bluuebunny/crossref_metadata_2025_split huggingface dataset:
An unnatural enzyme with endonuclease activity towards small non-coding RNAs
Authors: Ahmed Noreen , Ahmed Nadine , Bilodeau Didier A. , Pezacki John Paul 
Published: June 2023

AbstractEndonucleases are enzymes that cleave internal phosphodiester bonds within double-stranded DNA or RNA and are essential for biological functions. Herein, we use genetic code expansion to create an unnatural endonuclease that cleaves non-coding RNAs including short interfering RNA (siRNA) and microRNAs (miRNAs), a function that does not exist in nature. We introduce a metal-chelating unnatural amino acid, (2,2′-bipyridin-5-yl)alanine (BpyAla) to impart endonuclease activity to the viral suppressor of RNA silencing protein p19. Upon binding of copper, the mutant p19-T111BpyAla displays catalytic site-specific cleavage of siRNA and human miRNAs. Catalysis is confirmed using fluorescence polarization and fluorescence turn-on. Global miRNA profiling reveals that the engineered enzyme cleaves miRNAs in a human cell line. The therapeutic potential is demonstrated by targeting miR-122, a critical host factor for the hepatitis C virus (HCV). Unnatural endonuclease function is shown to deplete miR-122 levels with similar effects to an antagomir that reduces HCV levels therapeutically.
Radial bimetallic structures via wire arc directed energy deposition-based additive manufacturing
Authors: Squires Lile , Roberts Ethan , Bandyopadhyay Amit 
Published: June 2023

AbstractBimetallic wire arc additive manufacturing (AM) has traditionally been limited to depositions characterized by single planar interfaces. This study demonstrates a more complex radial interface concept, with in situ mechanical interlocking and as-built properties suggesting a prestressed compressive effect. A 308 L stainless core is surrounded by a mild steel casing, incrementally maintaining the interface throughout the Z-direction. A small difference in the thermal expansion coefficient between these steels creates residual stresses at their interface. X-ray diffraction analysis confirms phase purity and microstructural characterization reveals columnar grain growth independent of layer transitions. Hardness values are consistent with thermal dissipation characteristics, and the compressive strength of the bimetallic structures shows a 33% to 42% improvement over monolithic controls. Our results demonstrate that biomimetic radial bimetallic variation is feasible with improved mechanical response over monolithic compositions, providing a basis for advanced structural design and implementation using arc-based metal AM.
Dissolved-Cl2 triggered redox reaction enables high-performance perovskite solar cells
Authors: Luo Yujie , Liu Kaikai , Yang Liu , Feng Wenjing , Zheng Lingfang , Shen Lina , Jin Yongbin , Fang Zheng , Song Peiquan , Tian Wanjia , Xu Peng , Li Yuqing , Tian Chengbo , Xie Liqiang , Wei Zhanhua 
Published: June 2023

AbstractConstructing 2D/3D perovskite heterojunctions is effective for the surface passivation of perovskite solar cells (PSCs). However, previous reports that studying perovskite post-treatment only physically deposits 2D perovskite on the 3D perovskite, and the bulk 3D perovskite remains defective. Herein, we propose Cl2-dissolved chloroform as a multifunctional solvent for concurrently constructing 2D/3D perovskite heterojunction and inducing the secondary growth of the bulk grains. The mechanism of how Cl2 affects the performance of PSCs is clarified. Specifically, the dissolved Cl2 reacts with the 3D perovskite, leading to Cl/I ionic exchange and Ostwald ripening of the bulk grains. The generated Cl− further diffuses to passivate the bulk crystal and buried interface of PSCs. Hexylammonium bromide dissolved in the solvent reacts with the residual PbI2 to form 2D/3D heterojunctions on the surface. As a result, we achieved high-performance PSCs with a champion efficiency of 24.21% and substantially improved thermal, ambient, and operational stability.
NBEAL2 deficiency in humans leads to low CTLA-4 expression in activated conventional T cells
Authors: Delage Laure , Carbone Francesco , Riller Quentin , Zachayus Jean-Luc , Kerbellec Erwan , Buzy Armelle , Stolzenberg Marie-Claude , Luka Marine , de Cevins Camille , Kalouche Georges , Favier Rémi , Michel Alizée , Meynier Sonia , Corneau Aurélien , Evrard Caroline , Neveux Nathalie , Roudières Sébastien , Pérot Brieuc P. , Fusaro Mathieu , Lenoir Christelle , Pellé Olivier , Parisot Mélanie , Bras Marc , Héritier Sébastien , Leverger Guy , Korganow Anne-Sophie , Picard Capucine , Latour Sylvain , Collet Bénédicte , Fischer Alain , Neven Bénédicte , Magérus Aude , Ménager Mickaël , Pasquier Benoit , Rieux-Laucat Frédéric 
Published: June 2023

