bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rab4A-directed endosome traffic shapes pro-inflammatory mitochondrial metabolism in T cells via mitophagy, CD98 expression, and kynurenine-sensitive mTOR activation
Authors: Huang Nick , Winans Thomas , Wyman Brandon , Oaks Zachary , Faludi Tamas , Choudhary Gourav , Lai Zhi-Wei , Lewis Joshua , Beckford Miguel , Duarte Manuel , Krakko Daniel , Patel Akshay , Park Joy , Caza Tiffany , Sadeghzadeh Mahsa , Morel Laurence , Haas Mark , Middleton Frank , Banki Katalin , Perl Andras 
Published: March 2024

AbstractActivation of the mechanistic target of rapamycin (mTOR) is a key metabolic checkpoint of pro-inflammatory T-cell development that contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), however, the underlying mechanisms remain poorly understood. Here, we identify a functional role for Rab4A-directed endosome traffic in CD98 receptor recycling, mTOR activation, and accumulation of mitochondria that connect metabolic pathways with immune cell lineage development and lupus pathogenesis. Based on integrated analyses of gene expression, receptor traffic, and stable isotope tracing of metabolic pathways, constitutively active Rab4AQ72L exerts cell type-specific control over metabolic networks, dominantly impacting CD98-dependent kynurenine production, mTOR activation, mitochondrial electron transport and flux through the tricarboxylic acid cycle and thus expands CD4+ and CD3+CD4−CD8− double-negative T cells over CD8+ T cells, enhancing B cell activation, plasma cell development, antinuclear and antiphospholipid autoantibody production, and glomerulonephritis in lupus-prone mice. Rab4A deletion in T cells and pharmacological mTOR blockade restrain CD98 expression, mitochondrial metabolism and lineage skewing and attenuate glomerulonephritis. This study identifies Rab4A-directed endosome traffic as a multilevel regulator of T cell lineage specification during lupus pathogenesis.
BET inhibitors drive Natural Killer activation in non-small cell lung cancer via BRD4 and SMAD3
Authors: Reggiani Francesca , Talarico Giovanna , Gobbi Giulia , Sauta Elisabetta , Torricelli Federica , Manicardi Veronica , Zanetti Eleonora , Orecchioni Stefania , Falvo Paolo , Piana Simonetta , Lococo Filippo , Paci Massimiliano , Bertolini Francesco , Ciarrocchi Alessia , Sancisi Valentina 
Published: March 2024

AbstractNon-small-cell lung carcinoma (NSCLC) is the most common lung cancer and one of the pioneer tumors in which immunotherapy has radically changed patients’ outcomes. However, several issues are emerging and their implementation is required to optimize immunotherapy-based protocols. In this work, we investigate the ability of the Bromodomain and Extra-Terminal protein inhibitors (BETi) to stimulate a proficient anti-tumor immune response toward NSCLC. By using in vitro, ex-vivo, and in vivo models, we demonstrate that these epigenetic drugs specifically enhance Natural Killer (NK) cell cytotoxicity. BETi down-regulate a large set of NK inhibitory receptors, including several immune checkpoints (ICs), that are direct targets of the transcriptional cooperation between the BET protein BRD4 and the transcription factor SMAD3. Overall, BETi orchestrate an epigenetic reprogramming that leads to increased recognition of tumor cells and the killing ability of NK cells. Our results unveil the opportunity to exploit and repurpose these drugs in combination with immunotherapy.
Deciphering the critical role of interstitial volume in glassy sulfide superionic conductors
Authors: Su Han , Zhong Yu , Wang Changhong , Liu Yu , Hu Yang , Li Jingru , Wang Minkang , Jiao Longan , Zhou Ningning , Xiao Bing , Wang Xiuli , Sun Xueliang , Tu Jiangping 
Published: March 2024

