bluuebunny/crossref_metadata_2025_split huggingface dataset:
ERR-activated GPR35 promotes immune infiltration level of macrophages in gastric cancer tissues
Authors: Shu Chuanjun , Wang Can , Chen Saisai , Huang Xuan , Cui Jiahua , Li Wenchao , Xu Bin 
Published: November 2022

AbstractEnhancer release and retargeting (ERR) events could activate disease-causing gene promoters for increasing the expression level of oncogenes. Meanwhile, class A orphan GPCRs (oGPCRs) are known as potential biomarkers or drug targets for various cancers, such as gastric cancer (GC). Hence, systemic investigation of ERR events for class A oGPCRs in GC could help to explore biomarkers for GC. In this study, ENCODE and GTEx eQTL data were utilized to define ERR events in GC. Only GPR35 was then detected that could be activated by ERR in GC based on these data and ChIP-seq. Then, activated GPR35 functional in GC cells were explored by flow cytometry, cell-based wound healing assay, Transwell migration assay, and M2 polarization of macrophages assay. Meanwhile, according to TCGA and GEO database, overall survival, immune-related gene expression, and immune cell infiltration level in different GPR35 expressions were calculated. Here, we found ERR event activate GPR35 results in GC cells proliferation and migration, and partly immune cells significance exhaustion (CD8 + T-cells and CD4 + memory T-cells) and/or infiltration (T-cells and macrophage). Meanwhile, high GRP35 level leads to a poor prognosis in GC patients, probably partly due to it promoting the immune infiltration level of macrophages and then inducing polarization of M2 macrophages. Notably, GPR35’s high expression in CTSB+ and CD68 + macrophage could be a genetic indicator for early warning of primary GC. Hence, our findings provide a novel activation approach for oGPCRs, and GPR35 could be determined as a new drugable receptor and early genetic indicator for GC.
Mussel-inspired hydrogel with injectable self-healing and antibacterial properties promotes wound healing in burn wound infection
Authors: Sun Ao , Hu Danrong , He Xinye , Ji Xiao , Li Tao , Wei Xiawei , Qian Zhiyong 
Published: November 2022

AbstractBurn wound infections cause serious problems for public health. More than 180,000 patients die from burns every year worldwide. In addition, the difficulty of healing wounds and wound infections caused by burns affects the mental health of patients. Therefore, it is very important to develop a wound dressing that can promote wound repair and exhibits good antibacterial effects. Here, we used oxidized konjac glucomannan (OKGM), γ-poly(glutamic acid) modified with dopamine and L-cysteine (γ-PGA-DA-Cys) and ε-polylysine (ε-PL) to produce an OKGM/γ-PGA-DA-Cys/ε-PL (OKPP) hydrogel. This hydrogel was produced by thiol-aldehyde addition and Schiff-base reactions and has the ability to be injected and self-heal. The results showed that the hydrogel exhibits good antibacterial effects on Pseudomonas aeruginosa and Staphylococcus aureus and has antioxidant effects in vitro. Moreover, the hydrogel also exhibits good adhesion. In a burn wound infection model, the hydrogel promoted wound healing and reduced the production of inflammation. These results proved that the hydrogel has clinical potential as a wound dressing for burn wound infection.
On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation
Authors: Jeziorska D. M. , Tunnacliffe E. A. J. , Brown J. M. , Ayyub H. , Sloane-Stanley J. , Sharpe J. A. , Lagerholm B. C. , Babbs C. , Smith A. J. H. , Buckle V. J. , Higgs D. R. 
Published: November 2022

AbstractDetermining the mechanisms by which genes are switched on and off during development is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using an on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in transcriptional activity whereas at the peak of gene expression, in early erythroblasts, transcription is relatively stable. Later during differentiation as α-globin expression declines, we again observe more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of active transcriptional compartments as gene expression is regulated during differentiation.
Spatial analysis of the glioblastoma proteome reveals specific molecular signatures and markers of survival
Authors: Duhamel Marie , Drelich Lauranne , Wisztorski Maxence , Aboulouard Soulaimane , Gimeno Jean-Pascal , Ogrinc Nina , Devos Patrick , Cardon Tristan , Weller Michael , Escande Fabienne , Zairi Fahed , Maurage Claude-Alain , Le Rhun Émilie , Fournier Isabelle , Salzet Michel 
Published: November 2022

