bluuebunny/crossref_metadata_2025 huggingface dataset:
The Intraplate Stress Field of West Africa
Authors: Legre Jean‐Joel , Qin Yan , Kolawole Folarin , Olugboji Tolulope
Published: June 2024

West Africa continues to host a growing number of low and intermediate‐magnitude earthquakes (M2‐5) along its passive margins, and its continental interior. Earthquake activity in these regions raises the need to comprehend the causes and the tectonic controls of the seismicity. Unfortunately, such studies are rare. Here, we apply single‐station inversion techniques to constrain fourteen focal mechanisms, computed after compiling a set of high‐quality waveforms. We describe the connection between seismicity, the contemporary stress field, anthropogenic activity and Holocene fault scarps in the region. Our results indicate transpressive stresses acting on the inherited brittle structures in the passive margins. We also observe a compressive regime in the intracontinental failed rifts. We attribute the seismicity to the reactivation of “weak” faults in the Neoproterozoic and Mesozoic failed rifts, the passive transform structures, and the intracratonic Precambrian brittle shear zones.
Multiple Convection Cells Induced by In‐Front and Off‐Front Interactions Between the Obliquely Northward IMF and the Geomagnetic Field
Authors: Tanaka T. , Ebihara Y. , Watanabe M. , Fujita S. , Kataoka R.
Published: June 2024

From the global simulation, we reproduce the solar wind‐magnetosphere‐ionosphere (S‐M‐I) interaction under the northward interplanetary magnetic field (IMF) with negative By. Reconnection structures, the plasma sheet, and lobes are formed in magnetospheric convection, while lobe/round‐merging/reciprocal/nightside cells appear in the ionosphere. Associated with the S‐M interaction, northern open field is generated at the evening open‐closed (O/C) boundary, due to successive cusp and interchange reconnections (in round‐merging cell) or by Dungey‐type reconnection (in nightside cell). Corresponding interchange and Dungey‐type reconnections occur at the southern null. Dungey‐type reconnection at the same time generates southern open field on the outer‐most magnetopause. Open field injected into the northern polar cap/void/lobe constructs the open field part of the round‐merging and nightside cells. After open‐field convection in the lobe, reclosures occur by again successive cusp and interchange reconnections on the dayside separator, or separator reconnection on the nightside separator. Former closed field line proceeds toward the evening O/C boundary through the dayside closed‐field convection in the round‐merging cell, while latter closed field line through the nightside closed‐field convection in the nightside cell. Shear that causes the large‐scale sun‐aligned arc is generated by the process of injecting open magnetic field into the void and the conjugate of process of connecting return flux from the plasma sheet to the nightside cell in counter hemisphere.
Trends and Climate‐Sensitivity of Phenology in China's Natural and Planted Forests
Authors: Xian Ziyi , Yu Zhen , Agathokleous Evgenios , Han Wangya , You Weibin , Zhou Guoyi
Published: June 2024

Forest is the largest carbon sink on land, and the timing of forest phenology profoundly influences carbon uptake. However, disparities in the timing and sensitivity of forest phenology, particularly between planted forests (PF) and natural forests (NF), have yet to be determined. In this study, we analyzed the phenological trends and the climate‐sensitivities of China's NF and PF from 2000 to 2022 using field survey data and satellite data. We found that the start of the growing season (start of the season (SOS)) in NF and PF advanced significantly by 0.07 and 0.08 days yr−1, while the end of the growing season (end of the season (EOS)) in both NF and PF delayed by 0.06 days yr−1. Moreover, precipitation and air temperature jointly influenced the timing of phenological events. The pre‐season precipitation delayed the EOS by 0.009 days mm−1 and 0.006 days mm−1 in NF and PF. Moreover, the SOS was more sensitive to precipitation in PF than in NF in arid areas (i.e., pre‐season precipitation <100 mm). Air temperature significantly advanced the SOS by 0.74 and 0.95 days °C−1 in NF and PF and delayed the EOS by 0.89 and 0.71 days °C−1 in NF and PF. Additionally, the sensitivities of SOS and EOS to air temperature significantly differed between NF and PF. Our findings demonstrate a significant phenological discrepancy between PF and NF. The results suggest that NF and PF responded differently to climate variability, implying forest origin should be considered in the projection of carbon sequestration capability under changing climate.
The Impacts of Micro‐Porosity and Mineralogical Texture on Fractured Rock Alteration
Authors: Zhang Qian , Dong Yanhui , Molins Sergi , Deng Hang
Published: June 2024

