bluuebunny/crossref_metadata_2025_split huggingface dataset:
Present‐Day 3D Crustal Deformation of the Northeastern Tibetan Plateau From Space Geodesy
Authors: Wu Dong‐Lin , Ge Wei‐Peng , Liu Shao‐Zhuo , Yuan Dao‐Yang , Zhang Bo , Wei Cong‐Min 
Published: February 2024

AbstractHigh‐resolution present‐day earth surface deformation maps from satellites provide important data constraints, which help us better understand tectonic processes and analyze seismic hazards. Here, we use Sentinel‐1 Radar images (2014–2020) and accurate positioning measurements (2009–2019) to get a high‐resolution three‐dimensional earth surface velocity map for the northeastern Tibetan Plateau, and we invert the slip rate and coupling ratio of major regional faults. We find ∼4 mm/yr uplift along an arc from the Qilianshan to Lajishan, relative to the neighboring low‐elevation area to the east, which indicates ongoing rapid orogeny. We find transient deformation along the Laohushan and 1920 M8.5 Haiyuan rupture segments of the Haiyuan fault, whereas the western Haiyuan, southern Liupanshan, central Lajishan and central‐western West Qinling faults are essentially locked above 15–20 km, suggesting a potentially high seismic hazard.
PRX1-positive mesenchymal stem cells drive molar morphogenesis
Authors: Xu Xiaoqiao , Gong Xuyan , Zhang Lei , Zhang Han , Sun Yao 
Published: February 2024

AbstractMammalian teeth, developing inseparable from epithelial-mesenchymal interaction, come in many shapes and the key factors governing tooth morphology deserve to be answered. By merging single-cell RNA sequencing analysis with lineage tracing models, we have unearthed a captivating correlation between the contrasting morphology of mouse molars and the specific presence of PRX1+ cells within M1. These PRX1+ cells assume a profound responsibility in shaping tooth morphology through a remarkable divergence in dental mesenchymal cell proliferation. Deeper into the mechanisms, we have discovered that Wnt5a, bestowed by mesenchymal PRX1+ cells, stimulates mesenchymal cell proliferation while orchestrating molar morphogenesis through WNT signaling pathway. The loss of Wnt5a exhibits a defect phenotype similar to that of siPrx1. Exogenous addition of WNT5A can successfully reverse the inhibited cell proliferation and consequent deviant appearance exhibited in Prx1-deficient tooth germs. These findings bestow compelling evidence of PRX1-positive mesenchymal cells to be potential target in regulating tooth morphology.
FSP1 inhibition enhances olaparib sensitivity in BRCA-proficient ovarian cancer patients via a nonferroptosis mechanism
Authors: Miao Huixian , Meng Huangyang , Zhang Yashuang , Chen Tian , Zhang Lin , Cheng Wenjun 
Published: February 2024

AbstractPoly ADP-ribose polymerase inhibitors (PARPis) exhibit promising efficacy in patients with BRCA mutations or homologous repair deficiency (HRD) in ovarian cancer (OC). However, less than 40% of patients have HRD, it is vital to expand the indications for PARPis in BRCA-proficient patients. Ferroptosis suppressor protein 1 (FSP1) is a key protein in a newly identified ferroptosis-protective mechanism that occurs in parallel with the GPX4-mediated pathway and is associated with chemoresistance in several cancers. Herein, FSP1 is reported to be negatively correlated with the prognosis in OC patients. Combination therapy comprising olaparib and iFSP1 (a FSP1 inhibitor) strongly inhibited tumour proliferation in BRCA-proficient OC cell lines, patient-derived organoids (PDOs) and xenograft mouse models. Surprisingly, the synergistic killing effect could not be reversed by ferroptosis inhibitors, indicating that mechanisms other than ferroptosis were responsible for the synergistic lethality. In addition, cotreatment was shown to induce increased γH2A.X foci and to impair nonhomologous end joining (NHEJ) activity to a greater extent than did any single drug. Mass spectrometry and immunoprecipitation analyses revealed that FSP1 interacted with Ku70, a classical component recruited to and occupying the end of double-strand breaks (DSBs) in the NHEJ process. FSP1 inhibition decreased Ku70 PARylation, impaired subsequent DNA-PKcs recruitment to the Ku complex at DSB sites and was rescued by restoring PARylation. These findings unprecedentedly reveal a novel role of FSP1 in DNA damage repair and provide new insights into how to sensitize OC patients to PARPi treatment.
Epigenomic analyses identify FOXM1 as a key regulator of anti-tumor immune response in esophageal adenocarcinoma
Authors: Ziman Benjamin , Yang Qian , Zheng Yueyuan , Sheth Megha , Nam Chehyun , Zhao Hua , Zhang Le , Hu Boyan , Bhowmick Neil A. , Sinha Uttam K. , Lin De-Chen 
Published: February 2024

