bluuebunny/crossref_metadata_2025 huggingface dataset:
Surface‐Grafted Biocompatible Polymer Conductors for Stable and Compliant Electrodes for Brain Interfaces
Authors: Blau Rachel , Russman Samantha M. , Qie Yi , Shipley Wade , Lim Allison , Chen Alexander X. , Nyayachavadi Audithya , Ah Louis , Abdal Abdulhameed , Esparza Guillermo L. , Edmunds Samuel J. , Vatsyayan Ritwik , Dunfield Sean P. , Halder Moumita , Jokerst Jesse V. , Fenning David P. , Tao Andrea R. , Dayeh Shadi A. , Lipomi Darren J.
Published: July 2024

Durable and conductive interfaces that enable chronic and high‐resolution recording of neural activity are essential for understanding and treating neurodegenerative disorders. These chronic implants require long‐term stability and small contact areas. Consequently, they are often coated with a blend of conductive polymers and are crosslinked to enhance durability despite the potentially deleterious effect of crosslinking on the mechanical and electrical properties. Here the grafting of the poly(3,4 ethylenedioxythiophene) scaffold, poly(styrenesulfonate)‐b‐poly(poly(ethylene glycol) methyl ether methacrylate block copolymer brush to gold, in a controlled and tunable manner, by surface‐initiated atom‐transfer radical polymerization (SI‐ATRP) is described. This “block‐brush” provides high volumetric capacitance (120 F cm─3), strong adhesion to the metal (4 h ultrasonication), improved surface hydrophilicity, and stability against 10 000 charge–discharge voltage sweeps on a multiarray neural electrode. In addition, the block‐brush film showed 33% improved stability against current pulsing. This approach can open numerous avenues for exploring specialized polymer brushes for bioelectronics research and application.
Plant‐Based Shape Memory Cryogel for Hemorrhage Control
Authors: Deng J. , Zhao Z. , Yeo X.Y. , Yang C. , Yang J. , Ferhan A.R. , Jin B. , Oh C. , Jung S. , Suresh S. , Cho N.‐J.
Published: July 2024

The escalating global demand for sustainable manufacturing, motivated by concerns over energy conservation and carbon footprints, encounters challenges due to insufficient renewable materials and arduous fabrication procedures to fulfill specific requirements in medical and healthcare systems. Here, biosafe pollen cryogel is engineered as effective hemostats without additional harmful crosslinkers to treat deep noncompressible wounds. A straightforward and low‐energy approach is involved in forming stable macroporous cryogel, benefiting from the unique micro‐hierarchical structures and chemical components of non‐allergenic plant pollen. It is demonstrated that the pollen cryogel exhibits rapid water/blood‐triggered shape‐memory properties within 2 s. Owing to their inherent nano/micro hierarchical structure and abundant chemical functional groups on the pollen surface, the pollen cryogel shows effective hemostatic performance in a mouse liver penetration model, which is easily removed after usage. Overall, the self‐crosslinking pollen cryogel in this work pioneers a framework of potential clinical applications for the first‐hand treatment on deep noncompressible wounds.
Laser‐Printed All‐Carbon Responsive Material and Soft Robot
Authors: Yu Wenjie , Zhao Weiwei , Zhu Xinbei , Li Mingyue , Yi Xiaosu , Liu Xiaoqing
Published: July 2024

Responsive materials and actuators are the basis for the development of various leading‐edge technologies but have so far mostly been designed based on polymers, incurring key limitations related to sensitivity and environmental tolerance. This work reports a new responsive material, laser‐printed carbon film (LPCF), produced via direct laser transformation of a liquid organic precursor and consists of graphitic and amorphous carbons. The high activity of amorphous carbon combined with the dual‐gradient structure enables the LPCF to have a actuation speed of 9400° s−1 in response to the stimulus of organic vapor. LPCF exhibits a conductivity of 950 S m−1 and excellent resistance to various extreme environmental conditions, which are unachievable for polymer‐based materials. Additionally, an LPCF‐based all‐carbon soft robot that can mimic the complex continuous backward somersaulting motions without manual intervention is constructed. The locomotion velocity of the robot reaches a value of 1.19 BL s−1, which is almost one to two orders of magnitude faster than that of reported soft robots. This work not only offers a new paradigm for highly responsive materials but also provides a great design and engineering example for the next generation of biomimetic robots with life‐like performance.
Atomic‐Level Observation of Potential‐Dependent Variations at the Surface of an Oxide Catalyst during Oxygen Evolution Reaction
Authors: Park Chang Hyun , Lee Hyungdoh , Choi Jin‐Seok , Yun Tae Gyu , Lim Younghwan , Bae Hyung Bin , Chung Sung‐Yoon
Published: July 2024

Understanding the intricate details of the surface atomic structure and composition of catalysts during the oxygen evolution reaction (OER) is crucial for developing catalysts with high stability in water electrolyzers. While many notable studies highlight surface amorphization and reconstruction, systematic analytical tracing of the catalyst surface as a function of overpotential remains elusive. Heteroepitaxial (001) films of chemically stable and lattice‐oxygen‐inactive LaCoO3 are thus utilized as a model catalyst to demonstrate a series of atomic‐resolution observations of the film surface at different anodic potentials. The first key finding is that atoms at the surface are fairly dynamic even at lower overpotentials. Angstrom‐scale atomic displacements within the perovskite framework are identified below a certain potential level. Another noteworthy feature is that amorphization (or paracrystallization) with no long‐range order is finally induced at higher overpotentials. In particular, surface analyses consistently support that the oxidation of lattice oxygen is coupled with amorphous phase formation at the high potentials. Theoretical calculations also reveal an upward shift of oxygen 2p states toward the Fermi level, indicating enhanced lattice oxygen activation when atom displacement occurs more extensively. This study emphasizes that the degradation behavior of OER catalysts can distinctively vary depending on the overpotential level.
Biometabolically Derived Selenium Nanoparticles Armed with Protein Protective Suit toward High‐Performance Li‐Se Batteries
Authors: Xia Yang , Lu Chengwei , Fan Wenluxi , Fang Ruyi , Xu Lusheng , Huang Haichan , Xiao Zhen , Zhang Jun , Huang Hui , Gan Yongping , He Xinping , Tao Xinyong , Xia Xinhui , Zhang Wenkui
Published: July 2024