AbstractMolecular heterogeneity is a key feature of glioblastoma that impedes patient stratification and leads to large discrepancies in mean patient survival. Here, we analyze a cohort of 96 glioblastoma patients with survival ranging from a few months to over 4 years. 46 tumors are analyzed by mass spectrometry-based spatially-resolved proteomics guided by mass spectrometry imaging. Integration of protein expression and clinical information highlights three molecular groups associated with immune, neurogenesis, and tumorigenesis signatures with high intra-tumoral heterogeneity. Furthermore, a set of proteins originating from reference and alternative ORFs is found to be statistically significant based on patient survival times. Among these proteins, a 5-protein signature is associated with survival. The expression of these 5 proteins is validated by immunofluorescence on an additional cohort of 50 patients. Overall, our work characterizes distinct molecular regions within glioblastoma tissues based on protein expression, which may help guide glioblastoma prognosis and improve current glioblastoma classification.
Cross-platform comparison of arbitrary quantum states
Authors: Zhu D. , Cian Z. P. , Noel C. , Risinger A. , Biswas D. , Egan L. , Zhu Y. , Green A. M. , Alderete C. Huerta , Nguyen N. H. , Wang Q. , Maksymov A. , Nam Y. , Cetina M. , Linke N. M. , Hafezi M. , Monroe C. 
Published: November 2022

AbstractAs we approach the era of quantum advantage, when quantum computers (QCs) can outperform any classical computer on particular tasks, there remains the difficult challenge of how to validate their performance. While algorithmic success can be easily verified in some instances such as number factoring or oracular algorithms, these approaches only provide pass/fail information of executing specific tasks for a single QC. On the other hand, a comparison between different QCs preparing nominally the same arbitrary circuit provides an insight for generic validation: a quantum computation is only as valid as the agreement between the results produced on different QCs. Such an approach is also at the heart of evaluating metrological standards such as disparate atomic clocks. In this paper, we report a cross-platform QC comparison using randomized and correlated measurements that results in a wealth of information on the QC systems. We execute several quantum circuits on widely different physical QC platforms and analyze the cross-platform state fidelities.
Control of perovskite film crystallization and growth direction to target homogeneous monolithic structures
Authors: Zheng Daming , Raffin Florian , Volovitch Polina , Pauporté Thierry 
Published: November 2022

AbstractGetting performant organo-metal halide perovskite films for various application remains challenging. Here, we show the behavior of solvent and perovskite elements for four different perovskites families and nine different initial precursor solution systems in the case of the most popular preparation process which includes an anti-solvent dripping-assisted spin coating of a precursor solution and a subsequent thermal annealing. We show how the initial solution composition affects, first, the film formed by spin coating and anti-solvent dripping and, second, the processes occurring upon thermal annealing, including crystal domain evolution and the grain growth mechanism. We propose a universal typology which distinguishes three types for the growth direction of perovskite crystals: downward (Type I), upward (Type II) and lateral (Type III). The latter results in large, monolithic grains and we show that this mode must be targeted for the preparation of efficient perovskite light absorber thin films of solar cells.
Data-driven electron-diffraction approach reveals local short-range ordering in CrCoNi with ordering effects
Authors: Hsiao Haw-Wen , Feng Rui , Ni Haoyang , An Ke , Poplawsky Jonathan D. , Liaw Peter K. , Zuo Jian-Min 
Published: November 2022

