bluuebunny/crossref_metadata_2025 huggingface dataset:
A Divalent Chikungunya and Zika Nanovaccine with Thermostable Self‐Assembly Multivalent Scaffold LS‐SUMO
Authors: Li Qianlin , Zhang Jinsong , Deng Qiang , Liao Conghui , Qian Jun , Chen Zeliang , Lu Jiahai
Published: February 2024

The convergence strategies of antigenic subunits and synthetic nanoparticle scaffold platform improve the vaccine production efficiency and enhance vaccine‐induced immunogenicity. Selecting the appropriate nanoparticle scaffold is crucial to controlling target antigens immunologically. Lumazine synthase (LS) is an attractive candidate for a vaccine display system due to its thermostability, modification tolerance, and morphological plasticity. Here, the first development of a multivalent thermostable scaffold, LS‐SUMO (SUMO, small ubiquitin‐likemodifier), and a divalent nanovaccine covalently conjugated with Chikungunya virus E2 and Zika virus EDIII antigens, is reported. Compared with antigen monomers, LS‐SUMO nanoparticle vaccines elicit a higher humoral response and neutralizing antibodies against both antigen targets in mouse sera. Mice immunized with LS‐SUMO conjugates produce CD4+ T cell‐mediated Th2‐biased responses and promote humoral immunity. Importantly, LS‐SUMO conjugates possess equivalent humoral immunogenicity after heat treatment. Taken together, LS‐SUMO is a powerful biotargeting nanoplatform with high‐yield production, thermal stability and opens a new avenue for multivalent presentation of various antigens.
Biofabrication's Contribution to the Evolution of Cultured Meat
Authors: Albrecht Franziska Brigitte , Ahlfeld Tilman , Klatt Annemarie , Heine Simon , Gelinsky Michael , Kluger Petra Juliane
Published: February 2024

Cultured Meat (CM) is a growing field in cellular agriculture, driven by the environmental impact of conventional meat production, which contributes to climate change and occupies ≈70% of arable land. As demand for meat alternatives rises, research in this area expands. CM production relies on tissue engineering techniques, where a limited number of animal cells are cultured in vitro and processed to create meat‐like tissue comprising muscle and adipose components. Currently, CM is primarily produced on a small scale in pilot facilities. Producing a large cell mass based on suitable cell sources and bioreactors remains challenging. Advanced manufacturing methods and innovative materials are required to subsequently process this cell mass into CM products on a large scale. Consequently, CM is closely linked with biofabrication, a suite of technologies for precisely arranging cellular aggregates and cell‐material composites to construct specific structures, often using robotics. This review provides insights into contemporary biomedical biofabrication technologies, focusing on significant advancements in muscle and adipose tissue biofabrication for CM production. Novel materials for biofabricating CM are also discussed, emphasizing their edibility and incorporation of healthful components. Finally, initial studies on biofabricated CM are examined, addressing current limitations and future challenges for large‐scale production.
One‐Pot Construction of Articular Cartilage‐Like Hydrogel Coating for Durable Aqueous Lubrication
Authors: Huang Jiajun , Tang Youchen , Wang Peng , Zhou Hao , Li He , Cheng Ziying , Wu Yanfeng , Xie Zhongyu , Cai Zhaopeng , Wu Dingcai , Shen Huiyong
Published: February 2024

Articular cartilage has an appropriate multilayer structure and superior tribological properties and provides a structural paradigm for design of lubricating materials. However, mimicking articular cartilage traits on prosthetic materials with durable lubrication remains a huge challenge. Herein, an ingenious three‐in‐one strategy is developed for constructing an articular cartilage‐like bilayer hydrogel coating on the surface of ultra‐high molecular weight polyethylene (BH‐UPE), which makes full use of conceptions of interfacial interlinking, high‐entanglement crosslinking, and interface‐modulated polymerization. The hydrogel coating is tightly interlinked with UPE substrate through hydrogel‐UPE interchain entanglement and bonding. The hydrogel chains are highly entangled with each other to form a dense tough layer with negligible hysteresis for load‐bearing by reducing the amounts of crosslinker and hydrophilic initiator to p.p.m. levels. Meanwhile, the polymerization of monomers in the top surface region is suppressed via interface‐modulated polymerization, thus introducing a porous surface for effective aqueous lubrication. As a result, BH‐UPE exhibits an ultralow friction coefficient of 0.0048 during 10 000 cycles under a load of 0.9 MPa, demonstrating great potential as an advanced bearing material for disc prosthesis. This work may provide a new way to build stable bilayer coatings and have important implications for development of biological lubricating materials.
Monolithic Strong Coupling of Topological Surface Acoustic Wave Resonators on Lithium Niobate
Authors: Zhang Zi‐Dong , Yu Si‐Yuan , Xu Haitan , Lu Ming‐Hui , Chen Yan‐Feng
Published: February 2024

