bluuebunny/crossref_metadata_2025_split huggingface dataset:
HOXD3 promotes the migration and angiogenesis of hepatocellular carcinoma via modifying hepatocellular carcinoma cells exosome-delivered CCR6 and regulating chromatin conformation of CCL20
Authors: Wang Lumin , Qiao Chenyang , Han Lili , Wang Xiaofei , Miao Jiyu , Cao Li , Huang Chen , Wang Jinhai 
Published: March 2024

AbstractAngiogenesis plays an essential role in the microenvironment of hepatocellular carcinoma (HCC). HOXD3 is involved in the metastasis and invasion of HCC cells; Whereas the underlying molecular mechanisms in the microenvironment of HCC remain unknown. Wound healing, transwell invasion, tube formation and spheroid sprouting assays were carried out to identify the effects of HCC-HOXD3-exosomes and genes on the migration of HCC cells. ChIP–PCR was applied to test the binding region of HOXD3 on CCR6, Med15, and CREBBP promoter. Exosome isolation and mRNA-seq were applied to examine the morphological characteristics of exosomes and the contained mRNA in exosomes. Co-IP and Immunofluorescence assays were used to demonstrate the role of CREBBP in the chromatin conformation of CCL20. The nude mice were used to identify the function of genes in regulating migration of HCC in vivo. In this study, integrated cellular and bioinformatic analyses revealed that HOXD3 targeted the promoter region of CCR6 and induced its transcription. CCR6 was delivered by exosomes to endothelial cells and promoted tumour migration. Overexpression of CCR6 promoted metastasis, invasion in HCCs and angiogenesis in endothelial cells (ECs), whereas its downregulation suppressed these functions. The role of HOXD3 in the metastasis and invasion of HCC cells was reversed after the suppression of CCR6. Furthermore, CCL20 was demonstrated as the ligand of CCR6, and its high expression was found in HCC tissues and cells, which was clinically associated with the poor prognosis of HCC. Mechanistically, HOXD3 targets the promoter regions of CREBBP and Med15, which affect CCL20 chromatin conformation by regulating histone acetylation and expression of Pol II to enhance the migration of HCCs. This study demonstrated the function of the HOXD3–CREBBP/Med15–CCL20–CCR6 axis in regulating invasion and migration in HCC, thus providing new therapeutic targets for HCC.
Theoretical formulation of chemical equilibrium under vibrational strong coupling
Authors: Sun Kaihong , Ribeiro Raphael F. 
Published: March 2024

AbstractExperiments have suggested that strong interactions between molecular ensembles and infrared microcavities can be employed to control chemical equilibria. Nevertheless, the primary mechanism and key features of the effect remain largely unexplored. In this work, we develop a theory of chemical equilibrium in optical microcavities, which allows us to relate the equilibrium composition of a mixture in different electromagnetic environments. Our theory shows that in planar microcavities under strong coupling with polyatomic molecules, hybrid modes formed between all dipole-active vibrations and cavity resonances contribute to polariton-assisted chemical equilibrium shifts. To illustrate key aspects of our formalism, we explore a model SN2 reaction within a single-mode infrared resonator. Our findings reveal that chemical equilibria can be shifted towards either direction of a chemical reaction, depending on the oscillator strength and frequencies of reactant and product normal modes. Polariton-induced zero-point energy changes provide the dominant contributions, though the effects in idealized single-mode cavities tend to diminish quickly as the temperature and number of molecules increase. Our approach is valid in generic electromagnetic environments and paves the way for understanding and controlling chemical equilibria with microcavities.
Assessing intra- and inter-molecular charge transfer excitations in non-fullerene acceptors using electroabsorption spectroscopy
Authors: Mahadevan Sudhi , Liu Taili , Pratik Saied Md , Li Yuhao , Ho Hang Yuen , Ouyang Shanchao , Lu Xinhui , Yip Hin-Lap , Chow Philip C. Y. , Brédas Jean-Luc , Coropceanu Veaceslav , So Shu Kong , Tsang Sai-Wing 
Published: March 2024

AbstractOrganic photovoltaic cells using Y6 non-fullerene acceptors have recently achieved high efficiency, and it was suggested to be attributed to the charge-transfer (CT) nature of the excitations in Y6 aggregates. Here, by combining electroabsorption spectroscopy measurements and electronic-structure calculations, we find that the charge-transfer character already exists in isolated Y6 molecules but is strongly increased when there is molecular aggregation. Surprisingly, it is found that the large enhanced charge transfer in clustered Y6 molecules is not due to an increase in excited-state dipole moment, Δμ, as observed in other organic systems, but due to a reduced polarizability change, Δp. It is proposed that such a strong charge-transfer character is promoted by the stabilization of the charge-transfer energy upon aggregation, as deduced from density functional theory and four-state model calculations. This work provides insight into the correlation between molecular electronic properties and charge-transfer characteristics in organic electronic materials.
Hermitian and non-Hermitian topology from photon-mediated interactions
Authors: Roccati Federico , Bello Miguel , Gong Zongping , Ueda Masahito , Ciccarello Francesco , Chenu Aurélia , Carollo Angelo 
Published: March 2024

