function mechanisms. A clinical need remains for therapeutically relevant tools that potently modulate APOE expression.METHODSWe optimized small interfering RNAs (di‐siRNA, GalNAc) to potently silence brain or liver Apoe and evaluated the impact of each pool of Apoe on pathology.RESULTSIn adult 5xFAD mice, siRNAs targeting CNS Apoe efficiently silenced Apoe expression and reduced amyloid burden without affecting systemic cholesterol, confirming that potent silencing of brain Apoe is sufficient to slow disease progression. Mechanistically, silencing Apoe reduced APOE‐rich amyloid cores and activated immune system responses.DISCUSSIONThese results establish siRNA‐based modulation of Apoe as a viable therapeutic approach, highlight immune activation as a key pathway affected by Apoe modulation, and provide the technology to further evaluate the impact of APOE silencing on neurodegeneration.
Biocatalytic Steroidal 9α‐Hydroxylation and Fragmentation Enable the Concise Chemoenzymatic Synthesis of 9,10‐Secosteroids
Authors: Song Hanxin , Zhang Zeliang , Cao Chunyang , Tang Zhijun , Gui Jinghan , Liu Wen 
Published: February 2024

Abstract9,10‐Secosteroids are an important group of marine steroids with diverse biological activities. Herein, we report a chemoenzymatic strategy for the concise, modular, and scalable synthesis of ten naturally occurring 9,10‐secosteroids from readily available steroids in three to eight steps. The key feature lies in utilizing a Rieske oxygenase‐like 3‐ketosteroid 9α‐hydroxylase (KSH) as the biocatalyst to achieve efficient C9−C10 bond cleavage and A‐ring aromatization of tetracyclic steroids through 9α‐hydroxylation and fragmentation. With synthesized 9,10‐secosteroides, structure–activity relationship was evaluated based on bioassays in terms of previously unexplored anti‐infective activity. This study provides experimental evidence to support the hypothesis that the biosynthetic pathway through which 9,10‐secosteroids are formed in nature shares a similar 9α‐hydroxylation and fragmentation cascade. In addition to the development of a biomimetic approach for 9,10‐secosteroid synthesis, this study highlights the great potential of chemoenzymatic strategies in chemical synthesis.
Highly Conductive Imidazolate Covalent Organic Frameworks with Ether Chains as Solid Electrolytes for Lithium Metal Batteries
Authors: Yuan Yufei , Zhang Zeyu , Zhang Zhengyang , Bang Ki‐Taek , Tian Ye , Dang Zhengzheng , Gu Muhua , Wang Rui , Tao Ran , Lu Yingying , Wang Yanming , Kim Yoonseob 
Published: February 2024

AbstractPoly(ethylene oxide) (PEO)‐based electrolytes are often used for Li+ conduction as they can dissociate the Li salts efficiently. However, high entanglement of the chains and lack of pathways for rapid ion diffusion limit their applications in advanced batteries. Recent developments in ionic covalent organic frameworks (iCOFs) showed that their highly ordered structures provide efficient pathways for Li+ transport, solving the limitations of traditional PEO‐based electrolytes. Here, we present imidazolate COFs, PI‐TMEFB‐COFs, having methoxyethoxy chains, synthesized by Debus–Radziszewski multicomponent reactions and their ionized form, Li+@PI‐TMEFB‐COFs, showing a high Li+ conductivity of 8.81 mS cm−1 and a transference number of 0.974. The mechanism for such excellent electrochemical properties is that methoxyethoxy chains dissociate LiClO4, making free Li+, then those Li+ are transported through the imidazolate COFs’ pores. The synthesized Li+@PI‐TMEFB‐COFs formed a stable interface with Li metal. Thus, employing Li+@PI‐TMEFB‐COFs as the solid electrolyte to assemble LiFePO4 batteries showed an initial discharge capacity of 119.2 mAh g−1 at 0.5 C, and 82.0 % capacity and 99.9 % Coulombic efficiency were maintained after 400 cycles. These results show that iCOFs with ether chains synthesized via multicomponent reactions can create a new chapter for making solid electrolytes for advanced rechargeable batteries.
Cyclic Diaryl λ3‐Bromanes as a Precursor for Regiodivergent Alkynylation Reactions
Authors: De Abreu Maxime , Rogge Torben , Lanzi Matteo , Saiegh Tomas J. , Houk Kendall N. , Wencel‐Delord Joanna 
Published: February 2024

