bluuebunny/crossref_metadata_2025 huggingface dataset:
SUMOylation inhibition enhances multiple myeloma sensitivity to lenalidomide
Authors: Du Li , Liu Wei , Pichiorri Flavia , Rosen Steven T.
Published: March 2022

Despite the potent effect of lenalidomide (Len) in multiple myeloma (MM) treatment, patients develop Len resistance leading to progressive disease, demanding an urgent need to investigate the mechanisms mediating Len resistance. Our study identified SUMOylation as a potential mechanism regulating Len resistance in MM. Len-resistant MM cell line MMR10R presented much higher SUMO E1 (SAE2) expression and more global SUMOylation than Len-sensitive MM1S cell line. SUMOylation inhibition by using TAK-981, a novel and specific SUMO E1 inhibitor, significantly enhances myeloma sensitivity to Len in MM cell lines. Moreover, the enhanced anti-MM activity by TAK-981 and Len combination has been validated using primary relapsing MM patient samples. Overexpression of IRF4 and c-Myc is a major mechanism of Len resistance. Len showed limited effect on IRF4 and c-Myc level in Len-resistance cell line, but TAK-981 treatment reduced IRF4 and c-Myc expression in Len-resistant line and caused further decrease when combined with Len. We found SUMOylation inhibition decreases IRF4 at transcriptional and post-translational level. SUMOylation inhibition reduced DOT1L with decreased methylation of histone H3 lysine 79, to suppress IRF4 gene transcription. SUMOylation inhibition also reduced IRF4 protein level by enhancing degradation. Overall, our data revealed SUMOylation inhibition enhances Len sensitivity through downregulating IRF4.
Pseudophosphatase STYX is induced by Helicobacter pylori and promotes gastric cancer progression by inhibiting FBXO31 function
Authors: Liu Jiansong , Zang Yichen , Ma Cunying , Wang Dandan , Tian Zhuangfei , Xu Xia , Li Wenjuan , Jia Jihui , Liu Zhifang
Published: March 2022

Gastric cancer (GC) is one of the most common malignancies in the world and ranks third in terms of cancer-related deaths. The catalytically inactive pseudophosphatase STYX (serine/threonine/tyrosine interacting protein) is a member of the protein tyrosine phosphatase family. It has been recently reported that STYX functions as a potential oncogene in different types of cancers. However, the potential role and regulatory mechanism of STYX in GC remains unknown. In this study, we find that STYX is highly expressed in GC tissues compared with adjacent noncancerous tissues and closely correlates with the prognosis of GC patients. STYX overexpression facilitates the proliferation and migration in GC cells, whereas STYX knockdown has the opposite effects. Nude mice experiments indicate that STYX knockdown in GC cells dramatically suppresses the tumor growth and lung metastasis in vivo. Mechanically, our results suggest that STYX interacts with the F-box protein FBXO31 and disrupts the degradation function of FBXO31 to its target proteins CyclinD1 and Snail1, thereby increasing the level of CyclinD1 and Snail1 in GC. STYX-mediated biological changes can be reversed by the co-expression of STYX and FBXO31 in GC cells. In addition, transcription factor c-Jun can enhance the expression of STYX in GC. The expression of STYX can also be induced by Helicobacter pylori (H. pylori) infection in c-Jun-dependent manner. Together, our present study suggests that STYX plays an oncogenic role in GC by inhibiting FBXO31 function and represents a potential therapeutic target and prognostic biomarker in GC.
Targeting tumor innervation: premises, promises, and challenges
Authors: Li Xinyu , Peng Xueqiang , Yang Shuo , Wei Shibo , Fan Qing , Liu Jingang , Yang Liang , Li Hangyu
Published: March 2022

A high intratumoral nerve density is correlated with poor survival, high metastasis, and high recurrence across multiple solid tumor types. Recent research has revealed that cancer cells release diverse neurotrophic factors and exosomes to promote tumor innervation, in addition, infiltrating nerves can also mediate multiple tumor biological processes via exosomes and neurotransmitters. In this review, through seminal studies establishing tumor innervation, we discuss the communication between peripheral nerves and tumor cells in the tumor microenvironment (TME), and revealed the nerve-tumor regulation mechanisms on oncogenic process, angiogenesis, lymphangiogenesis, and immunity. Finally, we discussed the promising directions of ‘old drugs newly used’ to target TME communication and clarified a new line to prevent tumor malignant capacity.
Avian influenza viruses suppress innate immunity by inducing trans-transcriptional readthrough via SSU72
Authors: Zhao Yan , Huang Fengming , Zou Zhen , Bi Yuhai , Yang Yang , Zhang Cong , Liu Qiang , Shang Daozhen , Yan Yiwu , Ju Xiangwu , Mei Song , Xie Peng , Li Xiao , Tian Mingyao , Tan Shuguang , Lu Huijun , Han Zongsheng , Liu Kangtai , Zhang Yuqing , Liang Junbo , Liang Zhu , Zhang Qingchao , Chang Jiahui , Liu William J. , Feng Cong , Li Tanshi , Zhang Michael Q. , Wang Xiaoyue , Gao George F. , Liu Yingxia , Jin Ningyi , Jiang Chengyu
Published: March 2022

Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can better escape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by which transcriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouse lungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved in the disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishment increased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 induced TRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT by reducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.
Integrating deep learning and unbiased automated high-content screening to identify complex disease signatures in human fibroblasts
Authors: Schiff Lauren , Migliori Bianca , Chen Ye , Carter Deidre , Bonilla Caitlyn , Hall Jenna , Fan Minjie , Tam Edmund , Ahadi Sara , Fischbacher Brodie , Geraschenko Anton , Hunter Christopher J. , Venugopalan Subhashini , DesMarteau Sean , Narayanaswamy Arunachalam , Jacob Selwyn , Armstrong Zan , Ferrarotto Peter , Williams Brian , Buckley-Herd Geoff , Hazard Jon , Goldberg Jordan , Coram Marc , Otto Reid , Baltz Edward A. , Andres-Martin Laura , Pritchard Orion , Duren-Lubanski Alyssa , Daigavane Ameya , Reggio Kathryn ,   NYSCF Global Stem Cell Array® Team, Nelson Phillip C. , Frumkin Michael , Solomon Susan L. , Bauer Lauren , Aiyar Raeka S. , Schwarzbach Elizabeth , Noggle Scott A. , Monsma Frederick J. , Paull Daniel , Berndl Marc , Yang Samuel J. , Johannesson Bjarki
Published: March 2022

Drug discovery for diseases such as Parkinson’s disease are impeded by the lack of screenable cellular phenotypes. We present an unbiased phenotypic profiling platform that combines automated cell culture, high-content imaging, Cell Painting, and deep learning. We applied this platform to primary fibroblasts from 91 Parkinson’s disease patients and matched healthy controls, creating the largest publicly available Cell Painting image dataset to date at 48 terabytes. We use fixed weights from a convolutional deep neural network trained on ImageNet to generate deep embeddings from each image and train machine learning models to detect morphological disease phenotypes. Our platform’s robustness and sensitivity allow the detection of individual-specific variation with high fidelity across batches and plate layouts. Lastly, our models confidently separate LRRK2 and sporadic Parkinson’s disease lines from healthy controls (receiver operating characteristic area under curve 0.79 (0.08 standard deviation)), supporting the capacity of this platform for complex disease modeling and drug screening applications.
Pumilio protects Xbp1 mRNA from regulated Ire1-dependent decay
Authors: Cairrão Fátima , Santos Cristiana C. , Le Thomas Adrien , Marsters Scot , Ashkenazi Avi , Domingos Pedro M.
Published: March 2022

The unfolded protein response (UPR) maintains homeostasis of the endoplasmic reticulum (ER). Residing in the ER membrane, the UPR mediator Ire1 deploys its cytoplasmic kinase-endoribonuclease domain to activate the key UPR transcription factor Xbp1 through non-conventional splicing of Xbp1 mRNA. Ire1 also degrades diverse ER-targeted mRNAs through regulated Ire1-dependent decay (RIDD), but how it spares Xbp1 mRNA from this decay is unknown. Here, we identify binding sites for the RNA-binding protein Pumilio in the 3′UTR Drosophila Xbp1. In the developing Drosophila eye, Pumilio binds both the Xbp1unspliced and Xbp1spliced mRNAs, but only Xbp1spliced is stabilized by Pumilio. Furthermore, Pumilio displays Ire1 kinase-dependent phosphorylation during ER stress, which is required for its stabilization of Xbp1spliced. hIRE1 can phosphorylate Pumilio directly, and phosphorylated Pumilio protects Xbp1spliced mRNA against RIDD. Thus, Ire1-mediated phosphorylation enables Pumilio to shield Xbp1spliced from RIDD. These results uncover an unexpected regulatory link between an RNA-binding protein and the UPR.
Adrenal tropism of SARS-CoV-2 and adrenal findings in a post-mortem case series of patients with severe fatal COVID-19
Authors: Paul Tanja , Ledderose Stephan , Bartsch Harald , Sun Na , Soliman Sarah , Märkl Bruno , Ruf Viktoria , Herms Jochen , Stern Marcel , Keppler Oliver T. , Delbridge Claire , Müller Susanna , Piontek Guido , Kimoto Yuki Schneider , Schreiber Franziska , Williams Tracy Ann , Neumann Jens , Knösel Thomas , Schulz Heiko , Spallek Ria , Graw Matthias , Kirchner Thomas , Walch Axel , Rudelius Martina
Published: March 2022

Progressive respiratory failure and hyperinflammatory response is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. Despite mounting evidence of disruption of the hypothalamus-pituitary-adrenal axis in COVID-19, relatively little is known about the tropism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to adrenal glands and associated changes. Here we demonstrate adrenal viral tropism and replication in COVID-19 patients. Adrenal glands showed inflammation accompanied by inflammatory cell death. Histopathologic analysis revealed widespread microthrombosis and severe adrenal injury. In addition, activation of the glycerophospholipid metabolism and reduction of cortisone intensities were characteristic for COVID-19 specimens. In conclusion, our autopsy series suggests that SARS-CoV-2 facilitates the induction of adrenalitis. Given the central role of adrenal glands in immunoregulation and taking into account the significant adrenal injury observed, monitoring of developing adrenal insufficiency might be essential in acute SARS-CoV-2 infection and during recovery.
Genetic regulation of post-translational modification of two distinct proteins
Authors: Landini Arianna , Trbojević-Akmačić Irena , Navarro Pau , Tsepilov Yakov A. , Sharapov Sodbo Z. , Vučković Frano , Polašek Ozren , Hayward Caroline , Petrović Tea , Vilaj Marija , Aulchenko Yurii S. , Lauc Gordan , Wilson James F. , Klarić Lucija
Published: March 2022

