bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of superconducting properties in the La–Ce–H system at moderate pressures
Authors: Chen Wuhao , Huang Xiaoli , Semenok Dmitrii V. , Chen Su , Zhou Di , Zhang Kexin , Oganov Artem R. , Cui Tian 
Published: May 2023

AbstractTernary hydrides are regarded as an important platform for exploring high-temperature superconductivity at relatively low pressures. Here, we successfully synthesized the hcp-(La,Ce)H9-10 at 113 GPa with the initial La/Ce ratio close to 3:1. The high-temperature superconductivity was strikingly observed at 176 K and 100 GPa with the extrapolated upper critical field Hc2(0) reaching 235 T. We also studied the binary La-H system for comparison, which exhibited a Tc of 103 K at 78 GPa. The Tc and Hc2(0) of the La-Ce-H are respectively enhanced by over 80 K and 100 T with respect to the binary La-H and Ce-H components. The experimental results and theoretical calculations indicate that the formation of the solid solution contributes not only to enhanced stability but also to superior superconducting properties. These results show how better superconductors can be engineered in the new hydrides by large addition of alloy-forming elements.
Resveratrol intervention attenuates chylomicron secretion via repressing intestinal FXR-induced expression of scavenger receptor SR-B1
Authors: Pang Juan , Raka Fitore , Heirali Alya Abbas , Shao Weijuan , Liu Dinghui , Gu Jianqiu , Feng Jia Nuo , Mineo Chieko , Shaul Philip W. , Qian Xiaoxian , Coburn Bryan , Adeli Khosrow , Ling Wenhua , Jin Tianru 
Published: May 2023

AbstractTwo common features of dietary polyphenols have hampered our mechanistic understanding of their beneficial effects for decades: targeting multiple organs and extremely low bioavailability. We show here that resveratrol intervention (REV-I) in high-fat diet (HFD)-challenged male mice inhibits chylomicron secretion, associated with reduced expression of jejunal but not hepatic scavenger receptor class B type 1 (SR-B1). Intestinal mucosa-specific SR-B1-/- mice on HFD-challenge exhibit improved lipid homeostasis but show virtually no further response to REV-I. SR-B1 expression in Caco-2 cells cannot be repressed by pure resveratrol compound while fecal-microbiota transplantation from mice on REV-I suppresses jejunal SR-B1 in recipient mice. REV-I reduces fecal levels of bile acids and activity of fecal bile-salt hydrolase. In Caco-2 cells, chenodeoxycholic acid treatment stimulates both FXR and SR-B1. We conclude that gut microbiome is the primary target of REV-I, and REV-I improves lipid homeostasis at least partially via attenuating FXR-stimulated gut SR-B1 elevation.
The impact of introduction of the 10-valent pneumococcal conjugate vaccine on pneumococcal carriage in Nigeria
Authors: Adamu Aishatu L. , Ojal J. , Abubakar Isa A. , Odeyemi Kofo A. , Bello Musa M. , Okoromah Christy A. N. , Karia Boniface , Karani Angela , Akech Donald. , Inem Victor , Scott J. Anthony G. , Adetifa Ifedayo M. O. 
Published: May 2023

AbstractPneumococcal conjugate vaccines (PCVs) protect against invasive pneumococcal disease (IPD) among vaccinees. However, at population level, this protection is driven by indirect effects. PCVs prevent nasopharyngeal acquisition of vaccine-serotype (VT) pneumococci, reducing onward transmission. Each disease episode is preceded by infection from a carrier, so vaccine impacts on carriage provide a minimum estimate of disease reduction in settings lacking expensive IPD surveillance. We documented carriage prevalence and vaccine coverage in two settings in Nigeria annually (2016–2020) following PCV10 introduction in 2016. Among 4,684 rural participants, VT carriage prevalence fell from 21 to 12% as childhood (<5 years) vaccine coverage rose from 7 to 84%. Among 2,135 urban participants, VT carriage prevalence fell from 16 to 9% as uptake rose from 15 to 94%. Within these ranges, carriage prevalence declined with uptake. Increasing PCV10 coverage reduced pneumococcal infection at all ages, implying at least a comparable reduction in IPD.
Cellular automata imbedded memristor-based recirculated logic in-memory computing
Authors: Liu Yanming , Tian He , Wu Fan , Liu Anhan , Li Yihao , Sun Hao , Lanza Mario , Ren Tian-Ling 
Published: May 2023