AbstractLoss of NBEAL2 function leads to grey platelet syndrome (GPS), a bleeding disorder characterized by macro-thrombocytopenia and α-granule-deficient platelets. A proportion of patients with GPS develop autoimmunity through an unknown mechanism, which might be related to the proteins NBEAL2 interacts with, specifically in immune cells. Here we show a comprehensive interactome of NBEAL2 in primary T cells, based on mass spectrometry identification of altogether 74 protein association partners. These include LRBA, a member of the same BEACH domain family as NBEAL2, recessive mutations of which cause autoimmunity and lymphocytic infiltration through defective CTLA-4 trafficking. Investigating the potential association between NBEAL2 and CTLA-4 signalling suggested by the mass spectrometry results, we confirm by co-immunoprecipitation that CTLA-4 and NBEAL2 interact with each other. Interestingly, NBEAL2 deficiency leads to low CTLA-4 expression in patient-derived effector T cells, while their regulatory T cells appear unaffected. Knocking-down NBEAL2 in healthy primary T cells recapitulates the low CTLA-4 expression observed in the T cells of GPS patients. Our results thus show that NBEAL2 is involved in the regulation of CTLA-4 expression in conventional T cells and provide a rationale for considering CTLA-4-immunoglobulin therapy in patients with GPS and autoimmune disease.
The turbulent future brings a breath of fresh air
Authors: Stjern Camilla W. , Hodnebrog Øivind , Myhre Gunnar , Pisso Ignacio 
Published: June 2023

AbstractVentilation of health hazardous aerosol pollution within the planetary boundary layer (PBL) – the lowest layer of the atmosphere – is dependent upon turbulent mixing, which again is closely linked to the height of the PBL. Here we show that emissions of both CO2 and absorbing aerosols such as black carbon influence the number of severe air pollution episodes through impacts on turbulence and PBL height. While absorbing aerosols cause increased boundary layer stability and reduced turbulence through atmospheric heating, CO2 has the opposite effect over land through surface warming. In future scenarios with increasing CO2 concentrations and reduced aerosol emissions, we find that around 10% of the world’s population currently living in regions with high pollution levels are likely to experience a particularly strong increase in turbulence and PBL height, and thus a reduction in intense pollution events. Our results highlight how these boundary layer processes provide an added positive impact of black carbon mitigation to human health.
Carbon neutral hydrogen storage and release cycles based on dual-functional roles of formamides
Authors: Wei Duo , Shi Xinzhe , Junge Henrik , Du Chunyu , Beller Matthias 
Published: June 2023

AbstractThe development of alternative clean energy carriers is a key challenge for our society. Carbon-based hydrogen storage materials are well-suited to undergo reversible (de)hydrogenation reactions and the development of catalysts for the individual process steps is crucial. In the current state, noble metal-based catalysts still dominate this field. Here, a system for partially reversible and carbon-neutral hydrogen storage and release is reported. It is based on the dual-functional roles of formamides and uses a small molecule Fe-pincer complex as the catalyst, showing good stability and reusability with high productivity. Starting from formamides, quantitative production of CO-free hydrogen is achieved at high selectivity ( > 99.9%). This system works at modest temperatures of 90 °C, which can be easily supplied by the waste heat from e.g., proton-exchange membrane fuel cells. Employing such system, we achieve >70% H2 evolution efficiency and >99% H2 selectivity in 10 charge-discharge cycles, avoiding undesired carbon emission between cycles.
Mitochondrial aconitase suppresses immunity by modulating oxaloacetate and the mitochondrial unfolded protein response
Authors: Kim Eunah , Annibal Andrea , Lee Yujin , Park Hae-Eun H. , Ham Seokjin , Jeong Dae-Eun , Kim Younghun , Park Sangsoon , Kwon Sujeong , Jung Yoonji , Park JiSoo , Kim Sieun S. , Antebi Adam , Lee Seung-Jae V. 
Published: June 2023