Geochemically driven alterations of fractures in multi‐mineral media can create altered layers (ALs) at the fracture‐matrix interface. Spatial variations in the AL significantly influence mass transfer across the interface, and the hydraulic and mechanical properties of the fractured medium. A real‐rock based microfluidic experiment reported spatial variations in AL thickness despite the initially smooth fracture surface, suggesting potential effects of matrix heterogeneity on AL development. However, the respective contribution of structural and mineralogical characteristics is still poorly understood. Using the microfluidic experimental data and a micro‐continuum reactive transport model, we systematically evaluated how micro‐porosity and initial mineral texture impact AL development and thus the overall reactive transport behaviors. Our simulation results confirmed that the extent of AL spatial variations, mainly controlled by mineralogical texture, influences the evolution of reaction and permeability in different ways. Accounting for spatial heterogeneity in mineral distribution produces “channeling” structures in ALs and lower overall reaction (by up to 35.6%), but larger permeability increase (by up to 9.8%). The characteristic length of the reactive mineral cluster was observed to dominate the internal texture of ALs. Whereas the presence of micro‐porosity can enhance mineral accessibility via improving connectivity for flow and transport, and lead to both higher bulk reaction, that is, thicker ALs, and permeability enhancement. Considerations of surface roughness with characteristic length on the same order of magnitude as mineral texture did not change the overall development of AL, which further highlights the importance of accounting for rock matrix properties in predicting long‐term evolution of fractured media. The resulting spatial variations of ALs and their impacts on bulk properties, however, are expected to be further complicated by the coupling of chemical and mechanical processes, and may trigger matrix disaggregation, erosion and other mechanisms of fractured media alteration.
Combined Use of Multiple Cloud‐Free Snow Cover Products in China and Its High‐Mountain Region: Implications From Snow Cover Identification to Snow Phenology Detection
Authors: Zhang Longhui , Zhang Hongbo , Sun Xueyan , Luo Lun
Published: June 2024

Accurate snow phenology detection, including snow cover days (SCD), snow start date (SSD), and snow end date (SED), is increasingly important for understanding mountain hydrology such as snow heterogeneity and snowmelt seasonality. Multiple cloud‐free daily snow cover products have recently been developed in China, employing diverse retrieval algorithms and cloud‐gap‐filling methods, resulting in varying accuracy levels. However, comprehensive analysis of differences among products and their impact on snow phenology detection is lacking. This study systematically evaluates eight state‐of‐the‐art snow cover products in China, focusing on the challenging Tibetan Plateau (TP). We introduce a novel metric, the consistency‐weighted correlation coefficient (CWR), customized for SSD and SED detection, and propose product‐combining schemes like “ensemble voting” and “sensor preference” to enhance reliability. Our findings highlight the prime influence of retrieval algorithms under clear‐sky conditions on accuracy, surpassing the importance of cloud‐gap‐filling methods. Specifically, a product optimizing normalized difference snow index thresholds for diverse landcover types consistently outperforms others in detecting all three snow phenology parameters, with correlation coefficients for SCD of 0.82 and 0.69, and CWR values for SSD of 0.54 and 0.40, and for SED of 0.53 and 0.37 in both China and the TP, respectively. Moreover, our proposed scheme combining three high‐accuracy products significantly enhances snow cover identification and SCD detection, especially when the best‐performing product alone faces substantial uncertainty. These findings provide immediate, crucial implications for optimizing the use of multiple cloud‐free products to enhance snow phenology detection, ultimately advancing the applicability of derived snow parameters in mountain hydrology research.
Genetic association mapping leveraging Gaussian processes
Authors: Kumasaka Natsuhiko
Published: June 2024

Gaussian processes (GPs) are a powerful and useful approach for modelling nonlinear phenomena in various scientific fields, including genomics and genetics. This review focuses on the application of GPs in genetic association mapping. The aim is to identify genetic variants that alter gene regulation along continuous cellular states at the molecular level, as well as disease susceptibility over time and space at the population level. The challenges and opportunities in this field are also addressed.
Functional changes in sleep-related arousal after ketamine administration in individuals with treatment-resistant depression
Authors: Ballard Elizabeth D. , Greenstein Deanna , Reiss Philip T. , Crainiceanu Ciprian M. , Cui Erjia , Duncan Wallace C. , Hejazi Nadia S. , Zarate Carlos A.
Published: June 2024

The glutamatergic modulator ketamine is associated with changes in sleep, depression, and suicidal ideation (SI). This study sought to evaluate differences in arousal-related sleep metrics between 36 individuals with treatment-resistant major depression (TRD) and 25 healthy volunteers (HVs). It also sought to determine whether ketamine normalizes arousal in individuals with TRD and whether ketamine’s effects on arousal mediate its antidepressant and anti-SI effects. This was a secondary analysis of a biomarker-focused, randomized, double-blind, crossover trial of ketamine (0.5 mg/kg) compared to saline placebo. Polysomnography (PSG) studies were conducted one day before and one day after ketamine/placebo infusions. Sleep arousal was measured using spectral power functions over time including alpha (quiet wakefulness), beta (alert wakefulness), and delta (deep sleep) power, as well as macroarchitecture variables, including wakefulness after sleep onset (WASO), total sleep time (TST), rapid eye movement (REM) latency, and Post-Sleep Onset Sleep Efficiency (PSOSE). At baseline, diagnostic differences in sleep macroarchitecture included lower TST (p = 0.006) and shorter REM latency (p = 0.04) in the TRD versus HV group. Ketamine’s temporal dynamic effects (relative to placebo) in TRD included increased delta power earlier in the night and increased alpha and delta power later in the night. However, there were no significant diagnostic differences in temporal patterns of alpha, beta, or delta power, no ketamine effects on sleep macroarchitecture arousal metrics, and no mediation effects of sleep variables on ketamine’s antidepressant or anti-SI effects. These results highlight the role of sleep-related variables as part of the systemic neurobiological changes initiated after ketamine administration. Clinical Trials Identifier: NCT00088699.
Why does circadian timing of administration matter for immune checkpoint inhibitors’ efficacy?
Authors: Karaboué Abdoulaye , Innominato Pasquale F. , Wreglesworth Nicholas I. , Duchemann Boris , Adam René , Lévi Francis A.
Published: June 2024

Background

Tolerability and antitumour efficacy of chemotherapy and radiation therapy can vary largely according to their time of administration along the 24-h time scale, due to the moderation of their molecular and cellular mechanisms by circadian rhythms. Recent clinical data have highlighted a striking role of dosing time for cancer immunotherapy, thus calling for a critical evaluation.

