bluuebunny/crossref_metadata_2025 huggingface dataset:
Prebiotic diet normalizes aberrant immune and behavioral phenotypes in a mouse model of autism spectrum disorder
Authors: Prince Naika , Peralta Marzal Lucia N , Markidi Anastasia , Ahmed Sabbir , Adolfs Youri , Pasterkamp R Jeroen , Kumar Himanshu , Roeselers Guus , Garssen Johan , Kraneveld Aletta D , Perez-Pardo Paula
Published: April 2024

Autism spectrum disorder (ASD) is a cluster of neurodevelopmental disorders characterized by deficits in communication and behavior. Increasing evidence suggests that the microbiota-gut-brain axis and the likely related immune imbalance may play a role in the development of this disorder. Gastrointestinal deficits and gut microbiota dysfunction have been linked to the development or severity of autistic behavior. Therefore, treatments that focus on specific diets may improve gastrointestinal function and aberrant behavior in individuals with ASD. In this study, we investigated whether a diet containing specific prebiotic fibers, namely, 3% galacto-oligosaccharide/fructo-oligosaccharide (GOS/FOS; 9:1), can mitigate the adverse effects of in utero exposure to valproic acid (VPA) in mice. Pregnant BALB/cByJ dams were injected with VPA (600 mg/kg, sc.) or phosphate-buffered saline (PBS) on gestational day 11 (G11). Male offspring were divided into four groups: (1) in utero PBS-exposed with a control diet, (2) in utero PBS-exposed with GOS/FOS diet, (3) in utero VPA-exposed with a control diet, and (4) in utero VPA-exposed with GOS/FOS diet. Dietary intervention started from birth and continued throughout the duration of the experiment. We showed that the prebiotic diet normalized VPA-induced alterations in male offspring, including restoration of key microbial taxa, intestinal permeability, peripheral immune homeostasis, reduction of neuroinflammation in the cerebellum, and impairments in social behavior and cognition in mice. Overall, our research provides valuable insights into the gut-brain axis involvement in ASD development. In addition, dietary interventions might correct the disbalance in gut microbiota and immune responses and, ultimately, might improve detrimental behavioral outcomes in ASD.
Proteinase 3 depletion attenuates leukemia by promoting myeloid differentiation
Authors: Liu Huan , Sun Lu , Zhao Hongfei , Zhao Zihan , Zhang Shiyue , Jiang Shan , Cheng Tianran , Wang Xiaohan , Wang Tong , Shao Ya , Zhu Haiyan , Han Huijuan , Cao Yigeng , Jiang Erlie , Cao Yihai , Xu Yuanfu
Published: April 2024

Hematopoietic stem and progenitor cells (HSPCs) that have impaired differentiation can transform into leukemic blasts. However, the mechanism that controls differentiation remains elusive. Here, we show that the genetic elimination of Proteinase 3 (PRTN3) in mice led to spontaneous myeloid differentiation. Mechanistically, our findings indicate that PRTN3 interacts with the N-terminal of STAT3, serving as a negative regulator of STAT3-dependent myeloid differentiation. Specifically, PRTN3 promotes STAT3 ubiquitination and degradation, while simultaneously reducing STAT3 phosphorylation and nuclear translocation during G-CSF-stimulated myeloid differentiation. Strikingly, pharmacological inhibition of STAT3 (Stattic) partially counteracted the effects of PRTN3 deficiency on myeloid differentiation. Moreover, the deficiency of PRTN3 in primary AML blasts promotes the differentiation of those cells into functional neutrophils capable of chemotaxis and phagocytosis, ultimately resulting in improved overall survival rates for recipients. These findings indicate PRTN3 exerts an inhibitory effect on STAT3-dependent myeloid differentiation and could be a promising therapeutic target for the treatment of acute myeloid leukemia.
Transglutaminase 3 regulates cutaneous squamous carcinoma differentiation and inhibits progression via PI3K-AKT signaling pathway-mediated Keratin 14 degradation
Authors: Zhou Kaili , Wu Chenglong , Cheng Wenjie , Zhang Boyuan , Wei Ruoqu , Cheng Daian , Li Yan , Cao Yu , Zhang Wenqing , Yao Zhirong , Zhang Xue
Published: April 2024

Cutaneous squamous carcinoma is the second most common epithelial malignancy, associated with significant morbidity, mortality, and economic burden. However, the mechanisms underlying cSCC remain poorly understood. In this study, we identified TGM3 as a novel cSCC tumor suppressor that acts via the PI3K-AKT axis. RT-qPCR, IHC and western blotting were employed to assess TGM3 levels. TGM3-overexpression/knockdown cSCC cell lines were utilized to detect TGM3’s impact on epithelial differentiation as well as tumor cell proliferation, migration, and invasion in vitro. Additionally, subcutaneous xenograft tumor models were employed to examine the effect of TGM3 knockdown on tumor growth in vivo. Finally, molecular and biochemical approaches were employed to gain insight into the tumor-suppressing mechanisms of TGM3. TGM3 expression was increased in well-differentiated cSCC tumors, whereas it was decreased in poor-differentiated cSCC tumors. Loss of TGM3 is associated with poor differentiation and a high recurrence rate in patients with cSCC. TGM3 exhibited tumor-suppressing activity by regulating cell proliferation, migration, and invasion both in vitro and in vivo. As a novel cSCC tumor differentiation marker, TGM3 expression was positively correlated with cell differentiation. In addition, our results demonstrated an interaction between TGM3 and KRT14 that aids in the degradation of KRT14. TGM3 deficiency disrupts keratinocytes differentiation, and ultimately leads to tumorigenesis. Furthermore, RNA-sequence analysis revealed that loss of TGM3 enhanced EMT via the PI3K-AKT signaling pathway. Deguelin, a PI3K-AKT inhibitor, blocked cSCC tumor growth induced by TGM3 knockdown in vivo. Taken together, TGM3 inhibits cSCC tumor growth via PI3K-AKT signaling, which could also serve as a tumor differentiation marker and a potential therapeutic target for cSCC.
Slow magnetic relaxation in a europium(II) complex
Authors: Errulat Dylan , Harriman Katie L. M. , Gálico Diogo A. , Salerno Elvin V. , van Tol Johan , Mansikkamäki Akseli , Rouzières Mathieu , Hill Stephen , Clérac Rodolphe , Murugesu Muralee
Published: April 2024