Selenium (Se) serves as a burgeoning high‐energy‐density cathode material in lithium‐ion batteries. However, the development of Se cathode is strictly limited by low Se utilization and inferior cycling stability arising from intrinsic volume expansion and notorious shuttle effect. Herein, a microbial metabolism strategy is developed to prepare “functional vesicle‐like” Se globules via Bacillus subtilis subsp. from selenite in sewage, in which Se nanoparticles are armed with a natural biological protein membrane with rich nitrogen and phosphorus, achieving the eco‐efficient conversion of trash into treasure (selenite, SeO32− → Selenium, Se). The appealing‐design “functional vesicle‐like” Se globules are beneficial to accommodate volume changes of Se in electrochemical reactions, confining polyselenides via chemisorption, and enhancing mechanical strength of electrode by associated bacteria debris, realizing comprehensive utilization of microorganism. By conceptualizing “functional vesicle‐like” Se globules, rather than artificial Se‐host composites, as cathode for lithium–selenium batteries, it exhibits outstanding cycling stability and improved rate performance. This strategy opens the door to design smart electrode materials with unattainable structure that cannot be achieved by traditional approaches, achieving eco‐efficient conversion of pollutants into energy‐storage nanomaterials, which will be a promising research field for interdisciplinary of energy, biology, and environment.
Integration of Wallach's Rule into Intermolecular Charge Transfer: A Visual Strategy for Chiral Purification
Authors: Wang Wei , Gong Jianye , Zhao Jiaqiang , Zhang Hao , Wen Wei , Zhao Zujin , Li Yan Jie , Wang Jianguo , Huang Cheng Zhi , Gao Peng Fei
Published: July 2024

Exploring the molecular packing and interaction between chiral molecules, no matter single enantiomer or racemates, is important for recognition and resolution of chiral drugs. However, sensitive and non‐destructive analysis methods are lacking. Herein, an intermolecular‐charge transfer (ICT) based spectroscopy is reported to reveal the differences in interaction between the achiral acceptor 1,2,4,5‐tetracyanobenzene (TCNB) and the chiral donors, including S, R, and racemic naproxen (S/R/rac‐NAP). In this process, S‐NAP+TCNB and R‐NAP+TCNB display a narrower band gap attributed to the newly formed ICT state. In contrast, the mixed rac‐NAP and TCNB exhibit almost no significant change due to the strong affinity between the stereoisomers according to the Wallach's rule. Thus, S/R‐NAP can be easily distinguished from rac‐NAP based on significantly different optical behavior. The single crystal analysis, infrared spectroscopy, fluorescence spectroscopy, and theoretical calculation of naproxen confirm the importance of carboxyl for this differentiation in molecular packing and interaction. In addition, the esterification derivatization of naproxen achieves the manipulation of the intermolecular interaction model of racemates from the absolute Wallach's rule to a coexisting form of Wallach's rule and ICT. Further, visualized chiral purification of naproxen by the simple cocrystallization method is achieved through the collaboration of ICT and Wallach's rule.
Amplifying High‐Performance Organic Solar Cells Through Differencing Interactions of Solid Additive with Donor/Acceptor Materials Processed from Non‐Halogenated Solvent
Authors: Haris Muhammad , Ullah Zakir , Lee Seungjin , Ryu Du Hyeon , Ryu Seung Un , Kang Bong Joo , Jeon Nam Joong , Kim Bumjoon J. , Park Taiho , Shin Won Suk , Song Chang Eun
Published: July 2024

Developing non‐halogenated solvent‐processed organic solar cells (OSCs) demands precise control over the bulk‐heterojunction (BHJ) morphology of the photoactive layer. However, the limited solubility of halogen‐free solvents to photoactive materials hinders microstructure morphology fine‐tuning for boosting photovoltaic performance. This study not only examines the debated intermolecular interactions between the DBrDIB solid additive and photoactive materials but also analyzes the substantial influence of volatile solid additive on the BHJ morphological properties. The DBrDIB effectively restricts the excessive aggregation of Y6‐BO and regulates the phase separation, which is attributed to strong intermolecular interactions with Y6‐BO and rapid quenching during morphology formation. It then achieves a well‐mixed D/A phase with favorable domain size, resulting in a balanced aggregation and dispersion of D/A, ultimately leading to markedly enhanced charge transfer and transport as well as suppressed charge recombination. The transformative use of the o‐xylene/DBrDIB solvent system propels PM6:Y6‐BO and PM6:Y6‐HU OSCs to impressive efficiencies of 17.9% and 19.1%, respectively, outperforming those of the control devices. These findings provide crucial insights into theoretical and experimental areas, offering actionable guidelines for designing high‐performance OSCs processed from halogen‐free solvent.
Cretaceous and Paleocene fossils reveal an extinct higher clade within Cornales, the dogwood order
Authors: Nguyen Austin T. , Atkinson Brian A.
Published: July 2024

Premise

Characterization and phylogenetic integration of fossil angiosperms with uncertain affinities is relatively limited, which may obscure the diversity of extinct higher taxa in the flowering plant tree of life. The order Cornales contains a diversity of extinct taxa with uncertain familial affinities that make it an ideal group for studying turnover in angiosperms. Here, we describe a new extinct genus of Cornales unassignable to an extant family and conduct a series of phylogenetic analyses to reconstruct relationships of fossils across the order.