AbstractMemristor-based circuits offer low hardware costs and in-memory computing, but full-memristive circuit integration for different algorithm remains limited. Cellular automata (CA) has been noticed for its well-known parallel, bio-inspired, computational characteristics. Running CA on conventional chips suffers from low parallelism and high hardware costs. Establishing dedicated hardware for CA remains elusive. We propose a recirculated logic operation scheme (RLOS) using memristive hardware and 2D transistors for CA evolution, significantly reducing hardware complexity. RLOS’s versatility supports multiple CA algorithms on a single circuit, including elementary CA rules and more complex majority classification and edge detection algorithms. Results demonstrate up to a 79-fold reduction in hardware costs compared to FPGA-based approaches. RLOS-based reservoir computing is proposed for edge computing development, boasting the lowest hardware cost (6 components/per cell) among existing implementations. This work advances efficient, low-cost CA hardware and encourages edge computing hardware exploration.
Phase II trial of neoadjuvant sitravatinib plus nivolumab in patients undergoing nephrectomy for locally advanced clear cell renal cell carcinoma
Authors: Karam Jose A. , Msaouel Pavlos , Haymaker Cara L. , Matin Surena F. , Campbell Matthew T. , Zurita Amado J. , Shah Amishi Y. , Wistuba Ignacio I. , Marmonti Enrica , Duose Dzifa Y. , Parra Edwin R. , Soto Luisa Maren Solis , Laberiano-Fernandez Caddie , Lozano Marisa , Abraham Alice , Hallin Max , Chin Curtis D. , Olson Peter , Der-Torossian Hirak , Yan Xiaohong , Tannir Nizar M. , Wood Christopher G. 
Published: May 2023

AbstractSitravatinib is an immunomodulatory tyrosine kinase inhibitor that can augment responses when combined with programmed death-1 inhibitors such as nivolumab. We report a single-arm, interventional, phase 2 study of neoadjuvant sitravatinib in combination with nivolumab in patients with locally advanced clear cell renal cell carcinoma (ccRCC) prior to curative nephrectomy (NCT03680521). The primary endpoint was objective response rate (ORR) prior to surgery with a null hypothesis ORR = 5% and the alternative hypothesis set at ORR = 30%. Secondary endpoints were safety; pharmacokinetics (PK) of sitravatinib; immune effects, including changes in programmed cell death–ligand 1 expression; time-to-surgery; and disease-free survival (DFS). Twenty patients were evaluable for safety and 17 for efficacy. The ORR was 11.8%, and 24-month DFS probability was 88·0% (95% CI 61.0 to 97.0). There were no grade 4/5 treatment-related adverse events. Sitravatinib PK did not change following the addition of nivolumab. Correlative blood and tissue analyses showed changes in the tumour microenvironment resulting in an immunologically active tumour by the time of surgery (median time-to-surgery: 50 days). The primary endpoint of this study was not met as short-term neoadjuvant sitravatinib and nivolumab did not substantially increase ORR.
Nuclear spin diffusion in the central spin system of a GaAs/AlGaAs quantum dot
Authors: Millington-Hotze Peter , Manna Santanu , Covre da Silva Saimon F. , Rastelli Armando , Chekhovich Evgeny A. 
Published: May 2023

AbstractThe spin diffusion concept provides a classical description of a purely quantum-mechanical evolution in inhomogeneously polarized many-body systems such as nuclear spin lattices. The central spin of a localized electron alters nuclear spin diffusion in a way that is still poorly understood. Here, spin diffusion in a single GaAs/AlGaAs quantum dot is witnessed in the most direct manner from oscillatory spin relaxation dynamics. Electron spin is found to accelerate nuclear spin relaxation, from which we conclude that the long-discussed concept of a Knight-field-gradient diffusion barrier does not apply to GaAs epitaxial quantum dots. Our experiments distinguish between non-diffusion relaxation and spin diffusion, allowing us to conclude that diffusion is accelerated by the central electron spin. Such acceleration is observed up to unexpectedly high magnetic fields – we propose electron spin-flip fluctuations as an explanation. Diffusion-limited nuclear spin lifetimes range between 1 and 10 s, which is sufficiently long for quantum information storage and processing.
Structural mechanism of human oncochannel TRPV6 inhibition by the natural phytoestrogen genistein
Authors: Neuberger Arthur , Trofimov Yury A. , Yelshanskaya Maria V. , Nadezhdin Kirill D. , Krylov Nikolay A. , Efremov Roman G. , Sobolevsky Alexander I. 
Published: May 2023