Single-ion anisotropy is vital for the observation of Single-Molecule Magnet (SMM) properties (i.e., a slow dynamics of the magnetization) in lanthanide-based systems. In the case of europium, the occurrence of this phenomenon has been inhibited by the spin and orbital quantum numbers that give way to J = 0 in the trivalent state and the half-filled population of the 4f orbitals in the divalent state. Herein, by optimizing the local crystal field of a quasi-linear bis(silylamido) EuII complex, the [EuII(N{SiMePh2}2)2] SMM is described, providing an example of a europium complex exhibiting slow relaxation of its magnetization. This behavior is dominated by a thermally activated (Orbach-like) mechanism, with an effective energy barrier of approximately 8 K, determined by bulk magnetometry and electron paramagnetic resonance. Ab initio calculations confirm second-order spin-orbit coupling effects lead to non-negligible axial magnetic anisotropy, splitting the ground state multiplet into four Kramers doublets, thereby allowing for the observation of an Orbach-like relaxation at low temperatures.
Accelerated DNA replication fork speed due to loss of R-loops in myelodysplastic syndromes with SF3B1 mutation
Authors: Rombaut David , Lefèvre Carine , Rached Tony , Bondu Sabrina , Letessier Anne , Mangione Raphael M. , Farhat Batoul , Lesieur-Pasquier Auriane , Castillo-Guzman Daisy , Boussaid Ismael , Friedrich Chloé , Tourville Aurore , De Carvalho Magali , Levavasseur Françoise , Leduc Marjorie , Le Gall Morgane , Battault Sarah , Temple Marie , Houy Alexandre , Bouscary Didier , Willems Lise , Park Sophie , Raynaud Sophie , Cluzeau Thomas , Clappier Emmanuelle , Fenaux Pierre , Adès Lionel , Margueron Raphael , Wassef Michel , Alsafadi Samar , Chapuis Nicolas , Kosmider Olivier , Solary Eric , Constantinou Angelos , Stern Marc-Henri , Droin Nathalie , Palancade Benoit , Miotto Benoit , Chédin Frédéric , Fontenay Michaela
Published: April 2024

Myelodysplastic syndromes (MDS) with mutated SF3B1 gene present features including a favourable outcome distinct from MDS with mutations in other splicing factor genes SRSF2 or U2AF1. Molecular bases of these divergences are poorly understood. Here we find that SF3B1-mutated MDS show reduced R-loop formation predominating in gene bodies associated with intron retention reduction, not found in U2AF1- or SRSF2-mutated MDS. Compared to erythroblasts from SRSF2- or U2AF1-mutated patients, SF3B1-mutated erythroblasts exhibit augmented DNA synthesis, accelerated replication forks, and single-stranded DNA exposure upon differentiation. Importantly, histone deacetylase inhibition using vorinostat restores R-loop formation, slows down DNA replication forks and improves SF3B1-mutated erythroblast differentiation. In conclusion, loss of R-loops with associated DNA replication stress represents a hallmark of SF3B1-mutated MDS ineffective erythropoiesis, which could be used as a therapeutic target.
Mechanism of DNA origami folding elucidated by mesoscopic simulations
Authors: DeLuca Marcello , Duke Daniel , Ye Tao , Poirier Michael , Ke Yonggang , Castro Carlos , Arya Gaurav
Published: April 2024

Many experimental and computational efforts have sought to understand DNA origami folding, but the time and length scales of this process pose significant challenges. Here, we present a mesoscopic model that uses a switchable force field to capture the behavior of single- and double-stranded DNA motifs and transitions between them, allowing us to simulate the folding of DNA origami up to several kilobases in size. Brownian dynamics simulations of small structures reveal a hierarchical folding process involving zipping into a partially folded precursor followed by crystallization into the final structure. We elucidate the effects of various design choices on folding order and kinetics. Larger structures are found to exhibit heterogeneous staple incorporation kinetics and frequent trapping in metastable states, as opposed to more accessible structures which exhibit first-order kinetics and virtually defect-free folding. This model opens an avenue to better understand and design DNA nanostructures for improved yield and folding performance.
Wide field-of-hearing metalens for aberration-free sound capture
Authors: Lee Dongwoo , Oh Beomseok , Park Jeonghoon , Moon Seong-Won , Shin Kilsoo , Kim Sea-Moon , Rho Junsuk
Published: April 2024

Metalenses are instruments that manipulate waves and have exhibited remarkable capabilities to date. However, an important hurdle arises due to the severe hampering of the angular response originating from coma and field curvature aberrations, which result in a loss of focusing ability. Herein, we provide a blueprint by introducing the notion of a wide field-of-hearing (FOH) metalens, designed particularly for capturing and focusing sound with decreased aberrations. Employing an aberration-free planar-thin metalens that leverages perfect acoustic symmetry conversion, we experimentally realize a robust wide FOH capability of approximately 140∘in angular range. Moreover, our metalens features a relatively short focal length, enabling compact implementation by reducing the aperture-to-hearing plane distance. This is beneficial for space-efficient source-tracking sound sensing. Our strategy can be used across various platforms, potentially including energy harvesting, monitoring, imaging, and communication in auditory, ultrasonic, and submerged environments.
Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice
Authors: Dokoshi Tatsuya , Chen Yang , Cavagnero Kellen J. , Rahman Gibraan , Hakim Daniel , Brinton Samantha , Schwarz Hana , Brown Elizabeth A. , O’Neill Alan , Nakamura Yoshiyuki , Li Fengwu , Salzman Nita H. , Knight Rob , Gallo Richard L.
Published: April 2024