AbstractUnlike most cancer types, the incidence of esophageal adenocarcinoma (EAC) has rapidly escalated in the western world over recent decades. Using whole genome bisulfite sequencing (WGBS), we identify the transcription factor (TF) FOXM1 as an important epigenetic regulator of EAC. FOXM1 plays a critical role in cellular proliferation and tumor growth in EAC patient-derived organoids and cell line models. We identify ERBB2 as an upstream regulator of the expression and transcriptional activity of FOXM1. Unexpectedly, gene set enrichment analysis (GSEA) unbiased screen reveals a prominent anti-correlation between FOXM1 and immune response pathways. Indeed, syngeneic mouse models show that FOXM1 inhibits the infiltration of CD8+ T cells into the tumor microenvironment. Consistently, FOXM1 suppresses CD8+ T cell chemotaxis in vitro and antigen-dependent CD8+ T cell killing. This study characterizes FOXM1 as a significant EAC-promoting TF and elucidates its novel function in regulating anti-tumor immune response.
Fumarate induces LncRNA-MIR4435-2HG to regulate glutamine metabolism remodeling and promote the development of FH-deficient renal cell carcinoma
Authors: Zhu Liangsong , Hong Yilun , Zhu Ziran , Huang Jiwei , Wang Jianfeng , Li Ge , Wu Xiaoyu , Chen Yonghui , Xu Yunze , Zheng Liang , Huang Yiran , Kong Wen , Xue Wei , Zhang Jin 
Published: February 2024

AbstractFumarate hydratase (FH) deficient renal cell carcinoma (RCC) is a type of tumor with definite metabolic disorder, but the mechanism of metabolic remodeling is still unclear. LncRNA was reported to closely correlate with cancer metabolism, however the biological role of LncRNA in the development of progression of FH-deficent RCC was not well studied either. FH-deficient RCC samples were collected in my hospital and used for RNA-sequencing and Mass spectrometry analysis. FH-deficient RCC cell line UOK262 and control pFH cells were used for in vitro experiments, including proliferation assay, transwell assay, western-blot, mass spectrometry and so on. PDX mouse model was used for further drug inhibition experiments in vivo. In this study, we analyzed the profiles of LncRNA and mRNA in FH-deficienct RCC samples, and we found that the LncRNA-MIR4435-2GH was specifically highly expressed in FH-deficient RCC compared with ccRCC. In vitro experiments demonstrated that MIR4435-2HG was regulated by Fumarate through histone demethylation, and the deletion of this gene could inhibit glutamine metabolism. RNA-pulldown experiments showed that MIR4435-2HG specifically binds to STAT1, which can transcriptionally activate GLS1. GLS1 inhibitor CB-839 could significantly suppress tumor growth in PDX tumor models. This study analyzed the molecular mechanism of MIR4435-2HG in regulating metabolic remodeling of FH-deficient RCC in clinical samples, cells and animal models by combining transcriptional and metabolic methods. We found that that GLS1 was a therapeutic target for this tumor, and MIR4435-2HG can be used as a drug sensitivity marker.
8-Br-cGMP activates HSPB6 and increases the antineoplastic activity of quinidine in prostate cancer
Authors: Feng Yuankang , Huang Zhenlin , Lu Fubo , Song Liang , Liu Ruoyang , Zhang Yu , Li Ningyang , Han Xu , Li Xiang , Li Keqiang , Huang Budeng , Xie Guoqing , Guo Abao , Yang Jinjian , Jia Zhankui 
Published: February 2024