AbstractCalcium-selective oncochannel TRPV6 is the major driver of cell proliferation in human cancers. While significant effort has been invested in the development of synthetic TRPV6 inhibitors, natural channel blockers have been largely neglected. Here we report the structure of human TRPV6 in complex with the plant-derived phytoestrogen genistein, extracted from Styphnolobium japonicum, that was shown to inhibit cell invasion and metastasis in cancer clinical trials. Despite the pharmacological value, the molecular mechanism of TRPV6 inhibition by genistein has remained enigmatic. We use cryo-EM combined with electrophysiology, calcium imaging, mutagenesis, and molecular dynamics simulations to show that genistein binds in the intracellular half of the TRPV6 pore and acts as an ion channel blocker and gating modifier. Genistein binding to the open channel causes pore closure and a two-fold symmetrical conformational rearrangement in the S4–S5 and S6-TRP helix regions. The unprecedented mechanism of TRPV6 inhibition by genistein uncovers new possibilities in structure-based drug design.
Spatially resolved multi-omics highlights cell-specific metabolic remodeling and interactions in gastric cancer
Authors: Sun Chenglong , Wang Anqiang , Zhou Yanhe , Chen Panpan , Wang Xiangyi , Huang Jianpeng , Gao Jiamin , Wang Xiao , Shu Liebo , Lu Jiawei , Dai Wentao , Bu Zhaode , Ji Jiafu , He Jiuming 
Published: May 2023

AbstractMapping tumor metabolic remodeling and their spatial crosstalk with surrounding non-tumor cells can fundamentally improve our understanding of tumor biology, facilitates the designing of advanced therapeutic strategies. Here, we present an integration of mass spectrometry imaging-based spatial metabolomics and lipidomics with microarray-based spatial transcriptomics to hierarchically visualize the intratumor metabolic heterogeneity and cell metabolic interactions in same gastric cancer sample. Tumor-associated metabolic reprogramming is imaged at metabolic-transcriptional levels, and maker metabolites, lipids, genes are connected in metabolic pathways and colocalized in the heterogeneous cancer tissues. Integrated data from spatial multi-omics approaches coherently identify cell types and distributions within the complex tumor microenvironment, and an immune cell-dominated “tumor-normal interface” region where tumor cells contact adjacent tissues are characterized with distinct transcriptional signatures and significant immunometabolic alterations. Our approach for mapping tissue molecular architecture provides highly integrated picture of intratumor heterogeneity, and transform the understanding of cancer metabolism at systemic level.
Patterns of ontogenetic evolution across extant marsupials reflect different allometric pathways to ecomorphological diversity
Authors: Wilson Laura A. B. , López-Aguirre Camilo , Archer Michael , Hand Suzanne J. , Flores David , Abdala Fernando , Giannini Norberto P. 
Published: May 2023

AbstractThe relatively high level of morphological diversity in Australasian marsupials compared to that observed among American marsupials remains poorly understood. We undertake a comprehensive macroevolutionary analysis of ontogenetic allometry of American and Australasian marsupials to examine whether the contrasting levels of morphological diversity in these groups are reflected in their patterns of allometric evolution. We collate ontogenetic series for 62 species and 18 families of marsupials (n = 2091 specimens), spanning across extant marsupial diversity. Our results demonstrate significant lability of ontogenetic allometric trajectories among American and Australasian marsupials, yet a phylogenetically structured pattern of allometric evolution is preserved. Here we show that species diverging more than 65 million years ago converge in their patterns of ontogenetic allometry under animalivorous and herbivorous diets, and that Australasian marsupials do not show significantly greater variation in patterns of ontogenetic allometry than their American counterparts, despite displaying greater magnitudes of extant ecomorphological diversity.
Ligand-induced activation and G protein coupling of prostaglandin F2α receptor
Authors: Wu Canrong , Xu Youwei , He Qian , Li Dianrong , Duan Jia , Li Changyao , You Chongzhao , Chen Han , Fan Weiliang , Jiang Yi , Eric Xu H. 
Published: May 2023