Post-translational modifications diversify protein functions and dynamically coordinate their signalling networks, influencing most aspects of cell physiology. Nevertheless, their genetic regulation or influence on complex traits is not fully understood. Here, we compare the genetic regulation of the same PTM of two proteins – glycosylation of transferrin and immunoglobulin G (IgG). By performing genome-wide association analysis of transferrin glycosylation, we identify 10 significantly associated loci, 9 of which were not reported previously. Comparing these with IgG glycosylation-associated genes, we note protein-specific associations with genes encoding glycosylation enzymes (transferrin - MGAT5, ST3GAL4, B3GAT1; IgG - MGAT3, ST6GAL1), as well as shared associations (FUT6, FUT8). Colocalisation analyses of the latter suggest that different causal variants in the FUT genes regulate fucosylation of the two proteins. Glycosylation of these proteins is thus genetically regulated by both shared and protein-specific mechanisms.
Guide RNAs containing universal bases enable Cas9/Cas12a recognition of polymorphic sequences
Authors: Krysler Amanda R. , Cromwell Christopher R. , Tu Tommy , Jovel Juan , Hubbard Basil P.
Published: March 2022

CRISPR/Cas complexes enable precise gene editing in a wide variety of organisms. While the rigid identification of DNA sequences by these systems minimizes the potential for off-target effects, it consequently poses a problem for the recognition of sequences containing naturally occurring polymorphisms. The presence of genetic variance such as single nucleotide polymorphisms (SNPs) in a gene sequence can compromise the on-target activity of CRISPR systems. Thus, when attempting to target multiple variants of a human gene, or evolved variants of a pathogen gene using a single guide RNA, more flexibility is desirable. Here, we demonstrate that Cas9 can tolerate the inclusion of universal bases in individual guide RNAs, enabling simultaneous targeting of polymorphic sequences. Crucially, we find that specificity is selectively degenerate at the site of universal base incorporation, and remains otherwise preserved. We demonstrate the applicability of this technology to targeting multiple naturally occurring human SNPs with individual guide RNAs and to the design of Cas12a/Cpf1-based DETECTR probes capable of identifying multiple evolved variants of the HIV protease gene. Our findings extend the targeting capabilities of CRISPR/Cas systems beyond their canonical spacer sequences and highlight a use of natural and synthetic universal bases.
CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity
Authors: Joung Julia , Kirchgatterer Paul C. , Singh Ankita , Cho Jang H. , Nety Suchita P. , Larson Rebecca C. , Macrae Rhiannon K. , Deasy Rebecca , Tseng Yuen-Yi , Maus Marcela V. , Zhang Feng
Published: March 2022

The cellular processes that govern tumor resistance to immunotherapy remain poorly understood. To gain insight into these processes, here we perform a genome-scale CRISPR activation screen for genes that enable human melanoma cells to evade cytotoxic T cell killing. Overexpression of four top candidate genes (CD274 (PD-L1), MCL1, JUNB, and B3GNT2) conferred resistance in diverse cancer cell types and mouse xenografts. By investigating the resistance mechanisms, we find that MCL1 and JUNB modulate the mitochondrial apoptosis pathway. JUNB encodes a transcription factor that downregulates FasL and TRAIL receptors, upregulates the MCL1 relative BCL2A1, and activates the NF-κB pathway. B3GNT2 encodes a poly-N-acetyllactosamine synthase that targets >10 ligands and receptors to disrupt interactions between tumor and T cells and reduce T cell activation. Inhibition of candidate genes sensitized tumor models to T cell cytotoxicity. Our results demonstrate that systematic gain-of-function screening can elucidate resistance pathways and identify potential targets for cancer immunotherapy.
Electrical manipulation of skyrmions in a chiral magnet
Authors: Wang Weiwei , Song Dongsheng , Wei Wensen , Nan Pengfei , Zhang Shilei , Ge Binghui , Tian Mingliang , Zang Jiadong , Du Haifeng
Published: March 2022

Writing, erasing and computing are three fundamental operations required by any working electronic device. Magnetic skyrmions could be essential bits in promising in emerging topological spintronic devices. In particular, skyrmions in chiral magnets have outstanding properties like compact texture, uniform size, and high mobility. However, creating, deleting, and driving isolated skyrmions, as prototypes of aforementioned basic operations, have been a grand challenge in chiral magnets ever since the discovery of skyrmions, and achieving all these three operations in a single device is even more challenging. Here, by engineering chiral magnet Co8Zn10Mn2 into the customized micro-devices for in-situ Lorentz transmission electron microscopy observations, we implement these three operations of skyrmions using nanosecond current pulses with a low current density of about 1010 A·m−2 at room temperature. A notched structure can create or delete magnetic skyrmions depending on the direction and magnitude of current pulses. We further show that the magnetic skyrmions can be deterministically shifted step-by-step by current pulses, allowing the establishment of the universal current-velocity relationship. These experimental results have immediate significance towards the skyrmion-based memory or logic devices.
Metabolic engineering strategies to produce medium-chain oleochemicals via acyl-ACP:CoA transacylase activity
Authors: Yan Qiang , Cordell William T. , Jindra Michael A. , Courtney Dylan K. , Kuckuk Madeline K. , Chen Xuanqi , Pfleger Brian F.
Published: March 2022

Microbial lipid metabolism is an attractive route for producing oleochemicals. The predominant strategy centers on heterologous thioesterases to synthesize desired chain-length fatty acids. To convert acids to oleochemicals (e.g., fatty alcohols, ketones), the narrowed fatty acid pool needs to be reactivated as coenzyme A thioesters at cost of one ATP per reactivation - an expense that could be saved if the acyl-chain was directly transferred from ACP- to CoA-thioester. Here, we demonstrate such an alternative acyl-transferase strategy by heterologous expression of PhaG, an enzyme first identified in Pseudomonads, that transfers 3-hydroxy acyl-chains between acyl-carrier protein and coenzyme A thioester forms for creating polyhydroxyalkanoate monomers. We use it to create a pool of acyl-CoA’s that can be redirected to oleochemical products. Through bioprospecting, mutagenesis, and metabolic engineering, we develop three strains of Escherichia coli capable of producing over 1 g/L of medium-chain free fatty acids, fatty alcohols, and methyl ketones.
Spin-orbit enabled all-electrical readout of chiral spin-textures
Authors: Lima Fernandes Imara , Blügel Stefan , Lounis Samir
Published: March 2022