Methods

Here, we review the clinical data and we analyse the mechanisms through which circadian rhythms can influence outcomes on ICI therapies. We examine how circadian rhythm disorders can affect tumour immune microenvironment, as a main mechanism linking the circadian clock to the 24-h cycles in ICIs antitumour efficacy.

Results

Real-life data from 18 retrospective studies have revealed that early time-of-day (ToD) infusion of immune checkpoint inhibitors (ICIs) could enhance progression-free and/or overall survival up to fourfold compared to late ToD dosing. The studies involved a total of 3250 patients with metastatic melanoma, lung, kidney, bladder, oesophageal, stomach or liver cancer from 9 countries. Such large and consistent differences in ToD effects on outcomes could only result from a previously ignored robust chronobiological mechanism. The circadian timing system coordinates cellular, tissue and whole-body physiology along the 24-h timescale. Circadian rhythms are generated at the cellular level by a molecular clock system that involves 15 specific clock genes. The disruption of circadian rhythms can trigger or accelerate carcinogenesis, and contribute to cancer treatment failure, possibly through tumour immune evasion resulting from immunosuppressive tumour microenvironment.

Conclusions and perspective

Such emerging understanding of circadian rhythms regulation of antitumour immunity now calls for randomised clinical trials of ICIs timing to establish recommendations for personalised chrono-immunotherapies with current and forthcoming drugs.
Joint ABS-UKCGG-CanGene-CanVar consensus regarding the use of CanRisk in clinical practice
Authors: Tsoulaki Olga , Tischkowitz Marc , Antoniou Antonis C. , Musgrave Hannah , Rea Gillian , Gandhi Ashu , Cox Karina , Irvine Tracey , Holcombe Sue , Eccles Diana , Turnbull Clare , Cutress Ramsey ,   Meeting Attendees, Andreou Avgi , Badran Abdul , Bartlett Marion , Berlin Cheryl , Binysh Kathie , Brennan Paul , Cleaver Ruth , Corbett Gemma , Davidson Rosemarie , DeSouza Bianca , Evers Rachel , Ficorella Lorenzo , Fitzgerald Suzannah , Forman Andrea , Gilbert Fiona , Gold Rochelle , Greville-Heygate Steph , Hamilton Sarah , Hammond Carrie , Hart Rachel , Hawkes Lara , Hayward Jude , Holliday Debbie , Howell Antony , Hutchison Gillian , Jenkins Jacqui , Jewell Rosalyn , Kavanaugh Grace , Kemp Zoe , Kiesel Victoria , Kumar Ajith , Lalloo Fiona , Miedzybrodzka Zosia , Murray Jennie , Nisbet Sian , Ogunleye Della , Paramasivam Anbalakan , Searle Claire , Shaw Adam , Sheridan Eamon , Side Lucy , Smith Katherine , Speight Beverley , Teh William , Thorpe Eleanor , Whaite Anna , Wilkinson Louise , Wilkinson Siobhan , Woodward Emma R. , Youngs Alice , Archer Stephanie , Hanson Helen
Published: June 2024

Background

The CanRisk tool, which operationalises the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) is used by Clinical Geneticists, Genetic Counsellors, Breast Oncologists, Surgeons and Family History Nurses for breast cancer risk assessments both nationally and internationally. There are currently no guidelines with respect to the day-to-day clinical application of CanRisk and differing inputs to the model can result in different recommendations for practice.

Methods

To address this gap, the UK Cancer Genetics Group in collaboration with the Association of Breast Surgery and the CanGene-CanVar programme held a workshop on 16th of May 2023, with the aim of establishing best practice guidelines.

Results

Using a pre-workshop survey followed by structured discussion and in-meeting polling, we achieved consensus for UK best practice in use of CanRisk in making recommendations for breast cancer surveillance, eligibility for genetic testing and the input of available information to undertake an individualised risk assessment.

Conclusions

Whilst consensus recommendations were achieved, the meeting highlighted some of the barriers limiting the use of CanRisk in clinical practice and identified areas that require further work and collaboration with relevant national bodies and policy makers to incorporate wider use of CanRisk into routine breast cancer risk assessments.
Structural basis for recognition of 26RFa by the pyroglutamylated RFamide peptide receptor
Authors: Jin Sanshan , Guo Shimeng , Xu Youwei , Li Xin , Wu Canrong , He Xinheng , Pan Benxun , Xin Wenwen , Zhang Heng , Hu Wen , Yin Yuling , Zhang Tianwei , Wu Kai , Yuan Qingning , Xu H. Eric , Xie Xin , Jiang Yi
Published: June 2024