AbstractAccumulating evidence indicates that mitochondria play crucial roles in immunity. However, the role of the mitochondrial Krebs cycle in immunity remains largely unknown, in particular at the organism level. Here we show that mitochondrial aconitase, ACO-2, a Krebs cycle enzyme that catalyzes the conversion of citrate to isocitrate, inhibits immunity against pathogenic bacteria in C. elegans. We find that the genetic inhibition of aco-2 decreases the level of oxaloacetate. This increases the mitochondrial unfolded protein response, subsequently upregulating the transcription factor ATFS-1, which contributes to enhanced immunity against pathogenic bacteria. We show that the genetic inhibition of mammalian ACO2 increases immunity against pathogenic bacteria by modulating the mitochondrial unfolded protein response and oxaloacetate levels in cultured cells. Because mitochondrial aconitase is highly conserved across phyla, a therapeutic strategy targeting ACO2 may eventually help properly control immunity in humans.
Joint inference of exclusivity patterns and recurrent trajectories from tumor mutation trees
Authors: Luo Xiang Ge , Kuipers Jack , Beerenwinkel Niko 
Published: June 2023

AbstractCancer progression is an evolutionary process shaped by both deterministic and stochastic forces. Multi-region and single-cell sequencing of tumors enable high-resolution reconstruction of the mutational history of each tumor and highlight the extensive diversity across tumors and patients. Resolving the interactions among mutations and recovering recurrent evolutionary processes may offer greater opportunities for successful therapeutic strategies. To this end, we present a novel probabilistic framework, called TreeMHN, for the joint inference of exclusivity patterns and recurrent trajectories from a cohort of intra-tumor phylogenetic trees. Through simulations, we show that TreeMHN outperforms existing alternatives that can only focus on one aspect of the task. By analyzing datasets of blood, lung, and breast cancers, we find the most likely evolutionary trajectories and mutational patterns, consistent with and enriching our current understanding of tumorigenesis. Moreover, TreeMHN facilitates the prediction of tumor evolution and provides probabilistic measures on the next mutational events given a tumor tree, a prerequisite for evolution-guided treatment strategies.
Mutagenesis and structural studies reveal the basis for the specific binding of SARS-CoV-2 SL3 RNA element with human TIA1 protein
Authors: Zhang Dong , Qiao Lulu , Lei Xiaobo , Dong Xiaojing , Tong Yunguang , Wang Jianwei , Wang Zhiye , Zhou Ruhong 
Published: June 2023

AbstractViral RNA-host protein interactions are indispensable during RNA virus transcription and replication, but their detailed structural and dynamical features remain largely elusive. Here, we characterize the binding interface for the SARS-CoV-2 stem-loop 3 (SL3) cis-acting element to human TIA1 protein with a combined theoretical and experimental approaches. The highly structured SARS-CoV-2 SL3 has a high binding affinity to TIA1 protein, in which the aromatic stacking, hydrogen bonds, and hydrophobic interactions collectively direct this specific binding. Further mutagenesis studies validate our proposed 3D binding model and reveal two SL3 variants have enhanced binding affinities to TIA1. And disruptions of the identified RNA-protein interactions with designed antisense oligonucleotides dramatically reduce SARS-CoV-2 infection in cells. Finally, TIA1 protein could interact with conserved SL3 RNA elements within other betacoronavirus lineages. These findings open an avenue to explore the viral RNA-host protein interactions and provide a pioneering structural basis for RNA-targeting antiviral drug design.
Multiplexed ddPCR-amplicon sequencing reveals isolated Plasmodium falciparum populations amenable to local elimination in Zanzibar, Tanzania
Authors: Holzschuh Aurel , Lerch Anita , Gerlovina Inna , Fakih Bakar S. , Al-mafazy Abdul-wahid H. , Reaves Erik J. , Ali Abdullah , Abbas Faiza , Ali Mohamed Haji , Ali Mohamed Ali , Hetzel Manuel W. , Yukich Joshua , Koepfli Cristian 
Published: June 2023