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.
Essential role of lattice oxygen in hydrogen sensing reaction
Authors: Li Jiayu , Si Wenzhe , Shi Lei , Gao Ruiqin , Li Qiuju , An Wei , Zhao Zicheng , Zhang Lu , Bai Ni , Zou Xiaoxin , Li Guo-Dong
Published: April 2024

Understanding the sensing mechanism of metal oxide semiconductors is imperative to the development of high-performance sensors. The traditional sensing mechanism only recognizes the effect of surface chemisorbed oxygen from the air but ignores surface lattice oxygen. Herein, using in-situ characterizations, we provide direct experimental evidence that the surface chemisorbed oxygen participated in the sensing process can come from lattice oxygen of the oxides. Further density functional theory (DFT) calculations prove that the p-band center of O serves as a state of art for regulating the participation of lattice oxygen in gas-sensing reactions. Based on our experimental data and theoretical calculations, we discuss mechanisms that are fundamentally different from the conventional mechanism and show that the easily participation of lattice oxygen is helpful for the high response value of the materials.
p53 promotes revival stem cells in the regenerating intestine after severe radiation injury
Authors: Morral Clara , Ayyaz Arshad , Kuo Hsuan-Cheng , Fink Mardi , Verginadis Ioannis I. , Daniel Andrea R. , Burner Danielle N. , Driver Lucy M. , Satow Sloane , Hasapis Stephanie , Ghinnagow Reem , Luo Lixia , Ma Yan , Attardi Laura D. , Koumenis Constantinos , Minn Andy J. , Wrana Jeffrey L. , Lee Chang-Lung , Kirsch David G.
Published: April 2024

Ionizing radiation induces cell death in the gastrointestinal (GI) epithelium by activating p53. However, p53 also prevents animal lethality caused by radiation-induced acute GI syndrome. Through single-cell RNA-sequencing of the irradiated mouse small intestine, we find that p53 target genes are specifically enriched in regenerating epithelial cells that undergo fetal-like reversion, including revival stem cells (revSCs) that promote animal survival after severe damage of the GI tract. Accordingly, in mice with p53 deleted specifically in the GI epithelium, ionizing radiation fails to induce fetal-like revSCs. Using intestinal organoids, we show that transient p53 expression is required for the induction of revival stem cells and is controlled by an Mdm2-mediated negative feedback loop. Together, our findings reveal that p53 suppresses severe radiation-induced GI injury by promoting fetal-like reprogramming of irradiated intestinal epithelial cells.
Landslide hazard cascades can trigger earthquakes
Authors: Zhang Zhen , Liu Min , Tan Yen Joe , Walter Fabian , He Siming , Chmiel Małgorzata , Su Jinrong
Published: April 2024

While earthquakes are well-known to trigger surface hazards and initiate hazard cascades, whether surface hazards can instead trigger earthquakes remains underexplored. In 2018, two landslides on the Tibetan plateau created landslide-dammed lakes which subsequently breached and caused catastrophic outburst floods. Here we build an earthquake catalog using machine-learning and cross-correlation-based methods which shows there was a statistically significant increase in earthquake activity (local magnitude ≤ 2.6) as the landslide-dammed lake approached peak water level which returned to the background level after dam breach. We further find that ~90% of the seismicity occurred where Coulomb stress increased due to the combined effect of direct loading and pore pressure diffusion. The close spatial and temporal correlation between the calculated Coulomb stress increase and earthquake activity suggests that the earthquakes were triggered by these landslide hazard cascades. Finally, our Coulomb stress modeling considering the properties of landslide-dammed lakes and reservoir-induced earthquakes globally suggests that earthquake triggering by landslide-dammed lakes and similar structures may be a ubiquitous phenomenon. Therefore, we propose that earthquake-surface hazard interaction can include bidirectional triggering which should be properly accounted for during geological hazard assessment and management in mountainous regions.
Integration of pathologic characteristics, genetic risk and lifestyle exposure for colorectal cancer survival assessment
Authors: Xin Junyi , Gu Dongying , Li Shuwei , Qian Sangni , Cheng Yifei , Shao Wei , Ben Shuai , Chen Silu , Zhu Linjun , Jin Mingjuan , Chen Kun , Hu Zhibin , Zhang Zhengdong , Du Mulong , Shen Hongbing , Wang Meilin
Published: April 2024

The development of an effective survival prediction tool is key for reducing colorectal cancer mortality. Here, we apply a three-stage study to devise a polygenic prognostic score (PPS) for stratifying colorectal cancer overall survival. Leveraging two cohorts of 3703 patients, we first perform a genome-wide survival association analysis to develop eight candidate PPSs. Further using an independent cohort with 470 patients, we identify the 287 variants-derived PPS (i.e., PPS287) achieving an optimal prediction performance [hazard ratio (HR) per SD = 1.99, P = 1.76 × 10−8], accompanied by additional tests in two external cohorts, with HRs per SD of 1.90 (P = 3.21 × 10−14; 543 patients) and 1.80 (P = 1.11 × 10−9; 713 patients). Notably, the detrimental impact of pathologic characteristics and genetic risk could be attenuated by a healthy lifestyle, yielding a 7.62% improvement in the 5-year overall survival rate. Therefore, our findings demonstrate the integrated contribution of pathologic characteristics, germline variants, and lifestyle exposure to the prognosis of colorectal cancer patients.
The assembly platform FimD is required to obtain the most stable quaternary structure of type 1 pili
Authors: Zyla Dawid S. , Wiegand Thomas , Bachmann Paul , Zdanowicz Rafal , Giese Christoph , Meier Beat H. , Waksman Gabriel , Hospenthal Manuela K. , Glockshuber Rudi
Published: April 2024