The neuropeptide 26RFa, a member of the RF-amide peptide family, activates the pyroglutamylated RF-amide peptide receptor (QRFPR), a class A GPCR. The 26RFa/QRFPR system plays critical roles in energy homeostasis, making QRFPR an attractive drug target for treating obesity, diabetes, and eating disorders. However, the lack of structural information has hindered our understanding of the peptide recognition and regulatory mechanism of QRFPR, impeding drug design efforts. In this study, we determined the cryo-EM structure of the Gq-coupled QRFPR bound to 26RFa. The structure reveals a unique assembly mode of the extracellular region of the receptor and the N-terminus of the peptide, and elucidates the recognition mechanism of the C-terminal heptapeptide of 26RFa by the transmembrane binding pocket of QRFPR. The study also clarifies the similarities and distinctions in the binding pattern of the RF-amide moiety in five RF-amide peptides and the RY-amide segment in neuropeptide Y. These findings deepen our understanding of the RF-amide peptide recognition, aiding in the rational design of drugs targeting QRFPR and other RF-amide peptide receptors.
Why we thrive beneath a northern sky – genomic signals of selection in apple for adaptation to northern Sweden
Authors: Skytte af Sätra J. , Garkava-Gustavsson L. , Ingvarsson P. K.
Published: June 2024

Good understanding of the genomic regions underlying adaptation of apple to boreal climates is needed to facilitate efficient breeding of locally adapted apple cultivars. Proper infrastructure for phenotyping and evaluation is essential for identification of traits responsible for adaptation, and dissection of their genetic composition. However, such infrastructure is costly and currently not available for the boreal zone of northern Sweden. Therefore, we used historical pomological data on climate adaptation of 59 apple cultivars and whole genome sequencing to identify genomic regions that have undergone historical selection among apple cultivars recommended for cultivation in northern Sweden. We found the apple collection to be composed of two ancestral groups that are largely concordant with the grouping into ‘hardy’ and ‘not hardy’ cultivars based on the pomological literature. Using a number of genome-wide scans for signals of selection, we obtained strong evidence of positive selection at a genomic region around 29 MbHFTH1 of chromosome 1 among apple cultivars in the ‘hardy’ group. Using phased genotypic data from the 20 K apple Infinium® SNP array, we identified haplotypes associated with the two cultivar groups and traced transmission of these haplotypes through the pedigrees of some apple cultivars. This demonstrates that historical data from pomological literature can be analyzed by population genomic approaches as a step towards revealing the genomic control of a key property for a horticultural niche market. Such knowledge is needed to facilitate efficient breeding strategies for development of locally adapted apple cultivars in the future. The current study illustrates the response to a very strong selective pressure imposed on tree crops by climatic factors, and the importance of genetic research on this topic and feasibility of breeding efforts in the light of the ongoing climate change.
Heterogeneous organophotocatalytic HBr oxidation coupled with oxygen reduction for boosting bromination of arenes
Authors: Wang Jie , Liang Jiahao , Hou Hao , Liu Wei , Wu Hongru , Sun Hongli , Ou Wei , Su Chenliang , Liu Bin
Published: June 2024

Developing mild photocatalytic bromination strategies using sustainable bromo source has been attracting intense interests, but there is still much room for improvement. Full utilization of redox centers of photocatalysts for efficient generation of Br+ species is the key. Herein we report heterogenous organophotocatalytic HBr oxidation coupled with oxygen reduction to furnish Br2 and H2O2 for effective bromination of arenes over Al2O3 supported perylene-3,4,9,10-tetracarboxylic dianhydride (PTCDA). Mechanism studies suggest that O-vacancy in Al2O3 can provide Lewis-acid-type anchoring sites for O2, enabling unexpected dual-electron transfer from anchored photoexcited PTCDA to chemically bound O2 to produce H2O2. The in-situ generated H2O2 and Br2 over redox centers work together to generate HBrO for bromination of arenes. This work provides new insights that heterogenization of organophotocatalysts can not only help to improve their stability and recyclability, but also endow them with the ability to trigger unusual reaction mode via cooperative catalysis with supports.
Stretchable OLEDs based on a hidden active area for high fill factor and resolution compensation
Authors: Lee Donggyun , Kim Su-Bon , Kim Taehyun , Choi Dongho , Sim Jee Hoon , Lee Woochan , Cho Hyunsu , Yang Jong-Heon , Kim Junho , Hahn Sangin , Moon Hanul , Yoo Seunghyup
Published: June 2024

Stretchable organic light-emitting diodes (OLEDs) have emerged as promising optoelectronic devices with exceptional degree of freedom in form factors. However, stretching OLEDs often results in a reduction in the geometrical fill factor (FF), that is the ratio of an active area to the total area, thereby limiting their potential for a broad range of applications. To overcome these challenges, we propose a three-dimensional (3D) architecture adopting a hidden active area that serves a dual role as both an emitting area and an interconnector. For this purpose, an ultrathin OLED is first attached to a 3D rigid island array structure through quadaxial stretching for precise, deformation-free alignment. A portion of the ultrathin OLED is concealed by letting it ‘fold in’ between the adjacent islands in the initial, non-stretched condition and gradually surfaces to the top upon stretching. This design enables the proposed stretchable OLEDs to exhibit a relatively high FF not only in the initial state but also after substantial deformation corresponding to a 30% biaxial system strain. Moreover, passive-matrix OLED displays that utilize this architecture are shown to be configurable for compensation of post-stretch resolution loss, demonstrating the efficacy of the proposed approach in realizing the full potential of stretchable OLEDs.
Bacteriophage defends murine gut from Escherichia coli invasion via mucosal adherence
Authors: Wu Jiaoling , Fu Kailai , Hou Chenglin , Wang Yuxin , Ji Chengyuan , Xue Feng , Ren Jianluan , Dai Jianjun , Barr Jeremy J. , Tang Fang
Published: June 2024