AbstractSulfide electrolytes represent a crucial category of superionic conductors for all-solid-state lithium metal batteries. Among sulfide electrolytes, glassy sulfide is highly promising due to its long-range disorder and grain-boundary-free nature. However, the lack of comprehension regarding glass formation chemistry has hindered their progress. Herein, we propose interstitial volume as the decisive factor influencing halogen dopant solubility within a glass matrix. We engineer a Li3PS4-Li4SiS4 complex structure within the sulfide glassy network to facilitate the release of interstitial volume. Consequently, we increase the dissolution capacity of LiI to 40 mol% in 75Li2S-25P2S5 glass. The synthesized glass exhibits one of the highest ionic conductivities among reported glass sulfides. Furthermore, we develop a glassy/crystalline composite electrolyte to mitigate the shortcomings of argyrodite-type sulfides by utilizing our synthesized glass as the filler. The composite electrolytes effectively mitigate Li intrusion. This work unveils a protocol for the dissolution of halogen dopants in glass electrolytes.
Ultra-photostable small-molecule dyes facilitate near-infrared biophotonics
Authors: Yan Kui , Hu Zhubin , Yu Peng , He Zuyang , Chen Ying , Chen Jiajian , Sun Haitao , Wang Shangfeng , Zhang Fan 
Published: March 2024

AbstractLong-wavelength, near-infrared small-molecule dyes are attractive in biophotonics. Conventionally, they rely on expanded aromatic structures for redshift, which comes at the cost of application performance such as photostability, cell permeability, and functionality. Here, we report a ground-state antiaromatic strategy and showcase the concise synthesis of 14 cationic aminofluorene dyes with mini structures (molecular weights: 299–504 Da) and distinct spectra covering 700–1600 nm. Aminofluorene dyes are cell-permeable and achieve rapid renal clearance via a simple 44 Da carboxylation. This accelerates optical diagnostics of renal injury by 50 min compared to existing macromolecular approaches. We develop a compact molecular sensing platform for in vivo intracellular sensing, and demonstrate the versatile applications of these dyes in multispectral fluorescence and optoacoustic imaging. We find that aromaticity reversal upon electronic excitation, as indicated by magnetic descriptors, not only reduces the energy bandgap but also induces strong vibronic coupling, resulting in ultrafast excited-state dynamics and unparalleled photostability. These results support the argument for ground-state antiaromaticity as a useful design rule of dye development, enabling performances essential for modern biophotonics.
Nucleic-acid-base photofunctional cocrystal for information security and antimicrobial applications
Authors: Xu Wenqing , Huang Guanheng , Yang Zhan , Deng Ziqi , Zhou Chen , Li Jian-An , Li Ming-De , Hu Tao , Tang Ben Zhong , Phillips David Lee 
Published: March 2024

AbstractCocrystal engineering is an efficient and simple strategy to construct functional materials, especially for the exploitation of novel and multifunctional materials. Herein, we report two kinds of nucleic-acid-base cocrystal systems that imitate the strong hydrogen bond interactions constructed in the form of complementary base pairing. The two cocrystals studied exhibit different colors of phosphorescence from their monomeric counterparts and show the feature of rare high-temperature phosphorescence. Mechanistic studies reveal that the strong hydrogen bond network stabilizes the triplet state and suppresses non-radiative transitions, resulting in phosphorescence even at 425 K. Moreover, the isolation effects of the hydrogen bond network regulate the interactions between the phosphor groups, realizing the manipulation from aggregation to single-molecule phosphorescence. Benefiting from the long-lived triplet state with a high quantum yield, the generation of reactive oxygen species by energy transfer is also available to utilize for some applications such as in photodynamic therapy and broad-spectrum microbicidal effects. In vitro experiments show that the cocrystals efficiently kill bacteria on a tooth surface and significantly help prevent dental caries. This work not only provides deep insight into the relationship of the structure-properties of cocrystal systems, but also facilitates the design of multifunctional cocrystal materials and enriches their potential applications.
Multipeptide vaccines for melanoma in the adjuvant setting: long-term survival outcomes and post-hoc analysis of a randomized phase II trial
Authors: Ninmer Emily K. , Zhu Hong , Chianese-Bullock Kimberly A. , von Mehren Margaret , Haas Naomi B. , Ross Merrick I. , Dengel Lynn T. , Slingluff Craig L. 
Published: March 2024