Chirality and topology are intimately related fundamental concepts, which are heavily explored to establish spin-textures as potential magnetic bits in information technology. However, this ambition is inhibited since the electrical reading of chiral attributes is highly non-trivial with conventional current perpendicular-to-plane (CPP) sensing devices. Here we demonstrate from extensive first-principles simulations and multiple scattering expansion the emergence of the chiral spin-mixing magnetoresistance (C-XMR) enabling highly efficient all-electrical readout of the chirality and helicity of respectively one- and two-dimensional magnetic states of matter. It is linear with spin-orbit coupling in contrast to the quadratic dependence associated with the unveiled non-local spin-mixing anisotropic MR (X-AMR). Such transport effects are systematized on various non-collinear magnetic states – spin-spirals and skyrmions – and compared to the uncovered spin-orbit-independent multi-site magnetoresistances. Owing to their simple implementation in readily available reading devices, the proposed magnetoresistances offer exciting and decisive ingredients to explore with all-electrical means the rich physics of topological and chiral magnetic objects.
Coexistence of electron whispering-gallery modes and atomic collapse states in graphene/WSe2 heterostructure quantum dots
Authors: Zheng Qi , Zhuang Yu-Chen , Sun Qing-Feng , He Lin
Published: March 2022

The relativistic massless charge carriers with a Fermi velocity of about c/300 in graphene enable us to realize two distinct types of resonances (here, c is the speed of light in vacuum). One is the electron whispering-gallery mode in graphene quantum dots arising from the Klein tunneling of the massless Dirac fermions. The other is the atomic collapse state, which has never been observed in experiment with real atoms due to the difficulty of producing heavy nuclei with charge Z > 170; however, they can be realized near a Coulomb impurity in graphene with a charge Z ≥ 1 because of the “small” velocity of the Dirac excitations. Here we demonstrate that both the electron whispering-gallery modes and atomic collapse states coexist in graphene/WSe2 heterostructure quantum dots due to the Coulomb-like potential near their edges. By applying a perpendicular magnetic field, we explore the evolution from the atomic collapse states to unusual Landau levels in the collapse regime.
The speed limit of optoelectronics
Authors: Ossiander M. , Golyari K. , Scharl K. , Lehnert L. , Siegrist F. , Bürger J. P. , Zimin D. , Gessner J. A. , Weidman M. , Floss I. , Smejkal V. , Donsa S. , Lemell C. , Libisch F. , Karpowicz N. , Burgdörfer J. , Krausz F. , Schultze M.
Published: March 2022

Light-field driven charge motion links semiconductor technology to electric fields with attosecond temporal control. Motivated by ultimate-speed electron-based signal processing, strong-field excitation has been identified viable for the ultrafast manipulation of a solid’s electronic properties but found to evoke perplexing post-excitation dynamics. Here, we report on single-photon-populating the conduction band of a wide-gap dielectric within approximately one femtosecond. We control the subsequent Bloch wavepacket motion with the electric field of visible light. The resulting current allows sampling optical fields and tracking charge motion driven by optical signals. Our approach utilizes a large fraction of the conduction-band bandwidth to maximize operating speed. We identify population transfer to adjacent bands and the associated group velocity inversion as the mechanism ultimately limiting how fast electric currents can be controlled in solids. Our results imply a fundamental limit for classical signal processing and suggest the feasibility of solid-state optoelectronics up to 1 PHz frequency.
Ultrastructural insight into SARS-CoV-2 entry and budding in human airway epithelium
Authors: Pinto Andreia L. , Rai Ranjit K. , Brown Jonathan C. , Griffin Paul , Edgar James R. , Shah Anand , Singanayagam Aran , Hogg Claire , Barclay Wendy S. , Futter Clare E. , Burgoyne Thomas
Published: March 2022

Ultrastructural studies of SARS-CoV-2 infected cells are crucial to better understand the mechanisms of viral entry and budding within host cells. Here, we examined human airway epithelium infected with three different isolates of SARS-CoV-2 including the B.1.1.7 variant by transmission electron microscopy and tomography. For all isolates, the virus infected ciliated but not goblet epithelial cells. Key SARS-CoV-2 entry molecules, ACE2 and TMPRSS2, were found to be localised to the plasma membrane including microvilli but excluded from cilia. Consistently, extracellular virions were seen associated with microvilli and the apical plasma membrane but rarely with ciliary membranes. Profiles indicative of viral fusion where tomography showed that the viral membrane was continuous with the apical plasma membrane and the nucleocapsids diluted, compared with unfused virus, demonstrate that the plasma membrane is one site of entry where direct fusion releasing the nucleoprotein-encapsidated genome occurs. Intact intracellular virions were found within ciliated cells in compartments with a single membrane bearing S glycoprotein. Tomography showed concentration of nucleocapsids round the periphery of profiles strongly suggestive of viral budding into these compartments and this may explain how virions gain their S glycoprotein containing envelope.
Stripenn detects architectural stripes from chromatin conformation data using computer vision
Authors: Yoon Sora , Chandra Aditi , Vahedi Golnaz
Published: March 2022