Coherent phonon transfer via high‐quality factor (Q) mechanical resonator strong coupling has garnered significant interest. Yet, the practical applications of these strongly coupled resonator devices are largely constrained by their vulnerability to fabrication defects. In this study, topological strong coupling of gigahertz frequency surface acoustic wave (SAW) resonators with lithium niobate is achieved. The nanoscale grooves are etched onto the lithium niobate surface to establish robust SAW topological interface states (TISs). By constructing phononic crystal (PnC) heterostructures, a strong coupling of two SAW TISs, achieving a maximum Rabi splitting of 22 MHz and frequency quality factor product fQm of ≈1.2 × 1013 Hz, is realized. This coupling can be tuned by adjusting geometric parameters and a distinct spectral anticrossing is experimentally observed. Furthermore, a dense wavelength division multiplexing device based on the coupling of multiple TISs is demonstrated. These findings open new avenues for the development of practical topological acoustic devices for on‐chip sensing, filtering, phonon entanglement, and beyond.
3D Crown Ether Covalent Organic Framework as Interphase Layer toward High‐Performance Lithium Metal Batteries
Authors: Zheng Shuang , Bi Shuai , Fu Yubin , Wu Yang , Liu Minghao , Xu Qing , Zeng Gaofeng
Published: February 2024

The practical application of lithium (Li) metal batteries is inhibited by accumulative Li dendrites and continuous active Li consumption during cycling, which results in a low Coulombic efficiency and short lifetime. Constructing artificial solid‐electrolyte interphase (SEI) layer in Li anode, such as 2D covalent organic frameworks (COFs), is an effective strategy to restrain the formation of Li dendrites and improve cycling performance. However, the exploration of 3D COFs as protecting layers is rarely reported, because of the preconception that the interconnect pores in 3D COFs eventually cause Li dendrites in disordered direction. 3D crown ether‐based COF with ffc topology as interphase layer, in which the crown ether units are arranged in parallel and vertical orientation along the electrode, is demonstrated. The strong coupling effect between the crown ether and Li+ accelerates Li+ diffusion kinetics and enables homogeneous Li+ flux, resulting in a high Li+ transference number of 0.85 and smooth Li deposition in 3D direction. Li/COF‐Cu cells display a lower Li‐nucleation overpotential (17.4 mV) and high average Coulombic efficiency of ≈98.6% during 340 cycles with COF incorporation. This work gives a new insight into designing COFs for energy storage systems.
Dual‐Protection Inorganic‐Protein Coating on Mg‐Based Biomaterials through Tooth‐Enamel‐Inspired Biomineralization
Authors: Zhao Ziqian , Yu Wenting , Yang Wenshuai , Zhang Guohao , Huang Charley , Han Jianmin , Narain Ravin , Zeng Hongbo
Published: February 2024

Biocompatible magnesium alloys represent revolutionary implantable materials in dentistry and orthopedics but face challenges due to rapid biocorrosion, necessitating protective coatings to mitigate dysfunction. Directly integrating durable protective coatings onto Mg surfaces is challenging because of intrinsic low coating compactness. Herein, inspired by tooth enamel, a novel highly compact dual‐protection inorganic‐protein (inorganicPro) coating is in situ constructed on Mg surfaces through bovine serum albumin (BSA) protein‐boosted reaction between sodium fluoride (NaF) and Mg substrates. The association of Mg ions and BSA establishes a local hydrophobic domain that lowers the formation enthalpy of NaMgF3 nanoparticles. This process generates finer nanoparticles that function as “bricks,” facilitating denser packing, consequently reducing voidage inside coatings by over 50% and reinforcing mechanical durability. Moreover, the incorporation of BSA in and on the coatings plays two synergistic roles: 1) acting as “mortar” to seal residual cracks within coatings, thereby promoting coating compactness and tripling anticorrosion performance, and 2) mitigating fouling‐accelerated biocorrosion in complex biosystems via tenfold resistance against biofoulant attachments, including biofluids, proteins, and metabolites. This innovative strategy, leveraging proteins to alter inorganic reactions, benefits the future coating design for Mg‐based and other metallic materials with tailored anticorrosion and antifouling performances.
Advancing Catalysts by Stacking Fault Defects for Enhanced Hydrogen Production: A Review
Authors: Wang Yuan , Wang Tian , Arandiyan Hamidreza , Song Guoqiang , Sun Hongyu , Sabri Ylias , Zhao Chuan , Shao Zongping , Kawi Sibudjing
Published: February 2024

Green hydrogen, derived from water splitting powered by renewable energy such as solar and wind energy, provides a zero‐emission solution crucial for revolutionizing hydrogen production and decarbonizing industries. Catalysts, particularly those utilizing defect engineering involving the strategical introduction of atomic‐level imperfections, play a vital role in reducing energy requirements and enabling a more sustainable transition toward a hydrogen‐based economy. Stacking fault (SF) defects play an important role in enhancing the electrocatalytic processes by reshaping surface reactivity, increasing active sites, improving reactants/product diffusion, and regulating electronic structure due to their dense generation ability and profound impact on catalyst properties. This review explores SF in metal‐based materials, covering synthetic methods for the intentional introduction of SF and their applications in hydrogen production, including oxygen evolution reaction, photo‐ and electrocatalytic hydrogen evolution reaction, overall water splitting, and various other electrocatalytic processes such as oxygen reduction reaction, nitrate reduction reaction, and carbon dioxide reduction reaction. Finally, this review addresses the challenges associated with SF‐based catalysts, emphasizing the importance of a detailed understanding of the properties of SF‐based catalysts to optimize their electrocatalytic performance. It provides a comprehensive overview of their various applications in electrocatalytic processes, providing valuable insights for advancing sustainable energy technologies.
Locally Strained 2D Materials: Preparation, Properties, and Applications
Authors: Wang Jingwei , He Liqiong , Zhang Yunhao , Nong Huiyu , Li Shengnan , Wu Qinke , Tan Junyang , Liu Bilu
Published: February 2024