Bacteriophage are sophisticated cellular parasites that can not only parasitize bacteria but are increasingly recognized for their direct interactions with mammalian hosts. Phage adherence to mucus is known to mediate enhanced antimicrobial effects in vitro. However, little is known about the therapeutic efficacy of mucus-adherent phages in vivo. Here, using a combination of in vitro gastrointestinal cell lines, a gut-on-a-chip microfluidic model, and an in vivo murine gut model, we demonstrated that a E. coli phage, øPNJ-6, provided enhanced gastrointestinal persistence and antimicrobial effects. øPNJ-6 bound fucose residues, of the gut secreted glycoprotein MUC2, through domain 1 of its Hoc protein, which led to increased intestinal mucus production that was suggestive of a positive feedback loop mediated by the mucus-adherent phage. These findings extend the Bacteriophage Adherence to Mucus model into phage therapy, demonstrating that øPNJ-6 displays enhanced persistence within the murine gut, leading to targeted depletion of intestinal pathogenic bacteria.
Higher-order correlations reveal complex memory in temporal hypergraphs
Authors: Gallo Luca , Lacasa Lucas , Latora Vito , Battiston Federico
Published: June 2024

Many real-world complex systems are characterized by interactions in groups that change in time. Current temporal network approaches, however, are unable to describe group dynamics, as they are based on pairwise interactions only. Here, we use time-varying hypergraphs to describe such systems, and we introduce a framework based on higher-order correlations to characterize their temporal organization. The analysis of human interaction data reveals the existence of coherent and interdependent mesoscopic structures, thus capturing aggregation, fragmentation and nucleation processes in social systems. We introduce a model of temporal hypergraphs with non-Markovian group interactions, which reveals complex memory as a fundamental mechanism underlying the emerging pattern in the data.
Systematic evaluation of fMRI data-processing pipelines for consistent functional connectomics
Authors: Luppi Andrea I. , Gellersen Helena M. , Liu Zhen-Qi , Peattie Alexander R. D. , Manktelow Anne E. , Adapa Ram , Owen Adrian M. , Naci Lorina , Menon David K. , Dimitriadis Stavros I. , Stamatakis Emmanuel A.
Published: June 2024

Functional interactions between brain regions can be viewed as a network, enabling neuroscientists to investigate brain function through network science. Here, we systematically evaluate 768 data-processing pipelines for network reconstruction from resting-state functional MRI, evaluating the effect of brain parcellation, connectivity definition, and global signal regression. Our criteria seek pipelines that minimise motion confounds and spurious test-retest discrepancies of network topology, while being sensitive to both inter-subject differences and experimental effects of interest. We reveal vast and systematic variability across pipelines’ suitability for functional connectomics. Inappropriate choice of data-processing pipeline can produce results that are not only misleading, but systematically so, with the majority of pipelines failing at least one criterion. However, a set of optimal pipelines consistently satisfy all criteria across different datasets, spanning minutes, weeks, and months. We provide a full breakdown of each pipeline’s performance across criteria and datasets, to inform future best practices in functional connectomics.
Burkholderia pseudomallei BipD modulates host mitophagy to evade killing
Authors: Nan Dongqi , Rao Chenglong , Tang Zhiheng , Yang Wenbo , Wu Pan , Chen Jiangao , Xia Yupei , Yan Jingmin , Liu Wenzheng , Zhang Ziyuan , Hu Zhiqiang , Chen Hai , Liao Yaling , Mao Xuhu , Liu Xiaoyun , Zou Quanming , Li Qian
Published: June 2024

Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.
Bio-inspired multimodal learning with organic neuromorphic electronics for behavioral conditioning in robotics
Authors: Krauhausen Imke , Griggs Sophie , McCulloch Iain , den Toonder Jaap M. J. , Gkoupidenis Paschalis , van de Burgt Yoeri
Published: June 2024

Biological systems interact directly with the environment and learn by receiving multimodal feedback via sensory stimuli that shape the formation of internal neuronal representations. Drawing inspiration from biological concepts such as exploration and sensory processing that eventually lead to behavioral conditioning, we present a robotic system handling objects through multimodal learning. A small-scale organic neuromorphic circuit locally integrates and adaptively processes multimodal sensory stimuli, enabling the robot to interact intelligently with its surroundings. The real-time handling of sensory stimuli via low-voltage organic neuromorphic devices with synaptic functionality forms multimodal associative connections that lead to behavioral conditioning, and thus the robot learns to avoid potentially dangerous objects. This work demonstrates that adaptive neuro-inspired circuitry with multifunctional organic materials, can accommodate locally efficient bio-inspired learning for advancing intelligent robotics.
Highly reversible transition metal migration in superstructure-free Li-rich oxide boosting voltage stability and redox symmetry
Authors: Cui Tianwei , Xu Jialiang , Wang Xin , Liu Longxiang , Xiang Yuxuan , Zhu Hong , Li Xiang , Fu Yongzhu
Published: June 2024