Architectural stripes tend to form at genomic regions harboring genes with salient roles in cell identity and function. Therefore, the accurate identification and quantification of these features are essential for understanding lineage-specific gene regulation. Here, we present Stripenn, an algorithm rooted in computer vision to systematically detect and quantitate architectural stripes from chromatin conformation measurements using various technologies. We demonstrate that Stripenn outperforms existing methods and highlight its biological applications in the context of B and T lymphocytes. By comparing stripes across distinct cell types and different species, we find that these chromatin features are highly conserved and form at genes with prominent roles in cell-type-specific processes. In summary, Stripenn is a computational method that borrows concepts from widely used image processing techniques to demarcate and quantify architectural stripes.
PUMILIO proteins promote colorectal cancer growth via suppressing p21
Authors: Gong Yuanyuan , Liu Zukai , Yuan Yihang , Yang Zhenzhen , Zhang Jiawei , Lu Qin , Wang Wei , Fang Chao , Lin Haifan , Liu Sanhong
Published: March 2022

PUMILIO (PUM) proteins belong to the highly conserved PUF family post-transcriptional regulators involved in diverse biological processes. However, their function in carcinogenesis remains under-explored. Here, we report that Pum1 and Pum2 display increased expression in human colorectal cancer (CRC). Intestine-specific knockout of Pum1 and Pum2 in mice significantly inhibits the progression of colitis-associated cancer in the AOM/DSS model. Knockout or knockdown of Pum1 and/or Pum2 in human CRC cells result in a significant decrease in the tumorigenicity and delayed G1/S transition. We identify p21/Cdkn1a as a direct target of PUM1. Abrogation of the PUM1 binding site in the p21 mRNA also results in decreased cancer cell growth and delayed G1/S transition. Furthermore, intravenous injection of nanoparticle-encapsulated anti-Pum1 and Pum2 siRNAs reduces colorectal tumor growth in murine orthotopic colon cancer models. These findings reveal the requirement of PUM proteins for CRC progression and their potential as therapeutic targets.
Quantum transport and localization in 1d and 2d tight-binding lattices
Authors: Karamlou Amir H. , Braumüller Jochen , Yanay Yariv , Di Paolo Agustin , Harrington Patrick M. , Kannan Bharath , Kim David , Kjaergaard Morten , Melville Alexander , Muschinske Sarah , Niedzielski Bethany M. , Vepsäläinen Antti , Winik Roni , Yoder Jonilyn L. , Schwartz Mollie , Tahan Charles , Orlando Terry P. , Gustavsson Simon , Oliver William D.
Published: March 2022

Particle transport and localization phenomena in condensed-matter systems can be modeled using a tight-binding lattice Hamiltonian. The ideal experimental emulation of such a model utilizes simultaneous, high-fidelity control and readout of each lattice site in a highly coherent quantum system. Here, we experimentally study quantum transport in one-dimensional and two-dimensional tight-binding lattices, emulated by a fully controllable 3 × 3 array of superconducting qubits. We probe the propagation of entanglement throughout the lattice and extract the degree of localization in the Anderson and Wannier-Stark regimes in the presence of site-tunable disorder strengths and gradients. Our results are in quantitative agreement with numerical simulations and match theoretical predictions based on the tight-binding model. The demonstrated level of experimental control and accuracy in extracting the system observables of interest will enable the exploration of larger, interacting lattices where numerical simulations become intractable.
Patients seeking stem cell therapies—a prospective qualitative analysis from a Regenerative Medicine Consult Service
Authors: Arthurs Jennifer R. , Nordan Lisa M. , Hultgren Brian H. , Heckman Michael G. , Martinez Dayana , Master Zubin , Shapiro Shane A.
Published: March 2022

Despite patient demand for stem cell therapies (SCTs) for musculoskeletal conditions, there remains limited research on why patients seek SCTs or their sources of information. We employ three questions into a consult intake form: (1) Why are you interested in stem cell treatment for your condition? (2) How did you find out about stem cell treatment for your condition? (3) Have you contacted a stem cell clinic? Responses analyzed, using a qualitative content analysis approach to identify themes reveal many patients seek SCTs to treat pain or delay surgery which may align with some current clinical evidence while other patients express motivations as expected outcomes (e.g., SCTs are better than standard of care or can regenerate tissue) which are not supported by current medical evidence. These differences suggests that patient-centered counseling may help patients by addressing misconceptions and increasing health literacy about expected outcomes of SCTs for treating musculoskeletal conditions.
A robust method for designing multistable systems by embedding bistable subsystems
Authors: Wu Siyuan , Zhou Tianshou , Tian Tianhai
Published: March 2022

Although multistability is an important dynamic property of a wide range of complex systems, it is still a challenge to develop mathematical models for realising high order multistability using realistic regulatory mechanisms. To address this issue, we propose a robust method to develop multistable mathematical models by embedding bistable models together. Using the GATA1-GATA2-PU.1 module in hematopoiesis as the test system, we first develop a tristable model based on two bistable models without any high cooperative coefficients, and then modify the tristable model based on experimentally determined mechanisms. The modified model successfully realises four stable steady states and accurately reflects a recent experimental observation showing four transcriptional states. In addition, we develop a stochastic model, and stochastic simulations successfully realise the experimental observations in single cells. These results suggest that the proposed method is a general approach to develop mathematical models for realising multistability and heterogeneity in complex systems.
Open access dataset of task-free hemodynamic activity in 4-month-old infants during sleep using fNIRS
Authors: Blanco Borja , Molnar Monika , Carreiras Manuel , Caballero-Gaudes César
Published: March 2022