Type 1 pili are important virulence factors of uropathogenic Escherichia coli that mediate bacterial attachment to epithelial cells in the urinary tract. The pilus rod is comprised of thousands of copies of the main structural subunit FimA and is assembled in vivo by the assembly platform FimD. Although type 1 pilus rods can self-assemble from FimA in vitro, this reaction is slower and produces structures with lower kinetic stability against denaturants compared to in vivo-assembled rods. Our study reveals that FimD-catalysed in vitro-assembled type 1 pilus rods attain a similar stability as pilus rods assembled in vivo. Employing structural, biophysical and biochemical analyses, we show that in vitro assembly reactions lacking FimD produce pilus rods with structural defects, reducing their stability against dissociation. Overall, our results indicate that FimD is not only required for the catalysis of pilus assembly, but also to control the assembly of the most stable quaternary structure.
Exciton engineering of 2D Ruddlesden–Popper perovskites by synergistically tuning the intra and interlayer structures
Authors: Guo Songhao , Mihalyi-Koch Willa , Mao Yuhong , Li Xinyu , Bu Kejun , Hong Huilong , Hautzinger Matthew P. , Luo Hui , Wang Dong , Gu Jiazhen , Zhang Yifan , Zhang Dongzhou , Hu Qingyang , Ding Yang , Yang Wenge , Fu Yongping , Jin Song , Lü Xujie
Published: April 2024

Designing two-dimensional halide perovskites for high-performance optoelectronic applications requires deep understanding of the structure-property relationship that governs their excitonic behaviors. However, a design framework that considers both intra and interlayer structures modified by the A-site and spacer cations, respectively, has not been developed. Here, we use pressure to synergistically tune the intra and interlayer structures and uncover the structural modulations that result in improved optoelectronic performance. Under applied pressure, (BA)2(GA)Pb2I7 exhibits a 72-fold boost of photoluminescence and 10-fold increase of photoconductivity. Based on the observed structural change, we introduce a structural descriptor χ that describes both the intra and interlayer characteristics and establish a general quantitative relationship between χ and photoluminescence quantum yield: smaller χ correlates with minimized trapped excitons and more efficient emission from free excitons. Building on this principle, we design a perovskite (CMA)2(FA)Pb2I7 that exhibits a small χ and an impressive photoluminescence quantum yield of 59.3%.
Basal actomyosin pulses expand epithelium coordinating cell flattening and tissue elongation
Authors: Li Shun , Liu Zong-Yuan , Li Hao , Zhou Sijia , Liu Jiaying , Sun Ningwei , Yang Kai-Fu , Dougados Vanessa , Mangeat Thomas , Belguise Karine , Feng Xi-Qiao , Liu Yiyao , Wang Xiaobo
Published: April 2024

Actomyosin networks constrict cell area and junctions to alter cell and tissue shape. However, during cell expansion under mechanical stress, actomyosin networks are strengthened and polarized to relax stress. Thus, cells face a conflicting situation between the enhanced actomyosin contractile properties and the expansion behaviour of the cell or tissue. To address this paradoxical situation, we study late Drosophila oogenesis and reveal an unusual epithelial expansion wave behaviour. Mechanistically, Rac1 and Rho1 integrate basal pulsatile actomyosin networks with ruffles and focal adhesions to increase and then stabilize basal area of epithelial cells allowing their flattening and elongation. This epithelial expansion behaviour bridges cell changes to oocyte growth and extension, while oocyte growth in turn deforms the epithelium to drive cell spreading. Basal pulsatile actomyosin networks exhibit non-contractile mechanics, non-linear structures and F-actin/Myosin-II spatiotemporal signal separation, implicating unreported expanding properties. Biophysical modelling incorporating these expanding properties well simulates epithelial cell expansion waves. Our work thus highlights actomyosin expanding properties as a key mechanism driving tissue morphogenesis.
Universal inter-molecular radical transfer reactions on metal surfaces
Authors: Wang Junbo , Niu Kaifeng , Zhu Huaming , Xu Chaojie , Deng Chuan , Zhao Wenchao , Huang Peipei , Lin Haiping , Li Dengyuan , Rosen Johanna , Liu Peinian , Allegretti Francesco , Barth Johannes V. , Yang Biao , Björk Jonas , Li Qing , Chi Lifeng
Published: April 2024

On-surface synthesis provides tools to prepare low-dimensional supramolecular structures. Traditionally, reactive radicals are a class of single-electron species, serving as exceptional electron-withdrawing groups. On metal surfaces, however, such species are affected by conduction band screening effects that may even quench their unpaired electron characteristics. As a result, radicals are expected to be less active, and reactions catalyzed by surface-stabilized radicals are rarely reported. Herein, we describe a class of inter-molecular radical transfer reactions on metal surfaces. With the assistance of aryl halide precursors, the coupling of terminal alkynes is steered from non-dehydrogenated to dehydrogenated products, resulting in alkynyl-Ag-alkynyl bonds. Dehalogenated molecules are fully passivated by detached hydrogen atoms. The reaction mechanism is unraveled by various surface-sensitive technologies and density functional theory calculations. Moreover, we reveal the universality of this mechanism on metal surfaces. Our studies enrich the on-surface synthesis toolbox and develop a pathway for producing low-dimensional organic materials.
Stress increases hepatic release of lipocalin 2 which contributes to anxiety-like behavior in mice
Authors: Yan Lan , Yang Fengzhen , Wang Yajie , Shi Lingling , Wang Mei , Yang Diran , Wang Wenjing , Jia Yanbin , So Kwok-Fai , Zhang Li
Published: April 2024