2D materials are promising for strain engineering due to their atomic thickness and exceptional mechanical properties. In particular, non‐uniform and localized strain can be induced in 2D materials by generating out‐of‐plane deformations, resulting in novel phenomena and properties, as witnessed in recent years. Therefore, the locally strained 2D materials are of great value for both fundamental studies and practical applications. This review discusses techniques for introducing local strains to 2D materials, and their feasibility, advantages, and challenges. Then, the unique effects and properties that arise from local strain are explored. The representative applications based on locally strained 2D materials are illustrated, including memristor, single photon emitter, and photodetector. Finally, concluding remarks on the challenges and opportunities in the emerging field of locally strained 2D materials are provided.
Anion‐Reinforced Solvating Ionic Liquid Electrolytes Enabling Stable High‐Nickel Cathode in Lithium‐Metal Batteries
Authors: Zou Wenhong , Zhang Jun , Liu Mengying , Li Jidao , Ren Zejia , Zhao Wenlong , Zhang Yanyan , Shen Yanbin , Tang Yuxin
Published: February 2024

Ionic liquid electrolytes (ILEs) are promising to develop high‐safety and high‐energy‐density lithium‐metal batteries (LMBs). Unfortunately, ILEs normally face the challenge of sluggish Li+ transport due to increased ions’ clustering caused by Coulombic interactions. Here a type of anion‐reinforced solvating ILEs (ASILEs) is discovered, which reduce ions’ clustering by enhancing the anion–cation coordination and promoting more anions to enter the internal solvation sheath of Li+ to address this concern. The designed ASILEs, incorporating chlorinated hydrocarbons and two anions, bis(fluorosulfonyl) imide (FSI−) and bis(trifluoromethanesulfonyl) imide (TFSI−), aim to enhance Li+ transport ability, stabilize the interface of the high‐nickel cathode material (LiNi0.8Co0.1Mn0.1O2, NCM811), and retain fire‐retardant properties. With these ASILEs, the Li/NCM811 cell exhibits high initial specific capacity (203 mAh g−1 at 0.1 C), outstanding capacity retention (81.6% over 500 cycles at 1.0 C), and excellent average Coulombic efficiency (99.9% over 500 cycles at 1.0 C). Furthermore, an Ah‐level Li/NCM811 pouch cell achieves a notable energy density of 386 Wh kg−1, indicating the practical feasibility of this electrolyte. This research offers a practical solution and fundamental guidance for the rational design of advanced ILEs, enabling the development of high‐safety and high‐energy‐density LMBs.
Near‐Infrared and Visible Dual‐Emitting Peptide by Modular Assembly of Nitrobenzoxadiazole and Neodymium Complexes
Authors: Yeung Yik‐Hoi , Chau Ho‐Fai , Kai Hei‐Yui , Zhou Wanqi , Chan Kaitlin Hao‐Yi , Thor Waygen , Charbonnière Loïc J. , Zhang Fan , Fan Yong , Wu Yue , Wong Ka‐Leung
Published: February 2024

The synthetic difficulty of target‐specific lanthanide complexes, despite their unique characteristics, limits their use in in vitro/ in vivo studies and biomedical applications. With commercially available and affordable reagents, a facile synthetic approach is developed to modularly deploy nitrobenzoxadiazole and neodymium complexes onto bioactive peptides. The yielded probes show observable neodymium emission with specific localization to corresponding biotargets in vitro, which became the first example of a stable, water‐soluble, and target‐specific neodymium(III) complex applicable for in vitro imaging with detectable brightness.
Enhanced parameter estimation with improved particle swarm optimization algorithm for cell culture process modeling
Authors: Fu Zhongwang , Wang Zheyu , Chen Gong
Published: February 2024

Mechanism models and model‐assisted process optimization play a vital role in biopharmaceutical industry. However, the parameter estimation remains a challenging task in modeling due to the presence of multiple local optima and ill‐conditioning. In this study, we firstly presented a comparative evaluation of particle swarm optimization (PSO), genetic algorithm (GA), and simulated annealing (SA) for parameter estimation and confirmed PSO was the most efficient approach. Then an improved PSO algorithm using second‐order oscillation and particle replacement strategies was developed to enhance fitting performance in fed‐batch cell culture modeling. The results of fitting and model validation demonstrated that the improved PSO could explore more reasonable parameters and leading to a significantly enhancement in predictive accuracy throughout the entire cell culture process under varying conditions. Moreover, 10 diverse fed‐batch experiments were conducted to validate the fitting abilities on different process condition and clones, the improved PSO method exhibited improvements in accuracy and universality of parameter estimation for modeling various cultivation processes, particularly those lacking any prior knowledge. This improved algorithm is implemented to make it available to both the scientific community and industry, offering customized solutions for specific projects.
The human biology of spaceflight
Authors: Sarma Mallika S. , Shelhamer Mark
Published: February 2024