The further practical applications of Li-rich layered oxides are impeded by voltage decay and redox asymmetry, which are closely related to the structural degradation involving irreversible transition metal migration. It has been demonstrated that the superstructure ordering in O2-type materials can effectively suppress voltage decay and redox asymmetry. Herein, we elucidate that the absence of this superstructure ordering arrangement in a Ru-based O2-type oxide can still facilitate the highly reversible transition metal migration. We certify that Ru in superstructure-free O2-type structure can unlock a quite different migration path from Mn in mostly studied cases. The highly reversible migration of Ru helps the cathode maintain the structural robustness, thus realizing terrific capacity retention with neglectable voltage decay and inhibited oxygen redox asymmetry. We untie the knot that the absence of superstructure ordering fails to enable a high-performance Li-rich layered oxide cathode material with suppressed voltage decay and redox asymmetry.
Orthogonal proteogenomic analysis identifies the druggable PA2G4-MYC axis in 3q26 AML
Authors: Marchesini Matteo , Gherli Andrea , Simoncini Elisa , Tor Lucas Moron Dalla , Montanaro Anna , Thongon Natthakan , Vento Federica , Liverani Chiara , Cerretani Elisa , D’Antuono Anna , Pagliaro Luca , Zamponi Raffaella , Spadazzi Chiara , Follini Elena , Cambò Benedetta , Giaimo Mariateresa , Falco Angela , Sammarelli Gabriella , Todaro Giannalisa , Bonomini Sabrina , Adami Valentina , Piazza Silvano , Corbo Claudia , Lorusso Bruno , Mezzasoma Federica , Lagrasta Costanza Anna Maria , Martelli Maria Paola , La Starza Roberta , Cuneo Antonio , Aversa Franco , Mecucci Cristina , Quaini Federico , Colla Simona , Roti Giovanni
Published: June 2024

The overexpression of the ecotropic viral integration site-1 gene (EVI1/MECOM) marks the most lethal acute myeloid leukemia (AML) subgroup carrying chromosome 3q26 abnormalities. By taking advantage of the intersectionality of high-throughput cell-based and gene expression screens selective and pan-histone deacetylase inhibitors (HDACis) emerge as potent repressors of EVI1. To understand the mechanism driving on-target anti-leukemia activity of this compound class, here we dissect the expression dynamics of the bone marrow leukemia cells of patients treated with HDACi and reconstitute the EVI1 chromatin-associated co-transcriptional complex merging on the role of proliferation-associated 2G4 (PA2G4) protein. PA2G4 overexpression rescues AML cells from the inhibitory effects of HDACis, while genetic and small molecule inhibition of PA2G4 abrogates EVI1 in 3q26 AML cells, including in patient-derived leukemia xenografts. This study positions PA2G4 at the crosstalk of the EVI1 leukemogenic signal for developing new therapeutics and urges the use of HDACis-based combination therapies in patients with 3q26 AML.
One-step formation of polymorphous sperm-like microswimmers by vortex turbulence-assisted microfluidics
Authors: Tan Rong , Yang Xiong , Lu Haojian , Shen Yajing
Published: June 2024

Microswimmers are considered promising candidates for active cargo delivery to benefit a wide spectrum of biomedical applications. Yet, big challenges still remain in designing the microswimmers with effective propelling, desirable loading and adaptive releasing abilities all in one. Inspired by the morphology and biofunction of spermatozoa, we report a one-step formation strategy of polymorphous sperm-like magnetic microswimmers (PSMs) by developing a vortex turbulence-assisted microfluidics (VTAM) platform. The fabricated PSM is biodegradable with a core-shell head and flexible tail, and their morphology can be adjusted by vortex flow rotation speed and calcium chloride solution concentration. Benefiting from the sperm-like design, our PSM exhibits both effective motion ability under remote mag/netic actuation and protective encapsulation ability for material loading. Further, it can also realize the stable sustain release after alginate-chitosan-alginate (ACA) layer coating modification. This research proposes and verifies a new strategy for the sperm-like microswimmer construction, offering an alternative solution for the target delivery of diverse drugs and biologics for future biomedical treatment. Moreover, the proposed VTAM could also be a general method for other sophisticated polymorphous structures fabrication that isn’t achievable by conventional laminar flow.
Structure and mechanism of the K+/H+ exchanger KefC
Authors: Gulati Ashutosh , Kokane Surabhi , Perez-Boerema Annemarie , Alleva Claudia , Meier Pascal F. , Matsuoka Rei , Drew David
Published: June 2024

Intracellular potassium (K+) homeostasis is fundamental to cell viability. In addition to channels, K+ levels are maintained by various ion transporters. One major family is the proton-driven K+ efflux transporters, which in gram-negative bacteria is important for detoxification and in plants is critical for efficient photosynthesis and growth. Despite their importance, the structure and molecular basis for K+-selectivity is poorly understood. Here, we report ~3.1 Å resolution cryo-EM structures of the Escherichia coli glutathione (GSH)-gated K+ efflux transporter KefC in complex with AMP, AMP/GSH and an ion-binding variant. KefC forms a homodimer similar to the inward-facing conformation of Na+/H+ antiporter NapA. By structural assignment of a coordinated K+ ion, MD simulations, and SSM-based electrophysiology, we demonstrate how ion-binding in KefC is adapted for binding a dehydrated K+ ion. KefC harbors C-terminal regulator of K+ conductance (RCK) domains, as present in some bacterial K+-ion channels. The domain-swapped helices in the RCK domains bind AMP and GSH and they inhibit transport by directly interacting with the ion-transporter module. Taken together, we propose that KefC is activated by detachment of the RCK domains and that ion selectivity exploits the biophysical properties likewise adapted by K+-ion-channels.
How liquids charge the superhydrophobic surfaces
Authors: Jin Yuankai , Yang Siyan , Sun Mingzi , Gao Shouwei , Cheng Yaqi , Wu Chenyang , Xu Zhenyu , Guo Yunting , Xu Wanghuai , Gao Xuefeng , Wang Steven , Huang Bolong , Wang Zuankai
Published: June 2024

