bluuebunny/crossref_metadata_2025_split huggingface dataset:
Amelioration of the brain structural connectivity is accompanied with changes of gut microbiota in a tuberous sclerosis complex mouse model
Authors: Hsieh Christine Chin-jung , Lo Yu-Chun , Wang Hsin-Hui , Shen Hsin-Ying , Chen You-Yin , Lee Yi-Chao 
Published: January 2024

AbstractTuberous sclerosis complex (TSC) is a genetic disease that causes benign tumors and dysfunctions in many organs, including the brain. Aside from the brain malformations, many individuals with TSC exhibit neuropsychiatric symptoms. Among these symptoms, autism spectrum disorder (ASD) is one of the most common co-morbidities, affecting up to 60% of the population. Past neuroimaging studies strongly suggested that the impairments in brain connectivity contribute to ASD, whether or not TSC-related. Specifically, the tract-based diffusion tensor imaging (DTI) analysis provides information on the fiber integrity and has been used to study the neuropathological changes in the white matter of TSC patients with ASD symptoms. In our previous study, curcumin, a diet-derived mTOR inhibitor has been shown to effectively mitigate learning and memory deficits and anxiety-like behavior in Tsc2+/− mice via inhibiting astroglial proliferation. Recently, gut microbiota, which is greatly influenced by the diet, has been considered to play an important role in regulating several components of the central nervous system, including glial functions. In this study, we showed that the abnormal social behavior in the Tsc2+/− mice can be ameliorated by the dietary curcumin treatment. Second, using tract-based DTI analysis, we found that the Tsc2+/− mice exhibited altered fractional anisotropy, axial and radial diffusivities of axonal bundles connecting the prefrontal cortex, nucleus accumbens, hypothalamus, and amygdala, indicating a decreased brain network. Third, the dietary curcumin treatment improved the DTI metrics, in accordance with changes in the gut microbiota composition. At the bacterial phylum level, we showed that the abundances of Actinobacteria, Verrucomicrobia, and Tenericutes were significantly correlated with the DTI metrics FA, AD, and RD, respectively. Finally, we revealed that the expression of myelin-associated proteins, myelin bassic protein (MBP) and proteolipid protein (PLP) was increased after the treatment. Overall, we showed a strong correlation between structural connectivity alterations and social behavioral deficits, as well as the diet-dependent changes in gut microbiota composition.
High-throughput computational stacking reveals emergent properties in natural van der Waals bilayers
Authors: Pakdel Sahar , Rasmussen Asbjørn , Taghizadeh Alireza , Kruse Mads , Olsen Thomas , Thygesen Kristian S. 
Published: January 2024

AbstractStacking of two-dimensional (2D) materials has emerged as a facile strategy for realising exotic quantum states of matter and engineering electronic properties. Yet, developments beyond the proof-of-principle level are impeded by the vast size of the configuration space defined by layer combinations and stacking orders. Here we employ a density functional theory (DFT) workflow to calculate interlayer binding energies of 8451 homobilayers created by stacking 1052 different monolayers in various configurations. Analysis of the stacking orders in 247 experimentally known van der Waals crystals is used to validate the workflow and determine the criteria for realisable bilayers. For the 2586 most stable bilayer systems, we calculate a range of electronic, magnetic, and vibrational properties, and explore general trends and anomalies. We identify an abundance of bistable bilayers with stacking order-dependent magnetic or electrical polarisation states making them candidates for slidetronics applications.
DeepFocus: fast focus and astigmatism correction for electron microscopy
Authors: Schubert P. J. , Saxena R. , Kornfeld J. 
Published: January 2024