To expand the human exploration footprint and reach Mars in the 2030s, we must explore how humans survive and thrive in demanding, unusual, and novel ecologies (i.e., extreme environments). In the extreme conditions encountered during human spaceflight, there is a need to understand human functioning and response in a more rigorous theoretically informed way. Current models of human performance in space‐relevant environments and human space science are often operationally focused, with emphasis on acute physiological or behavioral outcomes. However, integrating current perspectives in human biology allows for a more holistic and complete understanding of how humans function over a range of time in an extreme environment. Here, we show how the use of evolution‐informed frameworks (i.e., models of life history theory to organize the adaptive pressures of spaceflight and biocultural perspectives) coupled with the use of mixed‐methodological toolkits can shape models that better encompass the scope of biobehavioral human adjustment to long‐duration space travel and extra‐terrestrial habitation. Further, we discuss how we can marry human biology perspectives with the rigorous programmatic structures developed for spaceflight to model other unknown and nascent extremes.
Tailoring Rhodamine Probes: Oxyethylene Chains, Conjugation, and End Substituents in the Quest for Superior Hg2+ Sensing
Authors: Barkale Harshal V. , Dey Nilanjan
Published: February 2024

This study explores the impact of incorporating oxyethylene (OE) chains into rhodamine‐based dye molecules for the enhancement of photophysical properties in the context of chemical sensing. The introduction of OE chains provides several advantages, including improved water solubility, photostability and resistance to self‐assembled nanoaggregates formation. Despite these, the compound with oxyethylene chains showed poor response (~2‐fold) towards Hg2+ ions than that of dimeric probe (~20 fold) with no such substituents. Notably, dimeric compound shows a remarkable three‐fold larger response to Hg2+ ion compared to monomeric compound. This intriguing outcome is attributed to the extended conjugation within the dimeric structure, which can induce conformational change of the overall molecule. Moreover, the study investigates the effects of end substituents, such as electron‐donating (−OMe, improved response) and electron‐withdrawing (−NO2, poor response) groups, on the interaction with Hg2+ ions. The excellent sensitivity of the probe molecules is also evident in significantly low detection limits for Hg2+ ion (5–8 ppb) in real‐life water samples. The high recovery values (>95 %) with sufficient low standard deviation (<5%) indicates that quantitative analysis of Hg2+ is achievable using the current protocol. Beyond that, we have employed the probe 1 for intracellular (HEK293T cells) fluorescence imaging of Hg2+.
A Three‐Dimensionally Extended Metal–Organic Ladder Compound Exhibiting Proton Conduction
Authors: Liang Hao , Otsubo Kazuya , Wakabayashi Yusuke , Sagayama Hajime , Kawaguchi Shogo , Kitagawa Hiroshi
Published: February 2024

Ladder systems situated in the dimensional crossover region have attracted much attention because their electronic states and physical properties depend strongly on the electronic correlations among the constituent legs. Generally, two‐/three‐legged transition metal‐oxide ladder compounds are studied as representative ladder systems, but two‐/three‐dimensional (2D/3D) extensions based on such ladder systems with a few numbers of legs are difficult because of the extreme synthesis conditions. Here, for the first time, we report the successful creation of a 3D extended two‐legged ladder compound, [Pt(en)(dpye)I]2(NO3)4 ⋅ 2H2O (en=ethylenediamine; dpye=1,2‐Di(4‐pyridyl)ethane), which is obtained by simple oxidative polymerization of a small Pt macrocyclic complex using elemental I2. The unique 3D extended lattice consists of 1D mixed‐valence halogen‐bridged metal chains (⋅⋅⋅Pt−I−Pt−I⋅⋅⋅) and helically arranged macrocyclic units as the constituent legs and rungs, as confirmed by single‐crystal X‐ray diffraction. Diffuse X‐ray scattering analyses and optical measurements revealed that the out‐of‐phase mixed‐valence Pt2+/Pt4+ arrangement arises from the weak interchain correlation among adjacent legs. In addition, this compound shows an increase in proton conductivity by a factor of up to 1000, depending on humidity.
Photoinduced Precise Synthesis of Diatomic Ir1Pd1‐In2O3 for CO2 Hydrogenation to Methanol via Angstrom‐Scale‐Distance Dependent Synergistic Catalysis
Authors: Chen Jie , Zhang Dongjian , Liu Bing , Zheng Ke , Li Yufeng , Xu Yuebing , Li Zaijun , Liu Xiaohao
Published: February 2024

The atomically dispersed metal catalysts with full atomic utilization and well‐defined site structure hold great promise for various catalytic reactions. However, the single metallic site limits the comprehensive reaction performance in most reactions. Here, we demonstrated a photo‐induced neighbour‐deposition strategy for the precise synthesis of diatomic Ir1Pd1 on In2O3 applied for CO2 hydrogenation to methanol. The proximity synergism between diatomic sites enabled a striking promotion in both CO2 conversion (10.5 %) and methanol selectivity (97 %) with good stability of 100 h run. It resulted in record‐breaking space‐time yield to methanol (187.1 gMeOH gmetal−1 hour−1). The promotional effect mainly originated from stronger CO2 adsorption on Ir site with assistance of H‐spillover from Pd site, thus leading to a lower energy barrier for *HCOO pathway. It was confirmed that this synergistic effect strongly depended on the dual‐site distance in an angstrom scale, which was attributed to weaker *H spillover and less electron transfer from Pd to Ir site as the Pd‐to‐Ir distance increased. The average dual‐site distance was evaluated by our firstly proposed photoelectric model. Thus, this study introduced a pioneering strategy to precisely synthesize homonuclear/heteronuclear diatomic catalysts for facilitating the desired reaction route via diatomic synergistic catalysis.
The Fundamental Disorder Unit in (Si, P)−(O, N) Networks
Authors: Dialer Marwin , Witthaut Kristian , Bräuniger Thomas , Schmidt Peter J. , Schnick Wolfgang
Published: February 2024