Liquid-solid contact electrification (CE) is essential to diverse applications. Exploiting its full implementation requires an in-depth understanding and fine-grained control of charge carriers (electrons and/or ions) during CE. Here, we decouple the electrons and ions during liquid-solid CE by designing binary superhydrophobic surfaces that eliminate liquid and ion residues on the surfaces and simultaneously enable us to regulate surface properties, namely work function, to control electron transfers. We find the existence of a linear relationship between the work function of superhydrophobic surfaces and the as-generated charges in liquids, implying that liquid-solid CE arises from electron transfer due to the work function difference between two contacting surfaces. We also rule out the possibility of ion transfer during CE occurring on superhydrophobic surfaces by proving the absence of ions on superhydrophobic surfaces after contact with ion-enriched acidic, alkaline, and salt liquids. Our findings stand in contrast to existing liquid-solid CE studies, and the new insights learned offer the potential to explore more applications.
A combined experimental and computational study of ligand-controlled Chan-Lam coupling of sulfenamides
Authors: Han Kaiming , Liu Hong , Rotella Madeline E. , Xu Zeyu , Tao Lizhi , Chen Shufeng , Kozlowski Marisa C. , Jia Tiezheng
Published: June 2024

The unique features of the sulfenamides’ S(II)-N bond lead to interesting stereochemical properties and significant industrial functions. Here we present a chemoselective Chan–Lam coupling of sulfenamides to prepare N-arylated sulfenamides. A tridentate pybox ligand governs the chemoselectivity favoring C–N bond formation, and overrides the competitive C-S bond formation by preventing the S,N-bis-chelation of sulfenamides to copper center. The Cu(II)-derived resting state of catalyst is captured by UV-Vis spectra and EPR technique, and the key intermediate is confirmed by the EPR isotope response using 15N-labeled sulfenamide. A computational mechanistic study reveals that N-arylation is both kinetically and thermodynamically favorable, with deprotonation of the sulfenamide nitrogen atom occurring prior to reductive elimination. The origin of ligand-controlled chemoselectivity is explored, with the interaction between the pybox ligand and the sulfenamide substrate controlling the energy of the S-arylation and the corresponding product distribution, in agreement with the EPR studies and kinetic results.
Changes in planned and unplanned canopy openings are linked in Europe’s forests
Authors: Seidl Rupert , Senf Cornelius
Published: June 2024

Canopy openings are increasing in Europe’s forests, yet the contributions of anthropogenic and ecological agents of disturbance to this increase remain debated. Here we attribute the root cause of all stand-replacing canopy disturbances identified for Europe in the period 1986–2020 from Landsat data (417,000 km²), distinguishing between planned and unplanned canopy openings (i.e., disturbance by human land use versus by wind, bark beetles, and wildfire). We show that canopy openings by humans dominate the European forest disturbance regime, accounting for 82% of the area disturbed. Both planned and unplanned canopy openings increased in the early 21st century (+24% and +30% relative to the late 20th century). Their changes are linked, with simultaneous increases in planned and unplanned canopy openings on 68% of Europe’s forest area. We conclude that an important direction for tackling disturbance change in policy and management is to break the link between planned and unplanned canopy openings in Europe’s forests.
Shear force effect of the dry process on cathode contact coverage in all-solid-state batteries
Authors: Lee Dongkyu , Shim Yejin , Kim Youngsung , Kwon Guhan , Choi Seung Ho , Kim KyungSu , Yoo Dong-Joo
Published: June 2024

The state-of-the-art all-solid-state batteries have emerged as an alternative to the traditional flammable lithium-ion batteries, offering higher energy density and safety. Nevertheless, insufficient intimate contact at electrode-electrolyte surface limits their stability and electrochemical performance, hindering the commercialization of all-solid-state batteries. Herein, we conduct a systematic investigation into the effects of shear force in the dry electrode process by comparing binder-free hand-mixed pellets, wet-processed electrodes, and dry-processed electrodes. Through digitally processed images, we quantify a critical factor, ‘coverage’, the percentage of electrolyte-covered surface area of the active materials. The coverage of dry electrodes was significantly higher (67.2%) than those of pellets (30.6%) and wet electrodes (33.3%), enabling superior rate capability and cyclability. A physics-based electrochemical model highlights the effects of solid diffusion by elucidating the impact of coverage on active material utilization under various current densities. These results underscore the pivotal role of the electrode fabrication process, with the focus on the critical factor of coverage.
FTO deficiency in older livers exacerbates ferroptosis during ischaemia/reperfusion injury by upregulating ACSL4 and TFRC
Authors: Li Rong , Yan Xijing , Xiao Cuicui , Wang Tingting , Li Xuejiao , Hu Zhongying , Liang Jinliang , Zhang Jiebin , Cai Jianye , Sui Xin , Liu Qiuli , Wu Manli , Xiao Jiaqi , Chen Haitian , Liu Yasong , Jiang Chenhao , Lv Guo , Chen Guihua , Zhang Yingcai , Yao Jia , Zheng Jun , Yang Yang
Published: June 2024

