bluuebunny/crossref_metadata_2025 huggingface dataset:
Notes on the Work of Tomasz Kacper, the Architect
Authors: Stankiewicz Aleksander
Published: February 2025

Lenkų mokslų tyrimų apie LDK priklausiusios Žemaitijos kunigaikštystės bažnyčias, statytas XVII a. pirmaisiais dešimtmečiais, beveik nėra. Jos nebuvo paminėtos ir Adomo Miłobędzkio monumentalioje sintezėje apie XVII a. architektūros istoriją. Tuo tarpu lietuvių literatūroje jos dar nesulaukė išplėstinės, kritinės savo architektūrinės formos analizės. Iš šių statinių didžiausio tyrinėtojų susidomėjimo sulaukė Kretingos ir Tytuvėnų bernardinų bažnyčios. Jos išsiskiria meistrišku pastatymu ir mastu, prilygsta reikšmingiausiems ankstyvojo baroko XVII a. pirmųjų dešimtmečių Vilniaus kūriniams, tačiau visiškai nuo jų skiriasi. Ypač intriguoja faktas, kad – neįprastai buvusios Abiejų Tautų Respublikos tokio tipo projektams – galima nustatyti konkretų jų kūrėją – Tomaszą Kacperį arba Kacperovičių, šaltiniuose minimą 1610–1645 m. T. Kacperio pastatyti bernardinų vienuolynai ir bažnyčios Kretingoje (apie 1609–1619 m.) ir Tytuvėnuose (1619–1635 m.) reprezentuoja savitą, apie 1600 m. architektūrai būdingą stilių, jungiantį gotikinės ir itališkos architektūros elementus. Būdinga šiuose pastatuose panaudota konstrukcinių ir dekoratyvinių sprendimų visuma išryškina ir kitą reikšmingą, bet dar mažai aptartą LDK architektūros statinį – Kauno bernardinų vienuolyną ir bažnyčią (1624–1634 m.). Šis straipsnis skirtas išnagrinėti visus tris šiuos projektus ir išdėstyti juos platesniame vienuolijos ir Europos architektūros kontekste.
Listening Awry: Lacan and the Electric Guitar at the Intersection of Music, Technology, and Identity
Authors: Morris Jacob
Published: February 2025

Contemporary positions on technology tend to emphasize that its import lies in its appropriation by a given social actor (group or individual), by how it is used. This paper does not categorically deny that such is often the case, but suggests that its inversion is widely overlooked. Overlooked, because much like the skull in Holbein’s The Ambassadors, evidence of technology’s active effect on the user is distorted until viewed from a particular vantage point. This paper takes Lacanian psychoanalysis as its vantage point and the musical technoculture of the electric guitarist as its object, revealing in the electric guitarist’s pursuit of identity through timbre that technology functions as the object-cause of desire, the objet petit a. Evidence of such an anamorphosis certainly supports the need for psychoanalysis in a critical musicology, but the larger implication is for thinkers of all disciplinary stripes to give technology a second look (or in this case a second listen) in order to move beyond the usual determinist, voluntarist, or even Luddite approaches.
Working from Within: Observations of Non-Governmental Efforts to Decrease Social Marginalization in Buenos Aires
Authors: Tilstra Elisabeth
Published: February 2025

This essay is a modification of an excerpt from the senior thesis written for the Chancellor’s Honors Program at The University of Tennessee. The complete project—titled “Bringing the Outside In: An Examination of Non-Governmental Aid Organizations in Buenos Aires”—first examines the political and economic history of Argentina as a context from which to understand the current stage of actors in the social sector. Then, drawing from my fieldwork in the slums surrounding urban Buenos Aires, it introduces the twelve organizations I studied that work with issues of poverty and development, exploring organizational elements that aid or limit a nonprofit’s efficacy. Finally, it concludes with my own project proposal; a submission of a way to incorporate the most effective elements into one organization. As this paper is just a piece of a larger work, I have chosen to highlight only the data from my time spent in Buenos Aires in 2011, leaving out the introductory sections that give political and economic context, as well as the project proposal. This paper assumes the economic context as briefly mentioned above, and focuses wholly on the characteristics of the studied organizations, and how they enhance – or hinder – organizational efficacy. It examines the structure and program implementation of these organizations, critically reviewing them as agents of change.
Key Factors and Trends in Transportation Mode and Carrier Selection
Authors: Roberts Keith
Published: February 2025

Companies across the country must deal with the daily question of determining the best way to get their product in the hands of their customers. Weighing all of the various factors that play into this decision can prove to be very difficult at times, and these factors are ever changing as the market fluctuates with varying consumer demand which, in turn, affects the demand for transportation. This paper will look into these factors and relevant market trends to determine what factors play the largest role in a company’s decision of how to deliver its products, focusing specifically on the modal and carrier choice decision process. Market trends such as shrinking capacity, tightening cost structures, and the growing importance of environmental friendliness all will be shown to play a significant role in this decision-making process.
African Irregular Migrants in Malta: Exploring Perceptions and Renegotiating the Socio-Cultural Siege of Malta
Authors: Durick Hannah
Published: February 2025