AbstractHigh-throughput 2D and 3D scanning electron microscopy, which relies on automation and dependable control algorithms, requires high image quality with minimal human intervention. Classical focus and astigmatism correction algorithms attempt to explicitly model image formation and subsequently aberration correction. Such models often require parameter adjustments by experts when deployed to new microscopes, challenging samples, or imaging conditions to prevent unstable convergence, making them hard to use in practice or unreliable. Here, we introduce DeepFocus, a purely data-driven method for aberration correction in scanning electron microscopy. DeepFocus works under very low signal-to-noise ratio conditions, reduces processing times by more than an order of magnitude compared to the state-of-the-art method, rapidly converges within a large aberration range, and is easily recalibrated to different microscopes or challenging samples.
Nanoconfinement-triggered oligomerization pathway for efficient removal of phenolic pollutants via a Fenton-like reaction
Authors: Zhang Xiang , Tang Jingjing , Wang Lingling , Wang Chuan , Chen Lei , Chen Xinqing , Qian Jieshu , Pan Bingcai 
Published: January 2024

AbstractHeterogeneous Fenton reaction represents one of the most reliable technologies to ensure water safety, but is currently challenged by the sluggish Fe(III) reduction, excessive input of chemicals for organic mineralization, and undesirable carbon emission. Current endeavors to improve the catalytic performance of Fenton reaction are mostly focused on how to accelerate Fe(III) reduction, while the pollutant degradation step is habitually overlooked. Here, we report a nanoconfinement strategy by using graphene aerogel (GA) to support UiO-66-NH2-(Zr) binding atomic Fe(III), which alters the carbon transfer route during phenol removal from kinetically favored ring-opening route to thermodynamically favored oligomerization route. GA nanoconfinement favors the Fe(III) reduction by enriching the reductive intermediates and allows much faster phenol removal than the unconfined analog (by 208 times in terms of first-order rate constant) and highly efficient removal of total organic carbon, i.e., 92.2 ± 3.7% versus 3.6 ± 0.3% in 60 min. Moreover, this oligomerization route reduces the oxidant consumption for phenol removal by more than 95% and carbon emission by 77.9%, compared to the mineralization route in homogeneous Fe2++H2O2 system. Our findings may upgrade the regulatory toolkit for Fenton reactions and provide an alternative carbon transfer route for the removal of aqueous pollutants.
Collective total synthesis of stereoisomeric yohimbine alkaloids
Authors: Tang Meiyi , Lu Haigen , Zu Liansuo 
Published: January 2024

AbstractStereoisomeric polycyclic natural products are important for drug discovery-based screening campaigns, due to the close correlation of stereochemistry with diversified bioactivities. Nature generates the stereoisomeric yohimbine alkaloids using bioavailable monoterpene secolaganin as the ten-carbon building block. In this work, we reset the stage by the development of a bioinspired coupling, in which the rapid construction of the entire pentacyclic skeleton and the complete control of all five stereogenic centers are achieved through enantioselective kinetic resolution of an achiral, easily accessible synthetic surrogate. The stereochemical diversification from a common intermediate allows for the divergent and collective synthesis of all four stereoisomeric subfamilies of yohimbine alkaloids through orchestrated tackling of thermodynamic and kinetic preference.
Reaction hijacking inhibition of Plasmodium falciparum asparagine tRNA synthetase
Authors: Xie Stanley C. , Wang Yinuo , Morton Craig J. , Metcalfe Riley D. , Dogovski Con , Pasaje Charisse Flerida A. , Dunn Elyse , Luth Madeline R. , Kumpornsin Krittikorn , Istvan Eva S. , Park Joon Sung , Fairhurst Kate J. , Ketprasit Nutpakal , Yeo Tomas , Yildirim Okan , Bhebhe Mathamsanqa N. , Klug Dana M. , Rutledge Peter J. , Godoy Luiz C. , Dey Sumanta , De Souza Mariana Laureano , Siqueira-Neto Jair L. , Du Yawei , Puhalovich Tanya , Amini Mona , Shami Gerry , Loesbanluechai Duangkamon , Nie Shuai , Williamson Nicholas , Jana Gouranga P. , Maity Bikash C. , Thomson Patrick , Foley Thomas , Tan Derek S. , Niles Jacquin C. , Han Byung Woo , Goldberg Daniel E. , Burrows Jeremy , Fidock David A. , Lee Marcus C. S. , Winzeler Elizabeth A. , Griffin Michael D. W. , Todd Matthew H. , Tilley Leann 
Published: January 2024