Spontaneous, task-free, hemodynamic activity of the brain provides useful information about its functional organization, as it can describe how different brain regions communicate to each other. Neuroimaging studies measuring the spontaneous activity of the brain are conducted while the participants are not engaged in a particular task or receiving any external stimulation. This approach is particularly useful in developmental populations as brain activity can be measured without the need for infant compliance and the risks of data contamination due to motion artifacts. In this project we sought to i) characterize the intrinsic functional organization of the brain in 4-month-old infants and ii) investigate whether bilingualism, as a specific environmental factor, could lead to adaptations on functional brain network development at this early age. Measures of spontaneous hemodynamic activity were acquired in 4-month-old infants (n = 104) during natural sleep using functional near-infrared spectroscopy (fNIRS). Emphasis was placed on acquiring high-quality data that could lead to reproducible results and serve as a valuable resource for researchers investigating the developing functional connectome.
City- and county-level spatio-temporal energy consumption and efficiency datasets for China from 1997 to 2017
Authors: Chen Jiandong , Liu Jialu , Qi Jie , Gao Ming , Cheng Shulei , Li Ke , Xu Chong
Published: March 2022

Understanding the evolution of energy consumption and efficiency in China would contribute to assessing the effectiveness of the government’s energy policies and the feasibility of meeting its international commitments. However, sub-national energy consumption and efficiency data have not been published for China, hindering the identification of drivers of differences in energy consumption and efficiency, and implementation of differentiated energy policies between cities and counties. This study estimated the energy consumption of 336 cities and 2,735 counties in China by combining Defense Meteorological Satellite Program/Operational Line-scan System (DMSP/OLS) and Suomi National Polar-Orbiting Partnership/Visible Infrared Imaging Radiometer Suite (NPP/VIIRS) satellite nighttime light data using particle swarm optimization-back propagation (PSO-BP). The energy efficiency of these cities and counties was measured using energy consumption per unit GDP and data envelopment analysis (DEA). These data can facilitate further research on energy consumption and efficiency issues at the city and county levels in China. The developed estimation methods can also be used in other developing countries and regions where official energy statistics are limited.
Pronounced mito-nuclear discordance and various Wolbachia infections in the water ringlet Erebia pronoe have resulted in a complex phylogeographic structure
Authors: Wendt Martin , Kulanek Dustin , Varga Zoltan , Rákosy Laszlo , Schmitt Thomas
Published: March 2022

Several morphological and mitochondrial lineages of the alpine ringlet butterfly species Erebia pronoe have been described, indicating a complex phylogenetic structure. However, the existing data were insufficient and allow neither a reconstruction of the biogeographic history, nor an assessment of the genetic lineages. Therefore, we analysed mitochondrial (COI, NDI) and nuclear (EF1α, RPS5) gene sequences and compared them with sequences from the sister species Erebia melas. Additionally, we combined this information with morphometric data of the male genitalia and the infection patterns with Wolbachia strains, based on a WSP analysis. We obtained a distinct phylogeographic structure within the E. pronoe-melas complex with eight well-distinguishable geographic groups, but also a remarkable mito-nuclear discordance. The mito-nuclear discordance in E. melas and E. pronoe glottis can be explained by different ages of Wolbachia infections with different Wolbachia strains, associated selective sweeps, and hybridisation inhibition. Additionally, we found indications for incipient speciation of E. pronoe glottis in the Pyrenees and a pronounced range dynamic within and among the other high mountain systems of Europe. Our results emphasize the importance of combined approaches in reconstructing biogeographic patterns and evaluating phylogeographic splits.
Nigratine as dual inhibitor of necroptosis and ferroptosis regulated cell death
Authors: Delehouzé Claire , Comte Arnaud , Leon-Icaza Stephen Adonai , Cougoule Céline , Hauteville Marcelle , Goekjian Peter , Bulinski Jeannette Chloë , Dimanche-Boitrel Marie-Thérèse , Meunier Etienne , Rousselot Morgane , Bach Stéphane
Published: March 2022

Nigratine (also known as 6E11), a flavanone derivative of a plant natural product, was characterized as highly specific non-ATP competitive inhibitor of RIPK1 kinase, one of the key components of necroptotic cell death signaling. We show here that nigratine inhibited both necroptosis (induced by Tumor Necrosis Factor-α) and ferroptosis (induced by the small molecules glutamate, erastin, RSL3 or cumene hydroperoxide) with EC50 in the µM range. Taken together, our data showed that nigratine is a dual inhibitor of necroptosis and ferroptosis cell death pathways. These findings open potential new therapeutic avenues for treating complex necrosis-related diseases.
Effects of COVID-19 lockdowns on shorebird assemblages in an urban South African sandy beach ecosystem
Authors: Lewis Jemma , Collison Jayden , Pillay Deena
Published: March 2022

Human pressures are pervasive in coastal ecosystems, but their effect magnitudes are masked by methodological limitations. Government lockdowns associated with the global COVID-19 pandemic can address this gap since lockdowns are effectively manipulations of human presence in ecosystems at scales unachievable otherwise. We illustrate this using a study on shorebirds in an urban South African sandy beach ecosystem. Data collected prior to (2019) and during the COVID-19 (2020) pandemic indicated an inverse relationship between shorebird and human numbers, but this was stronger in 2020. In 2020, human exclusion resulted in a six-fold increase in shorebird abundance relative to 2019. Following easing of lockdowns, shorebird abundance declined by 79.6% with a 34.1% increase in human density. Our findings highlight the sensitivity of shorebirds to recreational disturbance, the potential for current methodological approaches to underestimate repercussions of disturbance and the capacity for COVID-19 lockdowns to refine understanding of human-induced stress in ecosystems.
Investigation of the hydrodynamic characteristics of an axial flow pump system under special utilization conditions
Authors: Zhang Xiaowen , Tang Fangping
Published: March 2022