AbstractThe critical roles of CD4+ T cells have been understudied for cancer vaccines. Here we report long-term clinical outcomes of a randomized multicenter phase II clinical trial (NCT00118274), where patients with high-risk melanoma received a multipeptide vaccine targeting CD8+ T cells (12MP) and were randomized to receive either of two vaccines for CD4+ (helper) T cells: 6MHP (6 melanoma-specific helper peptides), or tet (a nonspecific helper peptide from tetanus toxoid). Cyclophosphamide (Cy) pre-treatment was also assessed. Primary outcomes for T cell responses to 12MP, 6MHP, and tet were previously reported, suggesting immunogenicity of both vaccines but that CD8 T cell responses to 12MP were lower when tet was replaced with 6MHP. Here, in post-hoc analyses, we report durable prolongation of overall survival by adding 6MHP instead of tet. That benefit was experienced only by male patients. A favorable interaction of 6MHP and Cy is also suggested. Multivariable Cox regression analysis of the intent-to-treat population identify vaccine arm (12MP + 6MHP+Cy) and patient sex (male) as the two significant predictors of enhanced survival. These findings support the value of adding cognate T cell help to cancer vaccines and also suggest a need to assess the impact of patient sex on immune therapy outcomes.
Single cell deciphering of progression trajectories of the tumor ecosystem in head and neck cancer
Authors: Liu Z. L. , Meng X. Y. , Bao R. J. , Shen M. Y. , Sun J. J. , Chen W. D. , Liu F. , He Y. 
Published: March 2024

AbstractHead and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.
Niche availability and competitive loss by facilitation control proliferation of bacterial strains intended for soil microbiome interventions
Authors: Čaušević Senka , Dubey Manupriyam , Morales Marian , Salazar Guillem , Sentchilo Vladimir , Carraro Nicolas , Ruscheweyh Hans-Joachim , Sunagawa Shinichi , van der Meer Jan Roelof 
Published: March 2024

AbstractMicrobiome engineering – the targeted manipulation of microbial communities – is considered a promising strategy to restore ecosystems, but experimental support and mechanistic understanding are required. Here, we show that bacterial inoculants for soil microbiome engineering may fail to establish because they inadvertently facilitate growth of native resident microbiomes. By generating soil microcosms in presence or absence of standardized soil resident communities, we show how different nutrient availabilities limit outgrowth of focal bacterial inoculants (three Pseudomonads), and how this might be improved by adding an artificial, inoculant-selective nutrient niche. Through random paired interaction assays in agarose micro-beads, we demonstrate that, in addition to direct competition, inoculants lose competitiveness by facilitating growth of resident soil bacteria. Metatranscriptomics experiments with toluene as selective nutrient niche for the inoculant Pseudomonas veronii indicate that this facilitation is due to loss and uptake of excreted metabolites by resident taxa. Generation of selective nutrient niches for inoculants may help to favor their proliferation for the duration of their intended action while limiting their competitive loss.
Serotonergic modulation of vigilance states in zebrafish and mice
Authors: Zhao Yang , Huang Chun-Xiao , Gu Yiming , Zhao Yacong , Ren Wenjie , Wang Yutong , Chen Jinjin , Guan Na N. , Song Jianren 
Published: March 2024

AbstractVigilance refers to being alertly watchful or paying sustained attention to avoid potential threats. Animals in vigilance states reduce locomotion and have an enhanced sensitivity to aversive stimuli so as to react quickly to dangers. Here we report that an unconventional 5-HT driven mechanism operating at neural circuit level which shapes the internal state underlying vigilance behavior in zebrafish and male mice. The neural signature of internal vigilance state was characterized by persistent low-frequency high-amplitude neuronal synchrony in zebrafish dorsal pallium and mice prefrontal cortex. The neuronal synchronization underlying vigilance was dependent on intense release of 5-HT induced by persistent activation of either DRN 5-HT neuron or local 5-HT axon terminals in related brain regions via activation of 5-HTR7. Thus, we identify a mechanism of vigilance behavior across species that illustrates the interplay between neuromodulators and neural circuits necessary to shape behavior states.
Enhanced CO2 uptake of the coastal ocean is dominated by biological carbon fixation
Authors: Mathis Moritz , Lacroix Fabrice , Hagemann Stefan , Nielsen David Marcolino , Ilyina Tatiana , Schrum Corinna 
Published: March 2024