Methods

Two permineralized endocarps were collected from the Cedar District Formation (Campanian, 82–80 Ma) of Sucia Island, State of Washington, United States. Fossils were sectioned with the cellulose acetate peel technique and incorporated into a morphological dataset. To assess the utility of this dataset to accurately place taxa in their respective clades, we used a series of phylogenetic pseudofossilization analyses. We then conducted a total‐evidence analysis and a scaffold‐based approach to determine relationships of fossils.

Results

Based on their unique combination of characters, the fossils represent a new genus, Fenestracarpa washingtonensis gen. nov. et sp. nov. Pseudofossilization analyses indicate that our morphological dataset can be used to accurately recover taxa at the major clade to family level, generally with moderate to high support. The total‐evidence and scaffold‐based analyses recovered Fenestracarpa and other fossil genera in an entirely extinct clade within Cornales.

Conclusions

Our findings increase the reported diversity of extinct Cornales and indicate that the order's initial radiation likely included the divergence of an extinct higher clade that endured the end‐Cretaceous Mass extinction but perished during the Cenozoic.
V‐Y advancement flap for the repair of localized cutaneous defects following nasal closure in severe hereditary hemorrhagic telangiectasia
Authors: Jama Guled M. , Gane Simon
Published: July 2024

Key points

In patients with severe refractory epistaxis due to hereditary hemorrhagic telangiectasia, the most effective results are achieved by surgical closure of the nares to permanently prevent nasal airflow.

Flap failure and dehiscence can occur and result in fistula formation and clinical relapse.

We describe the utility of a V‐Y advancement flap in repairing localized cutaneous defects in patients who have previously undergone nasal closure for severe HHT.
Prospects and challenges in using neuronal extracellular vesicles in biomarker research
Authors: Rocha Debora A. S. , Santos Luis E. , Da Fonseca Pedro B. , De Felice Fernanda G.
Published: July 2024

Extracellular vesicles (EVs) hold promise as a source of disease biomarkers. The diverse molecular cargo of EVs can potentially indicate the status of their tissue of origin, even against the complex background of whole plasma. The main tools currently available for assessing biomarkers of brain health include brain imaging and analysis of the cerebrospinal fluid of patients. Given the costs and difficulties associated with these methods, isolation of EVs of neuronal origin (NEVs) from the blood is an attractive approach to identify brain‐specific biomarkers. This perspective describes current key challenges in EV‐ and NEV‐based biomarker research. These include the relative low abundance of EVs, the lack of validated isolation methods, and the difficult search for an adequate target for immunocapturing NEVs. We discuss that these challenges must be addressed before NEVs can fulfill their potential for biomarker research.

Highlights

NEVs are promising sources of biomarkers for brain disorders.

Immunocapturing NEVs from complex biofluids presents several challenges.

The choice of surface target for capture will determine NEV yield.

Contamination by non‐EV sources is relevant for biomarkers at low concentrations.
A Chemoselective Enrichment Strategy for In‐Depth Coverage of the Methyllysine Proteome
Authors: Yan Lufeng , Zheng Manqian , Fan Mingzhu , Yao Rui , Zou Kun , Feng Shan , Wu Mingxuan
Published: July 2024

Proteomics is a powerful method to comprehensively understand cellular posttranslational modifications (PTMs). Owing to low abundance, tryptic peptides with PTMs are usually enriched for enhanced coverage by liquid chromatography‐mass spectrometry/mass spectrometry (LC–MS/MS). Affinity chromatography for phosphoproteomes by metal‐oxide and pan‐specific antibodies for lysine acetylome allow identification of tens of thousands of modification sites. Lysine methylation is a significant PTM; however, only hundreds of methylation sites were identified by available approaches. Herein we report an aryl diazonium based chemoselective strategy that enables enrichment of monomethyllysine (Kme1) peptides through covalent bonds with extraordinary sensitivity. We identified more than 10000 Kme1 peptides from diverse cell lines and mouse tissues, which implied a wide lysine methylation impact on cellular processes. Furthermore, we found a significant amount of methyl marks that were not S‐adenosyl methionine (SAM)‐dependent by isotope labeling experiments.
Light‐Activated Nanocatalyst for Precise In‐Situ Antimicrobial Synthesis via Photoredox‐Catalytic Click Reaction
Authors: Zhao Minyang , Cao Lei , Bai Qingqing , Lu Yaru , Li Bowen , Wu Wenbo , Ye Jinzhou , Chen Xinhan , Wang Zhihong , Liu Bin , Mao Duo
Published: July 2024

The excessive and prolonged use of antibiotics contributes to the emergence of drug‐resistant S. aureus strains and potential dysbacteriosis‐related diseases, necessitating the exploration of alternative therapeutic approaches. Herein, we present a light‐activated nanocatalyst for synthesizing in situ antimicrobials through photoredox‐catalytic click reaction, achieving precise, site‐directed elimination of S. aureus skin infections. Methylene blue (MB), a commercially available photosensitizer, was encapsulated within the CuII‐based metal–organic framework, MOF‐199, and further enveloped with Pluronic F‐127 to create the light‐responsive nanocatalyst MB@PMOF. Upon exposure to red light, MB participates in a photoredox‐catalytic cycle, driven by the 1,3,5‐benzenetricarboxylic carboxylate salts (BTC−) ligand presented in the structure of MOF‐199. This light‐activated MB then catalyzes the reduction of CuII to CuI through a single‐electron transfer (SET) process, efficiently initiating the click reaction to form active antimicrobial agents under physiological conditions. Both in vitro and in vivo results demonstrated the effectiveness of MB@PMOF‐catalyzed drug synthesis in inhibiting S. aureus, including their methicillin‐resistant strains, thereby accelerating skin healing in severe bacterial infections. This study introduces a novel design paradigm for controlled, on‐site drug synthesis, offering a promising alternative to realize precise treatment of bacterial infections without undesirable side effects.
Temperature‐Responsive Formation Cycling Enabling LiF‐Rich Cathode‐Electrolyte Interphase
Authors: Hong Luxi , Zhang Yi , Mei Pan , Ai Bing , Zhang Yuan , Zhou Chenhuan , Bao Xiaoguang , Zhang Wei
Published: July 2024