In actual operation, axial flow pump stations are often used for various special purposes to meet changing needs. However, because the hydrodynamic characteristics of axial flow pump systems are still unclear when used for special purposes, there are many risks when pump systems are used for special purposes. To explore the hydrodynamic characteristics of an axial flow pump system under special utilization conditions, a high-precision full-feature test bench for an axial flow pump system is established in this paper. For the first time, an energy characteristics experiment and a pressure fluctuation measurement for a pump are carried out for a large axial flow pump system model under zero head, reverse pump and reverse power generation conditions. Then, ANSYS CFX software is used to solve the continuous equation and Reynolds average Navier–Stokes equation, combined with the SST k–ω turbulence model, and the characteristic curve and internal flow field of the pump system under special conditions are obtained. Finally, the numerical simulation results are compared with the experimental results. The results show that the velocity gradient distribution in the pump is uniform under the near zero head condition (NZHC), and there is no obvious flow collision and reflux phenomenon in the pump. Compared with the designed condition (DC), the peak-to-peak value (PPV) of pressure pulsation at the inlet of the impeller decreased by 67.16%, and the PPV at the outlet of the impeller decreased by 8.14% at H = 0 m. The maximum value of the main frequency amplitude (MFA) in the impeller area appears at the impeller inlet. Under reverse pump conditions (RPC), the phenomenon of unstable flow in the pump system is obvious, and a large range of recirculation zones appears in the nonworking face of the blade. Compared with the DC, the PPV of the impeller inlet at the optimal point of RPC increased by 122.61%, and the impeller outlet PPV increased by 11.37%. The maximum value of MFA in the impeller area appears at the impeller inlet. Under the reverse power generation condition (RPGC), no obvious flow separation was found in the nonworking face of the impeller. Compared to the DC, the PPV of the impeller inlet at the optimal point of the RPGC increased by 65.34%, and the PPV of the impeller outlet increased by 206.40%.
How atoms of polycrystalline Nb20.6Mo21.7Ta15.6W21.1V21.0 refractory high-entropy alloys rearrange during the melting process
Authors: Ju Shin-Pon , Li Chen-Chun , Shih Huai-Ting
Published: March 2022

The melting mechanism of single crystal and polycrystalline Nb20.6Mo21.7Ta15.6W21.1V21.0 refractory high entropy alloys (RHEAs) were investigated by the molecular dynamics (MD) simulation using the second-nearest neighbor modified embedded-atom method (2NN MEAM) potential. For the single crystal RHEA, the density profile displays an abrupt drop from 11.25 to 11.00 g/cm3 at temperatures from 2910 to 2940 K, indicating all atoms begin significant local structural rearrangement. For polycrystalline RHEAs, a two-stage melting process is found. In the first melting stage, the melting of the grain boundary (GB) regions firstly occurs at the pre-melting temperature, which is relatively lower than the corresponding system-melting point. At the pre-melting temperature, most GB atoms have enough kinetic energies to leave their equilibrium positions, and then gradually induce the rearrangement of grain atoms close to GB. In the second melting stage at the melting point, most grain atoms have enough kinetic energies to rearrange, resulting in the chemical short-ranged order changes of all pairs.
The association between prehospital vital signs of children and their critical clinical outcomes at hospitals
Authors: Kurosawa Hiroshi , Shiima Yuko , Miyakoshi Chisato , Nezu Mari , Someya Maki , Yoshida Minae , Nagase Hiroaki , Nozu Kandai , Kosaka Yoshiyuki , Iijima Kazumoto
Published: March 2022

Vital signs are important for patient assessment, but little is known about interpreting those of children in prehospital settings. We conducted an observational study to investigate the association between prehospital vital signs of children and their clinical outcomes in hospitals. We plotted the data of patients with critical outcomes on published reference ranges, such as those of healthy children to evaluate the clinical relevance. Of the 18,493 children screened, 4477 transported to tertiary hospitals were included in the analysis. The outcomes 12 h after being transported to a tertiary hospital were as follows: deceased, 41; hospitalization with critical deterioration events, 65; hospitalization without critical deterioration events, 1086; returned home, 3090; and unknown, 195. The reference ranges of the heart rates (sensitivity: 57.7%, specificity: 67.5%) and respiratory rates (sensitivity: 54.5%, specificity: 67.7%) of healthy children worked best to detect the critical outcomes. Therefore, the reference ranges of healthy children were concluded to be suitable in prehospital settings; however, excessive reliance on vital signs carried potential risks due to their limited sensitivities and specificities. Future studies are warranted to investigate indicators with higher sensitivities and specificities.
A benzocoumarin-based fluorescent probe for ultra-sensitive and fast detection of endogenous/exogenous hypochlorous acid and its applications
Authors: Liu Kui , Fan Long , Huang Sujie , Sun Jie , Wang Xiaofeng , Li Huixue , Si Changdai , Zhang Wei , Li Tianrong , Yang Zhengyin
Published: March 2022

Hypochlorous acid (HOCl) is widely used in daily production and life because of its green and strongly oxidizing properties.
Amorphous metal–organic frameworks obtained from a crystalline precursor for the capture of iodine with high capacities
Authors: Feng Ying , Zou Ming-Yan , Hu Hao-Chen , Li Wan-Han , Cai Song-Liang , Zhang Wei-Guang , Zheng Sheng-Run
Published: March 2022

