bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining allostatic load, neighborhood socioeconomic status, symptom burden and mortality in multiple myeloma patients
Authors: Obeng-Gyasi Samilia , Graham Noah , Kumar Shaji , Lee Ju-Whei , Jacobus Susanna , Weiss Matthias , Cella David , Zhao Fengmin , Ip Edward H. , O’Connell Nathaniel , Hong Fangxin , Peipert Devin J. , Gareen IIana. F. , Timsina Lava R. , Gray Robert , Wagner Lynne I. , Carlos Ruth C.
Published: April 2022

The objective of this study is to examine the association between neighborhood socioeconomic status (nSES) and baseline allostatic load (AL) and clinical trial endpoints in patients enrolled in the E1A11 therapeutic trial in multiple myeloma (MM). Study endpoints were symptom burden (pain, fatigue, and bother) at baseline and 5.5 months, non-completion of induction therapy, overall survival (OS) and progression-free survival (PFS). Multivariable logistic and Cox regression examined associations between nSES, AL and patient outcomes. A 1-unit increase in baseline AL was associated with greater odds of high fatigue at baseline (adjusted OR [95% CI] = 1.21 [1.08–1.36]) and a worse OS (adjusted hazard ratio, [95% CI] = 1.21 [1.06–1.37]). High nSES was associated with worse baseline bother (middle OR = 4.22 [1.11–16.09] and high 4.49 [1.16–17.43]) compared to low nSES. There was no association between AL or nSES and symptom burden at 5.5 months, non-completion of induction therapy or PFS. Additionally, there was no association between nSES and OS. AL may have utility as a predictive marker for OS among patients with MM and may allow individualization of treatment. Future studies should standardize and validate AL patients with MM.
Loss of neurodevelopmental-associated miR-592 impairs neurogenesis and causes social interaction deficits
Authors: Fu Yu , Zhou Yang , Zhang Yuan-Lin , Zhao Bo , Zhang Xing-Liao , Zhang Wan-Ting , Lu Yi-Jun , Lu Aiping , Zhang Jun , Zhang Jing
Published: April 2022

microRNA-592 (miR-592) has been linked to neurogenesis, but the influence of miR-592 knockout in vivo remains unknown. Here, we report that miR-592 knockout represses IPC-to-mature neuron transition, impairs motor coordination and reduces social interaction. Combining the RNA-seq and tandem mass tagging-based quantitative proteomics analysis (TMT protein quantification) and luciferase reporter assays, we identified MeCP2 as the direct targetgene of miR-592 in the mouse cortex. In Tg(MECP2)mice, lipofection of miR-592 efficiently reducedMECP2expression in the brains of Tg(MECP2)mice at E14.5. Furthermore, treatment with miR-592 partially ameliorated the autism-like phenotypes observed in adult Tg(MECP2) mice. The findings demonstrate that miR-592 might play a novel role in treating the neurodevelopmental-associated disorder.
The Lck inhibitor, AMG-47a, blocks necroptosis and implicates RIPK1 in signalling downstream of MLKL
Authors: Jacobsen Annette V. , Pierotti Catia L. , Lowes Kym N. , Au Amanda E. , Zhang Ying , Etemadi Nima , Fitzgibbon Cheree , Kersten Wilhelmus J. A. , Samson André L. , van Delft Mark F. , Huang David C. S. , Sabroux Hélène Jousset , Lessene Guillaume , Silke John , Murphy James M.
Published: April 2022

Necroptosis is a form of caspase-independent programmed cell death that arises from disruption of cell membranes by the mixed lineage kinase domain-like (MLKL) pseudokinase after its activation by the upstream kinases, receptor interacting protein kinase (RIPK)-1 and RIPK3, within a complex known as the necrosome. Dysregulated necroptosis has been implicated in numerous inflammatory pathologies. As such, new small molecule necroptosis inhibitors are of great interest, particularly ones that operate downstream of MLKL activation, where the pathway is less well defined. To better understand the mechanisms involved in necroptosis downstream of MLKL activation, and potentially uncover new targets for inhibition, we screened known kinase inhibitors against an activated mouse MLKL mutant, leading us to identify the lymphocyte-specific protein tyrosine kinase (Lck) inhibitor AMG-47a as an inhibitor of necroptosis. We show that AMG-47a interacts with both RIPK1 and RIPK3, that its ability to protect from cell death is dependent on the strength of the necroptotic stimulus, and that it blocks necroptosis most effectively in human cells. Moreover, in human cell lines, we demonstrate that AMG-47a can protect against cell death caused by forced dimerisation of MLKL truncation mutants in the absence of any upstream signalling, validating that it targets a process downstream of MLKL activation. Surprisingly, however, we also found that the cell death driven by activated MLKL in this model was completely dependent on the presence of RIPK1, and to a lesser extent RIPK3, although it was not affected by known inhibitors of these kinases. Together, these results suggest an additional role for RIPK1, or the necrosome, in mediating human necroptosis after MLKL is phosphorylated by RIPK3 and provide further insight into reported differences in the progression of necroptosis between mouse and human cells.
Gelation and anomalous viscosity dynamics in aqueous dispersions of synthetic hectorite
Authors: Kimura Yuji , Shimizu Shoichi , Haraguchi Kazutoshi
Published: April 2022