Formation of LiF‐rich cathode‐electrolyte interphase is highly desirable for wide‐temperature battery, but its application is hindered by the unwanted side reactions associated with conventional method of introducing fluorinated additives. Here, we developed an additive‐free strategy to produce LiF‐rich cathode electrolyte interphase (CEI) by low‐temperature formation cycling. Using LiNi0.33Mn0.33Co0.33O2 as a model cathode, the atomic ratio of LiF in the CEI formed at −5 °C is about 17.7 %, enhanced by ~550 % compared to CEI formed at 25 °C (2.7 %). The underlying mechanism is uncovered by both experiments and theoretic simulation, indicating that the decomposition of LiPF6 to LiF is transformed into spontaneous and exothermic on positively charged cathode surface and lowering the temperature shift chemical equilibrium towards the formation of LiF‐rich CEI. Superior to conventional fluorinated additives, this approach is free from unwanted side reactions, imparting batteries with both high‐temperature (60 °C) cyclability and low‐temperature rate performance (capacity enhanced by 100 % at 3 C at −20 °C). This low‐temperature formation cycling to construct LiF‐rich CEI is extended to various cathode systems, such as LiNi0.8Mn0.1Co0.1O2, LiCoO2, LiMn2O4, demonstrating the versatility and potential impact of our strategy in advancing the performance and stability of wide‐temperature batteries and beyond.
Structural Basis of Cucurbituril‐Containing Self‐Assembled Supramolecular Chiral Materials
Authors: Xu Yunying , Hao Aiyou , Xing Pengyao
Published: July 2024

Macrocycle‐based host–guest complexation offers an intriguing protocol in producing chiroptical materials, while the bulky size and dynamic exchange between hosts and guests hinders the ordered aggregation to afford the long‐range chiral arrangement. It remains great challenges in assembling cucurbit[n]urils (CB[n]s) included complexes to induce supramolecular chirality ascribed to the excellent water solubility and flexible packing. Herein, we unveiled the structural basis on the formation of chiroptical coassemblies from CB[n] (n=6, 7) complexes. Perylene diimides (PDIs) with cationic chiral pendants formed complexes in the aqueous media, which selectively showed chiroptical properties. Chlorination at the bay position, increasing alkyl length of cationic chiral pendants or reducing the number of polyaromatic rings would hinder the chiral aggregation. In a comprehensive manner, CB[6] favors ordered aggregation into one‐dimensional fibrous nanoarchitectures that greatly facilitates the supramolecular chirality. In contrast, CB[7] with larger cavity and water solubility shrinks the ordered arrangement of complexes, reducing the formation possibility of supramolecular chiral nanoarchitectures. This work suggests the great potential of CB[6] in the preparation and manipulation of supramolecular chiral assemblies, shedding light on the macrocycle‐based functional chiroptical materials.
Se‐dopant Modulated Selective Co‐Insertion of H+ and Zn2+ in MnO2 for High‐Capacity and Durable Aqueous Zn‐Ion Batteries
Authors: Ye Jia‐Jia , Li Pei‐Hua , Hou Zhiguo , Zhang Wei , Zhu Wenhui , Jin Song , Ji Hengxing
Published: July 2024

MnO2 is commonly used as the cathode material for aqueous zinc‐ion batteries (AZIBs). The strong Coulombic interaction between Zn ions and the MnO2 lattice causes significant lattice distortion and, combined with the Jahn–Teller effect, results in Mn2+ dissolution and structural collapse. While proton intercalation can reduce lattice distortion, it changes the electrolyte pH, producing chemically inert byproducts. These issues greatly affect the reversibility of Zn2+ intercalation/extraction, leading to significant capacity degradation of MnO2. Herein, we propose a novel method to enhance the cycling stability of δ‐MnO2 through selenium doping (Se−MnO2). Our work indicates that varying the selenium doping content can regulate the intercalation ratio of H+ in MnO2, thereby suppressing the formation of ZnMn2O4 by‐products. Se doping mitigates the lattice strain of MnO2 during Zn2+ intercalation/deintercalation by reducing Mn−O octahedral distortion, modifying Mn−O bond length upon Zn2+ insertion, and alleviating Mn dissolution caused by the Jahn–Teller effect. The optimized Se−MnO2 (Se concentration of 0.8 at.%) deposited on carbon nanotube demonstrates a notable capacity of 386 mAh g−1 at 0.1 A g−1, with exceptional long‐term cycle stability, retaining 102 mAh g−1 capacity after 5000 cycles at 3.0 A g−1.
Enhancing Reversibility and Kinetics of Anionic Redox in O3‐NaLi1/3Mn2/3O2 through Controlled P2 Intergrowth
Authors: Yang Yihang , Wang Qing , Hou Jingrong , Liu Jie , Sun Tianyi , Tang Mingxue , Chen Chien‐Te , Kuo Chang‐Yang , Hu Zhiwei , Zheng Tingting , Yan Guochun , Ma Jiwei
Published: July 2024