AbstractProstaglandin F2α (PGF2α), an endogenous arachidonic acid metabolite, regulates diverse physiological functions in many tissues and cell types through binding and activation of a G-protein-coupled receptor (GPCR), the PGF2α receptor (FP), which also is the primary therapeutic target for glaucoma and several other diseases. Here, we report cryo-electron microscopy (cryo-EM) structures of the human FP bound to endogenous ligand PGF2α and anti-glaucoma drugs LTPA and TFPA at global resolutions of 2.67 Å, 2.78 Å, and 3.14 Å. These structures reveal distinct features of FP within the lipid receptor family in terms of ligand binding selectivity, its receptor activation, and G protein coupling mechanisms, including activation in the absence of canonical PIF and ERY motifs and Gq coupling through direct interactions with receptor transmembrane helix 1 and intracellular loop 1. Together with mutagenesis and functional studies, our structures reveal mechanisms of ligand recognition, receptor activation, and G protein coupling by FP, which could facilitate rational design of FP-targeting drugs.
Surface manipulation for prevention of migratory viscous crude oil fouling in superhydrophilic membranes
Authors: Zhao Yuanyuan , Yang Xiaobin , Cheng Zhongjun , Lau Cher Hon , Ma Jun , Shao Lu 
Published: May 2023

AbstractHere, we present a proactive fouling prevention mechanism that endows superhydrophilic membranes with antifouling capability against migratory viscous crude oil fouling. By simulating the hierarchical architecture/chemical composition of a dahlia leaf, a membrane surface is decorated with wrinkled-pattern microparticles, exhibiting a unique proactive fouling prevention mechanism based on a synergistic hydration layer/steric hindrance. The density functional theory and physicochemical characterizations demonstrate that the main chains of the microparticles are bent towards Fe3+ through coordination interactions to create nanoscale wrinkled patterns on smooth microparticle surfaces. Nanoscale wrinkled patterns reduce the surface roughness and increase the contact area between the membrane surface and water molecules, expanding the steric hindrance between the oil molecules and membrane surface. Molecular dynamic simulations reveal that the water-molecule densities and strengths of the hydrogen bonds are higher near the resultant membrane surface. With this concept, we can successfully inhibit the initial adhesion, migration, and deposition of oil, regardless of the viscosity, on the membrane surface and achieve migratory viscous crude oil antifouling. This research on the PFP mechanism opens pathways to realize superwettable materials for diverse applications in fields related to the environment, energy, health, and beyond.
Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico
Authors: Ponce-de-León Samuel , Torres Martha , Soto-Ramírez Luis Enrique , Calva Juan José , Santillán-Doherty Patricio , Carranza-Salazar Dora Eugenia , Carreño Juan Manuel , Carranza Claudia , Juárez Esmeralda , Carreto-Binaghi Laura E. , Ramírez-Martínez Luis , Paz De la Rosa Georgina , Vigueras-Moreno Rosalía , Ortiz-Stern Alejandro , López-Vidal Yolanda , Macías Alejandro E. , Torres-Flores Jesús , Rojas-Martínez Oscar , Suárez-Martínez Alejandro , Peralta-Sánchez Gustavo , Kawabata Hisaaki , González-Domínguez Irene , Martínez-Guevara José Luis , Sun Weina , Sarfati-Mizrahi David , Soto-Priante Ernesto , Chagoya-Cortés Héctor Elías , López-Macías Constantino , Castro-Peralta Felipa , Palese Peter , García-Sastre Adolfo , Krammer Florian , Lozano-Dubernard Bernardo 
Published: May 2023

AbstractThere is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.
Advanced hybrid nanosheet membranes with stable nanochannels for ultrafast molecular separation
Authors: Guo Qi , Xu Mao , Tang Qi , Liu Yuchen , Zhang Weiyu , Guo Chan , Zhao Xiaoli , Zhu Yujun , Ye Sheng , Liu Dan , Lei Weiwei , Chen Cheng 
Published: May 2023