This paper discusses the influx of African irregular migrants seeking asylum in Malta and how their arrival and growing presence in Malta is perceived by the Maltese. Since becoming an EU Member State in 2004 Malta has been overwhelmed by the number of irregular migrants arriving on its shores while en route to continental Europe. Due to its proximity to the North African coastline Malta becomes a frequent, albeit unintentional, destination for African migrants who are rescued in Maltese waters and subsequently placed in a closed detention facility until their legal status is determined in a court of law. Although it is simultaneously the smallest and most densely populated country in Europe, Malta is obligated to abide by the 2003 Dublin II Regulation, which places a disproportionately large burden on Malta—a small island nation with significant spatial and resource limitations. The international community’s criticism of Malta’s neglect and mismanagement of its humanitarian crisis, however, are not unwarranted. Social sanctums and domestic legal policies regarding how Malta’s irregular migrant population should be perceived and handled remain diametrically opposed and socio-economic, cultural and racial tensions between irregular migrants and Maltese citizens run high. Based on fieldwork conducted in Malta in 2011, this paper examines the problem of irregular migration in Malta and how existing Maltese perceptions are shaping some of the domestic policies that have been internationally criticized.
Acute aerobic exercise does not modulate pain potentially due to differences in fitness levels and sex effects – results from a pharmacological fMRI study
Authors: Nold Janne I , Fadai Tahmine , Büchel Christian
Published: February 2025

Exercise might lead to a release of endogenous opioids, potentially resulting in pain relief. However, the neurobiological underpinnings of this effect remain unclear. Using a pharmacological within-subject fMRI study with the opioid antagonist naloxone and different levels of aerobic exercise and pain we investigated exercise-induced hypoalgesia (
N
= 39, 21 female). Overall, we were unable to detect reduced pain after high-intensity aerobic exercise as compared to low-intensity aerobic exercise. Accordingly, we observed no significant changes in the descending pain modulatory system. The µ-opioid antagonist naloxone significantly increased overall pain ratings but showed no interaction with exercise intensity. An exploratory analysis suggested an influence of fitness level and sex where males showed greater hypoalgesia after high-intensity exercise with increasing fitness levels. This effect was attenuated by naloxone and mirrored by fMRI signal changes in the medial frontal cortex, where activation also varied with fitness level and sex, and was reversed by naloxone. These results indicate that aerobic exercise has no overall effect on pain in a mixed population sample, but individual factors such as fitness level and sex might play a role.
The reuniens nucleus of the thalamus facilitates hippocampo-cortical dialogue during sleep
Authors: Basha Diellor , Azarmehri Amirmohammad , Proulx Eliane , Chauvette Sylvain , Ghorbani Maryam , Timofeev Igor
Published: February 2025

Memory consolidation during sleep depends on the interregional coupling of slow waves, spindles, and sharp wave-ripples (SWRs), across the cortex, thalamus, and hippocampus. The reuniens nucleus of the thalamus, linking the medial prefrontal cortex (mPFC) and the hippocampus, may facilitate interregional coupling during sleep. To test this hypothesis we used intracellular, extracellular unit and local field potential recordings in anesthetized and head restrained non-anesthetized cats as well as computational modelling. Electrical stimulation of the reuniens evoked both antidromic and orthodromic intracellular mPFC responses, consistent with bidirectional functional connectivity between mPFC, reuniens and hippocampus in anesthetized state. The major finding obtained from behaving animals is that at least during NREM sleep hippocampo-reuniens-mPFC form a functional loop. SWRs facilitate the triggering of thalamic spindles, which later reach neocortex. In return, transition to mPFC UP states increase the probability of hippocampal SWRs and later modulate spindle amplitude. During REM sleep hippocampal theta activity provides periodic locking of reuniens neuronal firing and strong crosscorrelation at LFP level, but the values of reuniens-mPFC crosscorrelation was relatively low and theta power at mPFC was low. The neural mass model of this network demonstrates that the strength of bidirectional hippocampo-thalamic connections determines the coupling of oscillations, suggesting a mechanistic link between synaptic weights and the propensity for interregional synchrony. Our results demonstrate the presence of functional connectivity in hippocampo-thalamo-cortical network, but the efficacy of this connectivity is modulated by behavioral state.
Accelerated signal propagation speed in human neocortical dendrites
Authors: Oláh Gáspár , Lákovics Rajmund , Shapira Sapir , Leibner Yoni , Szűcs Attila , Csajbók Éva Adrienn , Barzó Pál , Molnár Gábor , Segev Idan , Tamás Gábor
Published: February 2025

Human-specific cognitive abilities depend on information processing in the cerebral cortex, where the neurons are significantly larger and their processes longer and sparser compared to rodents. We found that, in synaptically connected layer 2/3 pyramidal cells (L2/3 PCs), the delay in signal propagation from soma to soma is similar in humans and rodents. To compensate for the longer processes of neurons, membrane potential changes in human axons and/or dendrites must propagate faster. Dual somato-dendritic and somato-axonal patch recordings show that the propagation speed of action potentials (APs) is similar in human and rat axons, but the forward propagation of excitatory postsynaptic potentials (EPSPs) and the backward propagation of APs are 26 and 47% faster in human dendrites, respectively. Accurate biophysical models of human and rat L2/3 PCs, combined with pharmacological manipulations of membrane properties, have shown that various factors enhance EPSP propagation in humans; the key factor is the large conductance load imposed by the large basal dendritic tree in humans, the key factor responsible for the accelerated signal propagation in human cortical dendrites. Larger dendritic diameter in humans as well as differences in cable and ion channel properties, also contribute to the enhancement of signal propagation in human L2/3 dendrites.
Synchronous Ensembles of Hippocampal CA1 Pyramidal Neurons Associated with Theta but not Ripple Oscillations During Novel Exploration
Authors: Chen En-Li , Chen Tsai-Wen , Schreiter Eric R , Lin Bei-Jung
Published: February 2025