AbstractRegiodivergent reactions are a fascinating tool to rapidly access molecular diversity while using identical coupling partners. We have developed a new approach for regiodivergent synthesis using the dual character of hypervalent bromines. In addition to the recently reported reactivity of hypervalent bromines as aryne precursors, the first transition metal‐catalyzed reaction is reported. Accordingly, the development of these two complementary transformations allows for the alteration of regioselectivity to furnish both ortho‐ and meta‐substituted alkynylation products. Mechanistic and computational studies show how these selectivities are controlled.
Advancements in Olive‐derived Carbon: Preparation Methods and Sustainable Applications
Authors: Shabi A. H. , Prima Hardianto Yuda , Shaheen Shah Syed , Omar Al‐Qwairi Fatima , Mohamed Mostafa M. , Nasiruzzaman Shaikh M. , Saeed Alzahrani Atif , Aziz Md. Abdul 
Published: February 2024

AbstractIn the realm of material science, carbon materials, especially olive‐derived carbon (ODC), have become vital due to their sustainability and diverse properties. This review examines the sustainable extraction and use of ODC, a carbohydrate‐rich by‐product of olive biomass. We focus on innovative preparation techniques like pyrolysis, which are crucial forenhancing ODC′s microstructure and surface properties. Variables such as activating agents, impregnation ratios, and pyrolysis conditions significantly influence these properties. ODC′s high specific surface area renders it invaluable for applications in energy storage (batteries and supercapacitors) and environmental sectors (water purification, hydrogen storage). Its versatility and accessibility underscore its potential for broad industrial use, makingit as a key element in sustainable development. This review provides a detailed analysis of ODC preparation methodologies, its various applications, and its role in advancing sustainable energy solutions. We highlight the novelty of ODC research and its impact on future studies, establishing this review as a crucial resource for researchers and practitioners in sustainable carbon materials. As global focus shifts towards eco‐friendly solutions, ODC emerges as a critical component in shaping a sustainable, innovation‐driven future.
Using general‐case procedures outside of autism intervention: A systematic review
Authors: Hickey Carleana R. , Reeve Sharon A. , Reeve Kenneth F. , Deshais Meghan A. , Vladescu Jason C. 
Published: February 2024

AbstractRecently, there has been a call for the application of behavior analytic technology to more diverse domains. Although general‐case procedures are most often applied in autism service delivery, they can be applied to more diverse domains ranging from organizational behavior management to public health initiatives. This literature review, therefore, provides an overview of technological descriptions of general‐case procedures and their applications in areas other than autism intervention. Evaluated variables include the population, independent and dependent variables, generalization measures, and social validity assessments. The results suggest that most researchers are not using a technological description of general‐case procedures nor are they assessing for generalization. Recommendations for future researchers and clinicians include better descriptions of general‐case procedures, evaluation with different populations, assessment of acceptability and more comprehensive evaluations of generalization.
Evaluation of PDL1 positive cancer cell‐specific binding activity of recombinant anti‐PDL1 scFv
Authors: Kim Sun‐Hee , Park Hae‐Min , Jeong Hee‐Jin 
Published: February 2024

AbstractProgrammed cell death‐ligand 1 (PDL1) is a transmembrane protein that is characterized as an immune regulatory molecule. We recently developed a recombinant single‐chain fragment of variable domain (scFv) against PDL1, which showed high binding efficiency to purified recombinant PDL1 protein. However, at that time, proof‐of‐concept data for the effect of scFv using PDL1‐expressing cells was lacking. In this study, we conducted two kinds of cell‐based immunoassays, western blotting and enzyme‐linked immunosorbent assay, using anti‐PDL1 scFv. The results indicate that scFv can selectively and sensitively detect PDL1 from PDL1 positive human cancer cell lines. Our findings suggest that scFv could be used as a potential PDL1 inhibitor agent and probe for cell‐based immunoassays to detect PDL1.
Schizandrin A induces non‐small cell lung cancer apoptosis by suppressing the epidermal growth factor receptor activation
Authors: Zhu Linhai , Wang Yanye , Huang Xuhua , Liu Xide , Ye Bo , He Yi , Yu Haojie , Lv Wang , Wang Luming , Hu Jian 
Published: February 2024