AbstractThe exceptional mechanical strength of medium/high-entropy alloys has been attributed to hardening in random solid solutions. Here, we evidence non-random chemical mixing in a CrCoNi alloy, resulting from short-range ordering. A data-mining approach of electron nanodiffraction enabled the study, which is assisted by neutron scattering, atom probe tomography, and diffraction simulation using first-principles theory models. Two samples, one homogenized and one heat-treated, are observed. In both samples, results reveal two types of short-range-order inside nanoclusters that minimize the Cr–Cr nearest neighbors (L12) or segregate Cr on alternating close-packed planes (L11). The L11 is predominant in the homogenized sample, while the L12 formation is promoted by heat-treatment, with the latter being accompanied by a dramatic change in dislocation-slip behavior. These findings uncover short-range order and the resulted chemical heterogeneities behind the mechanical strength in CrCoNi, providing general opportunities for atomistic-structure study in concentrated alloys for the design of strong and ductile materials.
Pathogenic variants in SLF2 and SMC5 cause segmented chromosomes and mosaic variegated hyperploidy
Authors: Grange Laura J. , Reynolds John J. , Ullah Farid , Isidor Bertrand , Shearer Robert F. , Latypova Xenia , Baxley Ryan M. , Oliver Antony W. , Ganesh Anil , Cooke Sophie L. , Jhujh Satpal S. , McNee Gavin S. , Hollingworth Robert , Higgs Martin R. , Natsume Toyoaki , Khan Tahir , Martos-Moreno Gabriel Á. , Chupp Sharon , Mathew Christopher G. , Parry David , Simpson Michael A. , Nahavandi Nahid , Yüksel Zafer , Drasdo Mojgan , Kron Anja , Vogt Petra , Jonasson Annemarie , Seth Saad Ahmed , Gonzaga-Jauregui Claudia , Brigatti Karlla W. , Stegmann Alexander P. A. , Kanemaki Masato , Josifova Dragana , Uchiyama Yuri , Oh Yukiko , Morimoto Akira , Osaka Hitoshi , Ammous Zineb , Argente Jesús , Matsumoto Naomichi , Stumpel Constance T.R.M. , Taylor Alexander M. R. , Jackson Andrew P. , Bielinsky Anja-Katrin , Mailand Niels , Le Caignec Cedric , Davis Erica E. , Stewart Grant S. 
Published: November 2022

AbstractEmbryonic development is dictated by tight regulation of DNA replication, cell division and differentiation. Mutations in DNA repair and replication genes disrupt this equilibrium, giving rise to neurodevelopmental disease characterized by microcephaly, short stature and chromosomal breakage. Here, we identify biallelic variants in two components of the RAD18-SLF1/2-SMC5/6 genome stability pathway,SLF2andSMC5, in 11 patients with microcephaly, short stature, cardiac abnormalities and anemia. Patient-derived cells exhibit a unique chromosomal instability phenotype consisting of segmented and dicentric chromosomes with mosaic variegated hyperploidy. To signify the importance of these segmented chromosomes, we have named this disorder Atelís (meaning - incomplete) Syndrome. Analysis of Atelís Syndrome cells reveals elevated levels of replication stress, partly due to a reduced ability to replicate through G-quadruplex DNA structures, and also loss of sister chromatid cohesion. Together, these data strengthen the functional link between SLF2 and the SMC5/6 complex, highlighting a distinct role for this pathway in maintaining genome stability.
Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy
Authors: Yang Tiantian , Wang Aohua , Nie Di , Fan Weiwei , Jiang Xiaohe , Yu Miaorong , Guo Shiyan , Zhu Chunliu , Wei Gang , Gan Yong 
Published: November 2022

AbstractMutual interference between surface ligands on multifunctional nanoparticles remains a significant obstacle to achieving optimal drug-delivery efficacy. Here, we develop ligand-switchable nanoparticles which resemble viral unique surfaces, enabling them to fully display diverse functions. The nanoparticles are modified with a pH-responsive stretchable cell-penetrating peptide (Pep) and a liver-targeting moiety (Gal) (Pep/Gal-PNPs). Once orally administered, the acidic environments trigger the extension of Pep from surface in a virus-like manner, enabling Pep/Gal-PNPs to traverse intestinal barriers efficiently. Subsequently, Gal is exposed by Pep folding at physiological pH, thereby allowing the specific targeting of Pep/Gal-PNPs to the liver. As a proof-of-concept, insulin-loaded Pep/Gal-PNPs are fabricated which exhibit effective intestinal absorption and excellent hepatic deposition of insulin. Crucially, Pep/Gal-PNPs increase hepatic glycogen production by 7.2-fold, contributing to the maintenance of glucose homeostasis for effective diabetes management. Overall, this study provides a promising approach to achieving full potential of diverse ligands on multifunctional nanoparticles.
Identifying the geometric catalytic active sites of crystalline cobalt oxyhydroxides for oxygen evolution reaction
Authors: Wang Sihong , Jiang Qu , Ju Shenghong , Hsu Chia-Shuo , Chen Hao Ming , Zhang Di , Song Fang 
Published: November 2022