Anionic redox chemistry can surpass theoretical limits of conventional layered oxide cathodes in energy density. A recent model system of sodium‐ion batteries, O3‐NaLi1/3Mn2/3O2, demonstrated full anionic redox capacity but is limited in reversibility and kinetics due to irreversible structural rearrangement and oxygen loss. Solutions to these issues are missing due to the challenging synthesis. Here, we harness the unique structural richness of sodium layered oxides and realize a controlled ratio of P2 structural intergrowth in this model compound with the overall composition maintained. The resulted O3 with 27 % P2 intergrowth structure delivers an excellent initial Coulombic efficiency of 87 %, comparable to the state‐of‐the‐art Li‐rich NMCs. This improvement is attributed to the effective suppression of irreversible oxygen release and structural changes, evidenced by operando Differential Electrochemical Mass Spectroscopy and X‐ray Diffraction. The as‐prepared intergrowth material, based on the environmentally benign Mn, exhibits a reversible capacity of 226 mAh g−1 at C/20 rate with excellent cycling stability stemming from the redox reactions of oxygen and manganese. Our work isolates the role of P2 structural intergrowth and thereby introduces a novel strategy to enhance the reversibility and kinetics of anionic redox reactions in sodium layered cathodes without compromising capacity.
Sterically Controlled Lewis Acid−Base Interaction Toward para‐Selective Borylation of Aromatic Aldimines and Benzylamines
Authors: Guria Saikat , Hassan Mirja Md Mahamudul , Dey Sayan , Singh Krishna Nand , Chattopadhyay Buddhadeb
Published: July 2024

Site‐selective C−H bond functionalization of arenes at the para position remains extremely challenging primarily due to its relative inaccessibility from the catalytic site. As a consequence, it is significantly restricted to limited molecular scaffolds. Herein, we report a method for the para‐C−H borylation of aromatic aldimines and benzylamines using commercially available ligands under iridium catalysis. The established method displays excellent para selectivity for variously substituted aromatic aldimines, benzylamines and bioactive molecules. Based on several control experiments, it is proposed that a Lewis acid−base interaction between the nitrogen and boron functionality guides the para selectivity via a steric shield for the aromatic aldimines, where Bpin acts as a transient directing group. However, the steric shield of the in situ generated N−Bpin moiety controlled the overall selectivity for the para borylation of benzylamines.
From primers to pipettes: An immersive course introducing high school students to qPCR for quantifying chemical defense gene expression
Authors: Spooner Zeke T. , Encerrado‐Manriquez Angela M. , Truong Tina T. , Nicklisch Sascha C. T.
Published: July 2024

We created a 2‐week, dual‐module summer course introducing high school students to environmental toxicology by teaching them quantitative polymerase chain reaction (qPCR) as a way to quantify gene expression of chemical defense proteins in response to exposure to environmental pollutants. During the course, students are guided through the various stages of a successful qPCR experiment: in silico primer design and quality control, total RNA extraction and isolation, cDNA conversion, primer test PCR, and evaluation of results via agarose gel electrophoresis or UV/Vis spectra. The course combines lectures, discussions, and demonstrations with dry and wet laboratory sections to give students a thorough understanding of the scope, utility, and chemical principles of qPCR. At the end of the course, the students are taught how to analyze qPCR data and are encouraged to discuss their findings with other classmates to evaluate their hypotheses and assess possible sources of error. This course was designed to be easily adaptable to multiple test species, chemical exposures, and genes of interest. To explore both terrestrial and aquatic toxicology, the students use honey bees (Apis mellifera) and mosquitofish (Gambusia affinis) as test organisms, as well as ABC‐type efflux transporters, antioxidant enzymes, and cytochrome P450 enzymes as endpoints for assessing gene expression. We share this course setup and applied protocols to encourage others to design and offer similar courses that give high school students a hands‐on introduction to a broad swath of environmental toxicology research and an opportunity to develop scientific skills necessary for university‐level research.
Analysis of blood concentrations and clinical application of risdiplam in patients with spinal muscular atrophy using ultra‐high performance liquid chromatography–tandem mass spectrometry
Authors: Wu Xian , Lin Zhiyan , Liu Yan , Liu Xinzhu , Yi Zhenghong , Huang Xiaohui , Zhang Jian
Published: July 2024

Risdiplam, the first oral therapy approved for spinal muscular atrophy and made globally available in 2021, necessitates a highly sensitive and straightforward assay for therapeutic drug monitoring. This is crucial to manage potential toxicities linked to drug concentrations and supervise dosing regimens. A cutting‐edge ultra‐high performance liquid chromatography–tandem mass spectrometry bioassay for risdiplam in human serum has been developed. In this method, analytes were separated on a Phenomenex Kinetex XB C18 column using a 6.5‐min gradient elution after a single‐step protein precipitation. MS detection was conducted via electrospray ionization in positive mode with selected reaction monitoring. The validated range for risdiplam was determined to be 1.95–125.00 ng/mL. The precision and accuracy of intra‐ and inter‐batch analyses were within ±15%. The novel method met all other established criteria. This assay holds promise for monitoring drug concentrations and guiding clinical decisions in patients with spinal muscular atrophy.
Tissue clearing and its application in dental research
Authors: Meng Lingxi , Song Xinyu , Wang Junyi , Shi Wenxuan , Gao Liheng , Jiang Xinquan , Zhang Wenjie
Published: July 2024