AbstractMalaria poses an enormous threat to human health. With ever increasing resistance to currently deployed drugs, breakthrough compounds with novel mechanisms of action are urgently needed. Here, we explore pyrimidine-based sulfonamides as a new low molecular weight inhibitor class with drug-like physical parameters and a synthetically accessible scaffold. We show that the exemplar, OSM-S-106, has potent activity against parasite cultures, low mammalian cell toxicity and low propensity for resistance development. In vitro evolution of resistance using a slow ramp-up approach pointed to the Plasmodium falciparum cytoplasmic asparaginyl-tRNA synthetase (PfAsnRS) as the target, consistent with our finding that OSM-S-106 inhibits protein translation and activates the amino acid starvation response. Targeted mass spectrometry confirms that OSM-S-106 is a pro-inhibitor and that inhibition of PfAsnRS occurs via enzyme-mediated production of an Asn-OSM-S-106 adduct. Human AsnRS is much less susceptible to this reaction hijacking mechanism. X-ray crystallographic studies of human AsnRS in complex with inhibitor adducts and docking of pro-inhibitors into a model of Asn-tRNA-bound PfAsnRS provide insights into the structure-activity relationship and the selectivity mechanism.
Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats
Authors: Riesle-Sbarbaro S. A. , Wibbelt G. , Düx A. , Kouakou V. , Bokelmann M. , Hansen-Kant K. , Kirchoff N. , Laue M. , Kromarek N. , Lander A. , Vogel U. , Wahlbrink A. , Wozniak D. M. , Scott D. P. , Prescott J. B. , Schaade L. , Couacy-Hymann E. , Kurth A. 
Published: January 2024

AbstractThe natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles. Herein, we investigate the permissiveness of Angolan free-tailed bats (AFBs), known to harbour Bombali virus, to other filoviruses: Ebola, Marburg, Taï Forest and Reston viruses. We demonstrate that only the bats inoculated with EBOV show high and disseminated viral replication and infectious virus shedding, without clinical disease, while the other filoviruses fail to establish productive infections. Notably, we evidence placental-specific tissue tropism and a unique ability of EBOV to traverse the placenta, infect and persist in foetal tissues of AFBs, which results in distinct genetic signatures of adaptive evolution. These findings not only demonstrate plausible routes of horizontal and vertical transmission in these bats, which are expectant of reservoir hosts, but may also reveal an ancillary transmission mechanism, potentially required for the maintenance of EBOV in small reservoir populations.
Ubiquitin ligase RNF20 coordinates sequential adipose thermogenesis with brown and beige fat-specific substrates
Authors: Jeon Yong Geun , Nahmgoong Hahn , Oh Jiyoung , Lee Dabin , Kim Dong Wook , Kim Jane Eunsoo , Kim Ye Young , Ji Yul , Han Ji Seul , Kim Sung Min , Sohn Jee Hyung , Lee Won Taek , Kim Sun Won , Park Jeu , Huh Jin Young , Jo Kyuri , Cho Je-Yoel , Park Jiyoung , Kim Jae Bum 
Published: January 2024

AbstractIn mammals, brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) execute sequential thermogenesis to maintain body temperature during cold stimuli. BAT rapidly generates heat through brown adipocyte activation, and further iWAT gradually stimulates beige fat cell differentiation upon prolonged cold challenges. However, fat depot-specific regulatory mechanisms for thermogenic activation of two fat depots are poorly understood. Here, we demonstrate that E3 ubiquitin ligase RNF20 orchestrates adipose thermogenesis with BAT- and iWAT-specific substrates. Upon cold stimuli, BAT RNF20 is rapidly downregulated, resulting in GABPα protein elevation by controlling protein stability, which stimulates thermogenic gene expression. Accordingly, BAT-specific Rnf20 suppression potentiates BAT thermogenic activity via GABPα upregulation. Moreover, upon prolonged cold stimuli, iWAT RNF20 is gradually upregulated to promote de novo beige adipogenesis. Mechanistically, iWAT RNF20 mediates NCoR1 protein degradation, rather than GABPα, to activate PPARγ. Together, current findings propose fat depot-specific regulatory mechanisms for temporal activation of adipose thermogenesis.
Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial
Authors: Cao Xun , Huang Hao-Yang , Liang Chi-Xiong , Lin Zhuo-Chen , Zhou Jia-Yu , Chen Xi , Huang Ying-Ying , Zhan Ze-Jiang , Ke Liang-Ru , Han Lu-Jun , Xia Wei-Xiong , Tang Lin-Quan , Guo Shan-Shan , Liang Hu , Guo Xiang , Lv Xing 
Published: January 2024

