bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rescue of dendritic cells from glycolysis inhibition improves cancer immunotherapy in mice
Authors: Inamdar Sahil , Suresh Abhirami P. , Mangal Joslyn L. , Ng Nathan D. , Sundem Alison , Wu Christopher , Lintecum Kelly , Thumsi Abhirami , Khodaei Taravat , Halim Michelle , Appel Nicole , Jaggarapu Madhan Mohan Chandra Sekhar , Esrafili Arezoo , Yaron Jordan R. , Curtis Marion , Acharya Abhinav P. 
Published: September 2023

AbstractInhibition of glycolysis in immune cells and cancer cells diminishes their activity, and thus combining immunotherapies with glycolytic inhibitors is challenging. Herein, a strategy is presented where glycolysis is inhibited in cancer cells using PFK15 (inhibitor of PFKFB3, rate-limiting step in glycolysis), while simultaneously glycolysis and function is rescued in DCs by delivery of fructose-1,6-biphosphate (F16BP, one-step downstream of PFKFB3). To demonstrate the feasibility of this strategy, vaccine formulations are generated using calcium-phosphate chemistry, that incorporate F16BP, poly(IC) as adjuvant, and phosphorylated-TRP2 peptide antigen and tested in challenging and established YUMM1.1 tumours in immunocompetent female mice. Furthermore, to test the versatility of this strategy, adoptive DC therapy is developed with formulations that incorporate F16BP, poly(IC) as adjuvant and mRNA derived from B16F10 cells as antigens in established B16F10 tumours in immunocompetent female mice. F16BP vaccine formulations rescue DCs in vitro and in vivo, significantly improve the survival of mice, and generate cytotoxic T cell (Tc) responses by elevating Tc1 and Tc17 cells within the tumour. Overall, these results demonstrate that rescuing glycolysis of DCs using metabolite-based formulations can be utilized to generate immunotherapy even in the presence of glycolytic inhibitor.
MAVS integrates glucose metabolism and RIG-I-like receptor signaling
Authors: He Qiao-qiao , Huang Yu , Nie Longyu , Ren Sheng , Xu Gang , Deng Feiyan , Cheng Zhikui , Zuo Qi , Zhang Lin , Cai Huanhuan , Wang Qiming , Wang Fubing , Ren Hong , Yan Huan , Xu Ke , Zhou Li , Lu Mengji , Lu Zhibing , Zhu Ying , Liu Shi 
Published: September 2023

AbstractMAVS is an adapter protein involved in RIG-I-like receptor (RLR) signaling in mitochondria, peroxisomes, and mitochondria-associated ER membranes (MAMs). However, the role of MAVS in glucose metabolism and RLR signaling cross-regulation and how these signaling pathways are coordinated among these organelles have not been defined. This study reports that RLR action drives a switch from glycolysis to the pentose phosphate pathway (PPP) and the hexosamine biosynthesis pathway (HBP) through MAVS. We show that peroxisomal MAVS is responsible for glucose flux shift into PPP and type III interferon (IFN) expression, whereas MAMs-located MAVS is responsible for glucose flux shift into HBP and type I IFN expression. Mechanistically, peroxisomal MAVS interacts with G6PD and the MAVS signalosome forms at peroxisomes by recruiting TNF receptor-associated factor 6 (TRAF6) and interferon regulatory factor 1 (IRF1). By contrast, MAMs-located MAVS interact with glutamine-fructose-6-phosphate transaminase, and the MAVS signalosome forms at MAMs by recruiting TRAF6 and TRAF2. Our findings suggest that MAVS mediates the interaction of RLR signaling and glucose metabolism.
Associations of modern initial antiretroviral therapy regimens with all-cause mortality in people living with HIV in resource-limited settings: a retrospective multicenter cohort study in China
Authors: Wu Xinsheng , Wu Guohui , Ma Ping , Wang Rugang , Li Linghua , Chen Yuanyi , Xu Junjie , Li Yuwei , Li Quanmin , Yang Yuecheng , Wang Lijing , Xin Xiaoli , Qiao Ying , Fu Gengfeng , Huang Xiaojie , Su Bin , Zhang Tong , Wang Hui , Zou Huachun 
Published: September 2023