AbstractAs light can mediate interactions between atoms in a photonic environment, engineering it for endowing the photon-mediated Hamiltonian with desired features, like robustness against disorder, is crucial in quantum research. We provide general theorems on the topology of photon-mediated interactions in terms of both Hermitian and non-Hermitian topological invariants, unveiling the phenomena of topological preservation and reversal, and revealing a system-bath topological correspondence. Depending on the Hermiticity of the environment and the parity of the spatial dimension, the atomic and photonic topological invariants turn out to be equal or opposite. Consequently, the emergence of atomic and photonic topological boundary modes with opposite group velocities in two-dimensional Hermitian topological systems is established. Owing to its general applicability, our results can guide the design of topological systems.
Ultrasound-induced reorientation for multi-angle optical coherence tomography
Authors: Kvåle Løvmo Mia , Deng Shiyu , Moser Simon , Leitgeb Rainer , Drexler Wolfgang , Ritsch-Marte Monika 
Published: March 2024

AbstractOrganoid and spheroid technology provide valuable insights into developmental biology and oncology. Optical coherence tomography (OCT) is a label-free technique that has emerged as an excellent tool for monitoring the structure and function of these samples. However, mature organoids are often too opaque for OCT. Access to multi-angle views is highly desirable to overcome this limitation, preferably with non-contact sample handling. To fulfil these requirements, we present an ultrasound-induced reorientation method for multi-angle-OCT, which employs a 3D-printed acoustic trap inserted into an OCT imaging system, to levitate and reorient zebrafish larvae and tumor spheroids in a controlled and reproducible manner. A model-based algorithm was developed for the physically consistent fusion of multi-angle data from a priori unknown angles. We demonstrate enhanced penetration depth in the joint 3D-recovery of reflectivity, attenuation, refractive index, and position registration for zebrafish larvae, creating an enabling tool for future applications in volumetric imaging.
Genomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique
Authors: Brokhattingen Nanna , Matambisso Glória , da Silva Clemente , Neubauer Vickers Eric , Pujol Arnau , Mbeve Henriques , Cisteró Pau , Maculuve Sónia , Cuna Boaventura , Melembe Cardoso , Ndimande Nelo , Palmer Brian , García-Ulloa Manuel , Munguambe Humberto , Montaña-Lopez Júlia , Nhamussua Lidia , Simone Wilson , Chidimatembue Arlindo , Galatas Beatriz , Guinovart Caterina , Rovira-Vallbona Eduard , Saúte Francisco , Aide Pedro , Aranda-Díaz Andrés , Greenhouse Bryan , Macete Eusébio , Mayor Alfredo 
Published: March 2024

AbstractRoutine sampling of pregnant women at first antenatal care (ANC) visits could make Plasmodium falciparum genomic surveillance more cost-efficient and convenient in sub-Saharan Africa. We compare the genetic structure of parasite populations sampled from 289 first ANC users and 93 children from the community in Mozambique between 2015 and 2019. Samples are amplicon sequenced targeting 165 microhaplotypes and 15 drug resistance genes. Metrics of genetic diversity and relatedness, as well as the prevalence of drug resistance markers, are consistent between the two populations. In an area targeted for elimination, intra-host genetic diversity declines in both populations (p = 0.002-0.007), while for the ANC population, population genetic diversity is also lower (p = 0.0004), and genetic relatedness between infections is higher (p = 0.002) than control areas, indicating a recent reduction in the parasite population size. These results highlight the added value of genomic surveillance at ANC clinics to inform about changes in transmission beyond epidemiological data.
Axl and MerTK regulate synovial inflammation and are modulated by IL-6 inhibition in rheumatoid arthritis
Authors: Nerviani Alessandra , Boutet Marie-Astrid , Ghirardi Giulia Maria , Goldmann Katriona , Sciacca Elisabetta , Rivellese Felice , Pontarini Elena , Prediletto Edoardo , Abatecola Federico , Caliste Mattia , Pagani Sara , Mauro Daniele , Bellan Mattia , Cubuk Cankut , Lau Rachel , Church Sarah E. , Hudson Briana M. , Humby Frances , Bombardieri Michele , Lewis Myles J. , Pitzalis Costantino 
Published: March 2024