Exfoliated clay nanosheets (CNSs) of synthetic hectorite (s-hectorite) have been used for synthesizing advanced functional materials and gels that exhibit high transparency, high mechanical toughness, and many unprecedented characteristics like optical anisotropy, cell harvesting, instant strong adhesion, and self-healing. Therefore, it is important to determine the rheological properties of aqueous s-hectorite dispersions in terms of the CNS microstructures formed in the dispersion. Herein, viscosity changes in aqueous dispersions of s-hectorite were determined using a vibration viscometer to measure viscosity under agitated and static conditions. Upon varying the pH and salt concentration, aqueous dispersions of s-hectorite exhibited a maximum viscosity accompanied by gelation. Additionally, the aqueous dispersion with maximum viscosity exhibited large and complex time-dependent viscosity changes in the static state after cessation of stirring. The anomalous viscosity dynamics depended on the types of clay, acid (salt), temperature, repetitions, and agitation conditions used. The mechanisms for viscosity dynamics have been discussed in terms of variations in the CNS microstructures. It is inferred that anomalous viscosity dynamics are a general phenomenon in multicomponent dispersion systems containing CNSs.
100 Hz ROCS microscopy correlated with fluorescence reveals cellular dynamics on different spatiotemporal scales
Authors: Jünger Felix , Ruh Dominic , Strobel Dominik , Michiels Rebecca , Huber Dominik , Brandel Annette , Madl Josef , Gavrilov Alina , Mihlan Michael , Daller Caterina Cora , Rog-Zielinska Eva A. , Römer Winfried , Lämmermann Tim , Rohrbach Alexander
Published: April 2022

Fluorescence techniques dominate the field of live-cell microscopy, but bleaching and motion blur from too long integration times limit dynamic investigations of small objects. High contrast, label-free life-cell imaging of thousands of acquisitions at 160 nm resolution and 100 Hz is possible by Rotating Coherent Scattering (ROCS) microscopy, where intensity speckle patterns from all azimuthal illumination directions are added up within 10 ms. In combination with fluorescence, we demonstrate the performance of improved Total Internal Reflection (TIR)-ROCS with variable illumination including timescale decomposition and activity mapping at five different examples: millisecond reorganization of macrophage actin cortex structures, fast degranulation and pore opening in mast cells, nanotube dynamics between cardiomyocytes and fibroblasts, thermal noise driven binding behavior of virus-sized particles at cells, and, bacterial lectin dynamics at the cortex of lung cells. Using analysis methods we present here, we decipher how motion blur hides cellular structures and how slow structure motions cover decisive fast motions.
Defining the early stages of intestinal colonisation by whipworms
Authors: Duque-Correa María A. , Goulding David , Rodgers Faye H. , Gillis J. Andrew , Cormie Claire , Rawlinson Kate A. , Bancroft Allison J. , Bennett Hayley M. , Lotkowska Magda E. , Reid Adam J. , Speak Anneliese O. , Scott Paul , Redshaw Nicholas , Tolley Charlotte , McCarthy Catherine , Brandt Cordelia , Sharpe Catherine , Ridley Caroline , Moya Judit Gali , Carneiro Claudia M. , Starborg Tobias , Hayes Kelly S. , Holroyd Nancy , Sanders Mandy , Thornton David J. , Grencis Richard K. , Berriman Matthew
Published: April 2022

Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche.
A functional map of HIV-host interactions in primary human T cells
Authors: Hiatt Joseph , Hultquist Judd F. , McGregor Michael J. , Bouhaddou Mehdi , Leenay Ryan T. , Simons Lacy M. , Young Janet M. , Haas Paige , Roth Theodore L. , Tobin Victoria , Wojcechowskyj Jason A. , Woo Jonathan M. , Rathore Ujjwal , Cavero Devin A. , Shifrut Eric , Nguyen Thong T. , Haas Kelsey M. , Malik Harmit S. , Doudna Jennifer A. , May Andrew P. , Marson Alexander , Krogan Nevan J.
Published: April 2022

Human Immunodeficiency Virus (HIV) relies on host molecular machinery for replication. Systematic attempts to genetically or biochemically define these host factors have yielded hundreds of candidates, but few have been functionally validated in primary cells. Here, we target 426 genes previously implicated in the HIV lifecycle through protein interaction studies for CRISPR-Cas9-mediated knock-out in primary human CD4+ T cells in order to systematically assess their functional roles in HIV replication. We achieve efficient knockout (>50% of alleles) in 364 of the targeted genes and identify 86 candidate host factors that alter HIV infection. 47 of these factors validate by multiplex gene editing in independent donors, including 23 factors with restrictive activity. Both gene editing efficiencies and HIV-1 phenotypes are highly concordant among independent donors. Importantly, over half of these factors have not been previously described to play a functional role in HIV replication, providing numerous novel avenues for understanding HIV biology. These data further suggest that host-pathogen protein-protein interaction datasets offer an enriched source of candidates for functional host factor discovery and provide an improved understanding of the mechanics of HIV replication in primary T cells.
Pseudo-adsorption and long-range redox coupling during oxygen reduction reaction on single atom electrocatalyst
Authors: Chen Jie-Wei , Zhang Zisheng , Yan Hui-Min , Xia Guang-Jie , Cao Hao , Wang Yang-Gang
Published: April 2022