AbstractHeat shock protein family B [small] member 6 (HSPB6), widely found in various muscles, has been recently identified as a tumor suppressor gene. However, its role in prostate cancer remains unexplored. Herein, we investigated the expression of HSPB6 in prostate cancer and its association with prognosis. Our findings revealed that HSPB6 downregulation in prostate cancer correlated with a poor prognosis. Moreover, we discovered that HSPB6 can be phosphorylated and activated by 8-Br-cGMP, leading to apoptosis in prostate cancer cells by activating Cofilin. Additionally, we demonstrated that knocking down E2F1 by quinidine administration enhances the transcriptional level of HSPB6. Furthermore, we evaluated the combination of quinidine and 8-Br-cGMP as a potential therapeutic strategy for prostate cancer. Our results revealed that the combined treatment was more effective than either treatment alone in inhibiting the growth of prostate cancer through the HSPB6 pathway, both in vitro and in vivo. Overall, our study provides compelling evidence that HSPB6 suppresses malignant behavior in prostate cancer by inducing apoptosis. The combination of quinidine and 8-Br-cGMP emerges as a promising approach for the treatment of prostate cancer.
Liquid Madelung energy accounts for the huge potential shift in electrochemical systems
Authors: Takenaka Norio , Ko Seongjae , Kitada Atsushi , Yamada Atsuo 
Published: February 2024

AbstractAchievement of carbon neutrality requires the development of electrochemical technologies suitable for practical energy storage and conversion. In any electrochemical system, electrode potential is the central variable that regulates the driving force of redox reactions. However, quantitative understanding of the electrolyte dependence has been limited to the classic Debye-Hückel theory that approximates the Coulombic interactions in the electrolyte under the dilute limit conditions. Therefore, accurate expression of electrode potential for practical electrochemical systems has been a holy grail of electrochemistry research for over a century. Here we show that the ‘liquid Madelung potential’ based on the conventional explicit treatment of solid-state Coulombic interactions enables quantitatively accurate expression of the electrode potential, with the Madelung shift obtained from molecular dynamics reproducing a hitherto-unexplained huge experimental shift for the lithium metal electrode. Thus, a long-awaited method for the description of the electrode potential in any electrochemical system is now available.
Complexation-driven assembly of imine-linked helical receptors showing adaptive folding and temperature-dependent guest selection
Authors: Song Geunmoo , Lee Seungwon , Jeong Kyu-Sung 
Published: February 2024

AbstractThe development of synthetic receptors capable of selectively binding guests with diverse structures and multiple functional groups poses a significant challenge. Here, we present the efficient assembly of foldamer-based receptors for monosaccharides, utilising the principles of complexation-induced equilibrium shifting and adaptive folding. Diimine 4 can be quantitatively assembled from smaller components when d-galactose is added as a guest among monosaccharides we examined. During this assembly, dual complexation-induced equilibrium shifts toward both the formation of diimine 4 and the conversion of d-galactose into α-d-galactofuranose are observed. Diimine 6 is quantitatively assembled in the presence of two different guests, methyl β-d-glucopyranoside and methyl β-d-galactopyranoside, resulting in the formation of two dimeric complexes: (6-MP)2⊃(methyl β-d-glucopyranoside)2 and (6-MM)2⊃(methyl β-d-galactopyranoside∙2H2O)2, respectively. These two complexes exhibit distinct folding structures with domain-swapping cavities depending on the bound guest and temperature. Interestingly, (6-MM)2⊃(methyl β-d-galactopyranoside∙2H2O)2 is exclusively formed at lower temperatures, while (6-MP)2⊃(methyl β-d-glucopyranoside)2 is only formed at higher temperatures.
A single cell atlas of frozen shoulder capsule identifies features associated with inflammatory fibrosis resolution
Authors: Ng Michael T. H. , Borst Rowie , Gacaferi Hamez , Davidson Sarah , Ackerman Jessica E. , Johnson Peter A. , Machado Caio C. , Reekie Ian , Attar Moustafa , Windell Dylan , Kurowska-Stolarska Mariola , MacDonald Lucy , Alivernini Stefano , Garvilles Micon , Jansen Kathrin , Bhalla Ananya , Lee Angela , Charlesworth James , Chowdhury Rajat , Klenerman Paul , Powell Kate , Hackstein Carl-Philip ,   ICECAP Consortium, Rangan Amar , Gwilym Stephen , Little Christopher , Titchener Andrew , Chaudhury Salma , Holland Philip , Wheway Kim , Watkins Bridget , Beazley Debra , Vesty-Edwards Lois , Appleton Louise , Atkinson Marc , Kottam Lucksy , James Juliet , Clark Natalie , Furniss Dominic , Rees Jonathan , Gilroy Derek , Coles Mark , Carr Andrew J. , Sansom Stephen N. , Buckley Christopher D. , Dakin Stephanie G. 
Published: February 2024