AbstractThe TAM tyrosine kinases, Axl and MerTK, play an important role in rheumatoid arthritis (RA). Here, using a unique synovial tissue bioresource of patients with RA matched for disease stage and treatment exposure, we assessed how Axl and MerTK relate to synovial histopathology and disease activity, and their topographical expression and longitudinal modulation by targeted treatments. We show that in treatment-naive patients, high AXL levels are associated with pauci-immune histology and low disease activity and inversely correlate with the expression levels of pro-inflammatory genes. We define the location of Axl/MerTK in rheumatoid synovium using immunohistochemistry/fluorescence and digital spatial profiling and show that Axl is preferentially expressed in the lining layer. Moreover, its ectodomain, released in the synovial fluid, is associated with synovial histopathology. We also show that Toll-like-receptor 4-stimulated synovial fibroblasts from patients with RA modulate MerTK shedding by macrophages. Lastly, Axl/MerTK synovial expression is influenced by disease stage and therapeutic intervention, notably by IL-6 inhibition. These findings suggest that Axl/MerTK are a dynamic axis modulated by synovial cellular features, disease stage and treatment.
Structural and mechanistic insights into activation of the human RNA ligase RTCB by Archease
Authors: Gerber Janina Lara , Morales Guzmán Suria Itzel , Worf Lorenz , Hubbe Petra , Kopp Jürgen , Peschek Jirka 
Published: March 2024

AbstractRNA ligases of the RTCB-type play an essential role in tRNA splicing, the unfolded protein response and RNA repair. RTCB is the catalytic subunit of the pentameric human tRNA ligase complex. RNA ligation by the tRNA ligase complex requires GTP-dependent activation of RTCB. This active site guanylylation reaction relies on the activation factor Archease. The mechanistic interplay between both proteins has remained unknown. Here, we report a biochemical and structural analysis of the human RTCB-Archease complex in the pre- and post-activation state. Archease reaches into the active site of RTCB and promotes the formation of a covalent RTCB-GMP intermediate through coordination of GTP and metal ions. During the activation reaction, Archease prevents futile RNA substrate binding to RTCB. Moreover, monomer structures of Archease and RTCB reveal additional states within the RNA ligation mechanism. Taken together, we present structural snapshots along the reaction cycle of the human tRNA ligase.
Therapeutic targeting nudix hydrolase 1 creates a MYC-driven metabolic vulnerability
Authors: Ye Minhui , Fang Yingzhe , Chen Lu , Song Zemin , Bao Qing , Wang Fei , Huang Hao , Xu Jin , Wang Ziwen , Xiao Ruijing , Han Meng , Gao Song , Liu Hudan , Jiang Baishan , Qing Guoliang 
Published: March 2024

AbstractTumor cells must rewire nucleotide synthesis to satisfy the demands of unbridled proliferation. Meanwhile, they exhibit augmented reactive oxygen species (ROS) production which paradoxically damages DNA and free deoxy-ribonucleoside triphosphates (dNTPs). How these metabolic processes are integrated to fuel tumorigenesis remains to be investigated. MYC family oncoproteins coordinate nucleotide synthesis and ROS generation to drive the development of numerous cancers. We herein perform a Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-based functional screen targeting metabolic genes and identified nudix hydrolase 1 (NUDT1) as a MYC-driven dependency. Mechanistically, MYC orchestrates the balance of two metabolic pathways that act in parallel, the NADPH oxidase 4 (NOX4)-ROS pathway and the Polo like kinase 1 (PLK1)-NUDT1 nucleotide-sanitizing pathway. We describe LC-1-40 as a potent, on-target degrader that depletes NUDT1 in vivo. Administration of LC-1-40 elicits excessive nucleotide oxidation, cytotoxicity and therapeutic responses in patient-derived xenografts. Thus, pharmacological targeting of NUDT1 represents an actionable MYC-driven metabolic liability.
A universal system for boosting gene expression in eukaryotic cell-lines
Authors: Vaknin Inbal , Willinger Or , Mandl Jonathan , Heuberger Hadar , Ben-Ami Dan , Zeng Yi , Goldberg Sarah , Orenstein Yaron , Amit Roee 
Published: March 2024