Fundamental understanding of the dynamic behaviors at the electrochemical interface is crucial for electrocatalyst design and optimization. Here, we revisit the oxygen reduction reaction mechanism on a series of transition metal (M = Fe, Co, Ni, Cu) single atom sites embedded in N-doped nanocarbon by ab initio molecular dynamics simulations with explicit solvation. We have identified the dissociative pathways and the thereby emerged solvated hydroxide species for all the proton-coupled electron transfer (PCET) steps at the electrochemical interface. Such hydroxide species can be dynamically confined in a “pseudo-adsorption” state at a few water layers away from the active site and respond to the redox event at the catalytic center in a coupled manner within timescale less than 1 ps. In the PCET steps, the proton species (in form of hydronium in neutral/acidic media or water in alkaline medium) can protonate the pseudo-adsorbed hydroxide without needing to travel to the direct catalyst surface. This, therefore, expands the reactive region beyond the direct catalyst surface, boosting the reaction kinetics via alleviating mass transfer limits. Our work implies that in catalysis the reaction species may not necessarily bind to the catalyst surface but be confined in an active region.
Structural basis of FPR2 in recognition of Aβ42 and neuroprotection by humanin
Authors: Zhu Ya , Lin Xiaowen , Zong Xin , Han Shuo , Wang Mu , Su Yuxuan , Ma Limin , Chu Xiaojing , Yi Cuiying , Zhao Qiang , Wu Beili
Published: April 2022

Formyl peptide receptor 2 (FPR2) has been shown to mediate the cytotoxic effects of the β amyloid peptide Aβ42 and serves as a receptor for humanin, a peptide that protects neuronal cells from damage by Aβ42, implying its involvement in the pathogenesis of Alzheimer’s disease (AD). However, the interaction pattern between FPR2 and Aβ42 or humanin remains unknown. Here we report the structures of FPR2 bound to Gi and Aβ42 or N-formyl humanin (fHN). Combined with functional data, the structures reveal two critical regions that govern recognition and activity of Aβ42 and fHN, including a polar binding cavity within the receptor helical bundle and a hydrophobic binding groove in the extracellular region. In addition, the structures of FPR2 and FPR1 in complex with different formyl peptides were determined, providing insights into ligand recognition and selectivity of the FPR family. These findings uncover key factors that define the functionality of FPR2 in AD and other inflammatory diseases and would enable drug development.
Single-cell and spatial analysis reveal interaction of FAP+ fibroblasts and SPP1+ macrophages in colorectal cancer
Authors: Qi Jingjing , Sun Hongxiang , Zhang Yao , Wang Zhengting , Xun Zhenzhen , Li Ziyi , Ding Xinyu , Bao Rujuan , Hong Liwen , Jia Wenqing , Fang Fei , Liu Hongzhi , Chen Lei , Zhong Jie , Zou Duowu , Liu Lianxin , Han Leng , Ginhoux Florent , Liu Yingbin , Ye Youqiong , Su Bing
Published: April 2022

Colorectal cancer (CRC) is among the most common malignancies with limited treatments other than surgery. The tumor microenvironment (TME) profiling enables the discovery of potential therapeutic targets. Here, we profile 54,103 cells from tumor and adjacent tissues to characterize cellular composition and elucidate the potential origin and regulation of tumor-enriched cell types in CRC. We demonstrate that the tumor-specific FAP+ fibroblasts and SPP1+ macrophages were positively correlated in 14 independent CRC cohorts containing 2550 samples and validate their close localization by immuno-fluorescent staining and spatial transcriptomics. This interaction might be regulated by chemerin, TGF-β, and interleukin-1, which would stimulate the formation of immune-excluded desmoplasic structure and limit the T cell infiltration. Furthermore, we find patients with high FAP or SPP1 expression achieved less therapeutic benefit from an anti-PD-L1 therapy cohort. Our results provide a potential therapeutic strategy by disrupting FAP+ fibroblasts and SPP1+ macrophages interaction to improve immunotherapy.
USP1-trapping lesions as a source of DNA replication stress and genomic instability
Authors: Coleman Kate E. , Yin Yandong , Lui Sarah Kit Leng , Keegan Sarah , Fenyo David , Smith Duncan J. , Rothenberg Eli , Huang Tony T.
Published: April 2022

The deubiquitinase USP1 is a critical regulator of genome integrity through the deubiquitylation of Fanconi Anemia proteins and the DNA replication processivity factor, proliferating cell nuclear antigen (PCNA). Uniquely, following UV irradiation, USP1 self-inactivates through autocleavage, which enables its own degradation and in turn, upregulates PCNA monoubiquitylation. However, the functional role for this autocleavage event during physiological conditions remains elusive. Herein, we discover that cells harboring an autocleavage-defective USP1 mutant, while still able to robustly deubiquitylate PCNA, experience more replication fork-stalling and premature fork termination events. Using super-resolution microscopy and live-cell single-molecule tracking, we show that these defects are related to the inability of this USP1 mutant to be properly recycled from sites of active DNA synthesis, resulting in replication-associated lesions. Furthermore, we find that the removal of USP1 molecules from DNA is facilitated by the DNA-dependent metalloprotease Spartan to counteract the cytotoxicity caused by “USP1-trapping”. We propose a utility of USP1 inhibitors in cancer therapy based on their ability to induce USP1-trapping lesions and consequent replication stress and genomic instability in cancer cells, similar to how non-covalent DNA-protein crosslinks cause cytotoxicity by imposing steric hindrances upon proteins involved in DNA transactions.
Discovery of a signaling feedback circuit that defines interferon responses in myeloproliferative neoplasms
Authors: Saleiro Diana , Wen Jeremy Q. , Kosciuczuk Ewa M. , Eckerdt Frank , Beauchamp Elspeth M. , Oku Chidera V. , Blyth Gavin T. , Fischietti Mariafausta , Ilut Liliana , Colamonici Marco , Palivos William , Atsaves Paula A. , Tan Dean , Kocherginsky Masha , Weinberg Rona Singer , Fish Eleanor N. , Crispino John D. , Hoffman Ronald , Platanias Leonidas C.
Published: April 2022