AbstractLamellar graphene oxide (GO) membranes have gained substantial interest for molecular separation processes. However, GO membranes have shown inefficient separation performance levels due to their possession of sufficient functional groups that lead to swelling under applied hydraulic pressure. Herein, we demonstrate a highly stable and ultrafast filtrable graphene oxide-boron nitride (GOBN) hybrid membrane by incorporating boron nitride (BN) nanosheets into a GO membrane to restrict swelling and provide efficient hydraulic pressure separation characteristics. This new heterostructure retains the GOBN membrane microstructure and provides more nanochannels around the incorporation sites due to the small size of BN nanosheets; this phenomenon increases the permeance to 1310 Lm−2h−1bar−1, which is nearly six times higher than that of the pure GO membrane, with a high rejection reaching 99.2% for aqueous organic dyes. More importantly, the GOBN hybrid membrane shows an impressive permeance and dye molecule rejection performance characteristic across a range of organic solvents, such as methanol, ethanol, and isopropyl alcohol; the performance characteristics are better than those for the GO membrane. Our GOBN membrane with a stable microstructure opens opportunities for developing a high-performance multiple solvent nanofiltration membrane that surpasses the permeability-selectivity trade-off.
Widespread somatic L1 retrotransposition in normal colorectal epithelium
Authors: Nam Chang Hyun , Youk Jeonghwan , Kim Jeong Yeon , Lim Joonoh , Park Jung Woo , Oh Soo A , Lee Hyun Jung , Park Ji Won , Won Hyein , Lee Yunah , Jeong Seung-Yong , Lee Dong-Sung , Oh Ji Won , Han Jinju , Lee Junehawk , Kwon Hyun Woo , Kim Min Jung , Ju Young Seok 
Published: May 2023

AbstractThroughout an individual’s lifetime, genomic alterations accumulate in somatic cells1–11. However, the mutational landscape induced by retrotransposition of long interspersed nuclear element-1 (L1), a widespread mobile element in the human genome12–14, is poorly understood in normal cells. Here we explored the whole-genome sequences of 899 single-cell clones established from three different cell types collected from 28 individuals. We identified 1,708 somatic L1 retrotransposition events that were enriched in colorectal epithelium and showed a positive relationship with age. Fingerprinting of source elements showed 34 retrotransposition-competent L1s. Multidimensional analysis demonstrated that (1) somatic L1 retrotranspositions occur from early embryogenesis at a substantial rate, (2) epigenetic on/off of a source element is preferentially determined in the early organogenesis stage, (3) retrotransposition-competent L1s with a lower population allele frequency have higher retrotransposition activity and (4) only a small fraction of L1 transcripts in the cytoplasm are finally retrotransposed in somatic cells. Analysis of matched cancers further suggested that somatic L1 retrotransposition rate is substantially increased during colorectal tumourigenesis. In summary, this study illustrates L1 retrotransposition-induced somatic mosaicism in normal cells and provides insights into the genomic and epigenomic regulation of transposable elements over the human lifetime.
Structural basis of catalytic activation in human splicing
Authors: Schmitzová Jana , Cretu Constantin , Dienemann Christian , Urlaub Henning , Pena Vladimir 
Published: May 2023

AbstractPre-mRNA splicing follows a pathway driven by ATP-dependent RNA helicases. A crucial event of the splicing pathway is the catalytic activation, which takes place at the transition between the activated Bact and the branching-competent B* spliceosomes. Catalytic activation occurs through an ATP-dependent remodelling mediated by the helicase PRP2 (also known as DHX16)1–3. However, because PRP2 is observed only at the periphery of spliceosomes3–5, its function has remained elusive. Here we show that catalytic activation occurs in two ATP-dependent stages driven by two helicases: PRP2 and Aquarius. The role of Aquarius in splicing has been enigmatic6,7. Here the inactivation of Aquarius leads to the stalling of a spliceosome intermediate—the BAQR complex—found halfway through the catalytic activation process. The cryogenic electron microscopy structure of BAQR reveals how PRP2 and Aquarius remodel Bact and BAQR, respectively. Notably, PRP2 translocates along the intron while it strips away the RES complex, opens the SF3B1 clamp and unfastens the branch helix. Translocation terminates six nucleotides downstream of the branch site through an assembly of PPIL4, SKIP and the amino-terminal domain of PRP2. Finally, Aquarius enables the dissociation of PRP2, plus the SF3A and SF3B complexes, which promotes the relocation of the branch duplex for catalysis. This work elucidates catalytic activation in human splicing, reveals how a DEAH helicase operates and provides a paradigm for how helicases can coordinate their activities.