AbstractFrozen shoulder is a spontaneously self-resolving chronic inflammatory fibrotic human disease, which distinguishes the condition from most fibrotic diseases that are progressive and irreversible. Using single-cell analysis, we identify pro-inflammatory MERTKlowCD48+ macrophages and MERTK + LYVE1 + MRC1+ macrophages enriched for negative regulators of inflammation which co-exist in frozen shoulder capsule tissues. Micro-cultures of patient-derived cells identify integrin-mediated cell-matrix interactions between MERTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts, suggesting that matrix remodelling plays a role in frozen shoulder resolution. Cross-tissue analysis reveals a shared gene expression cassette between shoulder capsule MERTK+ macrophages and a respective population enriched in synovial tissues of rheumatoid arthritis patients in disease remission, supporting the concept that MERTK+ macrophages mediate resolution of inflammation and fibrosis. Single-cell transcriptomic profiling and spatial analysis of human foetal shoulder tissues identify MERTK + LYVE1 + MRC1+ macrophages and DKK3+ and POSTN+ fibroblast populations analogous to those in frozen shoulder, suggesting that the template to resolve fibrosis is established during shoulder development. Crosstalk between MerTK+ macrophages and pro-resolving DKK3+ and POSTN+ fibroblasts could facilitate resolution of frozen shoulder, providing a basis for potential therapeutic resolution of persistent fibrotic diseases.
Machine learning-based extrachromosomal DNA identification in large-scale cohorts reveals its clinical implications in cancer
Authors: Wang Shixiang , Wu Chen-Yi , He Ming-Ming , Yong Jia-Xin , Chen Yan-Xing , Qian Li-Mei , Zhang Jin-Ling , Zeng Zhao-Lei , Xu Rui-Hua , Wang Feng , Zhao Qi 
Published: February 2024

AbstractThe clinical implications of extrachromosomal DNA (ecDNA) in cancer therapy remain largely elusive. Here, we present a comprehensive analysis of ecDNA amplification spectra and their association with clinical and molecular features in multiple cohorts comprising over 13,000 pan-cancer patients. Using our developed computational framework, GCAP, and validating it with multifaceted approaches, we reveal a consistent pan-cancer pattern of mutual exclusivity between ecDNA amplification and microsatellite instability (MSI). In addition, we establish the role of ecDNA amplification as a risk factor and refine genomic subtypes in a cohort from 1015 colorectal cancer patients. Importantly, our investigation incorporates data from four clinical trials focused on anti-PD-1 immunotherapy, demonstrating the pivotal role of ecDNA amplification as a biomarker for guiding checkpoint blockade immunotherapy in gastrointestinal cancer. This finding represents clinical evidence linking ecDNA amplification to the effectiveness of immunotherapeutic interventions. Overall, our study provides a proof-of-concept of identifying ecDNA amplification from cancer whole-exome sequencing (WES) data, highlighting the potential of ecDNA amplification as a valuable biomarker for facilitating personalized cancer treatment.
PIBF1 regulates trophoblast syncytialization and promotes cardiovascular development
Authors: Lee Jong Geol , Yon Jung-Min , Kim Globinna , Lee Seul-Gi , Kim C-Yoon , Cheong Seung-A , Kim Hyun-Yi , Yu Jiyoung , Kim Kyunggon , Sung Young Hoon , Yoo Hyun Ju , Woo Dong-Cheol , Rho Jin Kyung , Ha Chang Hoon , Pack Chan-Gi , Oh Seak Hee , Lim Joon Seo , Han Yu Mi , Hong Eui-Ju , Seong Je Kyung , Lee Han-Woong , Lee Sang-Wook , Lee Ki-Up , Kim Chong Jai , Nam Sang-Yoon , Cho You Sook , Baek In-Jeoung 
Published: February 2024