Synchronous neuronal ensembles play a pivotal role in the consolidation of long-term memory in the hippocampus. However, their organization during the acquisition of spatial memory remains less clear. In this study, we used neuronal population voltage imaging to investigate the synchronization patterns of CA1 pyramidal neuronal ensembles during the exploration of a new environment, a critical phase for spatial memory acquisition. We found synchronous ensembles comprising approximately 40% of CA1 pyramidal neurons, firing simultaneously in brief windows (∼25ms) during immobility and locomotion in novel exploration. Notably, these synchronous ensembles were not associated with ripple oscillations but were instead phase-locked to local field potential theta waves. Specifically, the subthreshold membrane potentials of neurons exhibited coherent theta oscillations with a depolarizing peak at the moment of synchrony. Among newly formed place cells, pairs with more robust synchronization during locomotion displayed more distinct place-specific activities. These findings underscore the role of synchronous ensembles in coordinating place cells of different place fields.
Tanzimat Döneminde Ermeni Cemaatler Arası Mücadelelerin Adana’ya Yansımaları
Authors: Turan Mahmut
Published: February 2025

Tanzimat Dönemi'nde Osmanlı toplumundaki Hıristiyanların hukukî statülerinde değişimler yaşanmıştır. Bu çalışmanın amacı, Tanzimat Dönemi'nde Hıristiyanların hukukî statülerinde meydana gelen değişimlerin Adana'daki Hıristiyan Ermeniler üzerindeki etkilerini incelemektir. Tanzimat dönemine kadar Osmanlı Devleti tarafından tanınan Hıristiyan mezhepleri Ortodoksluk ve Gregoryenlik iken, bu dönemde Katoliklik ve Protestanlık da tanınmış ve bu mezhep mensuplarına kendilerini temsil ve yönetme hakkı verilmiştir. Yeni mezheplerin devlet tarafından tanınması, Adana'daki farklı mezheplere mensup Ermeni topluluklar arasında siyasi, sosyal ve ekonomik çatışmalara neden olmuştur. Adana, Osmanlı modernleşmesinin etkilerini derinden hisseden bir şehir olarak bu çatışmaların yoğunlaştığı bir şehirdir. Çalışmada, Ermenilerin mezhep değiştirme nedenleri ve bu değişimlerin Ermeni topluluklar arasında ne tür mücadelelere yol açtığı incelenmiştir. Çalışmanın önemi, Osmanlı toplumundaki değişimi anlamak adına Adana'daki Hıristiyan Ermeni cemaatler arasında yaşananları birincil el kaynaklar üzerinden ele almasıdır. Çalışmanın kaynaklarını arşiv belgeleri ve dönemin literatürü oluşturmaktadır. Sonuç olarak, mezhep değişikliklerinin Adana'daki Ermeni toplulukları arasında ciddi siyasi ve sosyal mücadelelere neden olduğu tespit edilmiştir.
Digital immigrants: Leveraging the technology acceptance model to increase digital literacy in older adults
Authors: McGinty Jacqueline , Oest Jess , Divido Jared
Published: April 2024

In “Digital Immigrants: Leveraging the Technology Acceptance Model to Increase Digital Literacy in Older Adults,” the authors delve into the vital importance of digital literacy for supporting older adults in living independently and staying connected with their community. They explore how the Technology Acceptance Model (TAM), which emphasizes the perceived usefulness of technology, can be effectively used to encourage older adults to embrace digital tools. The article highlights that well‐designed technology training can do much more than help older adults live independently; it can also significantly enhance their connections with family, friends, healthcare providers, and community services. Additionally, it offers practical guidelines for creating effective technology training programs that empower older adults to lead more connected, independent, and enriched lives.
Supporting future roles of millennials in rural agriculture retail: The role of technology in continuing education solutions
Authors: Brenny Katie , Yelich Biniecki Susan M.
Published: April 2024

Rural agriculture retailers, or those engaged in the production of food, fiber, and fuel, are pressed to find just‐in‐time solutions for continual learning with their adult employees, specifically millennials, the generation who will assume future leadership roles. Adult educators in rural settings, or lower populated areas, are encountering rapid technological change and need to transform how they impact learners in and out of the classroom through experiential learning. Technological solutions considered an integral component of Science, Technology, Engineering, and Math (STEM) initiatives, may provide continual learning avenues for millennial employees. This article offers effective ways to engage millennials in agriculture through facilitating peer mentoring, supporting soft skill development, and building the infinite potential of learning and growth in STEM content.
Strengthening inclusive teaching with a MOOC: Adult education and STEM as professional development partners
Authors: Murray‐Johnson Kayon , Dewsbury Bryan
Published: April 2024

This article explores the design and development of a Massive Open Online Course (MOOC) on inclusive teaching. Released in the Fall of 2023, the MOOC is particularly unique because of its intentional use of ethnically diverse voices and multimodal content to include art, music, spoken word, and storytelling. Modules range from Self and Empathy to Classroom Climate and Networks. MOOC production was graciously funded by a grant from the Howard Hughes Medical Institute. At its core, the article will share reflections on the rationale and process, describe how STEM and Adult Education scholar‐practitioners collaborated to infuse adult education and interdisciplinary concepts in MOOC development and outline meaningful implications for the field.
Towards effective collaborations: Reflections and recommendations for adult education and STEM
Authors: Zarestky Jil , Vilen Lauren , Love Hannah
Published: April 2024