Interferons (IFNs) are key initiators and effectors of the immune response against malignant cells and also directly inhibit tumor growth. IFNα is highly effective in the treatment of myeloproliferative neoplasms (MPNs), but the mechanisms of action are unclear and it remains unknown why some patients respond to IFNα and others do not. Here, we identify and characterize a pathway involving PKCδ-dependent phosphorylation of ULK1 on serine residues 341 and 495, required for subsequent activation of p38 MAPK. We show that this pathway is essential for IFN-suppressive effects on primary malignant erythroid precursors from MPN patients, and that increased levels of ULK1 and p38 MAPK correlate with clinical response to IFNα therapy in these patients. We also demonstrate that IFNα treatment induces cleavage/activation of the ULK1-interacting ROCK1/2 proteins in vitro and in vivo, triggering a negative feedback loop that suppresses IFN responses. Overexpression of ROCK1/2 is seen in MPN patients and their genetic or pharmacological inhibition enhances IFN-anti-neoplastic responses in malignant erythroid precursors from MPN patients. These findings suggest the clinical potential of pharmacological inhibition of ROCK1/2 in combination with IFN-therapy for the treatment of MPNs.
Shape and stiffness memory ionogels with programmable pressure-resistance response
Authors: Zhuo Shuyun , Song Cheng , Rong Qinfeng , Zhao Tianyi , Liu Mingjie
Published: April 2022

Flexible pressure sensors usually require functional materials with both mechanical compliance and appropriate electrical performance. Most sensors based on materials with limited compressibility can hardly balance between high sensitivity and broad pressure range. Here, we prepare a heterophasic ionogel with shape and stiffness memory for adaptive pressure sensors. By combining the microstructure alignment for stiffness changing and shape memory micro-inclusions for stiffness fixing, the heterophasic ionogels reveal tunable compressibility. This controllable pressure-deformation property of the ionogels results in the pressure sensors’ programmable pressure-resistance behavior with tunable pressure ranges, varied detection limits, and good resolution at high pressure. Broad pressure ranges to 220 and 380 kPa, and tunable detection limit from 120 to 330 and 950 Pa are realized by the stiffness memory ionogel sensors. Adaptive detection is also brought out to monitor tiny pressure changes at low stiffness and distinguish different human motions at high stiffness. Using shape and stiffness memory materials in pressure sensors is a general design to achieve programmable performance for more complex application scenarios.
Activity-induced interactions and cooperation of artificial microswimmers in one-dimensional environments
Authors: Ketzetzi Stefania , Rinaldin Melissa , Dröge Pim , Graaf Joost de , Kraft Daniela J.
Published: April 2022

Cooperative motion in biological microswimmers is crucial for their survival as it facilitates adhesion to surfaces, formation of hierarchical colonies, efficient motion, and enhanced access to nutrients. Here, we confine synthetic, catalytic microswimmers along one-dimensional paths and demonstrate that they too show a variety of cooperative behaviours. We find that their speed increases with the number of swimmers, and that the activity induces a preferred distance between swimmers. Using a minimal model, we ascribe this behavior to an effective activity-induced potential that stems from a competition between chemical and hydrodynamic coupling. These interactions further induce active self-assembly into trains where swimmers move at a well-separated, stable distance with respect to each other, as well as compact chains that can elongate, break-up, become immobilized and remobilized. We identify the crucial role that environment morphology and swimmer directionality play on these highly dynamic chain behaviors. These activity-induced interactions open the door toward exploiting cooperation for increasing the efficiency of microswimmer motion, with temporal and spatial control, thereby enabling them to perform intricate tasks inside complex environments.
High-performance hysteresis-free perovskite transistors through anion engineering
Authors: Zhu Huihui , Liu Ao , Shim Kyu In , Jung Haksoon , Zou Taoyu , Reo Youjin , Kim Hyunjun , Han Jeong Woo , Chen Yimu , Chu Hye Yong , Lim Jun Hyung , Kim Hyung-Jun , Bai Sai , Noh Yong-Young
Published: April 2022

Despite the impressive development of metal halide perovskites in diverse optoelectronics, progress on high-performance transistors employing state-of-the-art perovskite channels has been limited due to ion migration and large organic spacer isolation. Herein, we report high-performance hysteresis-free p-channel perovskite thin-film transistors (TFTs) based on methylammonium tin iodide (MASnI3) and rationalise the effects of halide (I/Br/Cl) anion engineering on film quality improvement and tin/iodine vacancy suppression, realising high hole mobilities of 20 cm2 V−1 s−1, current on/off ratios exceeding 107, and threshold voltages of 0 V along with high operational stabilities and reproducibilities. We reveal ion migration has a negligible contribution to the hysteresis of Sn-based perovskite TFTs; instead, minority carrier trapping is the primary cause. Finally, we integrate the perovskite TFTs with commercialised n-channel indium gallium zinc oxide TFTs on a single chip to construct high-gain complementary inverters, facilitating the development of halide perovskite semiconductors for printable electronics and circuits.
Deciphering spatial domains from spatially resolved transcriptomics with an adaptive graph attention auto-encoder
Authors: Dong Kangning , Zhang Shihua
Published: April 2022