Chronic stress induces anxiety disorders via both neural pathways and circulating factors. Although many studies have elucidated the neural circuits involved in stress-coping behaviors, the origin and regulatory mechanism of peripheral cytokines in behavioural regulation under stress conditions are not fully understood. Here, we identified a serum cytokine, lipocalin 2 (LCN2), that was upregulated in participants with anxiety disorders. Using a mouse model of chronic restraint stress (CRS), circulating LCN2 was found to be related to stress-induced anxiety-like behaviour via modulation of neural activity in the medial prefrontal cortex (mPFC). These results suggest that stress increases hepatic LCN2 via a neural pathway, leading to disrupted cortical functions and behaviour.
Immunoregulatory role of the gut microbiota in inflammatory depression
Authors: Liu Penghong , Liu Zhifen , Wang Jizhi , Wang Junyan , Gao Mingxue , Zhang Yanyan , Yang Chunxia , Zhang Aixia , Li Gaizhi , Li Xinrong , Liu Sha , Liu Lixin , Sun Ning , Zhang Kerang
Published: April 2024

Inflammatory depression is a treatment-resistant subtype of depression. A causal role of the gut microbiota as a source of low-grade inflammation remains unclear. Here, as part of an observational trial, we first analyze the gut microbiota composition in the stool, inflammatory factors and short-chain fatty acids (SCFAs) in plasma, and inflammatory and permeability markers in the intestinal mucosa of patients with inflammatory depression (ChiCTR1900025175). Gut microbiota of patients with inflammatory depression exhibits higherBacteroidesand lowerClostridium, with an increase in SCFA-producing species with abnormal butanoate metabolism. We then perform fecal microbiota transplantation (FMT) and probiotic supplementation in animal experiments to determine the causal role of the gut microbiota in inflammatory depression. After FMT, the gut microbiota of the inflammatory depression group shows increased peripheral and central inflammatory factors and intestinal mucosal permeability in recipient mice with depressive and anxiety-like behaviors.Clostridium butyricumadministration normalizes the gut microbiota, decreases inflammatory factors, and displays antidepressant-like effects in a mouse model of inflammatory depression. These findings suggest that inflammatory processes derived from the gut microbiota can be involved in neuroinflammation of inflammatory depression.
Stroma-infiltrating T cell spatiotypes define immunotherapy outcomes in adolescent and young adult patients with melanoma
Authors: Bai Xinyu , Attrill Grace H. , Gide Tuba N. , Ferguson Peter M. , Nahar Kazi J. , Shang Ping , Vergara Ismael A. , Palendira Umaimainthan , da Silva Ines Pires , Carlino Matteo S. , Menzies Alexander M. , Long Georgina V. , Scolyer Richard A. , Wilmott James S. , Quek Camelia
Published: April 2024

The biological underpinnings of therapeutic resistance to immune checkpoint inhibitors (ICI) in adolescent and young adult (AYA) melanoma patients are incompletely understood. Here, we characterize the immunogenomic profile and spatial architecture of the tumor microenvironment (TME) in AYA (aged ≤ 30 years) and older adult (aged 31–84 years) patients with melanoma, to determine the AYA-specific features associated with ICI treatment outcomes. We identify two ICI-resistant spatiotypes in AYA patients with melanoma showing stroma-infiltrating lymphocytes (SILs) that are distinct from the adult TME. The SILhigh subtype was enriched in regulatory T cells in the peritumoral space and showed upregulated expression of immune checkpoint molecules, while the SILlow subtype showed a lack of immune activation. We establish a young immunosuppressive melanoma score that can predict ICI responsiveness in AYA patients and propose personalized therapeutic strategies for the ICI-resistant subgroups. These findings highlight the distinct immunogenomic profile of AYA patients, and individualized TME features in ICI-resistant AYA melanoma that require patient-specific treatment strategies.
Concerted transformation of a hyper-paused transcription complex and its reinforcing protein
Authors: Zuber Philipp K. , Said Nelly , Hilal Tarek , Wang Bing , Loll Bernhard , González-Higueras Jorge , Ramírez-Sarmiento César A. , Belogurov Georgiy A. , Artsimovitch Irina , Wahl Markus C. , Knauer Stefan H.
Published: April 2024

RfaH, a paralog of the universally conserved NusG, binds to RNA polymerases (RNAP) and ribosomes to activate expression of virulence genes. In free, autoinhibited RfaH, an α-helical KOW domain sequesters the RNAP-binding site. Upon recruitment to RNAP paused at an ops site, KOW is released and refolds into a β-barrel, which binds the ribosome. Here, we report structures of ops-paused transcription elongation complexes alone and bound to the autoinhibited and activated RfaH, which reveal swiveled, pre-translocated pause states stabilized by an ops hairpin in the non-template DNA. Autoinhibited RfaH binds and twists the ops hairpin, expanding the RNA:DNA hybrid to 11 base pairs and triggering the KOW release. Once activated, RfaH hyper-stabilizes the pause, which thus requires anti-backtracking factors for escape. Our results suggest that the entire RfaH cycle is solely determined by the ops and RfaH sequences and provide insights into mechanisms of recruitment and metamorphosis of NusG homologs across all life.
Accurately clustering biological sequences in linear time by relatedness sorting
Authors: Wright Erik
Published: April 2024