AbstractWe demonstrate a transcriptional regulatory design algorithm that can boost expression in yeast and mammalian cell lines. The system consists of a simplified transcriptional architecture composed of a minimal core promoter and a synthetic upstream regulatory region (sURS) composed of up to three motifs selected from a list of 41 motifs conserved in the eukaryotic lineage. The sURS system was first characterized using an oligo-library containing 189,990 variants. We validate the resultant expression model using a set of 43 unseen sURS designs. The validation sURS experiments indicate that a generic set of grammar rules for boosting and attenuation may exist in yeast cells. Finally, we demonstrate that this generic set of grammar rules functions similarly in mammalian CHO-K1 and HeLa cells. Consequently, our work provides a design algorithm for boosting the expression of promoters used for expressing industrially relevant proteins in yeast and mammalian cell lines.
Maternal dietary fat during lactation shapes single nucleus transcriptomic profile of postnatal offspring hypothalamus in a sexually dimorphic manner in mice
Authors: Huang Yi , Wang Anyongqi , Zhou Wenjiang , Li Baoguo , Zhang Linshan , Rudolf Agata M. , Jin Zengguang , Hambly Catherine , Wang Guanlin , Speakman John R. 
Published: March 2024

AbstractMaternal overnutrition during lactation predisposes offspring to develop metabolic diseases and exacerbates the relevant syndromes in males more than females in later life. The hypothalamus is a heterogenous brain region that regulates energy balance. Here we combined metabolic trait quantification of mother and offspring mice under low and high fat diet (HFD) feeding during lactation, with single nucleus transcriptomic profiling of their offspring hypothalamus at peak lacation to understand the cellular and molecular alterations in response to maternal dietary pertubation. We found significant expansion in neuronal subpopulations including histaminergic (Hdc), arginine vasopressin/retinoic acid receptor-related orphan receptor β (Avp/Rorb) and agouti-related peptide/neuropeptide Y (AgRP/Npy) in male offspring when their mothers were fed HFD, and increased Npy-astrocyte interactions in offspring responding to maternal overnutrition. Our study provides a comprehensive offspring hypothalamus map at the peak lactation and reveals how the cellular subpopulations respond to maternal dietary fat in a sex-specific manner during development.
SpyMask enables combinatorial assembly of bispecific binders
Authors: Driscoll Claudia L. , Keeble Anthony H. , Howarth Mark R. 
Published: March 2024

AbstractBispecific antibodies are a successful and expanding therapeutic class. Standard approaches to generate bispecifics are complicated by the need for disulfide reduction/oxidation or specialized formats. Here we present SpyMask, a modular approach to bispecifics using SpyTag/SpyCatcher spontaneous amidation. Two SpyTag-fused antigen-binding modules can be precisely conjugated onto DoubleCatcher, a tandem SpyCatcher where the second SpyCatcher is protease-activatable. We engineer a panel of structurally-distinct DoubleCatchers, from which binders project in different directions. We establish a generalized methodology for one-pot assembly and purification of bispecifics in 96-well plates. A panel of binders recognizing different HER2 epitopes were coupled to DoubleCatcher, revealing unexpected combinations with anti-proliferative or pro-proliferative activity on HER2-addicted cancer cells. Bispecific activity depended sensitively on both binder orientation and DoubleCatcher scaffold geometry. These findings support the need for straightforward assembly in different formats. SpyMask provides a scalable tool to discover synergy in bispecific activity, through modulating receptor organization and geometry.
Long noncoding RNA Malat1 protects against osteoporosis and bone metastasis
Authors: Zhao Yang , Ning Jingyuan , Teng Hongqi , Deng Yalan , Sheldon Marisela , Shi Lei , Martinez Consuelo , Zhang Jie , Tian Annie , Sun Yutong , Nakagawa Shinichi , Yao Fan , Wang Hai , Ma Li 
Published: March 2024

AbstractMALAT1, one of the few highly conserved nuclear long noncoding RNAs (lncRNAs), is abundantly expressed in normal tissues. Previously, targeted inactivation and genetic rescue experiments identified MALAT1 as a suppressor of breast cancer lung metastasis. On the other hand, Malat1-knockout mice are viable and develop normally. On a quest to discover the fundamental roles of MALAT1 in physiological and pathological processes, we find that this lncRNA is downregulated during osteoclastogenesis in humans and mice. Remarkably, Malat1 deficiency in mice promotes osteoporosis and bone metastasis of melanoma and mammary tumor cells, which can be rescued by genetic add-back of Malat1. Mechanistically, Malat1 binds to Tead3 protein, a macrophage-osteoclast–specific Tead family member, blocking Tead3 from binding and activating Nfatc1, a master regulator of osteoclastogenesis, which results in the inhibition of Nfatc1-mediated gene transcription and osteoclast differentiation. Notably, single-cell transcriptome analysis of clinical bone samples reveals that reduced MALAT1 expression in pre-osteoclasts and osteoclasts is associated with osteoporosis and metastatic bone lesions. Altogether, these findings identify Malat1 as a lncRNA that protects against osteoporosis and bone metastasis.
Three-dimensional ultrafast charge-density-wave dynamics in CuTe
Authors: Nhat Quyen Nguyen , Tzeng Wen-Yen , Hsu Chih-En , Lin I-An , Chen Wan-Hsin , Jia Hao-Hsiang , Wang Sheng-Chiao , Liu Cheng-En , Chen Yu-Sheng , Chen Wei-Liang , Chou Ta-Lei , Wang I-Ta , Kuo Chia-Nung , Lin Chun-Liang , Wu Chien-Te , Lin Ping-Hui , Weng Shih-Chang , Cheng Cheng-Maw , Kuo Chang-Yang , Tu Chien-Ming , Chu Ming-Wen , Chang Yu-Ming , Lue Chin Shan , Hsueh Hung-Chung , Luo Chih-Wei 
Published: March 2024