This article presents a general and overarching view on partnerships between adult education and STEM disciplines. Drawing from their individual STEM backgrounds, personal perspectives and experiences with such partnerships, and the science of team science, the authors consider the benefits of adult eeducation for STEM, the benefits of STEM for adult education, and some best practices and pitfalls of collaborations. In this way, they address some of the “why?” and “how?” that adult educators may wish to consider as they seek new collaborations, or navigate existing partnerships.
Optimal captured power control of variable speed wind turbine systems: Adaptive dynamic programming approach
Authors: Vu Nga Thi‐Thuy
Published: April 2024

An adaptive optimal controller is proposed in this paper to maximize the captured power of a variable speed wind power system. The proposed controller is a combination of optimal and adaptive control components. The Adaptive Dynamic Programming technique is used to design the optimal control component to overcome the nonlinear problem of system dynamics and ensure stability. While the neural network is used to approximate unknown disturbances and system uncertainties. After that, the adaptive control component fully compensates for the effects of these unknown elements. Neither optimal nor adaptive control components necessitate prior knowledge of system dynamics. Furthermore, the approximation network updates only the weight matrix norm rather than the weight matrix of the neural network in each interval time, which significantly reduces computation. The stability analysis of the closed‐loop system is obtained using Lyapunov stability theory. The correctness and robustness of the control scheme are validated in two different scenarios using MATLAB/Simulink. The presented robust adaptive optimal controller is also compared to other existing controllers to demonstrate its benefits.
Emerging In Vitro and In Vivo Models: Hope for the Better Understanding of Cancer Progression and Treatment
Authors: Yadav Rachana , Mahajan Srushti , Singh Hoshiyar , Mehra Neelesh Kumar , Madan Jitender , Doijad Nandkumar , Singh Pankaj Kumar , Guru Santosh Kumar
Published: April 2024

Various cancer models have been developed to aid the understanding of the underlying mechanisms of tumor development and evaluate the effectiveness of various anticancer drugs in preclinical studies. These models accurately reproduce the critical stages of tumor initiation and development to mimic the tumor microenvironment better. Using these models for target validation, tumor response evaluation, resistance modeling, and toxicity comprehension can significantly enhance the drug development process. Herein, various in vivo or animal models are presented, typically consisting of several mice and in vitro models ranging in complexity from transwell models to spheroids and CRISPR‐Cas9 technologies. While in vitro models have been used for decades and dominate the early stages of drug development, they are still limited primary to simplistic tests based on testing on a single cell type cultivated in Petri dishes. Recent advancements in developing new cancer therapies necessitate the generation of complicated animal models that accurately mimic the tumor's complexity and microenvironment. Mice make effective tumor models as they are affordable, have a short reproductive cycle, exhibit rapid tumor growth, and are simple to manipulate genetically. Human cancer mouse models are crucial to understanding the neoplastic process and basic and clinical research improvements. The following review summarizes different in vitro and in vivo metastasis models, their advantages and disadvantages, and their ability to serve as a model for cancer research.
Polymer Backpack‐Loaded Tissue Infiltrating Monocytes for Treating Cancer
Authors: Kapate Neha , Dunne Michael , Gottlieb Alexander P. , Mukherji Malini , Suja Vineeth Chandran , Prakash Supriya , Park Kyung Soo , Kumbhojkar Ninad , Guerriero Jennifer L. , Mitragotri Samir
Published: April 2024

Adoptive cell therapies are dramatically altering the treatment landscape of cancer. However, treatment of solid tumors remains a major unmet need, in part due to limited adoptive cell infiltration into the tumor and in part due to the immunosuppressive tumor microenvironment. The heterogeneity of tumors and presence of nonresponders also call for development of antigen‐independent therapeutic approaches. Myeloid cells offer such an opportunity, given their large presence in the immunosuppressive tumor microenvironment, such as in triple negative breast cancer. However, their therapeutic utility is hindered by their phenotypic plasticity. Here, the impressive trafficking ability of adoptively transferred monocytes is leveraged into the immunosuppressive 4T1 tumor to develop an antitumor therapy. To control monocyte differentiation in the tumor microenvironment, surface‐adherent “backpacks” stably modified with interferon gamma (IFNγ) are developed to stimulate macrophage plasticity into a pro‐inflammatory, antitumor phenotype, a strategy as referred to as Ornate Polymer backpacks on Tissue Infiltrating Monocytes (OPTIMs). Treatment with OPTIMs substantially reduces tumor burden in a mouse 4T1 model and significantly increases survival. Cytokine and immune cell profiling reveal that OPTIMs remodeled the tumor microenvironment into a pro‐inflammatory state.
Room Temperature Phosphorescence from Natural, Organic Emitters and Their Application in Industrially Compostable Programmable Luminescent Tags
Authors: Thomas Heidi , Achenbach Tim , Hodgkinson Isla Marie , Spoerer Yvonne , Kuehnert Ines , Dornack Christina , Schellhammer Karl Sebastian , Reineke Sebastian
Published: April 2024

