bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gene Electrotransfer via Conductivity‐Clamped Electric Field Focusing Pivots Sensori‐Motor DNA Therapeutics: “A Spoonful of Sugar Helps the Medicine Go Down”
Authors: Pinyon Jeremy L. , von Jonquieres Georg , Crawford Edward N. , Abed Amr Al , Power John M. , Klugmann Matthias , Browne Cherylea J. , Housley David M. , Wise Andrew K. , Fallon James B. , Shepherd Robert K. , Lin John Y. , McMahon Catherine , McAlpine David , Birman Catherine S. , Lai Waikong , Enke Ya Lang , Carter Paul M. , Patrick James F. , Gay Robert D. , Marie Corinne , Scherman Daniel , Lovell Nigel H. , Housley Gary D. 
Published: June 2024

AbstractViral vectors and lipofection‐based gene therapies have dispersion‐dependent transduction/transfection profiles that thwart precise targeting. The study describes the development of focused close‐field gene electrotransfer (GET) technology, refining spatial control of gene expression. Integration of fluidics for precise delivery of “naked” plasmid deoxyribonucleic acid (DNA) in sucrose carrier within the focused electric field enables negative biasing of near‐field conductivity (“conductivity‐clamping”–CC), increasing the efficiency of plasma membrane molecular translocation. This enables titratable gene delivery with unprecedently low charge transfer. The clinic‐ready bionics‐derived CC‐GET device achieved neurotrophin‐encoding miniplasmid DNA delivery to the cochlea to promote auditory nerve regeneration; validated in deafened guinea pig and cat models, leading to improved central auditory tuning with bionics‐based hearing. The performance of CC‐GET is evaluated in the brain, an organ problematic for pulsed electric field‐based plasmid DNA delivery, due to high required currents causing Joule‐heating and damaging electroporation. Here CC‐GET enables safe precision targeting of gene expression. In the guinea pig, reporter expression is enabled in physiologically critical brainstem regions, and in the striatum (globus pallidus region) delivery of a red‐shifted channelrhodopsin and a genetically‐encoded Ca2+ sensor, achieved photoactivated neuromodulation relevant to the treatment of Parkinson's Disease and other focal brain disorders.
Comprehensive Study of Artificial Light‐Harvesting Systems with a Multi‐Step Sequential Energy Transfer Mechanism
Authors: Wu Yong , Wang Yuqian , Yu Xu , Song Qiao 
Published: June 2024

AbstractArtificial light‐harvesting systems (LHSs) with a multi‐step sequential energy transfer mechanism significantly enhance light energy utilization. Nonetheless, most of these systems exhibit an overall energy transfer efficiency below 80%. Moreover, due to challenges in molecularly aligning multiple donor/acceptor chromophores, systems featuring ≥3‐step sequential energy transfer are rarely reported. Here, a series of artificial LHSs is introduced featuring up to 4‐step energy transfer mechanism, constructed using a cyclic peptide‐based supramolecular scaffold. These LHSs showed remarkably high energy transfer efficiencies (≥90%) and satisfactory fluorescence quantum yields (ranging from 17.6% to 58.4%). Furthermore, the structural robustness of the supramolecular scaffold enables a comprehensive study of these systems, elucidating the associated energy transfer pathways, and identifying additional energy transfer processes beyond the targeted sequential energy transfer. Overall, this comprehensive investigation not only enhances the understanding of these LHSs, but also underscores the versatility of cyclic peptide‐based supramolecular scaffolds in advancing energy harvesting technologies.
Aligned Permanent Magnet Made in Seconds–An In Situ Diffraction Study
Authors: Laursen Amalie P. , Frandsen Jens P. , Shyam Priyank , Mørch Mathias I. , Gjørup Frederik H. , Vijayan Harikrishnan , Jørgensen Mads R. V. , Christensen Mogens 
Published: June 2024

AbstractThe synthesis of a strontium hexaferrite magnet is studied using in situ synchrotron powder X‐ray diffraction (PXRD) with a 16‐ms time resolution. The precursor material is cold compacted shape‐controlled goethite and strontium carbonate. The time evolution of the phases is modeled with sequential Rietveld refinements revealing that strontium hexaferrite forms within seconds at ≈1173 K. Texture analysis is performed on selected PXRD frames throughout the experiment, and the preferred orientation introduced by cold‐pressing goethite prevails through the iron oxide phase transitions (goethite → hematite → strontium hexaferrite). Electron backscatter diffraction (EBSD) data on the final pellet confirms the preferred orientation observed with PXRD. The resulting magnet has respectable magnetic properties, considering the simplicity of the preparation method, with an energy product (BHmax) of 18.6(8) kJ m−3.
Remote and unsupervised digital memory assessments can reliably detect cognitive impairment in Alzheimer's disease
Authors: Berron David , Olsson Emil , Andersson Felix , Janelidze Shorena , Tideman Pontus , Düzel Emrah , Palmqvist Sebastian , Stomrud Erik , Hansson Oskar 
Published: June 2024