AbstractZanzibar has made significant progress toward malaria elimination, but recent stagnation requires novel approaches. We developed a highly multiplexed droplet digital PCR (ddPCR)-based amplicon sequencing method targeting 35 microhaplotypes and drug-resistance loci, and successfully sequenced 290 samples from five districts covering both main islands. Here, we elucidate fine-scale Plasmodium falciparum population structure and infer relatedness and connectivity of infections using an identity-by-descent (IBD) approach. Despite high genetic diversity, we observe pronounced fine-scale spatial and temporal parasite genetic structure. Clusters of near-clonal infections on Pemba indicate persistent local transmission with limited parasite importation, presenting an opportunity for local elimination efforts. Furthermore, we observe an admixed parasite population on Unguja and detect a substantial fraction (2.9%) of significantly related infection pairs between Zanzibar and the mainland, suggesting recent importation. Our study provides a high-resolution view of parasite genetic structure across the Zanzibar archipelago and provides actionable insights for prioritizing malaria elimination efforts.
Surges in volcanic activity on the Moon about two billion years ago
Authors: Tian Heng-Ci , Zhang Chi , Yang Wei , Du Jun , Chen Yi , Xiao Zhiyong , Mitchell Ross N. , Hui Hejiu , Changela Hitesh G. , Zhang Tian-Xin , Tang Xu , Zhang Di , Lin Yangting , Li Xianhua , Wu Fuyuan 
Published: June 2023

AbstractThe history of mare volcanism critically informs the thermal evolution of the Moon. However, young volcanic eruptions are poorly constrained by remote observations and limited samples, hindering an understanding of mare eruption flux over time. The Chang’e-5 mission returned the youngest lunar basalts thus far, offering a window into the Moon’s late-stage evolution. Here, we investigate the mineralogy and geochemistry of 42 olivine and pyroxene crystals from the Chang’e-5 basalts. We find that almost all of them are normally zoned, suggesting limited magma recharge or shallow-level assimilation. Most olivine grains record a short timescale of cooling. Thermal modeling used to estimate the thickness and volume of the volcanism sampled by Chang’e-5 reveals enhanced magmatic flux ~2 billion years ago, suggesting that while overall lunar volcanic activity may decrease over time, episodic eruptions at the final stage could exhibit above average eruptive fluxes, thus revising models of lunar thermal evolution.
The narrowing gap in developed and developing country emission intensities reduces global trade’s carbon leakage
Authors: Meng Jing , Huo Jingwen , Zhang Zengkai , Liu Yu , Mi Zhifu , Guan Dabo , Feng Kuishuang 
Published: June 2023

AbstractInternational trade affects CO2emissions by redistributing production activities to places where the emission intensities are different from the place of consumption. This study focuses on the net emission change as the result of the narrowing gap in emission intensities between the exporter and importer. Here we show that the relocation of production activities from the global North (developed countries) to the global South (developing countries) in the early 2000s leads to an increase in global emissions due to the higher emission intensities in China and India. The related net emissions are about one-third of the total emissions embodied in the South-North trade. However, the narrowing emission intensities between South-North and the changing trade patterns results in declining net emissions in trade in the past decade. The convergence of emission intensities in the global South alleviates concerns that increasing South-South trade would lead to increased carbon leakage and carbon emissions. The mitigation opportunity to green the supply chain lies in sectors such as electricity, mineral products and chemical products, but calls for a universal assessment of emission intensities and concerted effort.
Plant community stability is associated with a decoupling of prokaryote and fungal soil networks
Authors: in ‘t Zandt Dina , Kolaříková Zuzana , Cajthaml Tomáš , Münzbergová Zuzana 
Published: June 2023

AbstractSoil microbial networks play a crucial role in plant community stability. However, we lack knowledge on the network topologies associated with stability and the pathways shaping these networks. In a 13-year mesocosm experiment, we determined links between plant community stability and soil microbial networks. We found that plant communities on soil abandoned from agricultural practices 60 years prior to the experiment promoted destabilising properties and were associated with coupled prokaryote and fungal soil networks. This coupling was mediated by strong interactions of plants and microbiota with soil resource cycling. Conversely, plant communities on natural grassland soil exhibited a high stability, which was associated with decoupled prokaryote and fungal soil networks. This decoupling was mediated by a large variety of past plant community pathways shaping especially fungal networks. We conclude that plant community stability is associated with a decoupling of prokaryote and fungal soil networks and mediated by plant-soil interactions.
Predicting in-hospital outcomes of patients with acute kidney injury
Authors: Wu Changwei , Zhang Yun , Nie Sheng , Hong Daqing , Zhu Jiajing , Chen Zhi , Liu Bicheng , Liu Huafeng , Yang Qiongqiong , Li Hua , Xu Gang , Weng Jianping , Kong Yaozhong , Wan Qijun , Zha Yan , Chen Chunbo , Xu Hong , Hu Ying , Shi Yongjun , Zhou Yilun , Su Guobin , Tang Ying , Gong Mengchun , Wang Li , Hou Fanfan , Liu Yongguo , Li Guisen 
Published: June 2023