Recent advances in spatially resolved transcriptomics have enabled comprehensive measurements of gene expression patterns while retaining the spatial context of the tissue microenvironment. Deciphering the spatial context of spots in a tissue needs to use their spatial information carefully. To this end, we develop a graph attention auto-encoder framework STAGATE to accurately identify spatial domains by learning low-dimensional latent embeddings via integrating spatial information and gene expression profiles. To better characterize the spatial similarity at the boundary of spatial domains, STAGATE adopts an attention mechanism to adaptively learn the similarity of neighboring spots, and an optional cell type-aware module through integrating the pre-clustering of gene expressions. We validate STAGATE on diverse spatial transcriptomics datasets generated by different platforms with different spatial resolutions. STAGATE could substantially improve the identification accuracy of spatial domains, and denoise the data while preserving spatial expression patterns. Importantly, STAGATE could be extended to multiple consecutive sections to reduce batch effects between sections and extracting three-dimensional (3D) expression domains from the reconstructed 3D tissue effectively.
Single-crystal two-dimensional material epitaxy on tailored non-single-crystal substrates
Authors: Li Xin , Wu Guilin , Zhang Leining , Huang Deping , Li Yunqing , Zhang Ruiqi , Li Meng , Zhu Lin , Guo Jing , Huang Tianlin , Shen Jun , Wei Xingzhan , Yu Ka Man , Dong Jichen , Altman Michael S. , Ruoff Rodney S. , Duan Yinwu , Yu Jie , Wang Zhujun , Huang Xiaoxu , Ding Feng , Shi Haofei , Tang Wenxin
Published: April 2022

The use of single-crystal substrates as templates for the epitaxial growth of single-crystal overlayers has been a primary principle of materials epitaxy for more than 70 years. Here we report our finding that, though counterintuitive, single-crystal 2D materials can be epitaxially grown on twinned crystals. By establishing a geometric principle to describe 2D materials alignment on high-index surfaces, we show that 2D material islands grown on the two sides of a twin boundary can be well aligned. To validate this prediction, wafer-scale Cu foils with abundant twin boundaries were synthesized, and on the surfaces of these polycrystalline Cu foils, we have successfully grown wafer-scale single-crystal graphene and hexagonal boron nitride films. In addition, to greatly increasing the availability of large area high-quality 2D single crystals, our discovery also extends the fundamental understanding of materials epitaxy.
Photo-induced non-volatile VO2 phase transition for neuromorphic ultraviolet sensors
Authors: Li Ge , Xie Donggang , Zhong Hai , Zhang Ziye , Fu Xingke , Zhou Qingli , Li Qiang , Ni Hao , Wang Jiaou , Guo Er-jia , He Meng , Wang Can , Yang Guozhen , Jin Kuijuan , Ge Chen
Published: April 2022

In the quest for emerging in-sensor computing, materials that respond to optical stimuli in conjunction with non-volatile phase transition are highly desired for realizing bioinspired neuromorphic vision components. Here, we report a non-volatile multi-level control of VO2 films by oxygen stoichiometry engineering under ultraviolet irradiation. Based on the reversible regulation of VO2 films using ultraviolet irradiation and electrolyte gating, we demonstrate a proof-of-principle neuromorphic ultraviolet sensor with integrated sensing, memory, and processing functions at room temperature, and also prove its silicon compatible potential through the wafer-scale integration of a neuromorphic sensor array. The device displays linear weight update with optical writing because its metallic phase proportion increases almost linearly with the light dosage. Moreover, the artificial neural network consisting of this neuromorphic sensor can extract ultraviolet information from the surrounding environment, and significantly improve the recognition accuracy from 24% to 93%. This work provides a path to design neuromorphic sensors and will facilitate the potential applications in artificial vision systems.
Fusion of Majorana bound states with mini-gate control in two-dimensional systems
Authors: Zhou Tong , Dartiailh Matthieu C. , Sardashti Kasra , Han Jong E. , Matos-Abiague Alex , Shabani Javad , Žutić Igor
Published: April 2022

A hallmark of topological superconductivity is the non-Abelian statistics of Majorana bound states (MBS), its chargeless zero-energy emergent quasiparticles. The resulting fractionalization of a single electron, stored nonlocally as a two spatially-separated MBS, provides a powerful platform for implementing fault-tolerant topological quantum computing. However, despite intensive efforts, experimental support for MBS remains indirect and does not probe their non-Abelian statistics. Here we propose how to overcome this obstacle in mini-gate controlled planar Josephson junctions (JJs) and demonstrate non-Abelian statistics through MBS fusion, detected by charge sensing using a quantum point contact, based on dynamical simulations. The feasibility of preparing, manipulating, and fusing MBS in two-dimensional (2D) systems is supported in our experiments which demonstrate the gate control of topological transition and superconducting properties with five mini gates in InAs/Al-based JJs. While we focus on this well-established platform, where the topological superconductivity was already experimentally detected, our proposal to identify elusive non-Abelian statistics motivates also further MBS studies in other gate-controlled 2D systems.
Soil microbial metabolism on carbon and nitrogen transformation links the crop-residue contribution to soil organic carbon
Authors: Xie Zhihuang , Yu Zhenhua , Li Yansheng , Wang Guanghua , Liu Xiaobing , Tang Caixian , Lian Tengxiang , Adams Jonathan , Liu Junjie , Liu Judong , Herbert Stephen J. , Jin Jian
Published: April 2022