AbstractINTRODUCTIONRemote unsupervised cognitive assessments have the potential to complement and facilitate cognitive assessment in clinical and research settings.METHODSHere, we evaluate the usability, validity, and reliability of unsupervised remote memory assessments via mobile devices in individuals without dementia from the Swedish BioFINDER‐2 study and explore their prognostic utility regarding future cognitive decline.RESULTSUsability was rated positively; remote memory assessments showed good construct validity with traditional neuropsychological assessments and were significantly associated with tau‐positron emission tomography and downstream magnetic resonance imaging measures. Memory performance at baseline was associated with future cognitive decline and prediction of future cognitive decline was further improved by combining remote digital memory assessments with plasma p‐tau217. Finally, retest reliability was moderate for a single assessment and good for an aggregate of two sessions.DISCUSSIONOur results demonstrate that unsupervised digital memory assessments might be used for diagnosis and prognosis in Alzheimer's disease, potentially in combination with plasma biomarkers.Highlights
Remote and unsupervised digital memory assessments are feasible in older adults and individuals in early stages of Alzheimer's disease.
Digital memory assessments are associated with neuropsychological in‐clinic assessments, tau‐positron emission tomography and magnetic resonance imaging measures.
Combination of digital memory assessments with plasma p‐tau217 holds promise for prognosis of future cognitive decline.
Future validation in further independent, larger, and more diverse cohorts is needed to inform clinical implementation.
Enhancement of Overall Kinetics by Se−Br Chemistry in Rechargeable Li−S Batteries
Authors: Lv Xucheng , Qian Zikai , Zhang Xiaobo , Zhang Xie , Zheng Hongfei , Liu Mingjie , Liu Yingchun , Lu Jun 
Published: June 2024

AbstractThe sluggish kinetics of lithium‐sulfur (Li−S) batteries severely impedes the application in extreme conditions. Bridging the sulfur cathode and lithium anode, the electrolyte plays a crucial role in regulating kinetic behaviors of Li−S batteries. Herein, we report a multifunctional electrolyte additive of phenyl selenium bromide (PhSeBr) to simultaneously exert positive influences on both electrodes and the electrolyte. For the cathode, an ideal conversion routine with lower energy barrier can be attained by the redox mediator and homogeneous catalyst derived from PhSeBr, thus improving the reaction kinetics and utilization of sulfur. Meanwhile, the presence of Se−Br bond helps to reconstruct a loose solvation sheath of lithium ions and a robust bilayer SEI with excellent ionic conductivity, which contributes to reducing the de‐solvation energy and simultaneously enhancing the interfacial kinetics. The Li−S battery with PhSeBr displays superior long cycling stability with a reversible capacity of 1164.7 mAh g−1 after 300 cycles at 0.5 C rate. And the pouch cell exhibits a maximum capacity of 845.3 mAh and a capacity retention of 94.8 % after 50 cycles. Excellent electrochemical properties are also obtained in extreme conditions of high sulfur loadings and low temperature of −20 °C. This work demonstrates the versatility and practicability of the special additive, striking out an efficient but simple method to design advanced Li−S batteries.
Tailoring Oxygen‐Depleted and Unitary Ti3C2Tx Surface Terminals by Molten Salt Electrochemical Etching Enables Dendrite‐Free Stable Zn Metal Anode
Authors: Tian Feng , Wang Fei , Nie Wei , Zhang Xueqiang , Xia Xuewen , Chang Linhui , Pang Zhongya , Yu Xing , Li Guangshi , Hu Shen , Xu Qian , Hsu Hsien‐Yi , Zhao Yufeng , Ji Li , Lu Xionggang , Zou Xingli 
Published: June 2024