For both animal and human tissues, translucence is an intrinsic property that gives them a milky appearance. This optical property arises due to the combined effects of light absorption and scattering and becomes the main impediment of deep imaging. To overcome these obstacles, the tissue‐clearing technique has experienced a resurgence over the past century and evolved from its initial use in neuroscience to encompass various samples due to the emergence of various clearing methods. Notably, these techniques unveil both macroscopic and microscopic details, offering valuable insights into tissue structures. In particular, the oral cavity is structured with both soft and hard tissues at the macroscopic level and is rich in neurovascular networks microscopically, providing a suitable application environment for tissue‐clearing techniques. Currently, tissue‐clearing techniques have provided a powerful tool for research on the dental pulp neurovascular system, oral tissue regeneration, dental implants, and maxillofacial surgical treatments. Hence, this review aims to give a general introduction to tissue‐clearing techniques and focus on their remarkable applications in dental research. At last, we will discuss the integration of tissue‐clearing methods with other techniques such as labeling and microscopy, hoping to offer valuable insights for the development of tissue‐clearing techniques in both bioscience and materials science.
Advances of therapy for Alzheimer's disease: An updated review
Authors: Mei Can , Zhan Jianbo , Zhu Shuzhen , Zhang Yutong , Xiong Chang‐e , Wang Jia , Xu Yu Jia , Zhong Hua , Cheng Jing
Published: July 2024

Alzheimer's disease (AD) is a type of dementia characterized by a decline in brain function, which leads to the inability to perform activities independently. Many researchers recognize abnormalities related to beta‐amyloid as the main cause of the disease (i.e., the beta‐amyloid hypothesis), but aging, genetics, coronary heart disease, environmental factors, gender, and other risk factors may also contribute to AD development. Three drugs with different mechanisms are available for AD treatment: cholinesterase inhibitors, N‐methyl d‐aspartate, and aducanumab. This study reviewed the therapies that are already applied in clinical practice and those that are currently being investigated for clinical use. These therapies include not only pharmacological treatments but also non‐pharmacological treatments, such as gut flora therapy and music therapy. A comprehensive understanding of these therapies is necessary to enable early intervention, improve patients' physical and mental conditions, delay the occurrence and development of AD, and extend patients' healthy lifespans.
Synthesis of Cytotoxic Benzofurans and Ethers Derivatives of Paeonol
Authors: Figueroa Laura P. R. , Domingos Helori V. , Pardo Jennifer B. , Santiago Pedro H. O. , Ellena Javier , Lacerda Junior Valdemar , Costa‐Lotufo Letícia V. , de S. Borges Warley
Published: July 2024

Paeonol is a broadly studied natural product due to its many biological activities. Using a methodology previously employed by our research group, 11 derivatives of paeonol were synthesized (seven of them are unpublished compounds), including four ethers and seven benzofurans. Additionally, we determined the crystal structure of one of these ether derivatives (1 a) and of five benzofuran derivatives (2 a, 2 b, 2 c, 2 f and 2 g) by single crystal X‐ray diffraction. To continue studying the cytotoxicity of this natural product and its derivatives, all compounds were tested against two cancer cell lines, HCT116 and MCF‐7. Compounds 2 b, 2 e, and 2 g were considered active against the colorectal adenocarcinoma cells HCT116 (Growth inhibition >60 %). Compound 2 e showed an IC50 of 0.2 μM and was selected for further analysis, results reinforce its anticancer potential.
Prenatal diagnosis of cystinuria with a heterozygous pathogenic variant in SLC7A9 gene associated with isolated hyperechogenic fetal kidneys: A case report
Authors: Aigbogun Osaretin Pamela , Vancoppenolle Noémie , Coppens Sandra , Marangoni Martina , Elsen Elodie , Cassart Marie , Gounongbe Caroline
Published: July 2024

Key Clinical Message

Cystinuria is suspected antenatally by a hyperechogenic fetal colonic content. We report the first prenatal case of autosomal dominant SLC7A9‐related cystinuria associated with isolated hyperechogenic kidneys as the only prenatal sonographic sign.
Uncommon cause of radiculopathy: A case of symptomatic Tarlov cyst in an elderly female and literature review
Authors: Devkota Shritik , Adhikari Sugat , Lamichhane Samiksha , Koirala Bishal , Sarmast Arif Hussain
Published: July 2024

Key Clinical Message

Tarlov cysts are uncommon causes of sacral radiculopathy, with particular predilection to second and third sacral roots, requiring timely diagnosis with lumbosacral MRI, and surgical management if symptomatic.

Tarlov cysts or Type II meningeal cysts, are CSF‐filled sacs located in the extradural space of the sacral spinal canal, commonly originating at the dorsal root ganglion. While they were first documented by Tarlov in 1938, their etiology remains uncertain, with theories suggesting trauma‐induced bleeding or congenital abnormalities. These cysts, estimated to affect between 1% and 9% of the adult population, typically manifest as incidental findings but may lead to symptoms such as radiculopathies, sacral pain, and weakness in related sacral muscles. We present a case of a 63‐year‐old female presenting with recurrent left buttock pain and radiating leg discomfort. Physical examination revealed tenderness in the left buttock region, positive straight leg raise test, and minimal sensory deficits in the S1‐S2 dermatomes. A provisional diagnosis of radiculopathy was made, prompting further evaluation with MRI, revealing a Tarlov cyst and absence of lumbar spinal canal stenosis or neural foraminal compromise. The patient declined intervention and was managed conservatively. This case highlights the diagnostic challenges and therapeutic considerations in managing symptomatic Tarlov cysts, emphasizing the importance of tailored treatment strategies.
Palpebral leishmaniasis
Authors: Sharifi Mohammad , Shiravi Tayebe , Bolouki Ali , Motamed Shariati Mehrdad
Published: July 2024