This study presents the synthesis and characterization of oxonitridosilicate phosphates Sr3SiP3O2N7, Sr5Si2P4ON12, and Sr16Si9P9O7N33 as the first of their kind. These compounds were synthesized under high‐temperature (1400 °C) and high‐pressure (3 GPa) conditions. A unique structural feature is their common fundamental building unit, a vierer single chain of (Si, P)(O, N)4 tetrahedra. All tetrahedra comprise substitutional disorder which is why we refer to it as the fundamental disorder unit (FDU). We classified four different FDU motifs, revealing systematic bonding patterns. Including literature known Sr5Si2P6N16, three of the four patterns were found in the presented compounds. Common techniques like single‐crystal X‐ray diffraction (SCXRD), elemental analyses, and 31P nuclear magnetic resonance (NMR) spectroscopy were utilized for structural analysis. Additionally, low‐cost crystallographic calculations (LCC) provided insights into the structure of Sr16Si9P9O7N33 where NMR data were unavailable due to the lack of bulk samples. The optical properties of these compounds, when doped with Eu2+, were investigated using photoluminescence excitation (PLE), photoluminescence (PL) measurements, and density functional theory (DFT) calculations. Factors influencing the emission properties, including thermal quenching mechanisms, were discussed. This research reveals the new class of oxonitridosilicate phosphates with unique systematic structural features that offer potential for theoretical studies of luminescence and band gap tuning in insulators.
Discovery of the First‐in‐Class Inhibitors of Hypoxia Up‐Regulated Protein 1 (HYOU1) Suppressing Pathogenic Fibroblast Activation
Authors: Papadopoulou Dimitra , Mavrikaki Vasiliki , Charalampous Filippos , Tzaferis Christos , Samiotaki Martina , Papavasileiou Konstantinos D. , Afantitis Antreas , Karagianni Niki , Denis Maria C. , Sanchez Julie , Lane J. Robert , Faidon Brotzakis Zacharias , Skretas Georgios , Georgiadis Dimitris , Matralis Alexios N. , Kollias George
Published: February 2024

Fibroblasts are key regulators of inflammation, fibrosis, and cancer. Targeting their activation in these complex diseases has emerged as a novel strategy to restore tissue homeostasis. Here, we present a multidisciplinary lead discovery approach to identify and optimize small molecule inhibitors of pathogenic fibroblast activation. The study encompasses medicinal chemistry, molecular phenotyping assays, chemoproteomics, bulk RNA‐sequencing analysis, target validation experiments, and chemical absorption, distribution, metabolism, excretion and toxicity (ADMET)/pharmacokinetic (PK)/in vivo evaluation. The parallel synthesis employed for the production of the new benzamide derivatives enabled us to a) pinpoint key structural elements of the scaffold that provide potent fibroblast‐deactivating effects in cells, b) discriminate atoms or groups that favor or disfavor a desirable ADMET profile, and c) identify metabolic “hot spots”. Furthermore, we report the discovery of the first‐in‐class inhibitor leads for hypoxia up‐regulated protein 1 (HYOU1), a member of the heat shock protein 70 (HSP70) family often associated with cellular stress responses, particularly under hypoxic conditions. Targeting HYOU1 may therefore represent a potentially novel strategy to modulate fibroblast activation and treat chronic inflammatory and fibrotic disorders.
Differentiating the aromatic positional isomers of methylbuphedrones and methoxybuphedrones via chemical ionization‐mass spectrometry
Authors: Tsunoi Shinji , Yasuhisa Tomohiro , Hisasue Takahiro , Suzuki Itaru , Shibata Ikuya
Published: February 2024

Discrimination of aromatic positional isomers of methylbuphedrones and methoxybuphedrones was successfully achieved. Meta isomers were discriminated by chemical ionization‐tandem mass spectrometry (CI‐MS/MS) using acetonitrile as a reagent gas. Furthermore, all the aromatic positional isomers were discriminated by CI‐MS/MS using vinyltrimethylsilane as a reagent gas.
Visualizing Amyloid Assembly at the Nanoscale: Insights from Super‐Resolution Imaging
Authors: Bhuskute Kaustubh R. , Kikuchi Kai , Luo Zijie , Kaur Amandeep
Published: February 2024

In the rapidly evolving landscape of molecular imaging, super‐resolution techniques emerge as indispensable tools, revolutionizing our capacity to decipher the intricacies of protein aggregation, and paving the way for molecular‐level understanding of the progression of neurodegenerative disorders. In this review article we provide an overview of the diverse super‐resolution imaging techniques applied to study amyloids at high resolution. We outline the strengths and limitations of each technique, offering insights into their applicability to different amyloid systems. We next delve into the diverse strategies employed for labeling amyloids in conjunction with super‐resolution imaging. From small organic dyes to fluorescent proteins and advanced chemical probes, the discussion encompasses the strengths and considerations associated with each labeling method. The comparative analysis not only evaluates the impact of labeling on resolution and specificity but also highlights emerging trends and future directions in the field.
Pregnancy‐related knowledge in women with epilepsy in childbearing age: A pilot questionnaire survey from China
Authors: Li Qiwei , Cao Yina , Zhang Jingxin , Fu Yanlu , Shen Beibei , Wang Shuang , Fang Jiajia
Published: February 2024

Purpose

We aim to understand the knowledge of and attitudes toward pregnancy issues among women with epilepsy (WWE) and their caregivers and analyze the answers from the questionnaire to expose topics that require educational activities; thus, WWE experiences pregnancy better.