AbstractTwo‐dimensional Ti3C2Tx MXene materials, with metal‐like conductivities and versatile terminals, have been considered to be promising surface modification materials for Zn‐metal‐based aqueous batteries (ZABs). However, the oxygen‐rich and hybridized terminations caused by conventional methods limit their advantages in inhibiting zinc dendrite growth and reducing corrosion‐related side reactions. Herein, −O‐depleted, −Cl‐terminated Ti3C2Tx was precisely fabricated by the molten salt electrochemical etching of Ti3AlC2, and controlled in situ terminal replacement from −Cl to unitary −S or −Se was achieved. The as‐prepared −O‐depleted and unitary‐terminal Ti3C2Tx as Zn anode coatings provided excellent hydrophobicity and enriched zinc‐ionophilic sites, facilitating Zn2+ horizontal transport for homogeneous deposition and effectively suppressing water‐induced side reactions. The as‐assembled Ti3C2Sx@Zn symmetric cell achieved a cycle life of up to 4200 h at a current density and areal capacity of 2 mA cm−2 and 1 mAh cm−2, respectively, with an impressive cumulative capacity of up to 7.25 Ah cm−2 at 5 mA cm−2//2 mAh cm−2. These findings provide an effective electrochemical strategy for tailoring −O‐depleted and unitary Ti3C2Tx surface terminals and advancing the understanding of the role of specific Ti3C2Tx surface chemistry in regulating the plating/stripping behaviors of metal ions.
A Strong Supramolecular Mechanophore with Controlled Mechanical Strength
Authors: Xia Yu , Wang Guannan , He Chengzhi , Chen Hao 
Published: June 2024

AbstractSupramolecular mechanophores typically exhibit much lower mechanical strengths than covalent counterparts, with strengths usually around 100 pN, which is significantly lower than the nN‐scale strength of covalent bonds. Inspired by the slow dissociation kinetics of the cucurbit[7]uril (CB[7])–hexanoate‐isoquinoline (HIQ) complex, we discovered that charge–dipole repulsion can be utilized to create strong supramolecular mechanophores. When activated at its −COO− state, the CB[7]−HIQ complex exhibits a high mechanical strength of ~700 pN, comparable to weak covalent bonds such as Au−S bonds or thiol–maleimide adducts. The strength of the CB[7]−HIQ complex can also be tuned with pH in a gradual manner, with a minimum value of ~150 pN at its −COOH state, similar to an ordinary supramolecular conjugate. This research may pave the way for the development of supramolecular architectures that combine the advantages of covalent and supramolecular systems.
1,3,5–2,4,6‐Functionalized Benzene Molecular Cage: An Environmentally Responsive Scaffold that Supports Hierarchical Superstructures
Authors: Pang Xin‐Yu , Zhou Hang , Xie Xiaojiang , Jiang Wei , Yang Yinhua , Sessler Jonathan L. , Gong Han‐Yuan 
Published: June 2024

AbstractNew stimulus‐responsive scaffolds are of interest as constituents of hierarchical supramolecular ensembles. 1,3,5–2,4,6‐Functionalized, facially segregated benzene moieties have a time‐honored role as building blocks for host molecules. However, their user as switchable motifs in the construction of multi‐component supramolecular structures remains poorly explored. Here, we report a molecular cage 1, which consists of a bent anthracene dimer 3 paired with 1,3,5‐tris(aminomethyl)‐2,4,6‐triethylbenzene 2. As the result of the pH‐induced ababab↔bababa isomerization of the constituent‐functionalized benzene units derived from 2, this cage can reversibly convert between an open state and a closed form, both in solution and in the solid state. Cage 1 was used to create stimuli‐responsive hierarchical superstructures, namely Russian doll‐like complexes with [K⊂18‐crown‐6⊂1]+ and [K⊂cryptand‐222⊂1]+. The reversible assembly and disassembly of these superstructures could be induced by switching cage 1 from its open to closed form. The present study thus provides an unusual example where pH‐triggered conformation motion within a cage‐like scaffold is used to control the formation and disassociation of hierarchical ensembles.
Benzothiazole derivatives in the design of antitumor agents
Authors: Paoletti Niccolò , Supuran Claudiu T. 
Published: June 2024

AbstractBenzothiazoles are a class of heterocycles with multiple applications as anticancer, antibiotic, antiviral, and anti‐inflammatory agents. Benzothiazole is a privileged scaffold in drug discovery programs for modulating a variety of biological functions. This review focuses on the design and synthesis of new benzothiazole derivatives targeting hypoxic tumors. Cancer is a major health problem, being among the leading causes of death. Tumor‐hypoxic areas promote proliferation, malignancy, and resistance to drug treatment, leading to the dysregulation of key signaling pathways that involve drug targets such as vascular endothelial growth factor, epidermal growth factor receptor, hepatocyte growth factor receptor, dual‐specificity protein kinase, cyclin‐dependent protein kinases, casein kinase 2, Rho‐related coil formation protein kinase, tunica interna endothelial cell kinase, cyclooxygenase‐2, adenosine kinase, lysophosphatidic acid acyltransferases, stearoyl‐CoA desaturase, peroxisome proliferator‐activated receptors, thioredoxin, heat shock proteins, and carbonic anhydrase IX/XII. In turn, they regulate angiogenesis, proliferation, differentiation, and cell survival, controlling the cell cycle, inflammation, the immune system, and metabolic alterations. A wide diversity of benzothiazoles were reported over the last years to interfere with various proteins involved in tumorigenesis and, more specifically, in hypoxic tumors. Many hypoxic targets are overexpressed as a result of the hypoxia‐inducible factor activation cascade and may not be present in normal tissues, providing a potential strategy for selectively targeting hypoxic cancers.
Lentiviral vector determinants of anion‐exchange chromatography elution heterogeneity
Authors: Pamenter George , Davies Lee , Lamont Ciaran , Rahim Danyal , Knevelman Carol , Miskin James , Mitrophanous Kyriacos , Dikicioglu Duygu , Bracewell Daniel G. 
Published: June 2024

AbstractThe demand for Lentiviral Vector (LV) drug substance is increasing. However, primary capture using convective anion‐exchange chromatography remains a significant manufacturing challenge. This stems from a poor understanding of the complex adsorption behaviors linked to LVs intricate and variable structure, such as high binding heterogeneity which is typically characterized by a gradient elution profile consisting of two peaks. Understanding which LV structural components drive these phenomena is therefore crucial for rational process design. This work identifies the key LV envelope components responsible for binding to quaternary‐amine membrane adsorbents. Eliminating the pseudotype protein (Vesicular Stomatitis Virus G glycoprotein [VSV‐G]) did not impact the heterogenous two‐peak elution profile, suggesting it is not a major binding species. Digestion of envelope glycosaminoglycans (GAGs), present on proteoglycans, leads to a dramatic reduction in the proportion of vector eluted in peak 2, decreasing from 50% to 3.1%, and a threefold increase in peak 1 maximum. Data from reinjection experiments point towards interparticle envelope heterogeneity from discrete LV populations, where the two‐peak profile emerges from a subpopulation of LVs interacting via highly charged GAGs (peak 2) along with a weaker binding population likely interacting through the phospholipid membrane and envelope protein (peak 1).
An assessment of the antihyperlipidemic ingredients of Qi Ge Decoction based on metabolomics combined with serum pharmacochemistry
Authors: Tang Hui , Guo Kai Xin , Huang Ke Er , Li Yan Fang , Chen Wei , Wei Hao Yang , Yu Xiao Qing , Ke Xue Hong 
Published: June 2024

AbstractThis study aims to explore the pharmacological substance basis of Qi Ge Decoction (QG) in antihyperlipidemia through a combination of metabolomics and serum pharmacochemistry. We used ultra‐performance liquid chromatography quadrupole‐time‐of‐flight/MS (UPLC Q‐TOF/MS) to analyze and identify the chemical constituents of QG in vitro and in blood chemical components. The metabolomics technology was used to analyze serum biomarkers of QG in preventing and treating hyperlipidemia. We constructed a mathematical model of the relationship between constituents absorbed into the blood and endogenous biomarkers and explored the potential therapeutic application of QG for the prevention and treatment of hyperlipidemia. Compared with the model group, the levels of total cholesterol and triglyceride in the QG group were significantly decreased (P < 0.01). A total of 12 chemical components absorbed into the blood were identified, and 48 biomarkers of the hyperlipidemia model were obtained from serum metabolomic analysis, of which 15 metabolites were backregulated after QG intervention. Puerarin, hesperetin, puerarin xyloside, calycosin, and monohydroxy‐tetramethoxyflavone had a high correlation with the biomarkers regulated by QG. This study elucidated the material basis of QG in the intervention of hyperlipidemia, thereby facilitating future research aimed at further revealing the pharmacodynamic material basis of QG's antihyperlipidemic effects.
The use of demeanour to assess the credibility of child victims in sexual interference trials
Authors: Denault Vincent , Talwar Victoria 
Published: June 2024