AbstractObjectiveThe purpose of this study is to explore the biological mechanism of Schizandrin A (SchA) inducing non‐small cell lung cancer (NSCLC) apoptosis.MethodsThe reverse molecular docking tool “Swiss Target Prediction” was used to predict the targets of SchA. Protein–protein interaction analysis was performed on potential targets using the String database. Functional enrichment analyses of potential targets were performed with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The conformation of SchA binding to target was simulated by chemical‐protein interactomics and molecular docking. The effect of SchA on the expression and phosphorylation level of EGFR was detected by Western blot. Lipofectamine 3000 and EGFR plasmids were used to overexpress EGFR. Apoptosis was tested with Annexin V‐FITC and propidium iodide staining, and cell cycle was detected by propidium iodide staining.ResultsThe “Swiss Target Prediction” database predicted 112 and 111 targets based on the 2D and 3D structures of SchA, respectively, of which kinases accounted for the most, accounting for 24%. Protein interaction network analyses showed that molecular targets such as ERBB family and SRC were at the center of the network. Functional enrichment analyses indicated that ERBB‐related signaling pathways were enriched. Compound‐protein interactomics and molecular docking revealed that SchA could bind to the ATP‐active pocket of the EGFR tyrosine kinase domain. Laboratory results showed that SchA inhibited the phosphorylation of EGFR. Insulin could counteract the cytotoxic effect of SchA. EGFR overexpression and excess EGF or IGF‐1 had limited impacts on the cytotoxicity of SchA.ConclusionsNetwork pharmacology analyses suggested that ERBB family members may be the targets of SchA. SchA can inhibit NSCLC at least in part by inhibiting EGFR phosphorylation, and activating the EGFR bypass can neutralize the cytotoxicity of SchA.
A Review on Catalytic Progress of Polysulfide Redox Reactions on Transition Metal Sulfides in Li‐S Batteries from Structural Perspective
Authors: Li Haocheng , Wang Xueyu , Ma Hongwei , Guo Daying , Wu Lianhui , Jin Huile , Chen Xi'an , Wang Shun 
Published: February 2024

AbstractThe commercialization of Li−S batteries is seriously hindered by polysulfides with severe shuttle effect, and the inherent insulating properties and slow reaction kinetics of insoluble Li2S products. Transition metal sulfides (TMSs) have a high adsorption capacity for polysulfides and have been shown to have a strong catalytic effect on polysulfide conversion reactions. This paper reviews the research on the application of Unary TMSs, heterostructures, etc. in Li−S batteries, and gives some research methods for TMD catalysts in Li−S batteries. Finally, it points out the main focuses and direction of future Li−S battery research and development. It aims to provide some insights into the design and manufacture of advanced Li−S batteries for commercial use.
Efficient Synthesis and Structural Analysis of Chiral 4,4′‐Biazulene
Authors: Hatakenaka Ryoji , Nishikawa Nanami , Mikata Yuji , Aoyama Hiroki , Yamashita Kohsuke , Shiota Yoshihito , Yoshizawa Kazunari , Kawasaki Yuuya , Tomooka Katsuhiko , Kamijo Shin , Tani Fumito , Murafuji Toshihiro 
Published: February 2024

Abstract4,4′‐Biazulene is a potentially attractive key component of an axially chiral biaryl compound, however, its structure and properties have not been clarified owing to the lack of its efficient synthesis. We report a breakthrough in the reliable synthesis of 4,4′‐biazulene, which is achieved by the access to azulen‐4‐ylboronic acid pinacol ester and 4‐iodoazulene as novel key synthetic intermediates for the Suzuki‐Miyaura cross‐coupling reaction. The X‐ray crystallographic analysis of 4,4′‐biazulene confirmed its axial chirality. The enantiomers of 4,4′‐biazulene were successfully resolved by HPLC on the chiral stationary phase column. The kinetic experiments and DFT calculations indicate that the racemization energy barrier of 4,4′‐biazulene is comparable to that of 1,1′‐binaphthyl.
When is an Imine Directing Group a Transient Imine Directing Group in C−H Functionalization?
Authors: Higham Joe I. , Ma Tsz‐Kan , Bull James A. 
Published: February 2024