The beneficial effect of crop residue amendment on soil organic carbon (SOC) stock and stability depends on the functional response of soil microbial communities. Here we synchronized microbial metagenomic analysis, nuclear magnetic resonance and plant-15N labeling technologies to gain understanding of how microbial metabolic processes affect SOC accumulation in responses to differences in N supply from residues. Residue amendment brought increases in the assemblage of genes involved in C-degradation profiles from labile to recalcitrant C compounds as well as N mineralization. The N mineralization genes were correlated with the C and N accumulation in the particulate and mineral-associated C pools, and plant-derived aliphatic forms of SOC. Thus, the combined C and N metabolic potential of the microbial community transforms residue into persistent organic compounds, thereby increasing C and N sequestration in stable SOC pools. This study emphasizes potential microbially mediated mechanisms by which residue N affects C sequestration in soils.
Global spatiotemporally continuous MODIS land surface temperature dataset
Authors: Yu Pei , Zhao Tianjie , Shi Jiancheng , Ran Youhua , Jia Li , Ji Dabin , Xue Huazhu
Published: April 2022

Land surface temperature (LST) plays a critical role in land surface processes. However, as one of the effective means for obtaining global LST observations, remote sensing observations are inherently affected by cloud cover, resulting in varying degrees of missing data in satellite-derived LST products. Here, we propose a solution. First, the data interpolating empirical orthogonal functions (DINEOF) method is used to reconstruct invalid LSTs in cloud-contaminated areas into ideal, clear-sky LSTs. Then, a cumulative distribution function (CDF) matching-based method is developed to correct the ideal, clear-sky LSTs to the real LSTs. Experimental results prove that this method can effectively reconstruct missing LST data and guarantee acceptable accuracy in most regions of the world, with RMSEs of 1–2 K and R values of 0.820–0.996 under ideal, clear-sky conditions and RMSEs of 4–7 K and R values of 0.811–0.933 under all weather conditions. Finally, a spatiotemporally continuous MODIS LST dataset at 0.05° latitude/longitude grids is produced based on the above method.
Drivers of tropical forest loss between 2008 and 2019
Authors: Laso Bayas Juan Carlos , See Linda , Georgieva Ivelina , Schepaschenko Dmitry , Danylo Olga , Dürauer Martina , Bartl Hedwig , Hofhansl Florian , Zadorozhniuk Roman , Burianchuk Maksym , Sirbu Flavius , Magori Brigitte , Blyshchyk Kateryna , Blyshchyk Volodymyr , Rabia Ahmed Harb , Pawe Chandra Kant , Su Yuan-Fong , Ahmed Merajuddin , Panging Kripal , Melnyk Oleksandr , Vasylyshyn Olesia , Vasylyshyn Roman , Bilous Andrii , Bilous Svitlana , Das Krishna , Prestele Reinhard , Pérez-Hoyos Ana , Bungnamei Khangsembou , Lashchenko Andrii , Lakyda Maryna , Lakyda Ivan , Serediuk Oleksandr , Domashovets Galyna , Yurchuk Yuriy , Koper Michèle , Fritz Steffen
Published: April 2022

During December 2020, a crowdsourcing campaign to understand what has been driving tropical forest loss during the past decade was undertaken. For 2 weeks, 58 participants from several countries reviewed almost 115 K unique locations in the tropics, identifying drivers of forest loss (derived from the Global Forest Watch map) between 2008 and 2019. Previous studies have produced global maps of drivers of forest loss, but the current campaign increased the resolution and the sample size across the tropics to provide a more accurate mapping of crucial factors leading to forest loss. The data were collected using the Geo-Wiki platform (www.geo-wiki.org) where the participants were asked to select the predominant and secondary forest loss drivers amongst a list of potential factors indicating evidence of visible human impact such as roads, trails, or buildings. The data described here are openly available and can be employed to produce updated maps of tropical drivers of forest loss, which in turn can be used to support policy makers in their decision-making and inform the public.
A global map of planting years of plantations
Authors: Du Zhenrong , Yu Le , Yang Jianyu , Xu Yidi , Chen Bin , Peng Shushi , Zhang Tingting , Fu Haohuan , Harris Nancy , Gong Peng
Published: April 2022

Plantation is an important land use type that differs from natural forests and affects the economy and the environment. Tree age is one of the key factors used to quantify the impact of plantations. However, there is a lack of datasets explicitly documenting the planting years of global plantations. Here we used time-series Landsat archive from 1982 to 2020 and the LandTrendr algorithm to generate global maps of planting years based on the global plantation extent products in Google Earth Engine (GEE) platform. The datasets developed in this study are in a GeoTIFF format with 30-meter spatial resolution by recording gridded specie types and planting years of global plantations. The derived dataset could be used for yield prediction of tree crops and social and ecological cost-benefit analysis of plantations.
AB-DB: Force-Field parameters, MD trajectories, QM-based data, and Descriptors of Antimicrobials
Authors: Gervasoni Silvia , Malloci Giuliano , Bosin Andrea , Vargiu Attilio V. , Zgurskaya Helen I. , Ruggerone Paolo
Published: April 2022