Methods

WWE at their childbearing age and/or their caregivers who entered the Fourth Affiliated Hospital of Zhejiang University for treatment of their condition were invited to fill out a questionnaire between March 1 and November 31, 2022.

Results

A combined total of 205 WWE and 142 caregivers completed the questionnaires. Among the surveyed WWE, a majority (63.74%) reported experiencing at least one miscarriage or induced abortion. However, a significant proportion (84.62%) of these WWE were still able to successfully give birth to at least one child. Furthermore, the offspring of these WWE showed no significant differences compared to the offspring of women without epilepsy, as reported by 93.51% of the participants. The participants’ knowledge regarding the impact of epilepsy on pregnancy was found to be comparable, with average scores of 7.74 and 7.84, respectively. The participants exhibited a limited comprehension of antiseizure medications (ASMs)‐related knowledge, specifically pertaining to ASMs adjustment during pregnancy (17.56% vs. 16.90%) and offspring outcomes (30.24% vs. 26.06%). Statistical analysis revealed significant correlations between the overall score and education level (p < .001), as well as epilepsy duration (p = .008). Regarding the source of knowledge, participants acknowledged primarily relying on neurologists, who remained their preferred choice for consultation.

Conclusion

In our study, the understanding of pregnancy‐related knowledge did not differ from WWE and their caregivers, both are far from satisfactory in certain areas. It is urgent for WWE and their caregivers to improve their pregnancy‐related knowledge of epilepsy. As their primary access is from knowledgeable health care professionals like neurologists, well‐trained neurologists in epilepsy management during pregnancy are in need.
UK Medical Cannabis Registry: Assessment of clinical outcomes in patients with insomnia
Authors: Vivek Kavyesh , Karagozlu Zekiye , Erridge Simon , Holvey Carl , Coomber Ross , Rucker James J. , Weatherall Mark W. , Sodergren Mikael H
Published: February 2024

Introduction

The primary aim of this study was to assess changes in sleep‐specific health‐related quality of life (HRQoL) for those prescribed cannabis‐based medicinal products (CBMPs) for insomnia.

Methods

A case series of UK patients with insomnia was analyzed. Primary outcomes were changes in the Single‐Item Sleep‐Quality Scale (SQS), Generalized Anxiety Disorder‐7 (GAD‐7), and EQ‐5D‐5L at up to 6 months from baseline. Statistical significance was identified as a p value < .050.

Results

61 patients were included in the analysis. There was an improvement in the SQS from baseline at 1, 3, and 6 months (p < .001). There were also improvements in the EQ‐5D‐5L Index value and GAD‐7 at 1, 3, and 6 months (p < .050). There were 28 (45.9%) adverse events recorded by 8 patients (13.1%). There were no life‐threatening/disabling adverse events.

Conclusion

Patients with insomnia experienced an improvement in sleep quality following the initiation of CBMPs in this medium‐term analysis. Fewer than 15% of participants reported one or more adverse events. However, due to the limitations of the study design, further investigation is required before definitive conclusions can be drawn on the efficacy of CBMPs in treating insomnia.
A case of leukemia cutis showing annular erythema during the course of Philadelphia chromosome‐positive acute B‐lymphoblastic leukemia
Authors: Tomita Hizuru , Nobeyama Yoshimasa , Sakayori You , Matsumoto Rika , Chujo Satomi , Suzuki Hikaru , Asahina Akihiko
Published: February 2024

Key Clinical Message

We report a case of leukemia cutis showing annular erythema during the course of Philadelphia chromosome‐positive acute B‐lymphoblastic leukemia. The annular appearance may be developed by immunomodulatory effects of blinatumomab.
Spinal muscular atrophy type 1: A fatal case in a 1‐year‐old girl with delayed diagnosis
Authors: Rizvi Saira Batool , Ahmed Hafsa , Zaman Arbaz , Ali Ameenudeen Mohammed Nushrath , Shah Hussain Haider , Rauf Sameer Abdul , Dave Tirth
Published: February 2024

Key Clinical Message

Spinal muscular atrophy (SMA) is a growing clinical concern, necessitating higher awareness and early detection. This case study focuses on the difficulties and advances in detecting and treating SMA. It emphasizes the value of early detection, interdisciplinary care, genetic testing, and novel therapeutics in terms of improving outcomes.