Abstract‘Transient’ C−H functionalization has emerged in recent years to describe the use of a dynamic linkage, often an imine, to direct cyclometallation and subsequent functionalization. As the field continues to grow in popularity, we consider the features that make an imine directing group transient. A transient imine should be i) formed dynamically in situ, ii) avoid discrete introduction or cleavage steps, and iii) offer the potential for catalysis in both the directing group and metal. This concept article contrasts transient imines with pioneering early studies of imines as directing groups for the formation of metallacycles and the use of preformed imines in C−H functionalization. Leading developments in the use of catalytic additives to form transient directing groups (as aldehyde or amine) are covered including selected highlights of the most recent examples of catalytic imine directed C−H functionalization with transition metals.
Stabilisation of the [SiH6]2− Anion within a Supramolecular Assembly
Authors: Huo Ryan , Armstrong Alicia J. , Nelmes Gareth R. , Lawes Douglas J. , Edwards Alison J. , McMullin Claire L. , Hicks Jamie 
Published: February 2024

AbstractThe hypercoordinate [SiH6]2− anion is not stable in solution. Here, we report the room temperature, solution stable molecular [SiH6]2− complex, [{KCa(NON)(OEt2)}2][SiH6] (NON=4,5‐bis(2,6‐diisopropylanilido)‐2,7‐di‐tert‐butyl‐9,9‐dimethyl‐xanthene)), where the [SiH6]2− anion is stabilised within a supramolecular assembly that mimics the solid‐state environment of the anion in the lattice of K2SiH6. Solution‐state reactivity of the complex towards carbon monoxide, benzaldehyde, azobenzene and acetonitrile is reported, yielding a range of reduction and C−C coupled products.
Review on the Impact of Impeller‐induced Hydrodynamics on Suspension Cell Culture for Production of Biopharmaceuticals
Authors: Pörtner Ralf , Freiberger Fabian , Möller Johannes 
Published: February 2024

AbstractHydrodynamic effects continue to play a crucial role in the design and operation of bioreactors for cultivating mammalian cells. Despite intensive studies in the past the link between hydrodynamics and biological process behaviour is still not fully understood. Common methods to describe dependencies, which relay mostly on averaged hydrodynamic parameters, does not seem to be suitable, as they do not incorporate the hydrodynamic heterogeneity. Within this review first a brief introduction to hydrodynamic effects is given, followed by an evaluation of common process design approaches with respect to hydrodynamic effects and recommendations for process development.
Shortened telomere length in peripheral blood leukocytes is associated with cumulative radioactive iodine doses in patients with differentiated thyroid carcinoma
Authors: Choi Hoonsung , Cho Sun Wook , Kim Hwan Hee , Yi Ka Hee , Park Do Joon , Park Young Joo 
Published: February 2024

AbstractBackgroundTelomere length is associated with cancer risk and cancer aggressiveness. Radioactive iodine (RAI) therapy for thyroid cancer has raised concerns for second primary malignancy (SPM) in patients with high cumulative doses. The association between RAI dose and peripheral blood leukocyte telomere length was examined.MethodsA total of 425 patients were included who underwent total thyroidectomy and were followed up for at least 1 year with or without RAI treatment. The relative telomere length (RTL) of the patients was assessed via a quantitative polymerase chain reaction amplification method. RAI doses were divided into five groups on the basis of cumulative dose, and a comparison was made among these groups.ResultsThe number of patients with RAI treatment was 287 (67.5%), and the cumulative RAI dose was 3.33 GBq (range, 1.11–131.35 GBq). The mean RTL was significantly shorter in the highest RAI group (>22.2 GBq) compared to both the no‐RAI and lower dose groups. The association between RAI dose and RTL was positive in the lower RAI group (1.1–3.7 GBq) and negative in the highest RAI group in both univariate and multivariate analyses. We observed 59 (13.9%) SPMs and 20 (4.7%) mortalities, and RTL did not show a significant risk effect for all‐cause, thyroid cancer–specific, or SPM‐specific mortality.ConclusionsIn patients with thyroid cancer who underwent total thyroidectomy, peripheral blood leukocyte telomere length exhibited a significant association with cumulative RAI dose higher than 22.2 GBq. These results suggest the possibility of telomere length shortening in patients who undergo high‐dose RAI treatment.
How Do Risk Evaluation and Mitigation Strategies Impact Clinical Practice? A National Survey of Physicians
Authors: Sarpatwari Ameet , Lu Zhigang , Russo Massimiliano , Zakoul Heidi , Lee Su Been , Toyserkani Gita A. , Zhou Esther H. , LaCivita Cynthia , Shaw Katherine Hyatt Hawkins , Zendel Laura , Dal Pan Gerald J. , Kesselheim Aaron S. 
Published: February 2024