AbstractCharge density waves (CDWs) involved with electronic and phononic subsystems simultaneously are a common quantum state in solid-state physics, especially in low-dimensional materials. However, CDW phase dynamics in various dimensions are yet to be studied, and their phase transition mechanism is currently moot. Here we show that using the distinct temperature evolution of orientation-dependent ultrafast electron and phonon dynamics, different dimensional CDW phases are verified in CuTe. When the temperature decreases, the shrinking of c-axis length accompanied with the appearance of interchain and interlayer interactions causes the quantum fluctuations (QF) of the CDW phase until 220 K. At T < 220 K, the CDWs on the different ab-planes are finally locked with each other in anti-phase to form a CDW phase along the c-axis. This study shows the dimension evolution of CDW phases in one CDW system and their stabilized mechanisms in different temperature regimes.
Beyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria
Authors: Oelschlegel A. M. , Bhattacharjee R. , Wenk P. , Harit K. , Rothkötter H-J , Koch S. P. , Boehm-Sturm P. , Matuschewski K. , Budinger E. , Schlüter D. , Goldschmidt J. , Nishanth G. 
Published: March 2024

AbstractSequestration of infected red blood cells (iRBCs) in the microcirculation is a hallmark of cerebral malaria (CM) in post-mortem human brains. It remains controversial how this might be linked to the different disease manifestations, in particular brain swelling leading to brain herniation and death. The main hypotheses focus on iRBC-triggered inflammation and mechanical obstruction of blood flow. Here, we test these hypotheses using murine models of experimental CM (ECM), SPECT-imaging of radiolabeled iRBCs and cerebral perfusion, MR-angiography, q-PCR, and immunohistochemistry. We show that iRBC accumulation and reduced flow precede inflammation. Unexpectedly, we find that iRBCs accumulate not only in the microcirculation but also in large draining veins and sinuses, particularly at the rostral confluence. We identify two parallel venous streams from the superior sagittal sinus that open into the rostral rhinal veins and are partially connected to infected skull bone marrow. The flow in these vessels is reduced early, and the spatial patterns of pathology correspond to venous drainage territories. Our data suggest that venous efflux reductions downstream of the microcirculation are causally linked to ECM pathology, and that the different spatiotemporal patterns of edema development in mice and humans could be related to anatomical differences in venous anatomy.
Biomimetic nanocluster photoreceptors for adaptative circular polarization vision
Authors: Wen Wei , Liu Guocai , Wei Xiaofang , Huang Haojie , Wang Chong , Zhu Danlei , Sun Jianzhe , Yan Huijuan , Huang Xin , Shi Wenkang , Dai Xiaojuan , Dong Jichen , Jiang Lang , Guo Yunlong , Wang Hanlin , Liu Yunqi 
Published: March 2024

AbstractNanoclusters with atomically precise structures and discrete energy levels are considered as nanoscale semiconductors for artificial intelligence. However, nanocluster electronic engineering and optoelectronic behavior have remained obscure and unexplored. Hence, we create nanocluster photoreceptors inspired by mantis shrimp visual systems to satisfy the needs of compact but multi-task vision hardware and explore the photo-induced electronic transport. Wafer-scale arrayed photoreceptors are constructed by a nanocluster-conjugated molecule heterostructure. Nanoclusters perform as an in-sensor charge reservoir to tune the conductance levels of artificial photoreceptors by a light valve mechanism. A ligand-assisted charge transfer process takes place at nanocluster interface and it features an integration of spectral-dependent visual adaptation and circular polarization recognition. This approach is further employed for developing concisely structured, multi-task, and compact artificial visual systems and provides valuable guidelines for nanocluster neuromorphic devices.