Antibiotic resistance is a major threat to public health. The development of chemo-informatic tools to guide medicinal chemistry campaigns in the efficint design of antibacterial libraries is urgently needed. We present AB-DB, an open database of all-atom force-field parameters, molecular dynamics trajectories, quantum-mechanical properties, and curated physico-chemical descriptors of antimicrobial compounds. We considered more than 300 molecules belonging to 25 families that include the most relevant antibiotic classes in clinical use, such as β-lactams and (fluoro)quinolones, as well as inhibitors of key bacterial proteins. We provide traditional descriptors together with properties obtained with Density Functional Theory calculations. Noteworthy, AB-DB contains less conventional descriptors extracted from μs-long molecular dynamics simulations in explicit solvent. In addition, for each compound we make available force-field parameters for the major micro-species at physiological pH. With the rise of multi-drug-resistant pathogens and the consequent need for novel antibiotics, inhibitors, and drug re-purposing strategies, curated databases containing reliable and not straightforward properties facilitate the integration of data mining and statistics into the discovery of new antimicrobials.
Improved calibration of electrochemical aptamer-based sensors
Authors: Downs Alex M. , Gerson Julian , Leung Kaylyn K. , Honeywell Kevin M. , Kippin Tod , Plaxco Kevin W.
Published: April 2022

Electrochemical aptamer-based (EAB) sensors support the real-time, high frequency measurement of pharmaceuticals and metabolites in-situ in the living body, rendering them a potentially powerful technology for both research and clinical applications. Here we explore quantification using EAB sensors, examining the impact of media selection and temperature on measurement performance. Using freshly-collected, undiluted whole blood at body temperature as both our calibration and measurement conditions, we demonstrate accuracy of better than ± 10% for the measurement of our test bed drug, vancomycin. Comparing titrations collected at room and body temperature, we find that matching the temperature of calibration curve collection to the temperature used during measurements improves quantification by reducing differences in sensor gain and binding curve midpoint. We likewise find that, because blood age impacts the sensor response, calibrating in freshly collected blood can improve quantification. Finally, we demonstrate the use of non-blood proxy media to achieve calibration without the need to collect fresh whole blood.
A deep learning model (FociRad) for automated detection of γ-H2AX foci and radiation dose estimation
Authors: Wanotayan Rujira , Chousangsuntorn Khaisang , Petisiwaveth Phasit , Anuttra Thunchanok , Lertchanyaphan Waritsara , Jaikuna Tanwiwat , Jangpatarapongsa Kulachart , Uttayarat Pimpon , Tongloy Teerawat , Chousangsuntorn Chousak , Boonsang Siridech
Published: April 2022

DNA double-strand breaks (DSBs) are the most lethal form of damage to cells from irradiation. γ-H2AX (phosphorylated form of H2AX histone variant) has become one of the most reliable and sensitive biomarkers of DNA DSBs. However, the γ-H2AX foci assay still has limitations in the time consumed for manual scoring and possible variability between scorers. This study proposed a novel automated foci scoring method using a deep convolutional neural network based on a You-Only-Look-Once (YOLO) algorithm to quantify γ-H2AX foci in peripheral blood samples. FociRad, a two-stage deep learning approach, consisted of mononuclear cell (MNC) and γ-H2AX foci detections. Whole blood samples were irradiated with X-rays from a 6 MV linear accelerator at 1, 2, 4 or 6 Gy. Images were captured using confocal microscopy. Then, dose–response calibration curves were established and implemented with unseen dataset. The results of the FociRad model were comparable with manual scoring. MNC detection yielded 96.6% accuracy, 96.7% sensitivity and 96.5% specificity. γ-H2AX foci detection showed very good F1 scores (> 0.9). Implementation of calibration curve in the range of 0–4 Gy gave mean absolute difference of estimated doses less than 1 Gy compared to actual doses. In addition, the evaluation times of FociRad were very short (< 0.5 min per 100 images), while the time for manual scoring increased with the number of foci. In conclusion, FociRad was the first automated foci scoring method to use a YOLO algorithm with high detection performance and fast evaluation time, which opens the door for large-scale applications in radiation triage.
Bacteriocinogenic probiotic bacteria isolated from an aquatic environment inhibit the growth of food and fish pathogens
Authors: Pereira Wellison Amorim , Piazentin Anna Carolina M. , de Oliveira Rodrigo Cardoso , Mendonça Carlos Miguel N. , Tabata Yara Aiko , Mendes Maria Anita , Fock Ricardo Ambrósio , Makiyama Edson Naoto , Corrêa Benedito , Vallejo Marisol , Villalobos Elias Figueroa , de S. Oliveira Ricardo Pinheiro
Published: April 2022

The conditions of aquatic environments have a great influence on the microbiota of several animals, many of which are a potential source of microorganisms of biotechnological interest. In this study, bacterial strains isolated from aquatic environments were bioprospected to determine their probiotic profile and antimicrobial effect against fish and food pathogens. Two isolates, identified via 16S rRNA sequencing as Lactococcus lactis (L1 and L2) and one as Enterococcus faecium 135 (EF), produced a bacteriocin-like antimicrobial substance (BLIS), active against Listeria monocytogenes, Salmonella Choleraesuis and Salmonella Typhimurium. Antimicrobial activity of BLIS was reduced when exposed to high temperatures and proteolytic enzymes (trypsin, pepsin, papain and pancreatin). All strains were sensitive to 7 types of antibiotics (vancomycin, clindamycin, streptomycin, gentamicin, chloramphenicol, rifampicin and ampicillin), exhibited a high rate of adherence to Caco-2 cells and expressed no hemolysin and gelatinase virulence factors. EF showed some resistance at pH 2.5 and 3.0, and L2/EF showed higher resistance to the action of bile salts. Finally, the presence of bacteriocin genes encoding for proteins, including Nisin (L1 and L2), Enterocin A, B, P, and Mundticin KS (EF) was detected. The molecular and physiological evidence suggests that the bacterial isolates in this study could be used as natural antimicrobial agents and may be considered safe for probiotic application.
Tissue clearing may alter emission and absorption properties of common fluorophores
Authors: Eliat Farsam , Sohn Rebecca , Renner Henrik , Kagermeier Theresa , Volkery Stefan , Brinkmann Heike , Kirschnick Nils , Kiefer Friedemann , Grabos Martha , Becker Katharina , Bedzhov Ivan , Schöler Hans R. , Bruder Jan M.
Published: April 2022