Organic semiconductors provide the potential of biodegradable technologies, but prototypes do only rarely exist. Transparent, ultrathin programmable luminescent tags (PLTs) are presented for minimalistic yet efficient information storage that are fully made from biodegradable or at least industrially compostable, ready‐to‐use materials (bioPLTs). As natural emitters, the quinoline alkaloids show sufficient room temperature phosphorescence when being embedded in polymer matrices with cinchonine exhibiting superior performance. Polylactic acid provides a solution for both the matrix material and the flexible substrate. Room temperature phosphorescence can be locally controlled by the oxygen concentration in the film by using Exceval as additional oxygen blocking layers. These bioPLTs exhibit all function‐defining characteristics also found in their regular nonenvironmentally degradable analogs and, additionally, provide a simplified, high‐contrast readout under continuous‐wave illumination as a consequence of the unique luminescence properties of the natural emitter cinchonine. Limitations for flexible devices arise from limited thermal stability of the polylactic acid foil used as substrate allowing only for one writing cycle and preventing an annealing step during fabrication. Few‐cycle reprogramming is possible when using the architecture of the bioPLTs on regular quartz substrates. This work realizes the versatile platform of PLTs with less harmful materials offering more sustainable use in future.
The Transpeptidase Sortase A Binds Nucleic Acids and Mediates Mammalian Cell Labeling
Authors: Liu Yingzheng , Lu Zhike , Wu Panfeng , Liang Zhaohui , Yu Zhenxing , Ni Ke , Ma Lijia
Published: April 2024

Wild‐type sortase A is an important virulence factor displaying a diverse array of proteins on the surface of bacteria. This protein display relies on the transpeptidase activity of sortase A, which is widely engineered to allow protein ligation and protein engineering based on the interaction between sortase A and peptides. Here an unknown interaction is found between sortase A from Staphylococcus aureus and nucleic acids, in which exogenously expressed engineered sortase A binds oligonucleotides in vitro and is independent of its canonical transpeptidase activity. When incubated with mammalian cells, engineered sortase A further mediates oligonucleotide labeling to the cell surface, where sortase A attaches itself and is part of the labeled moiety. The labeling reaction can also be mediated by many classes of wild‐type sortases as well. Cell surface GAG appears involved in sortase‐mediated oligonucleotide cell labeling, as demonstrated by CRISPR screening. This interaction property is utilized to develop a technique called CellID to facilitate sample multiplexing for scRNA‐seq and shows the potential of using sortases to label cells with diverse oligonucleotides. Together, the binding between sortase A and nucleic acids opens a new avenue to understanding the virulence of wild‐type sortases and exploring the application of sortases in biotechnology.
Engineering Phage Nanocarriers Integrated with Bio‐Intelligent Plasmids for Personalized and Tunable Enzyme Delivery to Enhance Chemodynamic Therapy
Authors: Hou Xiao‐Lin , Zhang Bin , Cheng Kai , Zhang Fang , Xie Xiao‐Ting , Chen Wei , Tan Lin‐Fang , Fan Jin‐Xuan , Liu Bo , Xu Qiu‐Ran
Published: April 2024

Customizable and number‐tunable enzyme delivery nanocarriers will be useful in tumor therapy. Herein, a phage vehicle, T4‐Lox‐DNA‐Fe (TLDF), which adeptly modulates enzyme numbers using phage display technology to remodel the tumor microenvironment (TME) is presented. Regarding the demand for lactic acid in tumors, each phage is engineered to display 720 lactate oxidase (Lox), contributing to the depletion of lactic acid to restructure the tumor's energy metabolism. The phage vehicle incorporated dextran iron (Fe) with Fenton reaction capabilities. H2O2 is generated through the Lox catalytic reaction, amplifying the H2O2 supply for dextran iron‐based chemodynamic therapy (CDT). Drawing inspiration from the erythropoietin (EPO) biosynthetic process, an EPO enhancer is constructed to impart the EPO‐Keap1 plasmid (DNA) with tumor hypoxia‐activated functionality, disrupting the redox homeostasis of the TME. Lox consumes local oxygen, and positive feedback between the Lox and the plasmid promotes the expression of kelch ECH Associated Protein 1 (Keap1). Consequently, the downregulation of the antioxidant transcription factor Nrf2, in synergy with CDT, amplifies the oxidative killing effect, leading to tumor suppression of up to 78%. This study seamlessly integrates adaptable T4 phage vehicles with bio‐intelligent plasmids, presenting a promising approach for tumor therapy.
A Computational and Chemical Design Strategy for Manipulating Glycan‐Protein Recognition
Authors: Zhu Qiang , Geng Didi , Li Jingchao , Zhang Jinqiu , Sun Haofan , Fan Zhiya , He Jiahui , Hao Ninghui , Tian Yinping , Wen Liuqing , Li Tiehai , Qin Weijie , Chu Xiakun , Wang Yong , Yi Wen
Published: April 2024