Spinal muscular atrophy type 1 (SMA Type 1) is a rare genetic neuromuscular disease characterized by muscle atrophy and weakness. This case report presents the fatal outcome of a 1‐year‐old girl with delayed diagnosis of SMA Type 1. The child exhibited symptoms of muscle weakness and respiratory distress, which were initially overlooked. Despite a thorough examination and diagnostic tests, including genetic analysis, SMA Type 1 with a homozygous deletion in the survival motor neuron 1 (SMN1) gene was confirmed. The child received supportive measures and physiotherapy but experienced a progressive deterioration of her condition and eventually succumbed to the disease. This case underscores the challenges of diagnosing SMA and highlights the importance of early identification for appropriate management. Improved awareness, diagnostic protocols, and access to treatment options, including pharmacological drugs and gene therapy, are essential to improve outcomes for SMA Type 1 patients, particularly in resource‐limited settings. Early detection through newborn screening programs and timely intervention can significantly impact the prognosis and life expectancy of SMA Type 1 children, emphasizing the need for continued research and clinical trials to establish a definitive cure.
Construction of Bidentate Phosphines Enabled by Photoinduced Reductive Diphosphination of Alkenes
Authors: Liu Hongchi , Huang Hanmin
Published: February 2024

The diphosphination of alkenes through a radical pathway offers a promising approach for the rapid construction of aryl bisphosphines. However, such a synthetic strategy has not been successfully applied to the preparation of alkyl bisphosphines, partially due to the difficulties in the generation of phosphorus‐centered radicals from common alkyl phosphine compounds. We herein demonstrate that this challenge can be overcome by hiring Janus‐faced chlorophosphine as the phosphine source that can act as not only a radical precursor to generate phosphine‐centered radicals but also a radicalphile to capture alkyl radicals. With this novel strategy, a photocatalyzed reductive diphosphination reaction has been established, allowing for a straightforward synthesis of both aryl and alkyl 1,2‐bisphosphines from readily accessible alkenes and chlorophosphines.
Neuroblastoma and its Target Therapies: A Medicinal Chemistry Review
Authors: Gerges A. , Canning U.
Published: February 2024

Neuroblastoma (NB) is a childhood malignant tumour belonging to a group of embryonic tumours originating from progenitor cells of the sympathoadrenal lineage. The heterogeneity of NB is reflected in the survival rates of those with low and intermediate risk diseases who have survival rates ranging from 85 to 90 %. However, for those identified with high‐risk Stage 4 NB, the treatment options are much more limited. For this group, current treatment consists of immunotherapy (monoclonal antibodies) in combination with anti‐cancer drugs and has a 40 to 50 % survival rate. The purpose of this review is to summarise NB research from a medicinal chemistry perspective and to highlight advances in targeted drug therapy in the field. The review examines the medicinal chemistry of a number of drugs tested in research, some of which are currently under clinical trial. It concludes by proposing that future medicinal chemistry research into NB should consider other possible target therapies and adopt a multi‐target drug approach rather than a one‐drug‐one‐target approach for improved efficacy and less drug‐drug interaction for the treatment of NB Stage 4 (NBS4) patients.
Impact of Temperature on the Chiroptical Properties of Thin Films of Chiral Thiophene‐based Oligomers
Authors: Albano Gianluigi , Portus Lorenzo , Martinelli Elisa , Pescitelli Gennaro , Di Bari Lorenzo
Published: February 2024

According to the theoretical model based on the Mueller matrix approach, the experimental electronic circular dichroism (ECD) for thin films of chiral organic dyes can be expressed as the sum of several contributions, two of which are the most significant: 1) an intrinsic component (CDiso) invariant upon sample orientation, reflecting the molecular and/or supramolecular chirality, due to 3D‐chiral nanoscopic structures; 2) a non‐reciprocal component (LDLB) which inverts its sign upon sample flipping, which arises from the interaction of linear dichroism and linear birefringence in locally anisotropic domains, expression of 2D‐chiral micro/mesoscopic structures. In this work, we followed in parallel through ECD and differential scanning calorimetry (DSC) the temperature evolution of the supramolecular arrangements of thin films of five structurally related chiral thiophene‐based oligomers with different LDLB/CDiso ratio. By increasing the temperature, regardless of phase transitions observed by DSC analysis, systems with strong CDiso revealed no changes in the ECD spectrum, while compounds with dominant LDLB contribution underwent a gradual (and reversible) reduction of (apparent) ECD signals. These findings demonstrated that the concomitant occurrence of intrinsic and non‐reciprocal components in the ECD spectrum of thin films of chiral organic dyes is strictly correlated with solid‐state organizations of different stability.
Reinforcement Learning and PK‐PD Models Integration to Personalize the Adaptive Dosing Protocol of Erdafitinib in Patients with Metastatic Urothelial Carcinoma
Authors: De Carlo Alessandro , Tosca Elena Maria , Fantozzi Martina , Magni Paolo
Published: February 2024

The integration of pharmacokinetic‐pharmacodynamic (PK‐PD) modeling and simulations with artificial intelligence/machine learning algorithms is one of the most attractive areas of the pharmacometric research. These hybrid techniques are currently under investigation to perform several tasks, among which precision dosing. In this scenario, this paper presents and evaluates a new framework embedding PK‐PD models into a reinforcement learning (RL) algorithm, Q‐learning (QL), to personalize pharmacological treatment. Each patient is represented with a set of PK‐PD parameters and has a personal QL agent which optimizes the individual treatment. In the training phase, leveraging PK‐PD simulations, the QL agent assesses different actions, defined consistently with the clinical knowledge to consider only plausible dose‐adjustments, in order to find the optimal rules. The proposed framework was evaluated to optimize the erdafitinib treatment in patients with metastatic urothelial carcinoma. This drug was approved by the US Food and Drug Administration (FDA) with a dose‐adaptive protocol based on monitoring the levels of serum phosphate, which represent a biomarker of both treatment efficacy and toxicity. To evaluate the flexibility of the methodology, a heterogeneous virtual population of 141 patients was generated using an erdafitinib population PK (PopPK)‐PD literature model. For each patient, treatment response was simulated by using both QL‐optimized protocol and the clinical one. QL agents outperform the approved dose‐adaptive rules, increasing more than 10% the efficacy and the safety of treatment at each end point. Results confirm the great potentialities of the integration of PopPK‐PD models and RL algorithms to optimize precision dosing tasks.
Patients' values and preferences regarding endoscopic therapy for Barrett's esophagus: A cross‐sectional survey study
Authors: Qumseya Bashar J. , Estores David , Gorripati Venkata , Liu Nanlog , Qumseya Amira
Published: February 2024