In recent years, 3D cell culture has been gaining a more widespread following across many fields of biology. Tissue clearing enables optical analysis of intact 3D samples and investigation of molecular and structural mechanisms by homogenizing the refractive indices of tissues to make them nearly transparent. Here, we describe and quantify that common clearing solutions including benzyl alcohol/benzyl benzoate (BABB), PEG-associated solvent system (PEGASOS), immunolabeling-enabled imaging of solvent-cleared organs (iDISCO), clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC), and ScaleS4 alter the emission spectra of Alexa Fluor fluorophores and fluorescent dyes. Clearing modifies not only the emitted light intensity but also alters the absorption and emission peaks, at times to several tens of nanometers. The resulting shifts depend on the interplay of solvent, fluorophore, and the presence of cells. For biological applications, this increases the risk for unexpected channel crosstalk, as filter sets are usually not optimized for altered fluorophore emission spectra in clearing solutions. This becomes especially problematic in high throughput/high content campaigns, which often rely on multiband excitation to increase acquisition speed. Consequently, researchers relying on clearing in quantitative multiband excitation experiments should crosscheck their fluorescent signal after clearing in order to inform the proper selection of filter sets and fluorophores for analysis.
Magnetic UiO-66 functionalized with 4,4′-diamino-2,2′-stilbenedisulfonic as a highly recoverable acid catalyst for the synthesis of 4H-chromenes in green solvent
Authors: Khodabakhshi Mohammad Reza , Baghersad Mohammad Hadi
Published: April 2022

According to 4H-chromenes importance, we synthesized a novel magnetic UiO-66 functionalized with 4,4′-diamino-2,2′-stilbenedisulfonic as an efficient and reusable solid acid catalyst for synthesizing 4H-chromene skeletons via a one-pot three components reaction in a green solvent. The structure of the synthesized catalyst was confirmed by various techniques including FT-IR, XRD, BET, TGA, TEM, EDX, and SEM, and also the product yields were obtained in 83–96% of yields for all the reactions and under mild conditions. The reported procedure presents an environmentally friendly approach for synthesizing a significant number of 4H-chromene derivatives. Correspondingly, MOF-based catalyst makes it easy to separate from reaction media and reuse in the next runs.
Identifying influential spreaders in complex networks for disease spread and control
Authors: Wei Xiang , Zhao Junchan , Liu Shuai , Wang Yisi
Published: April 2022

Identifying influential spreaders is an important task in controlling the spread of information and epidemic diseases in complex networks. Many recent studies have indicated that the identification of influential spreaders is dependent on the spreading dynamics. Finding a general optimal order of node importance ranking is difficult because of the complexity of network structures and the physical background of dynamics. In this paper, we use four metrics, namely, betweenness, degree, H-index, and coreness, to measure the central attributes of nodes for constructing the disease spreading models and target immunization strategies. Numerical simulations show that spreading processes based on betweenness centrality lead to the widest range of propagation and the smallest epidemic threshold for all six networks (including four real networks and two BA scale-free networks generated according to Barabasi–Albert algorithm). The target immunization strategy based on the betweenness centrality of nodes is the most effective for BA scale-free networks but displays poor immune effect for real networks in identifying the most important spreaders for disease control. The immunization strategy based on node degrees is the most effective for the four real networks. Findings show that the target immune strategy based on the betweenness centrality of nodes works best for standard scale-free networks, whereas that based on node degrees works best for other nonstandard scale-free networks. The results can provide insights into understanding the different metrics of measuring node importance in disease transmission and control.
Structural basis to repurpose boron-based proteasome inhibitors Bortezomib and Ixazomib as β-lactamase inhibitors
Authors: Perbandt Markus , Werner Nadine , Prester Andreas , Rohde Holger , Aepfelbacher Martin , Hinrichs Winfried , Betzel Christian
Published: April 2022

β-lactamases are a major cause of rapidly emerging and spreading antibiotic resistance. Currently β-lactamase inhibitors (BLIs) in clinical use act only on Ambler Class A, C and some class D lactamases. The urgent need to identify new BLIs recently lead to FDA approval of boron-based compounds BLIs, e.g. Vaborbactam. The boron-based proteasome inhibitors Bortezomib and Ixazomib are used in cancer therapy as multiple myeloma drugs but they also bind to Ser-/Thr- proteases. In this study we show the crystal structures of the β-lactamase CTX-M-14 with covalently bound Bortezomib and Ixazomib at high resolutions of 1.3 and 1.1 Å, respectively. Ixazomib is well defined in electron density whereas Bortezomib show some disorder which corresponds to weaker inhibition efficiency observed for Ixazomib. Both inhibitors mimic the deacylation transition state of β-lactam hydrolysis, because they replace the deacylating water molecule. We further investigate differences in binding of Bortezomib/Ixazomib to CTX-M-14 and its target proteases as well as known β-lactamase drugs. Our findings can help to use Bortezomib/Ixazomib as lead compounds for development of new BLIs.