AbstractDespite the proven virological advantages, there remains some controversy regarding whether first-line integrase strand transfer inhibitors (INSTIs)-based antiretroviral therapy (ART) contributes to reducing mortality of people living with HIV (PLHIV) in clinical practice. Here we report a retrospective study comparing all-cause mortality among PLHIV in China who were on different initial ART regimens (nevirapine, efavirenz, dolutegravir, lopinavir, and others [including darunavir, raltegravie, elvitegravir and rilpivirine]) between 2017 and 2019. A total of 41,018 individuals were included across China, representing 21.3% of newly reported HIV/AIDS cases collectively in the country during this period. Only the differences in all-cause mortality of PLHIV between the efavirenz group and the nevirapine group, the dolutegravir group and the nevirapine group, and the lopinavir group and the nevirapine group, were observed in China. After stratifying the cause of mortality, we found that the differences in mortality between initial ART regimens were mainly observed in AIDS-related mortality.
Anisotropic flexibility and rigidification in a TPE-based Zr-MOFs with scu topology
Authors: Meng Sha-Sha , Xu Ming , Guan Hanxi , Chen Cailing , Cai Peiyu , Dong Bo , Tan Wen-Shu , Gu Yu-Hao , Tang Wen-Qi , Xie Lan-Gui , Yuan Shuai , Han Yu , Kong Xueqian , Gu Zhi-Yuan 
Published: September 2023

AbstractTetraphenylethylene (TPE)-based ligands are appealing for constructing metal-organic frameworks (MOFs) with new functions and responsiveness. Here, we report a non-interpenetrated TPE-based scu Zr-MOF with anisotropic flexibility, that is, Zr-TCPE (H4TCPE = 1,1,2,2-tetra(4-carboxylphenyl)ethylene), remaining two anisotropic pockets. The framework flexibility is further anisotropically rigidified by installing linkers individually at specific pockets. By individually installing dicarboxylic acid L1 or L2 at pocket A or B, the framework flexibility along the b-axis or c-axis is rigidified, and the intermolecular or intramolecular motions of organic ligands are restricted, respectively. Synergistically, with dual linker installation, the flexibility is completely rigidified with the restriction of ligand motion, resulting in MOFs with enhanced stability and improved separation ability. Furthermore, in situ observation of the flipping of the phenyl ring and its rigidification process is made by 2H solid-state NMR. The anisotropic rigidification of flexibility in scu Zr-MOFs guides the directional control of ligand motion for designing stimuli-responsive emitting or efficient separation materials.
Self-adaptive amorphous CoOxCly electrocatalyst for sustainable chlorine evolution in acidic brine
Authors: Xiao Mengjun , Wu Qianbao , Ku Ruiqi , Zhou Liujiang , Long Chang , Liang Junwu , Mavrič Andraž , Li Lei , Zhu Jing , Valant Matjaz , Li Jiong , Zeng Zhenhua , Cui Chunhua 
Published: September 2023

AbstractElectrochemical chlorine evolution reaction is of central importance in the chlor-alkali industry, but the chlorine evolution anode is largely limited by water oxidation side reaction and corrosion-induced performance decay in strong acids. Here we present an amorphous CoOxClycatalyst that has been deposited in situ in an acidic saline electrolyte containing Co2+and Cl-ions to adapt to the given electrochemical condition and exhibits ~100% chlorine evolution selectivity with an overpotential of ~0.1 V at 10 mA cm−2and high stability over 500 h. In situ spectroscopic studies and theoretical calculations reveal that the electrochemical introduction of Cl-prevents the Co sites from charging to a higher oxidation state thus suppressing the O-O bond formation for oxygen evolution. Consequently, the chlorine evolution selectivity has been enhanced on the Cl-constrained Co-O*sites via the Volmer-Heyrovsky pathway. This study provides fundamental insights into how the reactant Cl-itself can work as a promoter toward enhancing chlorine evolution in acidic brine.
Coordinated peptidoglycan synthases and hydrolases stabilize the bacterial cell wall
Authors: Zhang Huan , Venkatesan Srutha , Ng Emily , Nan Beiyan 
Published: September 2023

AbstractPeptidoglycan (PG) defines cell shape and protects bacteria against osmotic stress. The growth and integrity of PG require coordinated actions between synthases that insert new PG strands and hydrolases that generate openings to allow the insertion. However, the mechanisms of their coordination remain elusive. Moenomycin that inhibits a family of PG synthases known as Class-A penicillin-binding proteins (aPBPs), collapses rod shape despite aPBPs being non-essential for rod-like morphology in the bacterium Myxococcus xanthus. Here, we demonstrate that inhibited PBP1a2, an aPBP, accelerates the degradation of cell poles by DacB, a hydrolytic PG peptidase. Moenomycin promotes the binding between DacB and PG and thus reduces the mobility of DacB through PBP1a2. Conversely, DacB also regulates the distribution and dynamics of aPBPs. Our findings clarify the action of moenomycin and suggest that disrupting the coordination between PG synthases and hydrolases could be more lethal than eliminating individual enzymes.
Protein fibers with self-recoverable mechanical properties via dynamic imine chemistry
Authors: Sun Jing , He Haonan , Zhao Kelu , Cheng Wenhao , Li Yuanxin , Zhang Peng , Wan Sikang , Liu Yawei , Wang Mengyao , Li Ming , Wei Zheng , Li Bo , Zhang Yi , Li Cong , Sun Yao , Shen Jianlei , Li Jingjing , Wang Fan , Ma Chao , Tian Yang , Su Juanjuan , Chen Dong , Fan Chunhai , Zhang Hongjie , Liu Kai 
Published: September 2023