Introduction

Endoscopic eradication therapy (EET) has evolved as a minimally invasive and efficacious option to treat patients with dysplastic Barret's esophagus. We aimed to conduct a cross‐sectional study to assess patient values and preferences on EET.

Methods

All consecutive patients at our clinic and endoscopy center were enrolled between November 2020 and April 2022. The primary outcome was their willingness to undergo EET measured using a validated survey tool. Predictors of this outcome included patient demographics, disease characteristics, procedure types, and physician characteristics. We used a multivariable logistic regression model to assess the association between the primary outcome and its predictors.

Results

A total of 101 consecutive Barret's esophagus patients were surveyed. The median age was 67 years, and 71.3% were males. About 48% (n = 48) of the patients had dysplasia, 19% had no dysplasia and others were unsure about the presence or absence of dysplasia. About one‐third (30%, n = 30) of patients placed equal values on preventing cancer and avoiding adverse events, and 68% said they were somewhat or definitely willing to undergo EET (ablation and resection). On multivariable logistic regression analysis, the patient value of high emphasis on cancer prevention (odds ratio [OR] 2.9 [1.1–7.6], p = 0.0344) and positive relationship with a gastroenterologist (OR 4.7 [1.3–17], p = 0.02) were strongly associated with increased willingness to undergo EET.

Conclusions

In this single‐center prospective study of Barret's esophagus patients, the willingness to undergo EET was strongly associated with two predictors: high emphasis on cancer prevention and a positive relationship with the gastroenterologist.
Requirement of a novel gene, drish, in the zebrafish retinal ganglion cell and primary motor axon development
Authors: Gurung Suman , Restrepo Nicole K. , Anand Surendra Kumar , Sittaramane Vinoth , Sumanas Saulius
Published: February 2024

Background

During neurogenesis, growing axons must navigate through the complex extracellular environment and make correct synaptic connections for the proper functioning of neural circuits. The mechanisms underlying the formation of functional neural networks are still only partially understood.

Results

Here we analyzed the role of a novel gene si:ch73‐364h19.1/drish in the neural and vascular development of zebrafish embryos. We show that drish mRNA is expressed broadly and dynamically in multiple cell types including neural, glial, retinal progenitor and vascular endothelial cells throughout the early stages of embryonic development. To study Drish function during embryogenesis, we generated drish genetic mutant using CRISPR/Cas9 genome editing. drish loss‐of‐function mutant larvae displayed defects in early retinal ganglion cell, optic nerve and the retinal inner nuclear layer formation, as well as ectopic motor axon branching. In addition, drish mutant adults exhibited deficient retinal outer nuclear layer and showed defective light response and locomotory behavior. However, vascular patterning and blood circulation were not significantly affected.

Conclusions

Together, these data demonstrate important roles of zebrafish drish in the retinal ganglion cell, optic nerve and interneuron development and in spinal motor axon branching.
Land cover preferences and spatiotemporal associations of ungulates within a Scottish mammal community
Authors: Lovell Connor , Pettorelli Nathalie , Dawson Terence P.
Published: February 2024

In the degraded and modified environment of the Scottish Highlands, novel ungulate communities have arisen following local extinctions, reintroductions, and the introduction of non‐native species. An understanding of the dynamics and interactions within these unique mammal communities is important as many of these mammals represent keystone species with disproportionate impacts on the environment. Using a camera trap survey, we investigated land cover preferences and spatiotemporal interactions within a Scottish ungulate community: the sika deer (Cervus nippon), the roe deer (Capreolus capreolus), the red deer (Cervus elaphus), and the wild boar (Sus scrofa). We used generalised linear models to assess land cover preferences and the effect of human disturbance; spatiotemporal interactions were characterised using time interval modelling. We found that sika deer and roe deer preferred coniferous plantations and grasslands, with sika deer additionally preferring woodland. For red deer, we found a slight preference for wetland over woodland; however, the explained variance was low. Finally, wild boar preferred grassland and woodland and avoided coniferous plantations, heathland, and shrubland. Contrary to our expectations, we found no evidence that human disturbance negatively impacted ungulates' distributions, potentially because ungulates temporally avoid humans or because dense vegetation cover mitigates the impacts of humans on their distributions. Furthermore, we detected a spatiotemporal association between sika deer and roe deer. Although the underlying cause of this is unknown, we hypothesise that interactions such as grazing facilitation or an anti‐predator response to culling could be driving this pattern. Our work provides a preliminary analysis of the dynamics occurring within a novel ungulate community and also highlights current knowledge gaps in our understanding of the underlying mechanisms dictating the observed spatiotemporal associations.