Glycans are complex biomolecules that encode rich information and regulate various biological processes, such as fertilization, host‐pathogen binding, and immune recognition, through interactions with glycan‐binding proteins. A key driving force for glycan‐protein recognition is the interaction between the π electron density of aromatic amino acid side chains and polarized C─H groups of the pyranose (termed the CH–π interaction). However, the relatively weak binding affinity between glycans and proteins has hindered the application of glycan detection and imaging. Here, computational modeling and molecular dynamics simulations are employed to design a chemical strategy that enhances the CH–π interaction between glycans and proteins by genetically incorporating electron‐rich tryptophan derivatives into a lectin PhoSL, which specifically recognizes core fucosylated N‐linked glycans. This significantly enhances the binding affinity of PhoSL with the core fucose ligand and enables sensitive detection and imaging of core fucosylated glycans in vitro and in xenograft tumors in mice. Further, the study showed that this strategy is applicable to improve the binding affinity of GafD lectin for N‐acetylglucosamine‐containing glycans. The approach thus provides a general and effective way to manipulate glycan‐protein recognition for glycoscience applications.
Ammonolysis‐Driven Exsolution of Ru Nanoparticle Embedded in Conductive Metal Nitride Matrix to Boost Electrocatalyst Activity
Authors: Yun So Yeon , Lee Sangseob , Jin Xiaoyan , Soon Aloysius , Hwang Seong‐Ju
Published: April 2024

Exsolution is an effective method for synthesizing robust nanostructured metal‐based functional materials. However, no studies have investigated the exsolution of metal nanoparticles into metal nitride substrates. In this study, a versatile nitridation‐driven exsolution method is developed for embedding catalytically active metal nanoparticles in conductive metal nitride substrates via the ammonolysis of multimetallic oxides. Using this approach, Ti1−xRuxO2 nanowires are phase‐transformed into holey TiN nanotubes embedded with exsolved Ru nanoparticles. These Ru‐exsolved holey TiN nanotubes exhibit outstanding electrocatalytic activity for the hydrogen evolution reaction with excellent durability, which is significantly higher than that of Ru‐deposited TiN nanotubes. The enhanced stability of the Ru‐exsolved TiN nanotubes can be attributed to the Ru nanoparticles embedded in the robust metal nitride matrix and the formation of interfacial Ti3+─N─Ru4+ bonds. Density functional theory calculations reveal that the exsolved Ru nanoparticles have a lower d‐band center position and optimized hydrogen affinity than deposited Ru nanoparticles, indicating the superior electrocatalyst performance of the former. In situ Raman spectroscopic analysis reveals that the electron transfer from TiN to Ru nanoparticles is enhanced during the electrocatalytic process. The proposed approach opens a new avenue for stabilizing diverse metal nanostructures in many conductive matrices like metal phosphides and chalcogenides.
Photoswitchable Endocytosis of Biomolecular Condensates in Giant Vesicles
Authors: Mangiarotti Agustín , Aleksanyan Mina , Siri Macarena , Sun Tsu‐Wang , Lipowsky Reinhard , Dimova Rumiana
Published: April 2024

Interactions between membranes and biomolecular condensates can give rise to complex phenomena such as wetting transitions, mutual remodeling, and endocytosis. In this study, light‐triggered manipulation of condensate engulfment is demonstrated using giant vesicles containing photoswitchable lipids. UV irradiation increases the membrane area, which can be stored in nanotubes. When in contact with a condensate droplet, the UV light triggers rapid condensate endocytosis, which can be reverted by blue light. The affinity of the protein‐rich condensates to the membrane and the reversibility of the engulfment processes is quantified from confocal microscopy images. The degree of photo‐induced engulfment, whether partial or complete, depends on the vesicle excess area and the relative sizes of vesicles and condensates. Theoretical estimates suggest that utilizing the light‐induced excess area to increase the vesicle‐condensate adhesion interface is energetically more favorable than the energy gain from folding the membrane into invaginations and tubes. The overall findings demonstrate that membrane‐condensate interactions can be easily and quickly modulated via light, providing a versatile system for building platforms to control cellular events and design intelligent drug delivery systems for cell repair.
Phosphorylation of IDH1 Facilitates Progestin Resistance in Endometrial Cancer
Authors: Li Jingjie , Qin Zuoshu , Li Yunqi , Huang Baozhu , Xiao Qimeng , Chen Peiqin , Luo Yifan , Zheng Wenxin , Zhang Tao , Zhang Zhenbo
Published: April 2024

The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond well to initial therapy, progestin‐refractory disease inevitably emerges, and the molecular basis underlying progestin resistance has not been comprehensively elucidated. Herein, they demonstrated progestin results in p38‐dependent IDH1 Thr 77 phosphorylation (pT77‐IDH1). pT77‐IDH1 translocates into the nucleus and is recruited to chromatin through its interaction with OCT6. IDH1‐produced α‐ketoglutarate (αKG) then facilitates the activity of OCT6 to promote focal adhesion related target gene transcription to confer progestin resistance. Pharmacological inhibition of p38 or focal adhesion signaling sensitizes endometrial cancer cells to progestin in vivo. The study reveals p38‐dependent pT77‐IDH1 as a key mediator of progestin resistance and a promising target for improving the efficacy of progestin therapy.
Understanding the Cathode‐Electrolyte Interfacial Chemistry in Rechargeable Magnesium Batteries
Authors: Shi Hucheng , Wang Guixin , Wang Zhechen , Yang Lin , Zhang Shu , Dong Shanmu , Qu Baihua , Du Aobing , Li Zhenyou , Zhou Xiaoyuan , Cui Guanglei
Published: April 2024