AbstractAcute kidney injury (AKI) is prevalent and a leading cause of in-hospital death worldwide. Early prediction of AKI-related clinical events and timely intervention for high-risk patients could improve outcomes. We develop a deep learning model based on a nationwide multicenter cooperative network across China that includes 7,084,339 hospitalized patients, to dynamically predict the risk of in-hospital death (primary outcome) and dialysis (secondary outcome) for patients who developed AKI during hospitalization. A total of 137,084 eligible patients with AKI constitute the analysis set. In the derivation cohort, the area under the receiver operator curve (AUROC) for 24-h, 48-h, 72-h, and 7-day death are 95·05%, 94·23%, 93·53%, and 93·09%, respectively. For dialysis outcome, the AUROC of each time span are 88·32%, 83·31%, 83·20%, and 77·99%, respectively. The predictive performance is consistent in both internal and external validation cohorts. The model can predict important outcomes of patients with AKI, which could be helpful for the early management of AKI.
A randomized non-inferiority trial of therapeutic strategy with immunosuppressants versus biologics for Vogt-Koyanagi-Harada disease
Authors: Zhong Zhenyu , Dai Lingyu , Wu Qiuying , Gao Yu , Pu Yanlin , Su Guannan , Lu Xiaorong , Zhang Fuxiang , Tang Chong , Wang Yao , Zhou Chunjiang , Yang Peizeng 
Published: June 2023

AbstractBiologics are increasingly used to treat Vogt-Koyanagi-Harada disease, but head-to-head comparisons with conventional immunosuppressants are lacking. Here in this randomized trial (Chinese Clinical Trial Registry, ChiCTR2100043061), we assigned 110 patients (27 early-phase and 83 late-phase) to cyclosporine-based immunosuppressant strategy (N = 56) or adalimumab-based biologic strategy (N = 54), each combined with a modified corticosteroid regimen. The primary outcome is change from baseline in best-corrected visual acuity at week 26. The margin of non-inferiority for cyclosporine is −7 letters. The primary outcome is 11.2 letters (95% CI, 7.5 to 14.9) in the cyclosporine group and 6.3 letters (95% CI, 3.1 to 9.6) in the adalimumab group (difference, 4.9; 95% CI, 0.2 to 9.5; P < 0.001 for non-inferiority). The between-group difference is −0.8 letters (95% CI, −6.1 to 4.5) in early-phase disease and 5.7 letters (95% CI, 0.2 to 11.2) in late-phase. Serious adverse events are reported less frequently in the cyclosporine group than in the adalimumab group (0.70 vs. 1.21 events per patient-year). Here, we report that combined with a non-standard corticosteroid regimen, cyclosporine-based immunosuppressant strategy is non-inferior to adalimumab-based biologic strategy by 26 weeks for visual improvement in a cohort of patients with Vogt-Koyanagi-Harada disease, 75% of whom have a late-phase disease.
Direct observation of hot-electron-enhanced thermoelectric effects in silicon nanodevices
Authors: Xue Huanyi , Qian Ruijie , Lu Weikang , Gong Xue , Qin Ludi , Zhong Zhenyang , An Zhenghua , Chen Lidong , Lu Wei 
Published: June 2023

AbstractThe study of thermoelectric behaviors in miniatured transistors is of fundamental importance for developing bottom-level thermal management. Recent experimental progress in nanothermetry has enabled studies of the microscopic temperature profiles of nanostructured metals, semiconductors, two-dimensional material, and molecular junctions. However, observations of thermoelectric (such as nonequilibrium Peltier and Thomson) effect in prevailing silicon (Si)—a critical step for on-chip refrigeration using Si itself—have not been addressed so far. Here, we carry out nanothermometric imaging of both electron temperature (Te) and lattice temperature (TL) of a Si nanoconstriction device and find obvious thermoelectric effect in the vicinity of the electron hotspots: When the electrical current passes through the nanoconstriction channel generating electron hotspots (withTe~1500 K being much higher thanTL~320 K), prominent thermoelectric effect is directly visualized attributable to the extremely large electron temperature gradient (~1 K/nm). The quantitative measurement shows a distinctive third-power dependence of the observed thermoelectric on the electrical current, which is consistent with the theoretically predicted nonequilibrium thermoelectric effects. Our work suggests that the nonequilibrium hot carriers may be potentially utilized for enhancing the thermoelectric performance and therefore sheds new light on the nanoscale thermal management of post-Moore nanoelectronics.