AbstractThe manipulation of internal interactions at the molecular level within biological fibers is of particular importance but challenging, severely limiting their tunability in macroscopic performances and applications. It thus becomes imperative to explore new approaches to enhance biological fibers’ stability and environmental tolerance and to impart them with diverse functionalities, such as mechanical recoverability and stimulus-triggered responses. Herein, we develop a dynamic imine fiber chemistry (DIFC) approach to engineer molecular interactions to fabricate strong and tough protein fibers with recoverability and actuating behaviors. The resulting DIF fibers exhibit extraordinary mechanical performances, outperforming many recombinant silks and synthetic polymer fibers. Remarkably, impaired DIF fibers caused by fatigue or strong acid treatment are quickly recovered in water directed by the DIFC strategy. Reproducible mechanical performance is thus observed. The DIF fibers also exhibit exotic mechanical stability at extreme temperatures (e.g., −196 °C and 150 °C). When triggered by humidity, the DIFC endows the protein fibers with diverse actuation behaviors, such as self-folding, self-stretching, and self-contracting. Therefore, the established DIFC represents an alternative strategy to strengthen biological fibers and may pave the way for their high-tech applications.
Reversal of trends in global fine particulate matter air pollution
Authors: Li Chi , van Donkelaar Aaron , Hammer Melanie S. , McDuffie Erin E. , Burnett Richard T. , Spadaro Joseph V. , Chatterjee Deepangsu , Cohen Aaron J. , Apte Joshua S. , Southerland Veronica A. , Anenberg Susan C. , Brauer Michael , Martin Randall V. 
Published: September 2023

AbstractAmbient fine particulate matter (PM2.5) is the world’s leading environmental health risk factor. Quantification is needed of regional contributions to changes in global PM2.5 exposure. Here we interpret satellite-derived PM2.5 estimates over 1998-2019 and find a reversal of previous growth in global PM2.5 air pollution, which is quantitatively attributed to contributions from 13 regions. Global population-weighted (PW) PM2.5 exposure, related to both pollution levels and population size, increased from 1998 (28.3 μg/m3) to a peak in 2011 (38.9 μg/m3) and decreased steadily afterwards (34.7 μg/m3 in 2019). Post-2011 change was related to exposure reduction in China and slowed exposure growth in other regions (especially South Asia, the Middle East and Africa). The post-2011 exposure reduction contributes to stagnation of growth in global PM2.5-attributable mortality and increasing health benefits per µg/m3 marginal reduction in exposure, implying increasing urgency and benefits of PM2.5 mitigation with aging population and cleaner air.
Metallic W/WO2 solid-acid catalyst boosts hydrogen evolution reaction in alkaline electrolyte
Authors: Chen Zhigang , Gong Wenbin , Wang Juan , Hou Shuang , Yang Guang , Zhu Chengfeng , Fan Xiyue , Li Yifan , Gao Rui , Cui Yi 
Published: September 2023

AbstractThe lack of available protons severely lowers the activity of alkaline hydrogen evolution reaction process than that in acids, which can be efficiently accelerated by tuning the coverage and chemical environment of protons on catalyst surface. However, the cycling of active sites by proton transfer is largely dependent on the utilization of noble metal catalysts because of the appealing electronic interaction between noble metal atoms and protons. Herein, an all-non-noble W/WO2 metallic heterostructure serving as an efficient solid-acid catalyst exhibits remarkable hydrogen evolution reaction performance with an ultra-low overpotential of −35 mV at −10 mA/cm2 and a small Tafel slope (−34 mV/dec), as well as long-term durability of hydrogen production (>50 h) at current densities of −10 and −50 mA/cm2 in alkaline electrolyte. Multiple in situ and ex situ spectroscopy characterizations combining with first-principle density functional theory calculations discover that a dynamic proton-concentrated surface can be constructed on W/WO2 solid-acid catalyst under ultra-low overpotentials, which enables W/WO2 catalyzing alkaline hydrogen production to follow a kinetically fast Volmer-Tafel pathway with two neighboring protons recombining into a hydrogen molecule. Our strategy of solid-acid catalyst and utilization of multiple spectroscopy characterizations may provide an interesting route for designing advanced all-non-noble catalytic system towards boosting hydrogen evolution reaction performance in alkaline electrolyte.
Sulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish
Authors: Sun Wenwei , Wang Meimei , Zhao Jun , Zhao Shuang , Zhu Wenchao , Wu Xiaoting , Li Feifei , Liu Wei , Wang Zhuo , Gao Meng , Zhang Yiyue , Xu Jin , Zhang Meijia , Wang Qiang , Wen Zilong , Shen Juan , Zhang Wenqing , Huang Zhibin 
Published: September 2023