Older livers are more prone to hepatic ischaemia/reperfusion injury (HIRI), which severely limits their utilization in liver transplantation. The potential mechanism remains unclear. Here, we demonstrate older livers exhibit increased ferroptosis during HIRI. Inhibiting ferroptosis significantly attenuates older HIRI phenotypes. Mass spectrometry reveals that fat mass and obesity-associated gene (FTO) expression is downregulated in older livers, especially during HIRI. Overexpressing FTO improves older HIRI phenotypes by inhibiting ferroptosis. Mechanistically, acyl-CoA synthetase long chain family 4 (ACSL4) and transferrin receptor protein 1 (TFRC), two key positive contributors to ferroptosis, are FTO targets. For ameliorative effect, FTO requires the inhibition of Acsl4 and Tfrc mRNA stability in a m6A-dependent manner. Furthermore, we demonstrate nicotinamide mononucleotide can upregulate FTO demethylase activity, suppressing ferroptosis and decreasing older HIRI. Collectively, these findings reveal an FTO-ACSL4/TFRC regulatory pathway that contributes to the pathogenesis of older HIRI, providing insight into the clinical translation of strategies related to the demethylase activity of FTO to improve graft function after older donor liver transplantation.
Predicting polymerization reactions via transfer learning using chemical language models
Authors: Ferrari Brenda S. , Manica Matteo , Giro Ronaldo , Laino Teodoro , Steiner Mathias B.
Published: June 2024

Polymers are candidate materials for a wide range of sustainability applications such as carbon capture and energy storage. However, computational polymer discovery lacks automated analysis of reaction pathways and stability assessment through retro-synthesis. Here, we report an extension of transformer-based language models to polymerization for both reaction and retrosynthesis tasks. To that end, we have curated a polymerization dataset for vinyl polymers covering reactions and retrosynthesis for representative homo-polymers and co-polymers. Overall, we obtain a forward model Top-4 accuracy of 80% and a backward model Top-4 accuracy of 60%. We further analyze the model performance with representative polymerization examples and evaluate its prediction quality from a materials science perspective. To enable validation and reuse, we have made our models and data available in public repositories.
Significantly enhanced performance for phenol compounds removal by MOF-5 nano-composite via its surface modification
Authors: Razavi Leila , Raissi Heidar , Hashemzehi Ozra , Farzad Farzaneh
Published: June 2024

The present study is focused on the use of cubic metal-organic frameworks-5 (MOF-5) and its functionalized form in the removal of phenolic pollutants by molecular dynamics (MD) and Well-tempered metadynamics (WTMD) simulation methods. It was found that the adsorption mechanism of MOF-5s/phenolic compounds is mostly due to the van der Waals and π–π interactions. However, electrostatic and hydrogen bond (HB) interactions also play a significant role in removing phenolic pollutants by MOF-5 and its functionalized form. The results show that the fluorine functional group (F-MOF-5) increases the adsorption capacity of phenol compounds on the adsorbent surface. By functionalizing the MOF-5 with a methyl functional group (CH3-MOF-5), the adsorption strength decreases. The WTMD calculation confirmed that at the most stable state, the free energy (FE) value of system II (the most stable system in functionalized systems with –F functional group) is about −289.528 kJ mol−1. This value is ~5.781 and 35.514 kJ mol−1 more negative than the FE of the I and III systems (the most stable systems in the pristine and CH3-MOF-5/pollutant systems, respectively). Altogether, the results indicate that F-MOF-5 can be considered a more suitable adsorbent than MOF-5 and CH3-MOF-5 for phenolic pollutants removal from the environment for more assessment.
Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes
Authors: Alraies Zahraa , Rivera Claudia A. , Delgado Maria-Graciela , Sanséau Doriane , Maurin Mathieu , Amadio Roberto , Maria Piperno Giulia , Dunsmore Garett , Yatim Aline , Lacerda Mariano Livia , Kniazeva Anna , Calmettes Vincent , Sáez Pablo J. , Williart Alice , Popard Henri , Gratia Matthieu , Lamiable Olivier , Moreau Aurélie , Fusilier Zoé , Crestey Lou , Albaud Benoit , Legoix Patricia , Dejean Anne S. , Le Dorze Anne-Louise , Nakano Hideki , Cook Donald N. , Lawrence Toby , Manel Nicolas , Benvenuti Federica , Ginhoux Florent , Moreau Hélène D. , P. F. Nader Guilherme , Piel Matthieu , Lennon-Duménil Ana-Maria
Published: June 2024

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown. Here, we identify a shape-sensing mechanism that increases the expression of the chemokine receptor CCR7 and guides dendritic cell migration from peripheral tissues to lymph nodes at steady state. This mechanism relies on the lipid metabolism enzyme cPLA2, requires nuclear envelope tensioning and is finely tuned by the ARP2/3 actin nucleation complex. We also show that this shape-sensing axis reprograms dendritic cell transcription by activating an IKKβ–NF-κB-dependent pathway known to control their tolerogenic potential. These results indicate that cell shape changes experienced by immune cells can define their migratory behavior and immunoregulatory properties and reveal a contribution of the physical properties of tissues to adaptive immunity.