Key Clinical Message

Leishmaniasis can mimic many conditions, including hordeolum, basal cell carcinoma, and squamous cell carcinoma. The presence of kinetoplast in free‐form or intramacrophage amastigotes, ensuring us to establish the microscopic diagnosis of leishmaniasis.
Investigation of the CO2 Activation and Regeneration of Reduced VOx/CeO2 Catalysts Using Multiple In Situ Spectroscopies
Authors: Schumacher Leon , Ziemba Marc , Hess Christian
Published: July 2024

Ceria‐supported vanadium oxide (VOx/CeO2) is an important catalyst for various oxidation reactions. Recently, vanadia has emerged again as a less toxic alternative to CrOx‐based catalysts for the CO2‐assisted oxidative dehydrogenation (ODH) of alkanes. To establish a mechanistic understanding of catalyst regeneration during CO2 exposure, often described as the rate‐limiting step of these reactions, we investigated the regeneration of VOx/CeO2 catalysts with different vanadia loadings using multiple in situ spectroscopies, that is, multi‐wavelength Raman, UV‐Vis, IR and X‐ray photoelectron spectroscopy. Time‐dependent analysis reveals that ceria is only partially regenerated in the bulk but fully regenerated in the subsurface. At the surface, stable carbonates form at vacancies, which are able to regenerate the lattice and deactivate ceria surface oxygen. The VOx/CeO2 samples show a loading‐dependent behavior, with low‐loaded samples regenerating vanadia only partially, due to the high concentration of monomers, while at higher loadings, vanadia can be almost fully regenerated due to the higher nuclearities being thermodynamically more stable. Ceria is regenerated faster than vanadia, indicating that vanadia regenerates by oxygen spill‐over from the ceria lattice. Our results provide important mechanistic insight into CO2 activation over supported vanadia catalysts, which is of great relevance for CO2‐assisted ODH reactions.
Additive‐Free Pd/In2O3‐Catalyzed N‐methylation of Primary Amides by Using Formic Acid
Authors: Benaissa Idir , Dembélé Kassiogé , Cantat Thibault , Genre Caroline
Published: July 2024

Here we report on the use of formic acid as a green and safe reagent for the N‐methylation of primary amides in the presence of a Pd/In2O3 solid catalyst. No additive is needed and primary amides are selectively N‐methylated in good to excellent yields. The reaction operates through a formylation/reduction pathway, leaving the amide carbonyl untouched.
The Combined Effect of the Oxidizing Agent and its Concentration on the Oxidative Coupling of Methane
Authors: Cheng Yonggang , Mendes Pedro S. F. , Yazdani Parviz , Detavernier Christophe , Thybaut Joris W.
Published: July 2024

The combined use of O2 and CO2 as oxidizing agents in the oxidative coupling of methane (OCM) has been assessed over two representative OCM catalysts, i. e., La−Sr/CaO and NaMnW/SiO2, under a wide range of inlet O2 and CO2 concentrations. The overall impact of CO2 was found to depend on the operating conditions and the catalyst used. At O2‐rich conditions, a negative effect of CO2 was observed on C2 selectivity. At O2‐lean conditions, a positive effect of CO2 on both catalysts was observed, likely originating from an enhanced dehydrogenation of C2H6 to C2H4 and limited deep oxidation of the involving hydrocarbons and reaction intermediates. The behavior induced by CO2 is attributed to its mild oxidizing ability and interactions with the catalysts. The enhanced dehydrogenation of C2H6 was observed and confirmed by specific tests with a CO2 and C2H6 feed. Well‐controlled CO2 addition improved the value of the OCM product mixture, mainly due to a 9 % increase in C2H4 and a 19 % increase in CO selectivity, resulting in a 25 % reduction of CO2 at the outlet over the La−Sr/CaO catalyst. These findings provide new insight into the CO2 effect on OCM and the data to translate this research into OCM process alternatives.
Exploiting Nitroreductases for the Tailored Photoenzymatic Synthesis of Structurally Diverse Heterocyclic Compounds
Authors: Prats Luján Alejandro , Faizan Bhat Mohammad , Acosta Marko Edgar Eduardo , Fodran Peter , Poelarends Gerrit J.
Published: July 2024

N‐heterocyclic compounds have a broad range of applications and their selective synthesis is very appealing for the pharmaceutical and agrochemical industries. Herein we report the usage of the flavin‐dependent nitroreductase BaNTR1 for the photoenzymatic synthesis of various anthranils and quinolines from retro‐synthetically designed o‐nitrophenyl‐substituted carbonyl substrates, achieving high conversions (up to >99 %) and good product yields (up to 96 %). Whereas the effective production of anthranils required the inclusion of H2O2 in the reaction mixtures to accumulate the needed hydroxylamine intermediates, the formation of quinolines required the use of anaerobic or reducing conditions to efficiently generate the essential amine intermediates. Critical to our success was the high chemoselectivity of BaNTR1, performing selective reduction of the nitro group without reduction of the carbonyl moiety or the activated carbon‐carbon double bond. The results highlight the usefulness of an innocuous chlorophyll‐ and nitroreductase‐based photoenzymatic system for the tailored synthesis of diverse N‐heterocycles from simple nitro compounds.
Sinusoidal control strategy applied to continuous stirred‐tank reactors: Asymptotic and exponential convergence
Authors: Aguilar‐López Ricardo , González‐Viveros Iraiz , López‐Pérez Pablo A.
Published: July 2024