AbstractObservational reconstructions indicate a contemporary increase in coastal ocean CO2 uptake. However, the mechanisms and their relative importance in driving this globally intensifying absorption remain unclear. Here we integrate coastal carbon dynamics in a global model via regional grid refinement and enhanced process representation. We find that the increasing coastal CO2 sink is primarily driven by biological responses to climate-induced changes in circulation (36%) and increasing riverine nutrient loads (23%), together exceeding the ocean CO2 solubility pump (41%). The riverine impact is mediated by enhanced export of organic carbon across the shelf break, thereby adding to the carbon enrichment of the open ocean. The contribution of biological carbon fixation increases as the seawater capacity to hold CO2 decreases under continuous climate change and ocean acidification. Our seamless coastal ocean integration advances carbon cycle model realism, which is relevant for addressing impacts of climate change mitigation efforts.
Predicting quantum emitter fluctuations with time-series forecasting models
Authors: Ramezani Fereshteh , Strasbourg Matthew , Parvez Sheikh , Saxena Ravindra , Jariwala Deep , Borys Nicholas J. , Whitaker Bradley M. 
Published: March 2024

Abstract2D materials have important fundamental properties allowing for their use in many potential applications, including quantum computing. Various Van der Waals materials, including Tungsten disulfide (WS2), have been employed to showcase attractive device applications such as light emitting diodes, lasers and optical modulators. To maximize the utility and value of integrated quantum photonics, the wavelength, polarization and intensity of the photons from a quantum emission (QE) must be stable. However, random variation of emission energy, caused by the inhomogeneity in the local environment, is a major challenge for all solid-state single photon emitters. In this work, we assess the random nature of the quantum fluctuations, and we present time series forecasting deep learning models to analyse and predict QE fluctuations for the first time. Our trained models can roughly follow the actual trend of the data and, under certain data processing conditions, can predict peaks and dips of the fluctuations. The ability to anticipate these fluctuations will allow physicists to harness quantum fluctuation characteristics to develop novel scientific advances in quantum computing that will greatly benefit quantum technologies.
Activated fibroblasts modify keratinocyte stem niche through TET1 and IL-6 to promote their rapid transformation in a mouse model of prenatal arsenic exposure
Authors: Chauhan Anchal , Gangopadhyay Siddhartha , Koshta Kavita , Singh Sukhveer , Singh Dhirendra , Srivastava Vikas 
Published: March 2024

AbstractEarly life exposure to environmental pollutants such as arsenic (As) can increase the risk of cancers in the offspring. In an earlier study, we showed that only prenatal As exposure significantly increases epidermal stem cell proliferation and accelerates skin tumorigenesis in BALB/c mouse offspring. In the present work, we have examined the role of As-conditioned dermal fibroblasts (DFs) in creating pro-tumorigenic niches for Keratinocyte stem cells (KSCs) in the offspring. DFs isolated from prenatally exposed animals showed increased levels of activation markers (α-SMA, Fibronectin, Collagen IV), induction of ten-eleven translocation methylcytosine dioxygenase 1(TET1), and secreted high levels of niche modifying IL-6. This led to enhanced proliferation, migration, and survival of KSCs. Increased IL-6 production in As-conditioned fibroblast was driven through TET1 mediated 5-mC to 5-hmC conversion at -698/-526 and -856/-679 region on its promoter. IL-6 further acted through downstream activation of JAK2-STAT3 signaling, promoting epithelial-to-mesenchymal transition (EMT) in KSCs. Inhibition of pSTAT3 induced by IL-6 reduced the EMT process in KSCs resulting in a significant decrease in their proliferation, migration, and colony formation. Our results indicate that IL-6 produced by prenatally conditioned fibroblasts plays a major role in regulating the KSC niche and promoting skin tumor development in As-exposed offspring.
Synthesis of eco-friendly layered double hydroxide and nanoemulsion for jasmine and peppermint oils and their larvicidal activities against Culex pipiens Linnaeus
Authors: Radwan Ibrahim Taha , Khater Hanem F. , Mohammed Shaimaa H. , Khalil Abdelwahab , Farghali Mohamed A. , Mahmoud Mohammed G. , Selim Abdelfattah , Manaa Eman A. , Bagato Noha , Baz Mohamed M. 
Published: March 2024

AbstractMosquito-borne diseases represent a growing health challenge over time. Numerous potential phytochemicals are target-specific, biodegradable, and eco-friendly. The larvicidal activity of essential oils, a jasmine blend consisting of Jasmine oil and Azores jasmine (AJ) (Jasminum sambacandJasminum azoricum) and peppermint (PP)Mentha arvensisand their nanoformulations against 2nd and 4th instar larvae ofCulex pipiens, was evaluated after subjecting to different concentrations (62.5, 125, 250, 500, 1000, and 2000 ppm). Two forms of phase-different nanodelivery systems of layered double hydroxide LDH and oil/water nanoemulsions were formulated. The synthesized nanoemulsions showed particle sizes of 199 and 333 nm for AJ-NE and PP-NE, with a polydispersity index of 0.249 and 0.198, respectively. Chemical and physiochemical analysis of TEM, SEM, XRD, zeta potential, drug loading capacity, and drug release measurements were done to confirm the synthesis and loading efficiencies of essential oils' active ingredients. At high concentrations of AJ and PP nanoemulsions (2000 ppm), O/W nanoemulsions showed higher larval mortality than both LDH conjugates and crude oils. The mortality rate reached 100% for 2nd and 4th instar larvae. The relative toxicities revealed that PP nanoemulsion (MA-NE) was the most effective larvicide, followed by AJ nanoemulsion (AJ-NE). There was a significant increase in defensive enzymes, phenoloxidase, and α and β-esterase enzymes in the treated groups. After treatment of L4 with AJ, AJ-NE, PP, and PP-NE, the levels of phenoloxidase were 545.67, 731.00, 700.00, and 799.67 u/mg, respectively, compared with control 669.67 u/mg. The activity levels of α-esterase were 9.71, 10.32, 8.91, and 10.55 mg α-naphthol/min/mg protein, respectively. It could be concluded that the AJ-NE and PP-NE nanoformulations have promising larvicidal activity and could act as safe and effective alternatives to chemical insecticides.
Absolute and relative disparity mechanisms revealed by an equivalent noise analysis
Authors: Ding Jian , Lu Hilary H. , Levi Dennis M. 
Published: March 2024

AbstractThe precision of stereopsis and vergence are ultimately limited by internal binocular disparity noise. Here we propose an equivalent noise model with both global and local internal disparity noises to provide a unified explanation of both absolute and relative disparity thresholds. To test this model, we developed a psychophysical procedure to measure the equivalent internal disparity noise by adding external disparity noise to random-Gabor-patch stereograms. We used the method of constant stimuli to measure the minimum and maximum disparity thresholds (Dmin and Dmax) for both absolute and relative disparity. Consistent with previous studies, we found that Dmin thresholds are substantially worse for absolute disparity than for relative disparity. We tested three relative disparity mechanisms: (1) the difference between the monocular separations of targets projecting to the two eyes; (2) the direct measurement of relative disparity; and (3) the difference of absolute disparities of targets. Computing the difference of absolute disparities when detecting relative disparity, Mechanism 3 cancels global noise, resulting in a much lower relative Dmin threshold, and provides a reasonable fit to the experimental data. We also found that the presence of as much as 2400 arcsec of external disparity noise does not appear to affect the Dmax threshold. This observation suggests that Dmax is implicated in a mechanism that disregards the disparity variance of individual items, relying instead on the average disparity across all items, supporting the depth model proposed in our previous study (Ding & Levi, 2021), which posits distinct mechanisms governing Dmin and Dmax thresholds.