Clustering biological sequences into similar groups is an increasingly important task as the number of available sequences continues to grow exponentially. Search-based approaches to clustering scale super-linearly with the number of input sequences, making it impractical to cluster very large sets of sequences. Approaches to clustering sequences in linear time currently lack the accuracy of super-linear approaches. Here, I set out to develop and characterize a strategy for clustering with linear time complexity that retains the accuracy of less scalable approaches. The resulting algorithm, named Clusterize, sorts sequences by relatedness to linearize the clustering problem. Clusterize produces clusters with accuracy rivaling popular programs (CD-HIT, MMseqs2, and UCLUST) but exhibits linear asymptotic scalability. Clusterize generates higher accuracy and oftentimes much larger clusters than Linclust, a fast linear time clustering algorithm. I demonstrate the utility of Clusterize by accurately solving different clustering problems involving millions of nucleotide or protein sequences.
Ferrielectricity controlled widely-tunable magnetoelectric coupling in van der Waals multiferroics
Authors: Hu Qifeng , Huang Yuqiang , Wang Yang , Ding Sujuan , Zhang Minjie , Hua Chenqiang , Li Linjun , Xu Xiangfan , Yang Jinbo , Yuan Shengjun , Watanabe Kenji , Taniguchi Takashi , Lu Yunhao , Jin Chuanhong , Wang Dawei , Zheng Yi
Published: April 2024

The discovery of various primary ferroic phases in atomically-thin van der Waals crystals have created a new two-dimensional wonderland for exploring and manipulating exotic quantum phases. It may also bring technical breakthroughs in device applications, as evident by prototypical functionalities of giant tunneling magnetoresistance, gate-tunable ferromagnetism and non-volatile ferroelectric memory etc. However, two-dimensional multiferroics with effective magnetoelectric coupling, which ultimately decides the future of multiferroic-based information technology, has not been realized yet. Here, we show that an unconventional magnetoelectric coupling mechanism interlocked with heterogeneous ferrielectric transitions emerges at the two-dimensional limit in van der Waals multiferroic CuCrP2S6 with inherent antiferromagnetism and antiferroelectricity. Distinct from the homogeneous antiferroelectric bulk, thin-layer CuCrP2S6 under external electric field makes layer-dependent heterogeneous ferrielectric transitions, minimizing the depolarization effect introduced by the rearrangements of Cu+ ions within the ferromagnetic van der Waals cages of CrS6 and P2S6 octahedrons. The resulting ferrielectric phases are characterized by substantially reduced interlayer magnetic coupling energy of nearly 50% with a moderate electric field of 0.3 V nm−1, producing widely-tunable magnetoelectric coupling which can be further engineered by asymmetrical electrode work functions.
Fine-tuning the pore environment of ultramicroporous three-dimensional covalent organic frameworks for efficient one-step ethylene purification
Authors: Xie Yang , Wang Wenjing , Zhang Zeyue , Li Jian , Gui Bo , Sun Junliang , Yuan Daqiang , Wang Cheng
Published: April 2024

The construction of functional three-dimensional covalent organic frameworks (3D COFs) for gas separation, specifically for the efficient removal of ethane (C2H6) from ethylene (C2H4), is significant but challenging due to their similar physicochemical properties. In this study, we demonstrate fine-tuning the pore environment of ultramicroporous 3D COFs to achieve efficient one-step C2H4 purification. By choosing our previously reported 3D-TPB-COF-H as a reference material, we rationally design and synthesize an isostructural 3D COF (3D-TPP-COF) containing pyridine units. Impressively, compared with 3D-TPB-COF-H, 3D-TPP-COF exhibits both high C2H6 adsorption capacity (110.4 cm3 g−1 at 293 K and 1 bar) and good C2H6/C2H4 selectivity (1.8), due to the formation of additional C-H···N interactions between pyridine groups and C2H6. To our knowledge, this performance surpasses all other reported COFs and is even comparable to some benchmark porous materials. In addition, dynamic breakthrough experiments reveal that 3D-TPP-COF can be used as a robust absorbent to produce high-purity C2H4 directly from a C2H6/C2H4 mixture. This study provides important guidance for the rational design of 3D COFs for efficient gas separation.
Fast joint parity measurement via collective interactions induced by stimulated emission
Authors: Huai Sainan , Bu Kunliang , Gu Xiu , Zhang Zhenxing , An Shuoming , Yang Xiaopei , Li Yuan , Cai Tianqi , Zheng Yicong
Published: April 2024

Parity detection is essential in quantum error correction. Error syndromes coded in parity are detected routinely by sequential CNOT gates. Here, different from the standard CNOT-gate based scheme, we propose a reliable joint parity measurement (JPM) scheme inspired by stimulated emission. By controlling the collective behavior between data qubits and syndrome qubit, we realize the parity detection and experimentally implement the weight-2 and weight-4 JPM scheme in a tunable coupling superconducting circuit, which shows comparable performance to the CNOT scheme. Moreover, with the aid of the coupling tunability in quantum system, this scheme can be further utilized for specific joint entangling state preparation (JEP) with high fidelity, such as multiqubit entangled state preparation for non-adjacent qubits. This strategy, combined with the superconducting qubit system with tunable couplers, reveals tremendous potential and applications in the surface code architecture without adding extra circuit elements. Besides, the method we develop here can readily be applied in large-scale quantum computation and quantum simulation.
Optically induced charge-transfer in donor-acceptor-substituted p- and m- C2B10H12 carboranes
Authors: Wu Lin , Holzapfel Marco , Schmiedel Alexander , Peng Fuwei , Moos Michael , Mentzel Paul , Shi Junqing , Neubert Thomas , Bertermann Rüdiger , Finze Maik , Fox Mark A. , Lambert Christoph , Ji Lei
Published: April 2024