The US Food and Drug Administration can require risk evaluation and mitigation strategy (REMS) programs for prescription drugs to ensure the benefits of use outweigh the risks. We conducted a national survey of physicians' experiences prescribing eight REMS‐covered drugs: (1) ambrisentan; (2) bosentan; (3) clozapine; (4) isotretinoin; (5–7) the multiple myeloma (MM) drugs lenalidomide, pomalidomide, thalidomide; and (8) sodium oxybate. Between May 2022 and January 2023, we surveyed 5,331 physician prescribers of these drugs, and 1,295 (24%) returned surveys (range: 149 for bosentan to 226 for MM drugs). Although 765 (68%) respondents thought the certification process provided useful drug information, 757 (67%) wanted materials to include benefit data and 944 (84%) non‐REMS‐related risk data. A majority (704, 63%) thought the safe use requirements facilitated discussion with patients, but a similar number (637, 57%) attributed delayed medication access to these requirements. In multivariable modeling, MM drug and isotretinoin respondents were less likely than sodium oxybate respondents to agree that the certification process provided useful drug information (MM drug: odds ratio (OR) = 0.37, 95% confidence interval (CI) = 0.25–0.55; isotretinoin: OR = 0.39, 95% CI = 0.25–0.61), and isotretinoin, clozapine, and bosetan respondents were more likely than sodium oxybate respondents to agree that the safe use requirements often delayed medication access (isotretinoin: OR = 5.83, 95% CI = 3.70–9.19; clozapine: OR = 1.65, 95% CI = 1.08–2.54; bosentan: OR = 1.78, 95% CI = 1.12–2.85). Most physicians believe REMS programs convey useful drug safety information and facilitate discussion with patients but also seek information on benefits and non‐REMS‐related risks and better integration of REMS processes into clinical workflows.
ESG controversies and corporate performance: The moderating effect of governance mechanisms and ESG practices
Authors: Elamer Ahmed A. , Boulhaga Mounia 
Published: February 2024

AbstractThis paper investigates the relationship between Environmental, Social, and Governance (ESG) controversies and firm performance, examining the moderating influences of corporate governance structures and ESG practices. Utilizing quantitative methods, we analyze data from 5360 firm‐year observations. Our findings reveal a significant negative relation between ESG controversies and firm performance. However, well‐defined corporate governance frameworks and internal ESG strategies mitigate these adverse impacts and can transform these controversies into growth opportunities and reputation enhancement. A comparative analysis involving the United Kingdom and other European Union nations highlights the influence of geographical and regulatory contexts in shaping this dynamic. These results offer valuable insights for policymakers, corporate strategists, and investors, emphasizing the role of governance in navigating ESG controversies and enhancing firm resilience and adaptability. The study contributes to the sustainability field by providing a nuanced understanding of the interaction between ESG controversies, corporate governance, and firm performance.
Biodiesel as a Sustainable Platform Chemical Enabled by Selective Partial Hydrogenation: Compounds Outplace Combustion?!
Authors: Roth Thomas F. H. , Kühl Alexander , Spiekermann Maximilian L. , Wegener Hannes W. , Seidensticker Thomas 
Published: February 2024

AbstractThe hydrogenation of polyunsaturated fatty acids (PUFAs) in vegetable oils and their derivatives is essential for their use in many areas, such as biofuels and food chemistry. However, no attempts have been made to adapt this technology to the requirements of further chemical utilization of fatty acid methyl esters as molecular building blocks, especially for particularly promising double‐bond reactions. In this work, we, therefore, use three homogeneous catalytic model reactions (hydroformylation, isomerizing methoxycarbonylation, and ethenolysis) to show, firstly, that it is already known from the literature that high PUFA contents have a negative impact on activity and selectivity. Subsequently, using the example of soybean and canola biodiesel, we demonstrate that these key figures can be drastically improved by a preceding selective partial hydrogenation. This makes it possible to first reduce the share of PUFAs to <1 w % without causing significant overhydrogenation and then to carry out hydroformylation, methoxycarbonylation, and ethenolysis with significantly increased activity (up to twentyfold) and selectivity (up to 80 % increase). With these findings, we hope to convince the scientific and industrial world of the potential of selective partial hydrogenation as a key technology for utilizing renewable raw materials and to encourage its effective use in future work.