AbstractUnraveling the precise location and nature of active sites is of paramount significance for the understanding of the catalytic mechanism and the rational design of efficient electrocatalysts. Here, we use well-defined crystalline cobalt oxyhydroxides CoOOH nanorods and nanosheets as model catalysts to investigate the geometric catalytic active sites. The morphology-dependent analysis reveals a ~50 times higher specific activity of CoOOH nanorods than that of CoOOH nanosheets. Furthermore, we disclose a linear correlation of catalytic activities with their lateral surface areas, suggesting that the active sites are exclusively located at lateral facets rather than basal facets. Theoretical calculations show that the coordinatively unsaturated cobalt sites of lateral facets upshift the O 2p-band center closer to the Fermi level, thereby enhancing the covalency of Co-O bonds to yield the reactivity. This work elucidates the geometrical catalytic active sites and enlightens the design strategy of surface engineering for efficient OER catalysts.
YiaC and CobB regulate lysine lactylation in Escherichia coli
Authors: Dong Hanyang , Zhang Jianji , Zhang Hui , Han Yue , Lu Congcong , Chen Chen , Tan Xiaoxia , Wang Siyu , Bai Xue , Zhai Guijin , Tian Shanshan , Zhang Tao , Cheng Zhongyi , Li Enmin , Xu Liyan , Zhang Kai 
Published: November 2022

AbstractLysine lactylation (Kla) has recently been reported to participate in regulating transcription in human cells. However, the characterization, regulatory mechanism and functional consequence of Kla in prokaryotes remain unclear. Here, we report that YiaC functions as a lysine lactylase and that CobB serves as a lysine delactylase in the regulation of metabolism. We demonstrate that YiaC catalyzes the addition of Kla, while CobB erases this PTM both in vitro and intracellularly. Moreover, we show that YdiF can catalyze the formation of a lactyl-coenzyme A, which donates lactyl group for Kla. Quantitative proteomic analysis further reveals 446 endogenous Kla sites targeted by CobB and 79 candidates targeted by YiaC in Escherichia coli (E. coli). Furthermore, we present that Kla can influence the functions of metabolic enzymes. Interestingly, we demonstrate that CobB can specifically modulate the activity of PykF by regulating K382la, promoting glycolysis and bacterial growth. Our study identifies the regulatory enzymes and functional network of Kla and reveals a Kla-mediated molecular mechanism catalyzed by CobB for glycolysis regulation in E. coli.
Anisotropic charge trapping in phototransistors unlocks ultrasensitive polarimetry for bionic navigation
Authors: Pan Jing , Wu Yiming , Zhang Xiujuan , Chen Jinhui , Wang Jinwen , Cheng Shuiling , Wu Xiaofeng , Zhang Xiaohong , Jie Jiansheng 
Published: November 2022

AbstractBeing able to probe the polarization states of light is crucial for applications from medical diagnostics and intelligent recognition to information encryption and bio-inspired navigation. Current state-of-the-art polarimeters based on anisotropic semiconductors enable direct linear dichroism photodetection without the need for bulky and complex external optics. However, their polarization sensitivity is restricted by the inherent optical anisotropy, leading to low dichroic ratios of typically smaller than ten. Here, we unveil an effective and general strategy to achieve more than 2,000-fold enhanced polarization sensitivity by exploiting an anisotropic charge trapping effect in organic phototransistors. The polarization-dependent trapping of photogenerated charge carriers provides an anisotropic photo-induced gate bias for current amplification, which has resulted in a record-high dichroic ratio of >104, reaching over the extinction ratios of commercial polarizers. These findings further enable the demonstration of an on-chip polarizer-free bionic celestial compass for skylight-based polarization navigation. Our results offer a fundamental design principle and an effective route for the development of next-generation highly polarization-sensitive optoelectronics.
Tumor factors stimulate lysosomal degradation of tumor antigens and undermine their cross-presentation in lung cancer
Authors: Lu Zhen , Chen Jinyun , Yu Pengfei , Atherton Matthew J. , Gui Jun , Tomar Vivek S. , Middleton Justin D. , Sullivan Neil T. , Singhal Sunil , George Subin S. , Woolfork Ashley G. , Weljie Aalim M. , Hai Tsonwin , Eruslanov Evgeniy B. , Fuchs Serge Y. 
Published: November 2022

AbstractActivities of dendritic cells (DCs) that present tumor antigens are often suppressed in tumors. Here we report that this suppression is induced by tumor microenvironment-derived factors, which activate the activating transcription factor-3 (ATF3) transcription factor and downregulate cholesterol 25-hydroxylase (CH25H). Loss of CH25H in antigen presenting cells isolated from human lung tumors is associated with tumor growth and lung cancer progression. Accordingly, mice lacking CH25H in DCs exhibit an accelerated tumor growth, decreased infiltration and impaired activation of intratumoral CD8+ T cells. These mice do not establish measurable long-term immunity against malignant cells that undergo chemotherapy-induced immunogenic cell death. Mechanistically, downregulation of CH25H stimulates membrane fusion between endo-phagosomes and lysosomes, accelerates lysosomal degradation and restricts cross-presentation of tumor antigens in the intratumoral DCs. Administration of STING agonist MSA-2 reduces the lysosomal activity in DCs, restores antigen cross presentation, and increases therapeutic efficacy of PD-1 blockade against tumour challenge in a CH25H-dependent manner. These studies highlight the importance of downregulation of CH25H in DCs for tumor immune evasion and resistance to therapy.
Reward expectation extinction restructures and degrades CA1 spatial maps through loss of a dopaminergic reward proximity signal
Authors: Krishnan Seetha , Heer Chad , Cherian Chery , Sheffield Mark E. J. 
Published: November 2022

AbstractHippocampal place cells support reward-related spatial memories by forming a cognitive map that over-represents reward locations. The strength of these memories is modulated by the extent of reward expectation during encoding. However, the circuit mechanisms underlying this modulation are unclear. Here we find that when reward expectation is extinguished in mice, they remain engaged with their environment, yet place cell over-representation of rewards vanishes, place field remapping throughout the environment increases, and place field trial-to-trial reliability decreases. Interestingly, Ventral Tegmental Area (VTA) dopaminergic axons in CA1 exhibit a ramping reward-proximity signal that depends on reward expectation and inhibiting VTA dopaminergic neurons largely replicates the effects of extinguishing reward expectation. We conclude that changing reward expectation restructures CA1 cognitive maps and determines map reliability by modulating the dopaminergic VTA-CA1 reward-proximity signal. Thus, internal states of high reward expectation enhance encoding of spatial memories by reinforcing hippocampal cognitive maps associated with reward.
Three-dimensional open architecture enabling salt-rejection solar evaporators with boosted water production efficiency
Authors: Yang Kaijie , Pan Tingting , Dang Saichao , Gan Qiaoqiang , Han Yu 
Published: November 2022

AbstractDirect solar desalination exhibits considerable potential for alleviating the global freshwater crisis. However, the prevention of salt accumulation while maintaining high water production remains an important challenge that limits its practical applications because the methods currently employed for achieving rapid salt backflow usually result in considerable heat loss. Herein, we fabricate a solar evaporator featuring vertically aligned mass transfer bridges for water transport and salt backflow. The 3D open architecture constructed using mass transfer bridges enables the evaporator to efficiently utilize the conductive heat that would otherwise be lost, significantly improving the water evaporation efficiency without compromising on salt rejection. The fabricated evaporator can treat salt water with more than 10% salinity. Moreover, it can continuously and steadily work in a real environment under natural sunlight with a practical solar-to-water collection efficiency of >40%. Using the discharged water from reverse osmosis plants and sea water from the Red Sea, the evaporator demonstrates a daily freshwater generation rate of ~5 L/m2, which is sufficient to satisfy individual drinking water requirements. With strong salt rejection, high energy efficiency, and simple scalability, the 3D evaporator has considerable promise for freshwater supply for water-stressed and off-grid communities.