bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression
Authors: Shuai Yujun , Zhang Hui , Liu Changhao , Wang Junting , Jiang Yangkai , Sun Jiayin , Gao Xincheng , Bo Xiaochen , Xiao Xingyuan , Liao Xin , Huang Chao , Chen Hebing , Jiang Guosong 
Published: January 2024

AbstractChromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumors, whereas the specific mechanism of CLIC3 in tumor remains unclear. Here, we screened for key genes in bladder cancer through the identification of transcription factor binding site clustered region (TFCR) on the basis of chromatin accessibility and TF motif. CLIC3 was identified by joint profiling of chromatin accessibility data with TCGA database. Clinically, CLIC3 expression was significantly elevated in bladder cancer and was negatively correlated with patient survival. CLIC3 promoted the proliferation of bladder cancer cells by reducing p21 expression in vitro and in vivo. Mechanistically, CLIC3 interacted with NAT10 and inhibited the function of NAT10, resulting in the downregulation of ac4C modification and stability of p21 mRNA. Overall, these findings uncover an novel mechanism of mRNA ac4C modification and CLIC3 may act as a potential therapeutic target for bladder cancer.
Effects of methionine deficiency on B7H3-DAP12-CAR-T cells in the treatment of lung squamous cell carcinoma
Authors: Yu Tao , Nie Feng-Qi , Zhang Qi , Yu Shao-Kun , Zhang Mei-Ling , Wang Qian , Wang En-Xiu , Lu Kai-Hua , Sun Ming 
Published: January 2024

AbstractLung squamous cell carcinoma (LUSC) is a subtype of lung cancer for which precision therapy is lacking. Chimeric antigen receptor T-cells (CAR-T) have the potential to eliminate cancer cells by targeting specific antigens. However, the tumor microenvironment (TME), characterized by abnormal metabolism could inhibit CAR-T function. Therefore, the aim of this study was to improve CAR-T efficacy in solid TME by investigating the effects of amino acid metabolism. We found that B7H3 was highly expressed in LUSC and developed DAP12-CAR-T targeting B7H3 based on our previous findings. When co-cultured with B7H3-overexpressing LUSC cells, B7H3-DAP12-CAR-T showed significant cell killing effects and released cytokines including IFN-γ and IL-2. However, LUSC cells consumed methionine (Met) in a competitive manner to induce a Met deficiency. CAR-T showed suppressed cell killing capacity, reduced cytokine release and less central memory T phenotype in medium with lower Met, while the exhaustion markers were up-regulated. Furthermore, the gene NKG7, responsible for T cell cytotoxicity, was downregulated in CAR-T cells at low Met concentration due to a decrease in m5C modification. NKG7 overexpression could partially restore the cytotoxicity of CAR-T in low Met. In addition, the anti-tumor efficacy of CAR-T was significantly enhanced when co-cultured with SLC7A5 knockdown LUSC cells at low Met concentration. In conclusion, B7H3 is a prospective target for LUSC, and B7H3-DAP12-CAR-T cells are promising for LUSC treatment. Maintaining Met levels in CAR-T may help overcome TME suppression and improve its clinical application potential.
GRB2 is a BECN1 interacting protein that regulates autophagy
Authors: Montero-Vergara Jetsy , Plachetta Kira , Kinch Lisa , Bernhardt Stephan , Kashyap Kriti , Levine Beth , Thukral Lipi , Vetter Martina , Thomssen Christoph , Wiemann Stefan , Peña-Llopis Samuel , Jendrossek Verena , Vega-Rubin-de-Celis Silvia 
Published: January 2024

AbstractGRB2 is an adaptor protein of HER2 (and several other tyrosine kinases), which we identified as a novel BECN1 (Beclin 1) interacting partner. GRB2 co-immunoprecipitated with BECN1 in several breast cancer cell lines and regulates autophagy through a mechanism involving the modulation of the class III PI3Kinase VPS34 activity. In ovo studies in a CAM (Chicken Chorioallantoic Membrane) model indicated that GRB2 knockdown, as well as overexpression of GRB2 loss-of-function mutants (Y52A and S86A-R88A) compromised tumor growth. These differences in tumor growth correlated with differential autophagy activity, indicating that autophagy effects might be related to the effects on tumorigenesis. Our data highlight a novel function of GRB2 as a BECN1 binding protein and a regulator of autophagy.
Comparative single-cell analysis reveals heterogeneous immune landscapes in adenocarcinoma of the esophagogastric junction and gastric adenocarcinoma
Authors: Chen Jierong , Huang Qunsheng , Li Yi-Qi , Li Zhi , Zheng Jiabin , Hu Weixian , Yang Yuesheng , Wu Deqing , Bei Jin-Xin , Gu Bing , Wang Junjiang , Li Yong 
Published: January 2024