AbstractProper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that PIBF1 promotes the development of cardiovascular characteristics in heart organoids. Our findings show how SynTs organize the barrier and imply their possible roles in supporting embryogenesis, including cardiovascular development. SynT-derived factors and SynT within the placenta may play critical roles in ensuring proper organogenesis of other organs in the embryo.
Molecular co-assembled strategy tuning protein conformation for cartilage regeneration
Authors: Zhao Chengkun , Li Xing , Han Xiaowen , Li Zhulian , Bian Shaoquan , Zeng Weinan , Ding Mingming , Liang Jie , Jiang Qing , Zhou Zongke , Fan Yujiang , Zhang Xingdong , Sun Yong 
Published: February 2024

AbstractThe assembly of oligopeptide and polypeptide molecules can reconstruct various ordered advanced structures through intermolecular interactions to achieve protein-like biofunction. Here, we develop a “molecular velcro”-inspired peptide and gelatin co-assembly strategy, in which amphiphilic supramolecular tripeptides are attached to the molecular chain of gelatin methacryloyl via intra-/intermolecular interactions. We perform molecular docking and dynamics simulations to demonstrate the feasibility of this strategy and reveal the advanced structural transition of the co-assembled hydrogel, which brings more ordered β-sheet content and 10-fold or more compressive strength improvement. We conduct transcriptome analysis to reveal the role of co-assembled hydrogel in promoting cell proliferation and chondrogenic differentiation. Subcutaneous implantation evaluation confirms considerably reduced inflammatory responses and immunogenicity in comparison with type I collagen. We demonstrate that bone mesenchymal stem cells-laden co-assembled hydrogel can be stably fixed in rabbit knee joint defects by photocuring, which significantly facilitates hyaline cartilage regeneration after three months. This co-assembly strategy provides an approach for developing cartilage regenerative biomaterials.
Self-supervised dynamic learning for long-term high-fidelity image transmission through unstabilized diffusive media
Authors: Li Ziwei , Zhou Wei , Zhou Zhanhong , Zhang Shuqi , Shi Jianyang , Shen Chao , Zhang Junwen , Chi Nan , Dai Qionghai 
Published: February 2024

AbstractMultimode fiber (MMF) which supports parallel transmission of spatially distributed information is a promising platform for remote imaging and capacity-enhanced optical communication. However, the variability of the scattering MMF channel poses a challenge for achieving long-term accurate transmission over long distances, of which static optical propagation modeling with calibrated transmission matrix or data-driven learning will inevitably degenerate. In this paper, we present a self-supervised dynamic learning approach that achieves long-term, high-fidelity transmission of arbitrary optical fields through unstabilized MMFs. Multiple networks carrying both long- and short-term memory of the propagation model variations are adaptively updated and ensembled to achieve robust image recovery. We demonstrate >99.9% accuracy in the transmission of 1024 spatial degree-of-freedom over 1 km length MMFs lasting over 1000 seconds. The long-term high-fidelity capability enables compressive encoded transfer of high-resolution video with orders of throughput enhancement, offering insights for artificial intelligence promoted diffusive spatial transmission in practical applications.
Regulation of stress granule formation in human oligodendrocytes
Authors: Pernin Florian , Cui Qiao-Ling , Mohammadnia Abdulshakour , Fernandes Milton G. F. , Hall Jeffery A. , Srour Myriam , Dudley Roy W. R. , Zandee Stephanie E. J. , Klement Wendy , Prat Alexandre , Salapa Hannah E. , Levin Michael C. , Moore G. R. Wayne , Kennedy Timothy E. , Vande Velde Christine , Antel Jack P. 
Published: February 2024

AbstractOligodendrocyte (OL) injury and subsequent loss is a pathologic hallmark of multiple sclerosis (MS). Stress granules (SGs) are membrane-less organelles containing mRNAs stalled in translation and considered as participants of the cellular response to stress. Here we show SGs in OLs in active and inactive areas of MS lesions as well as in normal-appearing white matter. In cultures of primary human adult brain derived OLs, metabolic stress conditions induce transient SG formation in these cells. Combining pro-inflammatory cytokines, which alone do not induce SG formation, with metabolic stress results in persistence of SGs. Unlike sodium arsenite, metabolic stress induced SG formation is not blocked by the integrated stress response inhibitor. Glycolytic inhibition also induces persistent SGs indicating the dependence of SG formation and disassembly on the energetic glycolytic properties of human OLs. We conclude that SG persistence in OLs in MS reflects their response to a combination of metabolic stress and pro-inflammatory conditions.