The main goal of this proposal is to present a class of nonlinear controllers for regulation and set point changes in continuous chemical reactors. The proposed control law has in its mathematical structure a proportional term of the regulation error to provide closed‐loop stability and a sinusoidal term, which can compensate for the nonlinearities of the plant. The closed‐loop stability of the plant is demonstrated via Lyapunov analysis, which reveals an asymptotic convergence of the control output to the required set points. Furthermore, the analysis of the regulation error's dynamic under the considered assumptions leads us to conclude that exponential stability is also reached. The controller is implemented via numerical experiments in two examples to generalize the applicability of the proposed approach by considering continuous stirred‐tank reactors models. The first case considers autocatalytic chemical oscillatory reactions that induce chaotic behaviour. For the second case, a process of acetone, butanol, and ethanol (ABE) fermentation through Clostridium acetobutylicum is considered. The proposed strategy shows an adequate performance because it can reach the required set point without long time settings and overshoot. A comparison with a smooth sliding‐mode and a standard proportional‐integral (PI) controller indicates the advantages of the proposed control approach.
Structurally Divergent Synthesis of Azetidines, 5,6‐Dihydro‐1,3‐oxazines and 2,3‐Dihydro‐1,4‐oxazines through Palladium‐Catalyzed Tandem Allylic Substitution Reaction
Authors: Meng Ru‐Fang , Kong Yu‐Juan , Wu Xiao‐Yan , Zhang Huan , Wang Wei , Liang Wen‐Jie , Zheng Lan , Lin Chenxiang , Su Wei , Xiao Jun‐An
Published: July 2024

Comprehensive Summary

A regiodivergent synthesis of azetidines, 5,6‐dihydro‐1,3‐oxazines and 2,3‐dihydro‐1,4‐oxazines has been achieved through palladium‐catalyzed tandem allylic substitution reaction. This protocol provides a variety of heterocycles in satisfactory yields with good to excellent regioselectivities under mild reaction conditions.
Computational fluid dynamics of bladder voiding using 3D dynamic MRI
Authors: Shahid Labib , Gonzalez‐Pereira Juan Pablo , Johnson Cody , Bushman Wade , Roldán‐Alzate Alejandro
Published: July 2024

Over the last couple of decades, image‐based computational fluid dynamics (CFD) has revolutionized cardiovascular research by uncovering hidden features of wall strain, impact of vortices, and its use in treatment planning, as examples, that were simply not evident in the gold‐standard catheterization studies done previously. In the work presented here, we have applied magnetic resonance imaging (MRI)‐based CFD to study bladder voiding and to demonstrate the feasibility and potential of this approach. We used 3D dynamic MRI to image the bladder and urethra during voiding. A surface mesh processing tool was developed to process the bladder wall prior to executing a wall‐motion driven CFD simulation of the bladder and urethra. The obtained flow rate and pressure were used to calculate urodynamic nomograms, which are currently used in the clinical setting to assess bladder voiding dysfunction. These nomograms concluded that our healthy volunteer has an unobstructed bladder and normal contractility. We calculated the work done to void the bladder and propose this as an additional quantitative metric to comprehensively assess bladder function. Further, we discuss the areas that would improve this relatively new methodology of image‐based CFD in urodynamics.
A Modern Curriculum for Training Scientists in Model‐Informed Drug Development: Progress Report on FDA Grant to Train Regulatory Scientists
Authors: Barrett Jeffrey S. , Romero Klaus , Rayner Craig , Gastonguay Marc , Pillai Goonaseelan (Colin) , Tannenbaum Stacey , Kern Steven , Selich Mark , Francisco Dave
Published: July 2024

Under US Food and Drug Administration (FDA) grant (2U18FD005320‐06), the Critical Path Institute (C‐Path) and experienced private sector partners collaborated with global health organizations to create didactic video materials in an e‐learning format on model‐informed drug development (MIDD) topics relevant to a non‐modeling audience. Several multinational pharmaceutical companies contributed case studies illustrating the application of the MIDD approach in practice. Training videos were created and divided into several modules: introducing the MIDD landscape for drug development and regulatory science, a review of various model types used for MIDD, discussions of how models inform drug development and regulatory decisions, future goals of MIDD, and discussions on the interconnectedness of models used for MIDD. Examples and vignettes from stakeholders and thought leaders were included. These educational materials fill a gap between academic and “on the job training” for regulators, academic, and industry scientists, delivering insights and value for those performing modeling and non‐modelers reviewing the output of modeling and simulation work. A total of 13 hours of video content is currently available. A small panel of FDA reviewers is currently beta‐testing the learning management system (LMS). Future efforts for this MIDD training initiative will include expansion of the content via an expanded and diverse faculty, 1:1 online mentorship sessions, and eventually broader access to this resource consistent with an open science approach and curriculum. The MIDD training LMS can accommodate a diverse learning ecosystem; further development may also accommodate different audiences in the future.
Fruiting trees provide fruit and insect resources for four tropical deer species
Authors: Awasthi Balram , Chen Jin , McConkey Kim R.
Published: July 2024

Fruiting trees provide important fruit and seed resources for various animal species, but rarely are they considered to be rich sources of insects as well. During a study of seed dispersal of Trewia nudiflora (Euphorbiaceae) using camera traps in Nepal, we observed four tropical deer species (Axis axis, Muntiacus vaginalis, Rusa unicolor, Axis porcinus) foraging for insects, rather than fruits under the trees. These herbivorous deer are proven seed dispersers of Trewia, but 8%–38% of video captures (across each species) were of insectivory, rather than frugivory. The deer chased and consumed red cotton bugs (Dysdercus sp. family Pyrrhocoridae), which were seed predators that hoarded Trewia seeds. It is likely that other unidentified insect species were also consumed. Tropical deer species are considered to be fully herbivorous, so our observations extend their known diets and possibly indicate a seasonal requirement for protein. These findings also highlight tri‐trophic interactions among deer, insects, and fruits that could have important implications for seedling recruitment if seed predators are being consumed by seed dispersers (in addition to fruit consumption).