AbstractAdenocarcinoma of the esophagogastric junction (AEG) is a type of tumor that arises at the anatomical junction of the esophagus and stomach. Although AEG is commonly classified as a subtype of gastric adenocarcinoma (GAC), the tumor microenvironment (TME) of AEG remains poorly understood. To address this issue, we conducted single-cell RNA sequencing (scRNA-seq) on tumor and adjacent normal tissues from four AEG patients and performed integrated analysis with publicly available GAC single-cell datasets. Our study for the first time comprehensively deciphered the TME landscape of AEG, where heterogeneous AEG malignant cells were identified with diverse biological functions and intrinsic malignant nature. We also depicted transcriptional signatures and T cell receptor (TCR) repertoires for T cell subclusters, revealing enhanced exhaustion and reduced clone expansion along the developmental trajectory of tumor-infiltrating T cells within AEG. Notably, we observed prominent enrichment of tumorigenic cancer-associated fibroblasts (CAFs) in the AEG TME compared to GAC. These CAFs played a critical regulatory role in the intercellular communication network with other cell types in the AEG TME. Furthermore, we identified that the accumulation of CAFs in AEG might be induced by malignant cells through FGF-FGFR axes. Our findings provide a comprehensive depiction of the AEG TME, which underlies potential therapeutic targets for AEG patient treatment.
Targeting NEDD8 suppresses surgical stress-facilitated metastasis of colon cancer via restraining regulatory T cells
Authors: Jiang Yi , Gao Shenjia , Sun Hao , Wu Xinyi , Gu Jiahui , Wu Han , Liao Yun , Ben-Ami Ronen , Miao Changhong , Shen Rong , Liu Jinlong , Chen Wankun 
Published: January 2024

AbstractRegulatory T cells (Tregs) are a key determinant for the immunosuppressive and premetastatic niche for cancer progression after surgery resection. However, the precise mechanisms regulating Tregs function during surgical stress-facilitated cancer metastasis remain unknown. This study aims to unravel the mechanisms and explore potential strategies for preventing surgical stress-induced metastasis by targeting NEDD8. Using a surgical stress mouse model, we found that surgical stress results in the increased expression of NEDD8 in Tregs. NEDD8 depletion abrogates postoperative lung metastasis of colon cancer cells by inhibiting Treg immunosuppression and thereby partially recovering CD8+T cell and NK cell-mediated anti-tumor immunity. Furthermore, Treg mitophagy and mitochondrial respiration exacerbated in surgically stressed mice were attenuated by NEDD8 depletion. Our observations suggest that cancer progression may result from surgery-induced enhancement of NEDD8 expression and the subsequent immunosuppressive function of Tregs. More importantly, depleting or inhibiting NEDD8 can be an efficient strategy to reduce cancer metastasis after surgery resection by regulating the function of Tregs.
BRCA1 mutation promotes sprouting angiogenesis in inflammatory cancer-associated fibroblast of triple-negative breast cancer
Authors: Lee Chae Min , Hwang Yeseong , Jeong Jae Woong , Kim Minki , Lee Janghee , Bae Soong June , Ahn Sung Gwe , Fang Sungsoon 
Published: January 2024

AbstractTriple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with inferior outcomes owing to its low treatment response and high invasiveness. Based on abundant cancer-associated fibroblasts (CAFs) and frequent mutation of breast cancer-associated 1 (BRCA1) in TNBC, the characteristics of CAFs in TNBC patients with BRCA1 mutation compared to wild-type were investigated using single-cell analysis. Intriguingly, we observed that characteristics of inflammatory CAFs (iCAFs) were enriched in patients with BRCA1 mutation compared to the wild-type. iCAFs in patients with BRCA1 mutation exhibited outgoing signals to endothelial cells (ECs) clusters, including chemokine (C-X-C motif) ligand (CXCL) and vascular endothelial growth factor (VEGF). During CXCL signaling, the atypical chemokine receptor 1 (ACKR1) mainly interacts with CXCL family members in tumor endothelial cells (TECs). ACKR1-high TECs also showed high expression levels of angiogenesis-related genes, such as ANGPT2, MMP1, and SELE, which might lead to EC migration. Furthermore, iCAFs showed VEGF signals for FLT1 and KDR in TECs, which showed high co-expression with tip cell marker genes, including ZEB1 and MAFF, involved in sprouting angiogenesis. Moreover, BRCA1 mutation patients with relatively abundant iCAFs and tip cell gene expression exhibited a limited response to neoadjuvant chemotherapy, including cisplatin and bevacizumab. Importantly, our study observed the intricate link between iCAFs-mediated angiogenesis and chemoresistance in TNBC with BRCA1 mutation.
Ionizing radiation induces cells with past caspase activity that contribute to the adult organ in Drosophila and show reduced Loss of Heterozygosity
Authors: Colon Plaza Sarah , Su Tin Tin 
Published: January 2024

