bluuebunny/crossref_metadata_2025_split huggingface dataset:
Otilonium Bromide Exhibits Potent Antifungal Effects by Blocking Ergosterol Plasma Membrane Localization and Triggering Cytotoxic Autophagy in Candida Albicans
Authors: Zhen Cheng , Wang Li , Feng Yanru , Whiteway Malcolm , Hang Sijin , Yu Jinhua , Lu Hui , Jiang Yuanying 
Published: July 2024

AbstractCandidiasis, which presents a substantial risk to human well‐being, is frequently treated with azoles. However, drug‐drug interactions caused by azoles inhibiting the human CYP3A4 enzyme, together with increasing resistance of Candida species to azoles, represent serious issues with this class of drug, making it imperative to develop innovative antifungal drugs to tackle this growing clinical challenge. A drug repurposing approach is used to examine a library of Food and Drug Administration (FDA)‐approved drugs, ultimately identifying otilonium bromide (OTB) as an exceptionally encouraging antifungal agent. Mechanistically, OTB impairs vesicle‐mediated trafficking by targeting Sec31, thereby impeding the plasma membrane (PM) localization of the ergosterol transporters, such as Sip3. Consequently, OTB obstructs the movement of ergosterol across membranes and triggers cytotoxic autophagy. It is noteworthy that C. albicans encounters challenges in developing resistance to OTB because it is not a substrate for drug transporters. This study opens a new door for antifungal therapy, wherein OTB disrupts ergosterol subcellular distribution and induces cytotoxic autophagy. Additionally, it circumvents the hepatotoxicity associated with azole‐mediated liver enzyme inhibition and avoids export‐mediated drug resistance in C. albicans.
Secondary Order RC Sensor Neuron Circuit for Direct Input Encoding in Spiking Neural Network
Authors: Yang Simiao , Li Deli , Feng Jiuchao , Gong Binchen , Song Qing , Wang Yue , Yang Zhen , Chen Yonghua , Chen Qi , Huang Wei 
Published: July 2024

AbstractIn spiking neural networks (SNNs), artificial sensor neurons are crucial for converting real‐world analog information into encoded spikes. However, existing SNNs face challenges due to the inefficient implementation of input sensor neurons. Here, this study proposes an SNN‐compatible spike mode sensor, designed to directly convert analog current signals into real‐time encoded spikes, feeding the SNN concurrently. The input sensor neuron is realized using a stable neuron circuit employing a threshold switching (TS) memristor and secondary order RC block. This design enables time delay‐free spike firing, operates at low voltage, and offers a wide signal sensing range. Furthermore, this study presents an expression delineating the relationship between the pulse emission properties of the circuit and the parameters of its components, laying the basis for circuit components design and development. Analytical analysis confirms the sensor's efficacy in implementing rate‐based and time‐to‐first spike encoding schemes. Integrating the sensor into SNNs as the input layer for image training and recognition tasks yields an impressive accuracy of 87.58% on the MNIST dataset, showcasing its applicability as a crucial interface between the physical world and the SNN framework.
Estimation on growth parameters of Arius maculatus (Thunberg, 1792) along the Thanlwin River Estuary comparing with the observed length and back‐calculated length of otolith
Authors: Aung Thet Htwe , Htet Hsu Yadanar 
Published: July 2024

AbstractThis study examined the growth patterns of the spotted catfish, Arius maculatus (Thunberg, 1792) in the Thanlwin River Estuary throughout the analysis of standard lengths obtained from observed otolith data and back‐calculated data. Between April 2023 and January 2024, 516 fish ranging in standard lengths from 8.3 to 33 cm were collected. The annual deposition of annuli in otoliths was confirmed using the marginal increment ratio, with ages ranging from 2 to 9 years. The Dahl‐Lea back‐calculation method expanded the length at age data to 2472 records for ages 1–9 years. Growth was characterized using Von Bertalanffy growth curves, revealing the significant differences between the observed data (asymptotic length L∞ = 25.34 cm, growth coefficient K = 0.257 year−1 and growth performance index ϕ′ = 2.02) and the back‐calculated data (L∞ = 36.23 cm, K = 0.087 year−1 and ϕ′ = 2.21). The findings of the study suggested that the back‐calculated otolith data were more dependable for determining growth parameters compared to the observed otolith data. A. maculatus appears to exhibit slow growth characteristics, suggesting that the environmental conditions in the Thanlwin River Estuary may be deficient for this species. The insights gleaned from this research are crucial for guiding and shaping fishery management policies through informed advice and recommendations.
The transcriptome of MHV‐infected RAW264.7 cells offers an alternative model for macrophage innate immunity research
Authors: Liu Yun , Feng Ting‐Ting , Tong Wei , Guo Zhi , Li Xia , Kong Qi , Xiang Zhi‐Guang 
Published: July 2024

AbstractBackgroundMacrophages are the primary innate immune cells encountered by the invading coronaviruses, and their abilities to initiate inflammatory reactions, to maintain the immunity homeostasis by differential polarization, to train the innate immune system by epigenic modification have been reported in laboratory animal research.MethodsIn the current in vitro research, murine macrophage RAW 264.7 cell were infected by mouse hepatitis virus, a coronavirus existed in mouse. At 3‐, 6‐, 12‐, 24‐, and 48‐h post infection (hpi.), the attached cells were washed with PBS and harvested in Trizol reagent. Then The harvest is subjected to transcriptome sequencing.ResultsThe transcriptome analysis showed the immediate (3 hpi.) up regulation of DEGs related to inflammation, like Il1b and Il6. DEGs related to M2 differential polarization, like Irf4 showed up regulation at 24 hpi., the late term after viral infection. In addition, DEGs related to metabolism and histone modification, like Ezh2 were detected, which might correlate with the trained immunity of macrophages.ConclusionsThe current in vitro viral infection study showed the key innated immunity character of macrophages, which suggested the replacement value of viral infection cells model, to reduce the animal usage in preclinical research.
Assessment of the piroxicam‐incited model of synchronized colitis in T‐cell receptor alpha chain‐deficient mice
Authors: Lange Maximo E. , Bescucci Danisa M. , Boras Valerie F. , Montina Tony , Inglis G. Douglas 
Published: July 2024

AbstractBackgroundA multitude of mouse models are utilized to emulate and study intestinal inflammation. T‐cell receptor alpha chain (TCRα)‐deficient mice are used as a model of spontaneous colitis that has similarities with human ulcerative colitis. However, colitis is triggered late in the life of the mouse (age: 4–5 months), and inflammation does not develop at the same time in different mice. A previously conducted study reported that the administration of the drug piroxicam triggered predictable and early colitis in TCRα‐deficient mice at the age of 6–8 weeks. However, a detailed characterization of ensuing inflammation was not provided.MethodsWe conducted an in‐depth examination of piroxicam‐triggered colitis in TCRα‐deficient mice, with emphasis on spatial histopathologic changes and analysis of expression of inflammatory markers. Furthermore, we tested amelioration of colitis with dexamethasone.ResultsWe confirmed that piroxicam induced a time‐prescribed colitis and did so in the proximal colon as well as the cecum of TCRα‐deficient mice. Piroxicam administration was observed to induce epithelial hyperplasia, goblet cell loss, and leukocyte infiltration with occasional ulceration. A Swiss roll technique was used to examine the colon and cecum in its entirety. Importantly, we observed that inflammation was multifocal segmental, with areas of tissue damage in between healthy tissue. In addition, we observed variability in the severity of inflammation among replicate animals and treatments, and that the administration of dexamethasone only partially ameliorated inflammation in the proximal colon.ConclusionsPiroxicam consistently induced multifocal segmental colitis in the proximal colon and cecum, although the degree of inflammation was reduced in the latter. Importantly, spatial variability in inflammation in the large intestine and the inter‐replicate variation in the severity of inflammation must be taken into consideration when utilizing this murine model of synchronized colitis.
Unlocking the Multistage Redox Property of Graphenic Radicals by π‐Extension
Authors: Pu Zhaofangzhou , Xu Zhuofan , Zhang Xin , Guo Yupeng , Sun Zhe 
Published: July 2024

AbstractDelocalized organic π‐radicals are intrinsically amphoteric redox systems; however, achieving their multistage redox capability presents a challenge. In addition, their instability often hampers their synthesis, isolation, and characterization. Herein, we report the synthesis of a stable π‐extended nanographene π‐radical (NR1) and its isolation in the crystalline form. NR1 exhibits an unusual four‐stage amphoteric redox behavior, as revealed by cyclic voltammetry measurements. The stable charged species, including a cation and a radical dication, are characterized using spectroscopic methods. This study demonstrates that π‐extension could serve as a viable approach to unlock the multistage redox ability of delocalized organic radicals.
Development of a Fluorescent Probe with High Selectivity based on Thiol‐ene Click Nucleophilic Cascade Reactions for Delving into the Action Mechanism of Serotonin in Depression
Authors: Yue Lizhou , Huang Huawei , Lin Weiying 
Published: July 2024

AbstractThe intrinsic correlation between depression and serotonin (5‐HT) is a highly debated topic, with significant implications for the diagnosis, treatment, and advancement of drugs targeting neurological disorders. To address this important question, it is of utmost priority to understand the action mechanism of serotonin in depression through fluorescence imaging studies. However, the development of efficient molecular probes for serotonin is hindered by the lack of responsive sites with high selectivity for serotonin at the present time. Herein, we developed the first highly selective serotonin responsive site, 3‐mercaptopropionate, utilizing thiol‐ene click cascade nucleophilic reactions. The novel responsive site was then employed to construct the powerful molecular probe SJ‐5‐HT for imaging the serotonin level changes in the depression cells and brain tissues. Importantly, the imaging studies reveal that the level of serotonin in patients with depression may not be the primary factor, while the ability of neurons in patients with depression to release serotonin appears to be more critical. Additionally, this serotonin release capability correlates strongly with the levels of mTOR (intracellular mammalian target of rapamycin). These discoveries could offer valuable insights into the molecular mechanisms underpinning depression and furnish mTOR as a novel direction for the advancement of antidepressant therapies.
Enhanced Charge‐Carrier Dynamics and Efficient Photoelectrochemical Nitrate‐to‐Ammonia Conversion on Antimony Sulfide‐Based Photocathodes
Authors: Ren Shijie , Gao Rui‐Ting , Yu Jidong , Yang Yang , Liu Xianhu , Wu Limin , Wang Lei 
Published: July 2024

AbstractThe photoelectrochemical reduction of nitrate to ammonia (PEC NO3RR) has emerged as a promising pathway for facilitating the natural nitrogen cycle. The PEC NO3RR can lower the reduction potential needed for ammonia synthesis through photogenerated voltage, showcasing the significant potential for merging abundant solar energy with sustainable nitrogen fixation. However, it is influenced by the selective photocathodes with poor carrier kinetics, low catalytic selectivity, and ammonia yields. There are few reports on suitable photoelectrodes owning efficient charge transport on PEC NO3RR at low overpotentials. Herein, we rationally constructed the CuSn alloy co‐catalysts on the antimony sulfides with a highly selective PEC ammonia and an ultra‐low onset potential (0.62 VRHE). CuSn/TiO2/Sb2S3 photoelectrodes achieved an ammonia faradic efficiency of 97.82 % at a low applied potential of 0.4 VRHE, and an ammonia yield of 16.96 μmol h−1 cm−2 at 0 VRHE under one sun illumination. Dynamics experiments and theoretical calculations have demonstrated that CuSn/TiO2/Sb2S3 has an enhanced charge separation and transfer efficiency, facilitating photogenerated electrons to participate in PEC NO3RR quickly. Meanwhile, moderate NO2* adsorption on this photocathode optimizes the catalytic activity and increases the NH4+ yield. This work opens an avenue for designing sulfide‐based photocathodes for the efficient route of solar‐to‐ammonia conversion.
Reproducing Reaction Mechanisms with Machine‐Learning Models Trained on a Large‐Scale Mechanistic Dataset
Authors: Joung Joonyoung F. , Fong Mun Hong , Roh Jihye , Tu Zhengkai , Bradshaw John , Coley Connor W. 
Published: July 2024

AbstractMechanistic understanding of organic reactions can facilitate reaction development, impurity prediction, and in principle, reaction discovery. While several machine learning models have sought to address the task of predicting reaction products, their extension to predicting reaction mechanisms has been impeded by the lack of a corresponding mechanistic dataset. In this study, we construct such a dataset by imputing intermediates between experimentally reported reactants and products using expert reaction templates and train several machine learning models on the resulting dataset of 5,184,184 elementary steps. We explore the performance and capabilities of these models, focusing on their ability to predict reaction pathways and recapitulate the roles of catalysts and reagents. Additionally, we demonstrate the potential of mechanistic models in predicting impurities, often overlooked by conventional models. We conclude by evaluating the generalizability of mechanistic models to new reaction types, revealing challenges related to dataset diversity, consecutive predictions, and violations of atom conservation.
Modular Synthesis of Heterobenzylic Amines via Carbonyl Azinylative Amination
Authors: Rafaniello Alex A. , Kumar Roopender , Phillips Rachel C. , Gaunt Matthew J. 
Published: July 2024

AbstractTransformations enabling the synthesis of α‐alkyl, α′‐2‐azinyl amines by addition of 2‐heteroaryl‐based nucleophiles to in situ‐generated and non‐activated alkyl‐substituted iminium ions are extremely rare. Approaches involving classical 2‐azinyl organometallics, such as the corresponding Grignard reagents, often fail to produce the desired products. Here, we report an operationally straightforward solution to this problem through the development of a multicomponent coupling process wherein a soft 2‐azinyl indium nucleophile, generated in situ from the corresponding 2‐iodo heteroarene and indium powder, adds to an iminium ion that is also formed directly in the reaction. This modular carbonyl azinylative amination (CAzA) displays a broad scope and only a metal reductant is needed to generate a reactive 2‐azinyl nucleophile. Beyond the addition to iminium ions, the 2‐azinyl addition to polyfluoromethyl ketones forms the corresponding tertiary alcohols. Together, the products of these reactions possess a high degree of functionality, are typically challenging to synthesize by other methods, and contain motifs recognized as privileged in the context of pharmaceuticals and agrochemicals.
Bottom‐up Synthesis of Highly Chiral 1T Molybdenum Disulfide Nanosheets
Authors: Branzi Lorenzo , Fitzsimmons Lucy , Gun'ko Yurii K. 
Published: July 2024

AbstractChirality in inorganic nanostructures has recently stimulated the attention of many researchers, both to unravel fundamental questions on the origin of chirality in inorganic and hybrid materials, as well as to introduce novel promising properties that are originated by the symmetry breaking. MoS2 is one of the most investigated among the large family of layered transition metal dichalcogenides. In particular, the metastable metallic 1T−MoS2 phase is of large interest for potential applications. However, due to thermodynamic reasons, the synthesis of 1T−MoS2 phase is quite challenging. Herein, we present the first synthesis of chiral 1T−MoS2 phase which shows remarkably high chiroptical activity with a g‐factor up to 0.01. Chiral 1T−MoS2 was produced using tartaric acid as a chiral ligand to induce symmetry breaking during the material's growth under hydrothermal conditions, leading to the formation of distorted hierarchical nanosheet assemblies exhibiting chiral morphology. Thorough optimization of the synthetic conditions was carried out to maximize chiroptical activity, which is strongly related to the nanostructures’ morphology. Finally, the formation mechanism of the chiral 1T−MoS2 nanosheet assemblies was investigated, focusing on the role of molecular intermediates in the growth of the nanosheets and the transfer of chirality.
A Dibenzo[g,p]chrysene‐Based Organic Semiconductor with Small Exciton Binding Energy via Molecular Aggregation
Authors: Mori Hiroki , Jinnai Seihou , Hosoda Yasushi , Muraoka Azusa , Nakayama Ken‐ichi , Saeki Akinori , Ie Yutaka 
Published: July 2024

AbstractExciton binding energy (Eb) is understood as the energy required to dissociate an exciton in free‐charge carriers, and is known to be an important parameter in determining the performance of organic opto‐electronic devices. However, the development of a molecular design to achieve a small level of Eb in the solid state continues to lag behind. Here, to investigate the relationship between aggregation and Eb, star‐shaped π‐conjugated compounds DBC‐RD and TPE‐RD were developed using dibenzo[g,p]chrysene (DBC) and tetraphenylethylene (TPE). Theoretical calculations and physical measurements in solution showed no apparent differences between DBC‐RD and TPE‐RD, indicating that these molecules possess similar properties on a single‐molecule level. By contrast, pristine films incorporating these molecules showed significantly different levels of electron affinity, ionization potential, and optical gap. Also, DBC‐RD had a smaller Eb value of 0.24 eV compared with that of TPE‐RD (0.42 eV). However, these molecules showed similar Eb values under dispersed conditions, which suggested that the decreased Eb of DBC‐RD in pristine film is induced by molecular aggregation. By comparison with TPE‐RD, DBC‐RD showed superior performances in single‐component organic solar cells and organic photocatalysts. These results indicate that a molecular design suitable for aggregation is important to decrease the Eb in films.
Analysis of 5‐Methyl Cytosine Containing Oligomers Via Reduction of Tetracationic Di‐Viologen Derivatives Using Square Wave Voltammetry
Authors: Preston Victoria G. , Hvastkovs Eli G. 
Published: July 2024

Abstract5‐Methylcytosine (5 mC) is an epigenetic modification that plays several important roles ranging from development to disease progression. Local cytosine methylation is still detected and quantified utilizing bisulfite cytosine to uracil conversion and methylated base counting following PCR. Electrochemical approaches may offer more rapid means to provide this output. Here, small oligomeric DNA sequences from the CD8+ T‐cell reporter gene featuring between 0 and 4 5 mC sites were immobilized on Au electrodes via self‐assembly. 5 mC content was assayed via square wave voltametric reduction of a di‐viologen molecule (C12H25V2+C6H12V2+C12H25, V2+=4,4’‐bipyridyl or viologen) bound to the DNA. 5 mC presence induced subtle structural changes in the oligomers, which could be detected monitoring di‐viologen reduction current changes at −0.39 V vs. SCE after exposure to higher ionic strength conditions. Solution phase CD spectroscopy was employed to validate the DNA structural changes occurring at the electrode surface and provide insight into the structural perturbations resulting from 5 mC presence. Overall, this method provides a relatively simple electrochemical 5 mC monitoring approach for small gene sequences based on helical structure.
The influence of water released from particles in epoxy‐based nanocomposites
Authors: Waniek Tassilo , Omar Hassan , Szymoniak Paulina , Silbernagl Dorothee , Sturm Heinz 
Published: July 2024

AbstractRecent studies have hypothesized that the reinforcing effects of boehmite nanoparticles (BNPs) in polymer nanocomposites (PNCs) are partly related to the particles themselves and partly to the water released from the BNP during curing. In this work, PNCs made from dried BNP (dBNP) with concentrations up to 15 wt% are investigated to differentiate particle and water related effects. The observed trend of the storage modulus in dynamic mechanical thermal analysis measurements was found to be independent of the drying procedure. Stiffness maps from intermodulation atomic force microscopy showed that dBNP leads to a stiffening of the interphase surrounding the particles compared with the unaffected epoxy matrix, while a softer interphase was reported for PNCs with as received BNP. A slight decrease in the glass transition temperature was observed by broadband dielectric spectroscopy related to a lowered crosslink density due to the particles. A significantly higher decrease was reported for PNCs with BNP, attributed to water influencing the curing process. In conclusion, the stiffening of PNC with BNP is related to the particles themselves, while the release of water causes the formation of a soft interphase in the vicinity of the particles and a significant decrease in crosslink density.
Anomalous Tunneling Magnetoresistance Oscillation and Electrically Tunable Tunneling Anisotropic Magnetoresistance in Few‐Layer CrPS4
Authors: Fu ZhuangEn , Huang Hong‐Fei , Samarawickrama Piumi , Watanabe Kenji , Taniguchi Takashi , Wang Wenyong , Ackerman John , Zang Jiadong , Yu Jie‐Xiang , Tian Jifa 
Published: July 2024

Abstract2D van der Waals (vdW) magnets with layer‐dependent magnetic states and/or diverse magnetic interactions and anisotropies have attracted extensive research interest. Despite the advances, a notable challenge persists in effectively manipulating the tunneling anisotropic magnetoresistance (TAMR) of 2D vdW magnet‐based magnetic tunnel junctions (MTJs). Here, this study reports the novel and anomalous tunneling magnetoresistance (TMR) oscillations and pioneering demonstration of bias and gate voltage controllable TAMR in 2D vdW MTJs, utilizing few‐layer CrPS4. This material, inherently an antiferromagnet, transitions to a canted magnetic order upon application of external magnetic fields. Through TMR measurements, this work unveils the novel layer‐dependent oscillations in the tunneling resistance for few‐layer CrPS4 devices under both out‐of‐plane and in‐plane magnetic fields, with a pronounced controllability via gate voltage. Intriguingly, this study demonstrates that both the polarity and magnitude of TAMR in CrPS4 can be effectively tuned through either a bias or gate voltage. The mechanism behind this electrically tunable TAMR is further elucidated through first‐principles calculations. The implications of the findings are far‐reaching, providing new insights into 2D magnetism and opening avenues for the development of innovative spintronic devices based on 2D vdW magnets.