AbstractPatients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.
Nominally identical microplastic models differ greatly in their particle-cell interactions
Authors: Wieland Simon , Ramsperger Anja F. R. M. , Gross Wolfgang , Lehmann Moritz , Witzmann Thomas , Caspari Anja , Obst Martin , Gekle Stephan , Auernhammer Günter K. , Fery Andreas , Laforsch Christian , Kress Holger 
Published: January 2024

AbstractDue to the abundance of microplastics in the environment, research about its possible adverse effects is increasing exponentially. Most studies investigating the effect of microplastics on cells still rely on commercially available polystyrene microspheres. However, the choice of these model microplastic particles can affect the outcome of the studies, as even nominally identical model microplastics may interact differently with cells due to different surface properties such as the surface charge. Here, we show that nominally identical polystyrene microspheres from eight different manufacturers significantly differ in their ζ-potential, which is the electrical potential of a particle in a medium at its slipping plane. The ζ-potential of the polystyrene particles is additionally altered after environmental exposure. We developed a microfluidic microscopy platform to demonstrate that the ζ-potential determines particle-cell adhesion strength. Furthermore, we find that due to this effect, the ζ-potential also strongly determines the internalization of the microplastic particles into cells. Therefore, the ζ-potential can act as a proxy of microplastic-cell interactions and may govern adverse effects reported in various organisms exposed to microplastics.
A rechargeable Ca/Cl2 battery
Authors: Geng Shitao , Zhao Xiaoju , Xu Qiuchen , Yuan Bin , Wang Yan , Liao Meng , Ye Lei , Wang Shuo , Ouyang Zhaofeng , Wu Liang , Wang Yongyang , Ma Chenyan , Zhao Xiaojuan , Sun Hao 
Published: January 2024

AbstractRechargeable calcium (Ca) metal batteries are promising candidates for sustainable energy storage due to the abundance of Ca in Earth’s crust and the advantageous theoretical capacity and voltage of these batteries. However, the development of practical Ca metal batteries has been severely hampered by the current cathode chemistries, which limit the available energy and power densities, as well as their insufficient capacity retention and low-temperature capability. Here, we describe the rechargeable Ca/Cl2 battery based on a reversible cathode redox reaction between CaCl2 and Cl2, which is enabled by the use of lithium difluoro(oxalate)borate as a key electrolyte mediator to facilitate the dissociation and distribution of Cl-based species and Ca2+. Our rechargeable Ca/Cl2 battery can deliver discharge voltages of 3 V and exhibits remarkable specific capacity (1000 mAh g−1) and rate capability (500 mA g−1). In addition, the excellent capacity retention (96.5% after 30 days) and low-temperature capability (down to 0 °C) allow us to overcome the long-standing bottleneck of rechargeable Ca metal batteries.
Matrix viscoelasticity promotes liver cancer progression in the pre-cirrhotic liver
Authors: Fan Weiguo , Adebowale Kolade , Váncza Lóránd , Li Yuan , Rabbi Md Foysal , Kunimoto Koshi , Chen Dongning , Mozes Gergely , Chiu David Kung-Chun , Li Yisi , Tao Junyan , Wei Yi , Adeniji Nia , Brunsing Ryan L. , Dhanasekaran Renumathy , Singhi Aatur , Geller David , Lo Su Hao , Hodgson Louis , Engleman Edgar G. , Charville Gregory W. , Charu Vivek , Monga Satdarshan P. , Kim Taeyoon , Wells Rebecca G. , Chaudhuri Ovijit , Török Natalie J. 
Published: January 2024

AbstractType 2 diabetes mellitus is a major risk factor for hepatocellular carcinoma (HCC). Changes in extracellular matrix (ECM) mechanics contribute to cancer development1,2, and increased stiffness is known to promote HCC progression in cirrhotic conditions3,4. Type 2 diabetes mellitus is characterized by an accumulation of advanced glycation end-products (AGEs) in the ECM; however, how this affects HCC in non-cirrhotic conditions is unclear. Here we find that, in patients and animal models, AGEs promote changes in collagen architecture and enhance ECM viscoelasticity, with greater viscous dissipation and faster stress relaxation, but not changes in stiffness. High AGEs and viscoelasticity combined with oncogenic β-catenin signalling promote HCC induction, whereas inhibiting AGE production, reconstituting the AGE clearance receptor AGER1 or breaking AGE-mediated collagen cross-links reduces viscoelasticity and HCC growth. Matrix analysis and computational modelling demonstrate that lower interconnectivity of AGE-bundled collagen matrix, marked by shorter fibre length and greater heterogeneity, enhances viscoelasticity. Mechanistically, animal studies and 3D cell cultures show that enhanced viscoelasticity promotes HCC cell proliferation and invasion through an integrin-β1–tensin-1–YAP mechanotransductive pathway. These results reveal that AGE-mediated structural changes enhance ECM viscoelasticity, and that viscoelasticity can promote cancer progression in vivo, independent of stiffness.
Single-photon superradiance in individual caesium lead halide quantum dots
Authors: Zhu Chenglian , Boehme Simon C. , Feld Leon G. , Moskalenko Anastasiia , Dirin Dmitry N. , Mahrt Rainer F. , Stöferle Thilo , Bodnarchuk Maryna I. , Efros Alexander L. , Sercel Peter C. , Kovalenko Maksym V. , Rainò Gabriele 
Published: January 2024

AbstractThe brightness of an emitter is ultimately described by Fermi’s golden rule, with a radiative rate proportional to its oscillator strength times the local density of photonic states. As the oscillator strength is an intrinsic material property, the quest for ever brighter emission has relied on the local density of photonic states engineering, using dielectric or plasmonic resonators1,2. By contrast, a much less explored avenue is to boost the oscillator strength, and hence the emission rate, using a collective behaviour termed superradiance. Recently, it was proposed3 that the latter can be realized using the giant oscillator-strength transitions of a weakly confined exciton in a quantum well when its coherent motion extends over many unit cells. Here we demonstrate single-photon superradiance in perovskite quantum dots with a sub-100 picosecond radiative decay time, almost as short as the reported exciton coherence time4. The characteristic dependence of radiative rates on the size, composition and temperature of the quantum dot suggests the formation of giant transition dipoles, as confirmed by effective-mass calculations. The results aid in the development of ultrabright, coherent quantum light sources and attest that quantum effects, for example, single-photon emission, persist in nanoparticles ten times larger than the exciton Bohr radius.
Activation of recombinases at specific DNA loci by zinc-finger domain insertions
Authors: Mukhametzyanova Liliya , Schmitt Lukas Theo , Torres-Rivera Julia , Rojo-Romanos Teresa , Lansing Felix , Paszkowski-Rogacz Maciej , Hollak Heike , Brux Melanie , Augsburg Martina , Schneider Paul Martin , Buchholz Frank 
Published: January 2024

AbstractRecombinases have several potential advantages as genome editing tools compared to nucleases and other editing enzymes, but the process of engineering them to efficiently recombine predetermined DNA targets demands considerable investment of time and labor. Here we sought to harness zinc-finger DNA-binding domains (ZFDs) to program recombinase binding by developing fusions, in which ZFDs are inserted into recombinase coding sequences. By screening libraries of hybrid proteins, we optimized the insertion site, linker length, spacing and ZFD orientation and generated Cre-type recombinases that remain dormant unless the insertionally fused ZFD binds its target site placed in the vicinity of the recombinase binding site. The developed fusion improved targeted editing efficiencies of recombinases by four-fold and abolished measurable off-target activity in mammalian cells. The ZFD-dependent activity is transferable to a recombinase with relaxed specificity, providing the means for developing fully programmable recombinases. Our engineered recombinases provide improved genome editing tools with increased precision and efficiency.