AbstractThere is increasing recognition that cells may activate apoptotic caspases but not die, instead displaying various physiologically relevant consequences. Mechanisms that underlie the life-or-death decision in a cell that has activated apoptotic caspases, however, are incompletely understood. By optimizing a published reporter for past caspase activity, we were able to visualize cells that survived caspase activation specifically after exposure to ionizing radiation in Drosophila larval wing discs. We found that cells with X-ray-induced past active caspases (XPAC) did not arise at random but were born at specific locations within the developing wing imaginal discs of Drosophila larvae. Inhibiting key components of the apoptotic pathway decreased XPAC number, suggesting that apoptotic signaling is needed to induce XPAC cells. Yet, XPAC cells appeared in stereotypical patterns that did not follow the pattern of IR-induced apoptosis, suggesting additional controls at play. Functional testing identified the contribution of wingless (Drosophila Wnt1) and Ras signaling to the prevalence of XPAC cells. Furthermore, by following irradiated larvae into adulthood, we found that XPAC cells contribute to the adult wing. To address the relationship between XPAC and genome stability, we combined a reporter for past caspase activity with mwh, an adult marker for Loss of Heterozygosity (LOH). We found a lower incidence of LOH among XPAC compared to cells that did not activate the reporter for past caspase activity. In addition, at time points when wing disc cells are finishing DNA repair, XPAC cells show an anti-correlation with cells with unrepaired IR-induced double-stranded breaks. Our data suggest that non-lethal caspase activity safeguards the genome by facilitating DNA repair and reducing LOH after transient exposure to X-rays. These results identify a physiological role for non-lethal caspase activity during recovery from radiation damage.
Compact and wideband nanoacoustic pass-band filters for future 5G and 6G cellular radios
Authors: Giribaldi Gabriel , Colombo Luca , Simeoni Pietro , Rinaldi Matteo 
Published: January 2024

AbstractOver recent years, the surge in mobile communication has deepened global connectivity. With escalating demands for faster data rates, the push for higher carrier frequencies intensifies. The 7–20 GHz range, located between the 5G sub-6 GHz and the mm-wave spectra, provides an excellent trade-off between network capacity and coverage, and constitutes a yet-to-be-explored range for 5G and 6G applications. This work proposes a technological platform able to deliver CMOS-compatible, on-chip multi-frequency, low-loss, wide-band, and compact filters for cellular radios operating in this range by leveraging the micro-to-nano scaling of acoustic electromechanical resonators. The results showcase the first-ever demonstrated low insertion loss bank of 7 nanoacoustic passband filters in the X-band. Most of the filters showcase fractional bandwidths above 3% and sub-dB loss per stage in an extremely compact form factor, enabling the manufacturing of filters and duplexers for the next generation of mobile handsets operating in the X-band and beyond.
Multistate structures in a hydrogen-bonded polycatenation non-covalent organic framework with diverse resistive switching behaviors
Authors: Chen Shimin , Ju Yan , Yang Yisi , Xiang Fahui , Yao Zizhu , Zhang Hao , Li Yunbin , Zhang Yongfan , Xiang Shengchang , Chen Banglin , Zhang Zhangjing 
Published: January 2024

AbstractThe inherent structural flexibility and reversibility of non-covalent organic frameworks have enabled them to exhibit switchable multistate structures under external stimuli, providing great potential in the field of resistive switching (RS), but not well explored yet. Herein, we report the 0D+1D hydrogen-bonded polycatenation non-covalent organic framework (HOF-FJU-52), exhibiting diverse and reversible RS behaviors with the high performance. Triggered by the external stimulus of electrical field E at room temperature, HOF-FJU-52 has excellent resistive random-access memory (RRAM) behaviors, comparable to the state-of-the-art materials. When cooling down below 200 K, it was transferred to write-once-read-many-times memory (WORM) behaviors. The two memory behaviors exhibit reversibility on a single crystal device through the temperature changes. The RS mechanism of this non-covalent organic framework has been deciphered at the atomic level by the detailed single-crystal X-ray diffraction analyses, demonstrating that the structural dual-flexibility both in the asymmetric hydrogen bonded dimers within the 0D loops and in the infinite π–π stacking column between the loops and chains contribute to reversible structure transformations between multi-states and thus to its dual RS behaviors.
Secreted IgM modulates IL-10 expression in B cells
Authors: McGettigan Shannon Eileen , Aira Lazaro Emilio , Kumar Gaurav , Ballet Romain , Butcher Eugene C. , Baumgarth Nicole , Debes Gudrun F. 
Published: January 2024

AbstractIL-10+ B cells are critical for immune homeostasis and restraining immune responses in infection, cancer, and inflammation; however, the signals that govern IL-10+ B cell differentiation are ill-defined. Here we find that IL-10+ B cells expand in mice lacking secreted IgM ((s)IgM–/–) up to 10-fold relative to wildtype (WT) among all major B cell and regulatory B cell subsets. The IL-10+ B cell increase is polyclonal and presents within 24 hours of birth. In WT mice, sIgM is produced prenatally and limits the expansion of IL-10+ B cells. Lack of the high affinity receptor for sIgM, FcμR, in B cells translates into an intermediate IL-10+ B cell phenotype relative to WT or sIgM–/– mice. Our study thus shows that sIgM regulates IL-10 programming in B cells in part via B cell-expressed FcμR, thereby revealing a function of sIgM in regulating immune homeostasis.
Increasing tropical cyclone intensity in the western North Pacific partly driven by warming Tibetan Plateau
Authors: Xu Jing , Zhao Ping , