bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of viral RNA–host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2
Authors: Zhang Shaojun , Huang Wenze , Ren Lili , Ju Xiaohui , Gong Mingli , Rao Jian , Sun Lei , Li Pan , Ding Qiang , Wang Jianwei , Zhang Qiangfeng Cliff 
Published: November 2021

AbstractIn contrast to the extensive research about viral protein–host protein interactions that has revealed major insights about how RNA viruses engage with host cells during infection, few studies have examined interactions between host factors and viral RNAs (vRNAs). Here, we profiled vRNA–host protein interactomes for three RNA virus pathogens (SARS-CoV-2, Zika, and Ebola viruses) using ChIRP-MS. Comparative interactome analyses discovered both common and virus-specific host responses and vRNA-associated proteins that variously promote or restrict viral infection. In particular, SARS-CoV-2 binds and hijacks the host factor IGF2BP1 to stabilize vRNA and augment viral translation. Our interactome-informed drug repurposing efforts identified several FDA-approved drugs (e.g., Cepharanthine) as broad-spectrum antivirals in cells and hACE2 transgenic mice. A co-treatment comprising Cepharanthine and Trifluoperazine was highly potent against the newly emerged SARS-CoV-2 B.1.351 variant. Thus, our study illustrates the scientific and medical discovery utility of adopting a comparative vRNA–host protein interactome perspective.
Potential global impacts of alternative dosing regimen and rollout options for the ChAdOx1 nCoV-19 vaccine
Authors: Aguas Ricardo , Bharath Anouska , White Lisa J. , Gao Bo , Pollard Andrew J. , Voysey Merryn , Shretta Rima 
Published: November 2021

AbstractThe high efficacy, low cost, and long shelf-life of the ChAdOx1 nCoV-19 vaccine positions it well for use in in diverse socioeconomic settings. Using data from clinical trials, an individual-based model was constructed to predict its 6-month population-level impact. Probabilistic sensitivity analyses evaluated the importance of epidemiological, demographic and logistical factors on vaccine effectiveness. Rollout at various levels of availability and delivery speed, conditional on vaccine efficacy profiles (efficacy of each dose and interval between doses) were explored in representative countries. We highlight how expedient vaccine delivery to high-risk groups is critical in mitigating COVID-19 disease and mortality. In scenarios where the availability of vaccine is insufficient for high-risk groups to receive two doses, administration of a single dose of is optimal, even when vaccine efficacy after one dose is just 75% of the two doses. These findings can help inform allocation strategies particularly in areas constrained by availability.
Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer
Authors: Che Meixia , Chaturvedi Aashi , Munro Sarah A. , Pitzen Samuel P. , Ling Alex , Zhang Weijie , Mentzer Josh , Ku Sheng-Yu , Puca Loredana , Zhu Yanyun , Bergman Andries M. , Severson Tesa M. , Forster Colleen , Liu Yuzhen , Hildebrand Jacob , Daniel Mark , Wang Ting-You , Selth Luke A. , Hickey Theresa , Zoubeidi Amina , Gleave Martin , Bareja Rohan , Sboner Andrea , Tilley Wayne , Carroll Jason S. , Tan Winston , Kohli Manish , Yang Rendong , Hsieh Andrew C. , Murugan Paari , Zwart Wilbert , Beltran Himisha , Huang R. Stephanie , Dehm Scott M. 
Published: November 2021

AbstractEndocrine therapies for prostate cancer inhibit the androgen receptor (AR) transcription factor. In most cases, AR activity resumes during therapy and drives progression to castration-resistant prostate cancer (CRPC). However, therapy can also promote lineage plasticity and select for AR-independent phenotypes that are uniformly lethal. Here, we demonstrate the stem cell transcription factor Krüppel-like factor 5 (KLF5) is low or absent in prostate cancers prior to endocrine therapy, but induced in a subset of CRPC, including CRPC displaying lineage plasticity. KLF5 and AR physically interact on chromatin and drive opposing transcriptional programs, with KLF5 promoting cellular migration, anchorage-independent growth, and basal epithelial cell phenotypes. We identify ERBB2 as a point of transcriptional convergence displaying activation by KLF5 and repression by AR. ERBB2 inhibitors preferentially block KLF5-driven oncogenic phenotypes. These findings implicate KLF5 as an oncogene that can be upregulated in CRPC to oppose AR activities and promote lineage plasticity.
Elevating density functional theory to chemical accuracy for water simulations through a density-corrected many-body formalism
Authors: Dasgupta Saswata , Lambros Eleftherios , Perdew John P. , Paesani Francesco 
Published: November 2021

AbstractDensity functional theory (DFT) has been extensively used to model the properties of water. Albeit maintaining a good balance between accuracy and efficiency, no density functional has so far achieved the degree of accuracy necessary to correctly predict the properties of water across the entire phase diagram. Here, we present density-corrected SCAN (DC-SCAN) calculations for water which, minimizing density-driven errors, elevate the accuracy of the SCAN functional to that of “gold standard” coupled-cluster theory. Building upon the accuracy of DC-SCAN within a many-body formalism, we introduce a data-driven many-body potential energy function, MB-SCAN(DC), that quantitatively reproduces coupled cluster reference values for interaction, binding, and individual many-body energies of water clusters. Importantly, molecular dynamics simulations carried out with MB-SCAN(DC) also reproduce the properties of liquid water, which thus demonstrates that MB-SCAN(DC) is effectively the first DFT-based model that correctly describes water from the gas to the liquid phase.
MOFs-based nanoagent enables dual mitochondrial damage in synergistic antitumor therapy via oxidative stress and calcium overload
Authors: Bao Weier , Liu Ming , Meng Jiaqi , Liu Siyuan , Wang Shuang , Jia Rongrong , Wang Yugang , Ma Guanghui , Wei Wei , Tian Zhiyuan 
Published: November 2021

AbstractTargeting subcellular organelle with multilevel damage has shown great promise for antitumor therapy. Here, we report a core-shell type of nanoagent with iron (III) carboxylate metal-organic frameworks (MOFs) as shell while upconversion nanoparticles (UCNPs) as core, which enables near-infrared (NIR) light-triggered synergistically reinforced oxidative stress and calcium overload to mitochondria. The folate decoration on MOFs shells enables efficient cellular uptake of nanoagents. Based on the upconversion ability of UCNPs, NIR light mediates Fe3+-to-Fe2+ reduction and simultaneously activates the photoacid generator (pHP) encapsulated in MOFs cavities, which enables release of free Fe2+ and acidification of intracellular microenvironment, respectively. The overexpressed H2O2 in mitochondria, highly reactive Fe2+ and acidic milieu synergistically reinforce Fenton reactions for producing lethal hydroxyl radicals (•OH) while plasma photoacidification inducing calcium influx, leading to mitochondria calcium overload. The dual-mitochondria-damage-based therapeutic potency of the nanoagent has been unequivocally confirmed in cell- and patient-derived tumor xenograft models in vivo.
Faradaic junction and isoenergetic charge transfer mechanism on semiconductor/semiconductor interfaces
Authors: Chen Mingzhi , Dong Hongzheng , Xue Mengfan , Yang Chunsheng , Wang Pin , Yang Yanliang , Zhu Heng , Wu Congping , Yao Yingfang , Luo Wenjun , Zou Zhigang 
Published: November 2021

AbstractEnergy band alignment theory has been widely used to understand interface charge transfer in semiconductor/semiconductor heterojunctions for solar conversion or storage, such as quantum-dot sensitized solar cells, perovskite solar cells and photo(electro)catalysis. However, abnormally high open-circuit voltage and charge separation efficiency in these applications cannot be explained by the classic theory. Here, we demonstrate a Faradaic junction theory with isoenergetic charge transfer at semiconductor/semiconductor interface. Such Faradaic junction involves coupled electron and ion transfer, which is substantively different from the classic band alignment theory only involving electron transfer. The Faradaic junction theory can be used to explain these abnormal results in previous studies. Moreover, the characteristic of zero energy loss of charge transfer in a Faradaic junction also can provide a possibility to design a solar conversion device with a large open-circuit voltage beyond the Shockley-Queisser limit by the band alignment theory.
Photo-induced copper-catalyzed sequential 1,n-HAT enabling the formation of cyclobutanols
Authors: Cao Zhusong , Li Jianye , Zhang Guozhu 
Published: November 2021

AbstractCyclobutanols are privileged cyclic skeletons in natural products and synthetic building blocks. C(sp3)−H functionalization is a prolonged challenge in organic synthesis. The synthesis of cyclobutanols through double C(sp3)-H bond functionalization remains elusive. Here we report the efficient synthesis of cyclobutanols through intermolecular radical [3 + 1] cascade cyclization, involving the functionalization of two C − H bonds through sequential hydrogen atom transfer. The copper complex reduces the iodomethylsilyl alcohols efficiently under blue-light irradiation to initiate the tandem transformation. The mild reaction tolerates a broad range of functional groups and allows for the facile generation of elaborate polycyclic structures.
Magnitude and nucleation time of the 2017 Pohang Earthquake point to its predictable artificial triggering
Authors: Shapiro Serge A. , Kim Kwang-Hee , Ree Jin-Han 
Published: November 2021

AbstractA damaging Mw5.5 earthquake occurred at Pohang, South Korea, in 2017, after stimulating an enhanced geothermal system by borehole fluid injections. The earthquake was likely triggered by these operations. Current approaches for predicting maximum induced earthquake magnitude ($${M}_{\max }$$

M

max

) consider the volume of the injected fluid as the main controlling factor. However, these approaches are unsuccessful in predicting earthquakes, such as the Pohang one. Here we analyse the case histories of induced earthquakes, and find that $${M}_{\max }$$

M

max

scales with the logarithm of the elapsed time from the beginning of the fluid injection to the earthquake occurrence. This is also the case for the Pohang Earthquake. Its significant probability was predictable. These results validate an alternative to predicting $${M}_{\max }$$

M

max

. It is to monitor the exceedance probability of an assumed $${M}_{\max }$$

M

max

in real time by monitoring the seismogenic index, a quantity that characterizes the intensity of the fluid-induced seismicity per unit injected volume.
Gold nanoparticles enhance antibody effect through direct cancer cell cytotoxicity by differential regulation of phagocytosis
Authors: Fan Linyang , Wang Weizhi , Wang Zihua , Zhao Minzhi 
Published: November 2021

AbstractRamucirumab is the first FDA-approved monotherapy for advanced gastric cancer. In this study, Ramucirumab (Ab) is attached to gold nanoparticles to enhance uptake efficiency. Gold nanoparticles can induce direct cytotoxic effects to cancer cells in the presence of Ab, while individual Ab or gold nanoparticles don’t have such an effective anticancer effect even at extremely high concentrations. Proteomic and transcriptomic analyses reveal this direct cytotoxicity is derived predominantly from Ab-mediated phagocytosis. High affinity immunoglobulin gamma Fc receptor I shows differential up-regulation in gastric cancer cells treated by these nanodrugs compared with Ab, especially for Ab with gold nanorods. Simplified and powerful designs of smart nanoparticles are highly desired for clinical application. The enhancement of Ab accumulation with a simple composition, combined with direct cytotoxic effects specific to cancer cells brought improved therapeutic effects in vivo compared with Ab, which can promote further clinical application of gold nanomaterials in the diagnosis and therapeutics of gastric cancer.
Fast wide-field upconversion luminescence lifetime thermometry enabled by single-shot compressed ultrahigh-speed imaging
Authors: Liu Xianglei , Skripka Artiom , Lai Yingming , Jiang Cheng , Liu Jingdan , Vetrone Fiorenzo , Liang Jinyang 
Published: November 2021

AbstractPhotoluminescence lifetime imaging of upconverting nanoparticles is increasingly featured in recent progress in optical thermometry. Despite remarkable advances in photoluminescent temperature indicators, existing optical instruments lack the ability of wide-field photoluminescence lifetime imaging in real time, thus falling short in dynamic temperature mapping. Here, we report video-rate upconversion temperature sensing in wide field using single-shot photoluminescence lifetime imaging thermometry (SPLIT). Developed from a compressed-sensing ultrahigh-speed imaging paradigm, SPLIT first records wide-field luminescence intensity decay compressively in two views in a single exposure. Then, an algorithm, built upon the plug-and-play alternating direction method of multipliers, is used to reconstruct the video, from which the extracted lifetime distribution is converted to a temperature map. Using the core/shell NaGdF4:Er3+,Yb3+/NaGdF4 upconverting nanoparticles as the lifetime-based temperature indicators, we apply SPLIT in longitudinal wide-field temperature monitoring beneath a thin scattering medium. SPLIT also enables video-rate temperature mapping of a moving biological sample at single-cell resolution.
Serum apolipoprotein A-I potentiates the therapeutic efficacy of lysocin E against Staphylococcus aureus
Authors: Hamamoto Hiroshi , Panthee Suresh , Paudel Atmika , Ishii Kenichi , Yasukawa Jyunichiro , Su Jie , Miyashita Atsushi , Itoh Hiroaki , Tokumoto Kotaro , Inoue Masayuki , Sekimizu Kazuhisa 
Published: November 2021

AbstractLysocin E is a lipopeptide with antibiotic activity against methicillin-resistant Staphylococcus aureus. For unclear reasons, the antibacterial activity of lysocin E in a mouse systemic infection model is higher than expected from in vitro results, and the in vitro activity is enhanced by addition of bovine serum. Here, we confirm that serum from various species, including humans, increases lysocin E antimicrobial activity, and identify apolipoprotein A-I (ApoA-I) as an enhancing factor. ApoA-I increases the antibacterial activity of lysocin E when added in vitro, and the antibiotic displays reduced activity in ApoA-I gene knockout mice. Binding of ApoA-I to lysocin E is enhanced by lipid II, a cell-wall synthesis precursor found in the bacterial membrane. Thus, the antimicrobial activity of lysocin E is potentiated through interactions with host serum proteins and microbial components.
Spatial coherence of room-temperature monolayer WSe2 exciton-polaritons in a trap
Authors: Shan Hangyong , Lackner Lukas , Han Bo , Sedov Evgeny , Rupprecht Christoph , Knopf Heiko , Eilenberger Falk , Beierlein Johannes , Kunte Nils , Esmann Martin , Yumigeta Kentaro , Watanabe Kenji , Taniguchi Takashi , Klembt Sebastian , Höfling Sven , Kavokin Alexey V. , Tongay Sefaattin , Schneider Christian , Antón-Solanas Carlos 
Published: November 2021

AbstractThe emergence of spatial and temporal coherence of light emitted from solid-state systems is a fundamental phenomenon intrinsically aligned with the control of light-matter coupling. It is canonical for laser oscillation, emerges in the superradiance of collective emitters, and has been investigated in bosonic condensates of thermalized light, as well as exciton-polaritons. Our room temperature experiments show the strong light-matter coupling between microcavity photons and excitons in atomically thin WSe2. We evidence the density-dependent expansion of spatial and temporal coherence of the emitted light from the spatially confined system ground-state, which is accompanied by a threshold-like response of the emitted light intensity. Additionally, valley-physics is manifested in the presence of an external magnetic field, which allows us to manipulate K and K’ polaritons via the valley-Zeeman-effect. Our findings validate the potential of atomically thin crystals as versatile components of coherent light-sources, and in valleytronic applications at room temperature.
A Brainstem reticulotegmental neural ensemble drives acoustic startle reflexes
Authors: Guo Weiwei , Fan Sijia , Xiao Dan , Dong Hui , Xu Guangwei , Wan Zhikun , Ma Yuqian , Wang Zhen , Xue Tian , Zhou Yifeng , Li Yulong , Xiong Wei 
Published: November 2021

AbstractThe reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhibition of the RtTg glutamatergic neurons decreases the ASR amplitudes. Viral tracing reveals an ASR neural circuit that the cochlear nucleus carrying auditory information sends direct excitatory innervations to the RtTg glutamatergic neurons, which in turn project to spinal motor neurons. Together, our findings describe a functional role of RtTg and its related neural circuit in startle reflexes, and demonstrate how the RF connects auditory system with motor functions.
Supramolecular tessellations by the exo-wall interactions of pagoda[4]arene
Authors: Han Xiao-Ni , Han Ying , Chen Chuan-Feng 
Published: November 2021

AbstractSupramolecular tessellation has gained increasing interest in supramolecular chemistry for its structural aesthetics and potential applications in optics, magnetics and catalysis. In this work, a new kind of supramolecular tessellations (STs) have been fabricated by the exo-wall interactions of pagoda[4]arene (P4). ST with rhombic tiling pattern was first constructed by P4 itself through favorable π···π interactions between anthracene units of adjacent P4. Notably, various highly ordered STs with different tiling patterns have been fabricated based on exo-wall charge transfer interactions between electron-rich P4 and electron-deficient guests including 1,4-dinitrobenzene, terephthalonitrile and tetrafluoroterephthalonitrile. Interestingly, solvent modulation and guest selection played a crucial role in controlling the molecular arrangements in the co-crystal superstructures. This work not only proves that P4 is an excellent macrocyclic building block for the fabrication of various STs, but also provides a new perspective and opportunity for the design and construction of supramolecular two-dimensional organic materials.
Constitutive activation of the PI3K-Akt-mTORC1 pathway sustains the m.3243 A > G mtDNA mutation
Authors: Chung Chih-Yao , Singh Kritarth , Kotiadis Vassilios N. , Valdebenito Gabriel E. , Ahn Jee Hwan , Topley Emilie , Tan Joycelyn , Andrews William D. , Bilanges Benoit , Pitceathly Robert D. S. , Szabadkai Gyorgy , Yuneva Mariia , Duchen Michael R. 
Published: November 2021

AbstractMutations of the mitochondrial genome (mtDNA) cause a range of profoundly debilitating clinical conditions for which treatment options are very limited. Most mtDNA diseases show heteroplasmy – tissues express both wild-type and mutant mtDNA. While the level of heteroplasmy broadly correlates with disease severity, the relationships between specific mtDNA mutations, heteroplasmy, disease phenotype and severity are poorly understood. We have carried out extensive bioenergetic, metabolomic and RNAseq studies on heteroplasmic patient-derived cells carrying the most prevalent disease related mtDNA mutation, the m.3243 A > G. These studies reveal that the mutation promotes changes in metabolites which are associated with the upregulation of the PI3K-Akt-mTORC1 axis in patient-derived cells and tissues. Remarkably, pharmacological inhibition of PI3K, Akt, or mTORC1 reduced mtDNA mutant load and partially rescued cellular bioenergetic function. The PI3K-Akt-mTORC1 axis thus represents a potential therapeutic target that may benefit people suffering from the consequences of the m.3243 A > G mutation.
Tuning structural isomers of phenylenediammonium to afford efficient and stable perovskite solar cells and modules
Authors: Liu Cheng , Yang Yi , Rakstys Kasparas , Mahata Arup , Franckevicius Marius , Mosconi Edoardo , Skackauskaite Raminta , Ding Bin , Brooks Keith G. , Usiobo Onovbaramwen Jennifer , Audinot Jean-Nicolas , Kanda Hiroyuki , Driukas Simonas , Kavaliauskaite Gabriele , Gulbinas Vidmantas , Dessimoz Marc , Getautis Vytautas , De Angelis Filippo , Ding Yong , Dai Songyuan , Dyson Paul J. , Nazeeruddin Mohammad Khaja 
Published: November 2021

AbstractOrganic halide salt passivation is considered to be an essential strategy to reduce defects in state-of-the-art perovskite solar cells (PSCs). This strategy, however, suffers from the inevitable formation of in-plane favored two-dimensional (2D) perovskite layers with impaired charge transport, especially under thermal conditions, impeding photovoltaic performance and device scale-up. To overcome this limitation, we studied the energy barrier of 2D perovskite formation from ortho-, meta- and para-isomers of (phenylene)di(ethylammonium) iodide (PDEAI2) that were designed for tailored defect passivation. Treatment with the most sterically hindered ortho-isomer not only prevents the formation of surficial 2D perovskite film, even at elevated temperatures, but also maximizes the passivation effect on both shallow- and deep-level defects. The ensuing PSCs achieve an efficiency of 23.9% with long-term operational stability (over 1000 h). Importantly, a record efficiency of 21.4% for the perovskite module with an active area of 26 cm2 was achieved.
Shape shifter: redirection of prolate phage capsid assembly by staphylococcal pathogenicity islands
Authors: Hawkins N’Toia C. , Kizziah James L. , Penadés José R. , Dokland Terje 
Published: November 2021

AbstractStaphylococcus aureus pathogenicity islands (SaPIs) are molecular parasites that hijack helper phages for their transfer. SaPIbov5, the prototypical member of a family of cos type SaPIs, redirects the assembly of ϕ12 helper capsids from prolate to isometric. This size and shape shift is dependent on the SaPIbov5-encoded protein Ccm, a homolog of the ϕ12 capsid protein (CP). Using cryo-electron microscopy, we have determined structures of prolate ϕ12 procapsids and isometric SaPIbov5 procapsids. ϕ12 procapsids have icosahedral end caps with Tend = 4 architecture and a Tmid = 14 cylindrical midsection, whereas SaPIbov5 procapsids have T = 4 icosahedral architecture. We built atomic models for CP and Ccm, and show that Ccm occupies the pentameric capsomers in the isometric SaPIbov5 procapsids, suggesting that preferential incorporation of Ccm pentamers prevents the cylindrical midsection from forming. Our results highlight that pirate elements have evolved diverse mechanisms to suppress phage multiplication, including the acquisition of phage capsid protein homologs.