Rechargeable magnesium batteries (RMBs) have garnered significant attention due to their potential to provide high energy density, utilize earth‐abundant raw materials, and employ metal anode safely. Currently, the lack of applicable cathode materials has become one of the bottleneck issues for fully exploiting the technological advantages of RMBs. Recent studies on Mg cathodes reveal divergent storage performance depending on the electrolyte formulation, posing interfacial issues as a previously overlooked challenge. This minireview begins with an introduction of representative cathode‐electrolyte interfacial phenomena in RMBs, elaborating on the unique solvation behavior of Mg2+, which lays the foundation for interfacial chemistries. It is followed by presenting recently developed strategies targeting the promotion of Mg2+ desolvation in the electrolyte and alternative cointercalation approaches to circumvent the desolvation step. In addition, efforts to enhance the cathode‐electrolyte compatibility via electrolyte development and interfacial engineering are highlighted. Based on the abovementioned discussions, this minireview finally puts forward perspectives and challenges on the establishment of a stable interface and fast interfacial chemistry for RMBs.
Designing Complex Tapestries with Photography‐Inspired Manipulation of Self‐Organized Thin‐Films
Authors: van Campenhout C. T. , Bistervels M. H. , Rietveld J. , Schoenmaker H. , Kamp M. , Noorduin W. L.
Published: April 2024

Thin‐films patterned with complex motifs are of fundamental interest because of their advanced optical, mechanical and electronic properties, but fabrication of these materials remains challenging. Self‐organization strategies, such as immersion controlled reaction‐diffusion patterning, have shown great potential for production of patterned thin‐films. However, the autonomous nature of such processes limits controllable pattern customizability and complexity. Here, it is demonstrated that photography inspired manipulation processes can overcome this limitation to create highly‐complex tapestries of micropatterned films (MPF's). Inspired by classical photographic processes, MPF's are developed, bleached, exposed, fixed, and contoured into user‐defined shapes and photographic toning reactions are used to convert the chemical composition MPF's, while preserving the original stripe patterns. By applying principles of composite photography, highly complex tapestries composed of multiple MPF layers are designed, where each layer can be individually manipulated into a specific shape and composition. By overcoming fundamental limitations, this synergistic approach broadens the design possibilities of reaction‐diffusion processes, furthering the potential of self‐organization strategies for the development of complex materials.
Charge Photoaccumulation in Covalent Polymer Networks for Boosting Photocatalytic Nitrate Reduction to Ammonia
Authors: He Xinjia , Wen Yingke , Fang Yanjie , Li Mengjie , Shan Bing
Published: April 2024

In the design of photoelectrocatalytic cells, a key element is effective photogeneration of electron‐hole pairs to drive redox activation of catalysts. Despite recent progress in photoelectrocatalysis, experimental realization of a high‐performance photocathode for multi‐electron reduction of chemicals, such as nitrate reduction to ammonia, has remained a challenge due to difficulty in obtaining efficient electrode configurations for extraction of high‐throughput electrons from absorbed photons. This work describes a new design for catalytic photoelectrodes using chromophore assembly‐functionalized covalent networks for boosting eight‐electron reduction of nitrate to ammonia. Upon sunlight irradiation, the photoelectrode stores a mass of reducing equivalents at the photoexcited chromophore assembly for multielectron reduction of a copper catalyst, enabling efficient nitrate reduction to ammonia. By introducing the new photoelectrode structure, it is demonstrated that the electronic interplay between charge photo‐accumulating assembly and multi‐electron redox catalysts can be optimized to achieve proper balance between electron transfer dynamics and thermodynamic output of photoelectrocatalytic systems.
Radical‐Mediated Degradation of Thiol–Maleimide Hydrogels
Authors: Hebner Tayler S. , Kirkpatrick Bruce E. , Fairbanks Benjamin D. , Bowman Christopher N. , Anseth Kristi S. , Benoit Danielle S.W.
Published: April 2024

Michael addition between thiol‐ and maleimide‐functionalized molecules is a long‐standing approach used for bioconjugation, hydrogel crosslinking, and the functionalization of other advanced materials. While the simplicity of this chemistry enables facile synthesis of hydrogels, network degradation is also desirable in many instances. Here, the susceptibility of thiol–maleimide bonds to radical‐mediated degradation is reported. Irreversible degradation in crosslinked materials is demonstrated using photoinitiated and chemically initiated radicals in hydrogels and linear polymers. The extent of degradation is shown to be dependent on initiator concentration. Using a model linear polymer system, the radical‐mediated mechanism of degradation is elucidated, in which the thiosuccinimide crosslink is converted to a succinimide and a new thioether formed with an initiator fragment. Using laser stereolithography, high‐fidelity spatiotemporal control over degradation in crosslinked gels is demonstrated. Ultimately, this work establishes a platform for controllable, radical‐mediated degradation in thiol–maleimide hydrogels, further expanding their versatility as functional materials.
Carrier‐Free Self‐Assembly Nano‐Sonosensitizers for Sonodynamic‐Amplified Cuproptosis‐Ferroptosis in Glioblastoma Therapy
Authors: Zhu Yang , Niu Xuegang , Ding Chengyu , Lin Yuanxiang , Fang Wenhua , Yan Lingjun , Cheng Junjie , Zou Jianhua , Tian Yu , Huang Wei , Huang Wen , Pan Yuanbo , Wu Tiantian , Chen Xiaoyuan , Kang Dezhi
Published: April 2024

Cuproptosis is a newly discovered form of programmed cell death significantly depending on the transport efficacy of copper (Cu) ionophores. However, existing Cu ionophores, primarily small molecules with a short blood half‐life, face challenges in transporting enough amounts of Cu ions into tumor cells. This work describes the construction of carrier‐free nanoparticles (Ce6@Cu NPs), which self‐assembled by the coordination of Cu2+ with the sonosensitizer chlorin e6 (Ce6), facilitating sonodynamic‐triggered combination of cuproptosis and ferroptosis. Ce6@Cu NPs internalized by U87MG cells induce a sonodynamic effect and glutathione (GSH) depletion capability, promoting lipid peroxidation and eventually inducing ferroptosis. Furthermore, Cu+ concentration in tumor cells significantly increases as Cu2+ reacts with reductive GSH, resulting in the downregulation of ferredoxin‐1 and lipoyl synthase. This induces the oligomerization of lipoylated dihydrolipoamide S‐acetyltransferase, causing proteotoxic stress and irreversible cuproptosis. Ce6@Cu NPs possess a satisfactory ability to penetrate the blood‐brain barrier, resulting in significant accumulation in orthotopic U87MG‐Luc glioblastoma. The sonodynamic‐triggered combination of ferroptosis and cuproptosis in the tumor by Ce6@Cu NPs is evidenced both in vitro and in vivo with minimal side effects. This work represents a promising tumor therapeutic strategy combining ferroptosis and cuproptosis, potentially inspiring further research in developing logical and effective cancer therapies based on cuproptosis.
Hypervalent Iodine Mediated Synthesis of 2‐Aminobenzazoles and 2‐Aminobenzothiazoles
Authors: Gu Yi , Li Yao‐Dong , Ge Ye , Huang Jiang‐Long , Xu Hua‐Jin , Hu Yi
Published: April 2024

The hypervalent iodine mediated, silica gel promoted synthesis of 2‐aminobenzazoles and 2‐aminobenzothiazole derivatives under metal‐free mild conditions within short time (30 min) has been developed. Under this process, PhI(COOCF3)2 (PIFA) or PhI(COOCH3)2 (PIDA) acts as an oxidant and radical initiator direct activated the ortho‐C−H bond of substrate, silica gel as weakly lewis acid effectively increased the reactivity of the reaction system. This method is compatible with various of arylurea and arylthiourea substrates, which is green, efficient, simple to operate and suitable for practical application.
The Trotter collection: A review of Mildred Trotter's hair research and an update for studies of human variation
Authors: Koch Sandra L. , Zaidi Arslan , González Tomás , Shriver Mark D. , Jablonski Nina G.
Published: April 2024

Objectives

Mildred Trotter was an anatomist and physical anthropologist whose studies on hair morphology, growth, somatic distribution, and trait relationships to age and ethnogeographic population were foundational to the field of microscopical hair analysis. The collection of human hair samples she assembled for her research has been an underutilized resource for studies on human hair variation. We applied updated methods and reviewed Trotter's original data to reassess the relationship hair traits have to diverse population labels.

Methods

Hair form and pigmentation patterns were measured from a subset of the hair samples accumulated by Trotter and we compared our data to Trotter's original results. Variability in hair traits were tested within individuals, within populations, and among ethnogeographic groups.

Results

Measured hair cross‐section dimensions and melanosome density and distribution revealed substantial variability within individuals and ethnogeographic populations. Hair traits were found to not be distinctly separable by ancestry but instead showed continuous variation across human populations. Trotter's measurements were precise and the dataset she compiled remains valid, though the conclusions should be reviewed in light of our current understanding of human variation.

Discussion

Our findings support moving away from categorical ancestry classifications and eliminating the use of outdated racial typologies in favor of more descriptive trait analysis. Detailed analysis of trait pattern distributions are presented that may be useful for future research on human variation. We point to the need for additional research on human variation and hair trait relationships with reference to known population affinity.
Elucidation of Palmarumycin Spirobisnaphthalene Biosynthesis Reveals a Set of Previously Unrecognized Oxidases and Reductases
Authors: Zhao Siji , Shen Zhen , Zhai Ziqi , Yin Ruya , Xu Dan , Wang Mingan , Wang Qi , Peng You‐Liang , Zhou Ligang , Lai Daowan
Published: April 2024

Spirobisnaphthalenes (SBNs) are a class of highly oxygenated, fungal bisnaphthalenes containing a unique spiroketal bridge, that displayed diverse bioactivities. Among the reported SBNs, palmarumycins are the major type, which are precursors for the other type of SBNs structurally. However, the biosynthesis of SBNs is unclear. In this study, we elucidated the biosynthesis of palmarumycins, using gene disruption, heterologous expression, and substrate feeding experiments. The biosynthetic gene cluster for palmarumycins was identified to be distant from the polyketide synthase gene cluster, and included two cytochrome P450s (PalA and PalB), and one short chain dehydrogenase/reductase (PalC) encoding genes as key structural genes. PalA is an unusual, multifunctional P450 that catalyzes the oxidative dimerization of 1,8‐dihydroxynaphthalene to generate the spiroketal linkage and 2,3‐epoxy group. Chemical synthesis of key intermediate and in vitro biochemical assays proved that the oxidative dimerization proceeded via a binaphthyl ether. PalB installs the C‐5 hydroxy group, widely found in SBNs. PalC catalyzes 1‐keto reduction, the reverse 1‐dehydrogenation, and 2,3‐epoxide reduction. Moreover, an FAD‐dependent oxidoreductase, encoded by palD, which locates outside the cluster, functions as a 1‐dehydrogenase. These results provided the first genetic and biochemical evidence for the biosynthesis of palmarumycin SBNs.