AbstractHow do judges assess witness credibility? This question is particularly important in cases where child victims testify. These cases are usually of a sensitive nature (e.g., involving allegations of abuse) where there are no other testimonial or material evidence to corroborate the account of child victims. To better understand what actually happens when judges preside over trials about sexual interference, and how, in actual courtrooms, they use demeanour to assess the credibility of child victims, we conducted a qualitative thematic analysis of real courts judgements (n = 44). The results highlighted that when assessing credibility in actual courtrooms, judges make a variety of inferences from the demeanour of child victims who testify live, with striking differences (and similarities) when defendants are found not guilty than when they are found guilty. The results of our descriptive study also provided unique insights about (correct and incorrect) beliefs judges hold about child witnesses, and how, if children fail to display behaviour they are expected to display, or if they display behaviour they are not expected to display, child victims could face difficulties at several stages of the judicial process. We discuss the results based on the literature on nonverbal behaviour and child witnesses, explaining their scope for scholars and legal practitioners.
Two Undescribed Coumarins from Notopterygium Incisum with Anti‐Inflammatory Activity
Authors: Hu Yun‐Jie , Liu Meng‐Dan , Mu Yu‐Ting , Li Cong‐Cong , Zhao Min‐Hong , Guo Da‐Le , Huang Li‐Jun , Gu Yu‐Cheng , Xue Qing‐Cai , Deng Yun 
Published: June 2024

AbstractTwo previously undescribed coumarins (1–2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1–2 exhibits obviously anti‐inflammatory activity by inhibiting the expression of inflammatory mediators (COX‐2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p‐PI3K and p‐AKT.
Benzofuran Iboga‐Analogs Modulate Nociception and Inflammation in an Acute Mouse Pain Model
Authors: Bhattacharya Tuhin , Gupta Abhishek , Gupta Shalini , Saha Samrat , Ghosh Shatabdi , Shireen Zofa , Dey Sanjit , Sinha Surajit 
Published: June 2024

AbstractPain management following acute injury or post‐operative procedures is highly necessary for proper recovery and quality of life. Opioids and non‐steroidal anti‐inflammatory drugs (NSAIDS) have been used for this purpose, but opioids cause addiction and withdrawal symptoms whereas NSAIDS have several systemic toxicities. Derivatives of the naturally occurring iboga alkaloids have previously shown promising behavior in anti‐addiction of morphine by virtue of their interaction with opioid receptors. On this frontier, four benzofuran analogs of the iboga family have been synthesized and their analgesic effects have been studied in formalin induced acute pain model in male Swiss albino mice at 30 mg/kg of body weight dose administered intraperitoneally. The antioxidant, anti‐inflammatory and neuro‐modulatory effects of the analogs were analyzed. Reversal of tail flick latency, restricted locomotion and anxiogenic behavior were observed in iboga alcohol, primary amide and secondary amide. Local neuroinflammatory mediators’ substance P, calcitonin gene related peptide, cyclooxygenase‐2 and p65 were significantly decreased whereas the depletion of brain derived neurotrophic factor and glia derived neurotrophic factor was overturned on iboga analog treatment. Behavioral patterns after oral administration of the best analog were also analyzed. Taken together, these results show that the iboga family of alkaloid has huge potential in pain management.
Catalytic Relevance of Mg‐Al‐O Basic Centers in the Upgrade of Ethanol to n‐Butanol
Authors: Tian Wei , Herrera José E. 
Published: June 2024

AbstractThe catalytic relevance of different surface functionalities present on hydrotalcite‐derived Mg−Al mixed metal oxides (MgAlO) are investigated in the context of ethanol upgrade to n‐butanol. The catalyst structure and active sites were altered through changes in the Mg/Al ratio and introduction of additional redox metal oxide functionalities. After performing a series of catalytic activity tests, operando FTIR characterization, TGA measurements and in situ active center titration; qualitative and quantitative relationships between catalyst structure and catalytic performance are obtained. We found the Mg−Al mixed metal oxides system can catalyze the ethanol to n‐butanol process through a Guerbet reaction pathway, though the process is kinetically limited. By introducing redox active metal oxides to the catalyst formulation, such as MoO3 or V2O5, this problem can be partially solved, but at a cost of losing a significant fraction of high‐strength basic centers which are the most catalytically relevant function in the system, as they control enolate formation rates leading to the C−C coupling step required for n‐butanol formation.