AbstractNonsteroidal anti-inflammatory drugs compose one of the most widely used classes of medications, but the risks for early development remain controversial, especially in the nervous system. Here, we utilized zebrafish larvae to assess the potentially toxic effects of nonsteroidal anti-inflammatory drugs and found that sulindac can selectively induce apoptosis of GABAergic neurons in the brains of zebrafish larvae brains. Zebrafish larvae exhibit hyperactive behaviour after sulindac exposure. We also found that akt1 is selectively expressed in GABAergic neurons and that SC97 (an Akt1 activator) and exogenous akt1 mRNA can reverse the apoptosis caused by sulindac. Further studies showed that sulindac binds to retinoid X receptor alpha (RXRα) and induces autophagy in GABAergic neurons, leading to activation of the mitochondrial apoptotic pathway. Finally, we verified that sulindac can lead to hyperactivity and selectively induce GABAergic neuron apoptosis in mice. These findings suggest that excessive use of sulindac may lead to early neurodevelopmental toxicity and increase the risk of hyperactivity, which could be associated with damage to GABAergic neurons.
Integration of AIEgens into covalent organic frameworks for pyroptosis and ferroptosis primed cancer immunotherapy
Authors: Zhang Liang , Song An , Yang Qi-Chao , Li Shu-Jin , Wang Shuo , Wan Shu-Cheng , Sun Jianwei , Kwok Ryan T. K. , Lam Jacky W. Y. , Deng Hexiang , Tang Ben Zhong , Sun Zhi-Jun 
Published: September 2023

AbstractImmunogenic programmed cell death, such as pyroptosis and ferroptosis, efficiently induces an acute inflammatory response and boosts antitumor immunity. However, the exploration of dual-inducers, particularly nonmetallic inducers, capable of triggering both pyroptosis and ferroptosis remains limited. Here we show the construction of a covalent organic framework (COF-919) from planar and twisted AIEgen-based motifs as a dual-inducer of pyroptosis and ferroptosis for efficient antitumor immunity. Mechanistic studies reveal that COF-919 displays stronger near-infrared light absorption, lower band energy, and longer lifetime to favor the generation of reactive oxygen species (ROS) and photothermal conversion, triggering pyroptosis. Because of its good ROS production capability, it upregulates intracellular lipid peroxidation, leading to glutathione depletion, low expression of glutathione peroxidase 4, and induction of ferroptosis. Additionally, the induction of pyroptosis and ferroptosis by COF-919 effectively inhibits tumor metastasis and recurrence, resulting in over 90% tumor growth inhibition and cure rates exceeding 80%.
Interpreting biologically informed neural networks for enhanced proteomic biomarker discovery and pathway analysis
Authors: Hartman Erik , Scott Aaron M. , Karlsson Christofer , Mohanty Tirthankar , Vaara Suvi T. , Linder Adam , Malmström Lars , Malmström Johan 
Published: September 2023

AbstractThe incorporation of machine learning methods into proteomics workflows improves the identification of disease-relevant biomarkers and biological pathways. However, machine learning models, such as deep neural networks, typically suffer from lack of interpretability. Here, we present a deep learning approach to combine biological pathway analysis and biomarker identification to increase the interpretability of proteomics experiments. Our approach integrates a priori knowledge of the relationships between proteins and biological pathways and biological processes into sparse neural networks to create biologically informed neural networks. We employ these networks to differentiate between clinical subphenotypes of septic acute kidney injury and COVID-19, as well as acute respiratory distress syndrome of different aetiologies. To gain biological insight into the complex syndromes, we utilize feature attribution-methods to introspect the networks for the identification of proteins and pathways important for distinguishing between subtypes. The algorithms are implemented in a freely available open source Python-package (https://github.com/InfectionMedicineProteomics/BINN).
FAM3A reshapes VSMC fate specification in abdominal aortic aneurysm by regulating KLF4 ubiquitination
Authors: Lei Chuxiang , Kan Haoxuan , Xian Xiangyu , Chen Wenlin , Xiang Wenxuan , Song Xiaohong , Wu Jianqiang , Yang Dan , Zheng Yuehong 
Published: September 2023