Icosahedral carboranes, C2B10H12, have long been considered to be aromatic but the extent of conjugation between these clusters and their substituents is still being debated. m- and p-Carboranes are compared with m- and p-phenylenes as conjugated bridges in optical functional chromophores with a donor and an acceptor as substituents here. The absorption and fluorescence data for both carboranes from experimental techniques (including femtosecond transient absorption, time-resolved fluorescence and broadband fluorescence upconversion) show that the absorption and emission processes involve strong intramolecular charge transfer between the donor and acceptor substituents via the carborane cluster. From quantum chemical calculations on these carborane systems, the charge transfer process depends on the relative torsional angles of the donor and acceptor groups where an overlap between the two frontier orbitals exists in the bridging carborane cluster.
Water-assisted oxidative redispersion of Cu particles through formation of Cu hydroxide at room temperature
Authors: Fan Yamei , Li Rongtan , Wang Beibei , Feng Xiaohui , Du Xiangze , Liu Chengxiang , Wang Fei , Liu Conghui , Dong Cui , Ning Yanxiao , Mu Rentao , Fu Qiang
Published: April 2024

Sintering of active metal species often happens during catalytic reactions, which requires redispersion in a reactive atmosphere at elevated temperatures to recover the activity. Herein, we report a simple method to redisperse sintered Cu catalysts via O2-H2O treatment at room temperature. In-situ spectroscopic characterizations reveal that H2O induces the formation of hydroxylated Cu species in humid O2, pushing surface diffusion of Cu atoms at room temperature. Further, surface OH groups formed on most hydroxylable support surfaces such as γ-Al2O3, SiO2, and CeO2 in the humid atmosphere help to pull the mobile Cu species and enhance Cu redispersion. Both pushing and pulling effects of gaseous H2O promote the structural transformation of Cu aggregates into highly dispersed Cu species at room temperature, which exhibit enhanced activity in reverse water gas shift and preferential oxidation of carbon monoxide reactions. These findings highlight the important role of H2O in the dynamic structure evolution of supported metal nanocatalysts and lay the foundation for the regeneration of sintered catalysts under mild conditions.
Ultrafast piezocapacitive soft pressure sensors with over 10 kHz bandwidth via bonded microstructured interfaces
Authors: Zhang Yuan , Zhou Xiaomeng , Zhang Nian , Zhu Jiaqi , Bai Ningning , Hou Xingyu , Sun Tao , Li Gang , Zhao Lingyu , Chen Yingchun , Wang Liu , Guo Chuan Fei
Published: April 2024

Flexible pressure sensors can convert mechanical stimuli to electrical signals to interact with the surroundings, mimicking the functionality of the human skins. Piezocapacitive pressure sensors, a class of most widely used devices for artificial skins, however, often suffer from slow response-relaxation speed (tens of milliseconds) and thus fail to detect dynamic stimuli or high-frequency vibrations. Here, we show that the contact-separation behavior of the electrode-dielectric interface is an energy dissipation process that substantially determines the response-relaxation time of the sensors. We thus reduce the response and relaxation time to ~0.04 ms using a bonded microstructured interface that effectively diminishes interfacial friction and energy dissipation. The high response-relaxation speed allows the sensor to detect vibrations over 10 kHz, which enables not only dynamic force detection, but also acoustic applications. This sensor also shows negligible hysteresis to precisely track dynamic stimuli. Our work opens a path that can substantially promote the response-relaxation speed of piezocapacitive pressure sensors into submillisecond range and extend their applications in acoustic range.
Cryo-EM structure of the human Asc-1 transporter complex
Authors: Li Yaning , Guo Yingying , Bröer Angelika , Dai Lu , Brӧer Stefan , Yan Renhong
Published: April 2024

The Alanine-Serine-Cysteine transporter 1 (Asc-1 or SLC7A10) forms a crucial heterodimeric transporter complex with 4F2hc (SLC3A2) through a covalent disulfide bridge. This complex enables the sodium-independent transport of small neutral amino acids, including L-Alanine (L-Ala), Glycine (Gly), and D-Serine (D-Ser), within the central nervous system (CNS). D-Ser and Gly are two key endogenous glutamate co-agonists that activate N-methyl-d-aspartate (NMDA) receptors by binding to the allosteric site. Mice deficient in Asc-1 display severe symptoms such as tremors, ataxia, and seizures, leading to early postnatal death. Despite its physiological importance, the functional mechanism of the Asc-1-4F2hc complex has remained elusive. Here, we present cryo-electron microscopy (cryo-EM) structures of the human Asc-1-4F2hc complex in its apo state, D-Ser bound state, and L-Ala bound state, resolved at 3.6 Å, 3.5 Å, and 3.4 Å, respectively. Through detailed structural analysis and transport assays, we uncover a comprehensive alternating access mechanism that underlies conformational changes in the complex. In summary, our findings reveal the architecture of the Asc-1 and 4F2hc complex and provide valuable insights into substrate recognition and the functional cycle of this essential transporter complex.
A freely precessing magnetar following an X-ray outburst
Authors: Desvignes Gregory , Weltevrede Patrick , Gao Yong , Jones David Ian , Kramer Michael , Caleb Manisha , Karuppusamy Ramesh , Levin Lina , Liu Kuo , Lyne Andrew G. , Shao Lijing , Stappers Ben , Pétri Jérôme
Published: April 2024