Two amorphous metal–organic frameworks (aMOFs) were obtained from a crystalline Co-MOF (SCNU-Z6) precursor and exhibited high iodine uptake capacities.
A high-value-added application of the stems of Rheum palmatum L. as a healthy food: the nutritional value, chemical composition, and anti-inflammatory and antioxidant activities
Authors: Shang Xiaofei , Dai Lixia , He Jian , Yang Xiaorong , Wang Yu , Li Bing , Zhang Jiyu , Pan Hu , Gulnaz Ilgekbayeva
Published: March 2022

SRP is shown to have nutritional value, exhibit anti-inflammatory and antioxidant activities, and have the potential to be utilized as a sustainable resource in the food and pharmaceutical industries.
An approach to prepare high-purity TiSi2 for clean utilization of Ti-bearing blast furnace slag
Authors: Li Zhanchao , Lei Yun , Ma Wenhui , Zhang Yakun , Wang Shiding , Ren Yongsheng , Lv Guoqiang
Published: March 2022

An approach to achieve the dual purposes of the simultaneous preparation of high-purity TiSi2 and the clean utilization of Ti-bearing blast furnace slag.
A site-differentiated [4Fe–4S] cluster controls electron transfer reactivity of Clostridium acetobutylicum [FeFe]-hydrogenase I
Authors: Lubner Carolyn E. , Artz Jacob H. , Mulder David W. , Oza Aisha , Ward Rachel J. , Williams S. Garrett , Jones Anne K. , Peters John W. , Smalyukh Ivan I. , Bharadwaj Vivek S. , King Paul W.
Published: March 2022

Histidine coordination of the distal [4Fe–4S] cluster in [FeFe]-hydrogenase was demonstrated to tune the cluster spin-states, spin-pairing and surrounding molecular orbitals to enable more facile electron transfer compared to cysteine coordination.
Analytical determination of gold ions based on ranelate induced nanoparticle formation
Authors: Mattioni João Victor , Franciscato Douglas Santana , Sihn Luca Michael , Toma Henrique Eisi
Published: March 2022

A ranelate ion, an old antiosteoporotic drug, readily reacts with gold(iii) ions generating stable gold nanoparticles (AuNP@Ran).
Turn-on mode fluorescent diarylethene containing neopentyl substituents that undergoes all-visible-light switching
Authors: Nishimura Ryo , Fujisawa Eri , Ban Ifu , Iwai Ryota , Takasu Shoya , Morimoto Masakazu , Irie Masahiro
Published: March 2022

Introduction of neopentyl substituents at reactive carbons dramatically increases the cycloreversion (switching-off) quantum yield of fluorescent diarylethenes.
Potassium nitrilotriacetate as a multifunctional modifier of the buried interface for hysteresis-reduced perovskite solar cells
Authors: Yang Meiling , Han Gaoyi , Xiao Yaoming , Hou Wenjing
Published: March 2022

Modification of a buried interface with potassium ammonium triacetate can enhance the bilateral connection, improve perovskite morphology, suppress non-radiation recombination, and reduce hysteresis.
Effect of solvation on the aggregation-induced luminescence of tetraphenylethene derivatives
Authors: Yao Hui , Zhou Meijuan , Yu Xiaolong , Bai Ming
Published: March 2022

Possible mechanism for the ultrasound-responsive AIE properties of TPE-(α-NH2)2 in a water-THF mixture (fw = 90%).
2D and 3D metal–organic frameworks constructed with a mechanically rigidified [3]rotaxane ligand
Authors: Li Xia , Xie Jialin , Du Zhenglin , Yu Ruiyang , Jia Jianhua , Chen Zhong , Zhu Kelong
Published: March 2022

A flexible bis-isophthalic acid was successfully transformed to a [3]rotaxane ligand which facilitates the construction of a 2D or 3D metal–organic framework in a controlled manner.
Ethylene oxide functionalization enhances the ionic conductivity of a MOF
Authors: Shalini Sorout , Matzger Adam J.
Published: March 2022

A synergistic approach, combining methods known to enhance solid-state conductivity, is applied here resulting in a true solid-state lithium conducting MOF system with ionic conductivity similar to reported MOF/Li salt/solvent electrolytes.
Semi-empirical and linear-scaling DFT methods to characterize duplex DNA and G-quadruplexes in the presence of interacting small molecules
Authors: Ortiz de Luzuriaga Iker , Elleuchi Sawssen , Jarraya Khaled , Artacho Emilio , López Xabier , Gil Adrià
Published: March 2022

SIESTA LS-DFT method at LMKLL/DZDP level and PM6-DH2 semi-empirical method are suitable to obtain correct geometries for DNA structures interacting with small molecules. However, only the SIESTA method reproduces the interaction energies when comparing to DLPNO-CCSD(T) and data bases.
Exploring mechanistic routes for light alkane oxidation with an iron–triazolate metal–organic framework
Authors: Rosen Andrew S. , Notestein Justin M. , Snurr Randall Q.
Published: March 2022

An iron–triazolate metal–organic framework (MOF) is computationally investigated for the catalytic oxidation of strong C–H bonds. The MOF is predicted to form reactive iron-oxo active sites, and design rules to guide future experiments are discussed.
Direct optical fiber monitor on stress evolution of the sulfur-based cathodes for lithium–sulfur batteries
Authors: Miao Ziyun , Li Yanpeng , Xiao Xiangpeng , Sun Qizhen , He Bin , Chen Xue , Liao Yaqi , Zhang Yi , Yuan Lixia , Yan Zhijun , Li Zhen , Huang Yunhui
Published: March 2022

Fiber Bragg grating sensors are embedded within sulfur-based cathodes to systematically investigate the stress evolution in three types of Li–S cells.