AbstractReprogramming of vascular smooth muscle cell (VSMC) differentiation plays an essential role in abdominal aortic aneurysm (AAA). However, the underlying mechanisms are still unclear. We explore the expression of FAM3A, a newly identified metabolic cytokine, and whether and how FAM3A regulates VSMC differentiation in AAA. We discover that FAM3A is decreased in the aortas and plasma in AAA patients and murine models. Overexpression or supplementation of FAM3A significantly attenuate the AAA formation, manifested by maintenance of the well-differentiated VSMC status and inhibition of VSMC transformation toward macrophage-, chondrocyte-, osteogenic-, mesenchymal-, and fibroblast-like cell subpopulations. Importantly, FAM3A induces KLF4 ubiquitination and reduces its phosphorylation and nuclear localization. Here, we report FAM3A as a VSMC fate-shaping regulator in AAA and reveal the underlying mechanism associated with KLF4 ubiquitination and stability, which may lead to the development of strategies based on FAM3A to restore VSMC homeostasis in AAA.
TAZ2 truncation confers overactivation of p300 and cellular vulnerability to HDAC inhibition
Authors: Xu Longxia , Xuan Hongwen , He Wei , Zhang Liang , Huang Mengying , Li Kuai , Wen Hong , Xu Han , Shi Xiaobing 
Published: September 2023

AbstractThe histone acetyltransferase p300/CBP is composed of several conserved domains, among which, the TAZ2 domain is known as a protein-protein interaction domain that binds to E1A and various transcription factors. Here we show that TAZ2 has a HAT autoinhibitory function. Truncating p300/CBP at TAZ2 leads to hyperactive HAT and elevated histone H3K27 and H3K18 acetylation in cells. Mechanistically, TAZ2 cooperates with other HAT neighboring domains to maintain the HAT active site in a ‘closed’ state. Truncating TAZ2 or binding of transcription factors to TAZ2 induces a conformational change that ‘opens’ the active site for substrate acetylation. Importantly, genetic mutations that lead to p300/CBP TAZ2 truncations are found in human cancers, and cells with TAZ2 truncations are vulnerable to histone deacetylase inhibitors. Our study reveals a function of the TAZ2 domain in HAT autoinhibitory regulation and provides a potential therapeutic strategy for the treatment of cancers harboring p300/CBP TAZ2 truncations.
Ultra-fast interpretable machine-learning potentials
Authors: Xie Stephen R. , Rupp Matthias , Hennig Richard G. 
Published: September 2023

AbstractAll-atom dynamics simulations are an indispensable quantitative tool in physics, chemistry, and materials science, but large systems and long simulation times remain challenging due to the trade-off between computational efficiency and predictive accuracy. To address this challenge, we combine effective two- and three-body potentials in a cubic B-spline basis with regularized linear regression to obtain machine-learning potentials that are physically interpretable, sufficiently accurate for applications, as fast as the fastest traditional empirical potentials, and two to four orders of magnitude faster than state-of-the-art machine-learning potentials. For data from empirical potentials, we demonstrate the exact retrieval of the potential. For data from density functional theory, the predicted energies, forces, and derived properties, including phonon spectra, elastic constants, and melting points, closely match those of the reference method. The introduced potentials might contribute towards accurate all-atom dynamics simulations of large atomistic systems over long-time scales.
Frequency-insensitive spatiotemporal shaping of single photon in multiuser quantum network
Authors: Huang Yiwen , Qi Zhantong , Yang Yilin , Li Yuanhua , Sun Yiwei , Tang Yongzhi , Ni Fengchao , Li Lanting , Zheng Yuanlin , Chen Xianfeng 
Published: September 2023

AbstractExploiting the fundamental features of quantum mechanics, an entanglement-based quantum network offers a promising platform for many dramatic applications such as multi-user cryptography. Nevertheless, the implementation of a large-scale quantum network in real-world scenarios remains challenging owing to the multiple scattering events in complex environment, particularly those frequency-sensitive scatterings that disturb quantum correlation both spatially and temporally. Here, we demonstrate the frequency-insensitive spatiotemporal control of entangled photons in a fully connected network by leveraging a Fourier-transform setup and the genetic algorithm. Such an approach can effectively improve the entanglement distribution process through a multimode fiber while the quantum characteristic of the network can be maintained well after the spatiotemporal shaping. Our scheme can serve as a bridging technology to establish entanglement between remote nodes of spectrally interconnected quantum systems and has great potential applications in future real-world quantum networks.