Magnetars—highly magnetized neutron stars—are thought to be the most likely progenitors for fast radio bursts (FRBs). Freely precessing magnetars are further invoked to explain the repeating FRBs. We report here on new high-cadence radio observations of the magnetar XTE J1810–197 recorded shortly after an X-ray outburst. We interpret the polarization variations of the magnetar radio emission as evidence for the magnetar undergoing free precession following the outburst while its magnetosphere slowly untwists. The observations of precession being damped on a timescale of months argue against the scenario of freely precessing magnetars as the origin of repeating FRBs. Using free-precession models based on relaxing ellipticity with a decay of the wobble angle, we find the magnetar ellipticity to be in good agreement with theoretical predictions from nuclear physics. Our precise measurement of the magnetar’s geometry can also further help in refining the modelling of X-ray light curves and constrain the star’s compactness.
Transcription bodies regulate gene expression by sequestering CDK9
Authors: Ugolini Martino , Kerlin Maciej A. , Kuznetsova Ksenia , Oda Haruka , Kimura Hiroshi , Vastenhouw Nadine L.
Published: April 2024

The localization of transcriptional activity in specialized transcription bodies is a hallmark of gene expression in eukaryotic cells. It remains unclear, however, if and how transcription bodies affect gene expression. Here we disrupted the formation of two prominent endogenous transcription bodies that mark the onset of zygotic transcription in zebrafish embryos and analysed the effect on gene expression using enriched SLAM-seq and live-cell imaging. We find that the disruption of transcription bodies results in the misregulation of hundreds of genes. Here we focus on genes that are upregulated. These genes have accessible chromatin and are poised to be transcribed in the presence of the two transcription bodies, but they do not go into elongation. Live-cell imaging shows that disruption of the two large transcription bodies enables these poised genes to be transcribed in ectopic transcription bodies, suggesting that the large transcription bodies sequester a pause release factor. Supporting this hypothesis, we find that CDK9—the kinase that releases paused polymerase II—is highly enriched in the two large transcription bodies. Overexpression of CDK9 in wild-type embryos results in the formation of ectopic transcription bodies and thus phenocopies the removal of the two large transcription bodies. Taken together, our results show that transcription bodies regulate transcription by sequestering machinery, thereby preventing genes elsewhere in the nucleus from being transcribed.
Antarctic meteorites threatened by climate warming
Authors: Tollenaar Veronica , Zekollari Harry , Kittel Christoph , Farinotti Daniel , Lhermitte Stef , Debaille Vinciane , Goderis Steven , Claeys Philippe , Joy Katherine Helen , Pattyn Frank
Published: April 2024

More than 60% of meteorite finds on Earth originate from Antarctica. Using a data-driven analysis that identifies meteorite-rich sites in Antarctica, we show climate warming causes many extraterrestrial rocks to be lost from the surface by melting into the ice sheet. At present, approximately 5,000 meteorites become inaccessible per year (versus ~1,000 finds per year) and, independent of the emissions scenario, ~24% will be lost by 2050, potentially rising to ∼76% by 2100 under a high-emissions scenario.
Tumour-selective activity of RAS-GTP inhibition in pancreatic cancer
Authors: Wasko Urszula N. , Jiang Jingjing , Dalton Tanner C. , Curiel-Garcia Alvaro , Edwards A. Cole , Wang Yingyun , Lee Bianca , Orlen Margo , Tian Sha , Stalnecker Clint A. , Drizyte-Miller Kristina , Menard Marie , Dilly Julien , Sastra Stephen A. , Palermo Carmine F. , Hasselluhn Marie C. , Decker-Farrell Amanda R. , Chang Stephanie , Jiang Lingyan , Wei Xing , Yang Yu C. , Helland Ciara , Courtney Haley , Gindin Yevgeniy , Muonio Karl , Zhao Ruiping , Kemp Samantha B. , Clendenin Cynthia , Sor Rina , Vostrejs William P. , Hibshman Priya S. , Amparo Amber M. , Hennessey Connor , Rees Matthew G. , Ronan Melissa M. , Roth Jennifer A. , Brodbeck Jens , Tomassoni Lorenzo , Bakir Basil , Socci Nicholas D. , Herring Laura E. , Barker Natalie K. , Wang Junning , Cleary James M. , Wolpin Brian M. , Chabot John A. , Kluger Michael D. , Manji Gulam A. , Tsai Kenneth Y. , Sekulic Miroslav , Lagana Stephen M. , Califano Andrea , Quintana Elsa , Wang Zhengping , Smith Jacqueline A. M. , Holderfield Matthew , Wildes David , Lowe Scott W. , Badgley Michael A. , Aguirre Andrew J. , Vonderheide Robert H. , Stanger Ben Z. , Baslan Timour , Der Channing J. , Singh Mallika , Olive Kenneth P.
Published: April 2024

Broad-spectrum RAS inhibition has the potential to benefit roughly a quarter of human patients with cancer whose tumours are driven by RAS mutations1,2. RMC-7977 is a highly selective inhibitor of the active GTP-bound forms of KRAS, HRAS and NRAS, with affinity for both mutant and wild-type variants3. More than 90% of cases of human pancreatic ductal adenocarcinoma (PDAC) are driven by activating mutations in KRAS4. Here we assessed the therapeutic potential of RMC-7977 in a comprehensive range of PDAC models. We observed broad and pronounced anti-tumour activity across models following direct RAS inhibition at exposures that were well-tolerated in vivo. Pharmacological analyses revealed divergent responses to RMC-7977 in tumour versus normal tissues. Treated tumours exhibited waves of apoptosis along with sustained proliferative arrest, whereas normal tissues underwent only transient decreases in proliferation, with no evidence of apoptosis. In the autochthonous KPC mouse model, RMC-7977 treatment resulted in a profound extension of survival followed by on-treatment relapse. Analysis of relapsed tumours identified Myc copy number gain as a prevalent candidate resistance mechanism, which could be overcome by combinatorial TEAD inhibition in vitro. Together, these data establish a strong preclinical rationale for the use of broad-spectrum RAS-GTP inhibition in the setting of PDAC and identify a promising candidate combination therapeutic regimen to overcome monotherapy resistance.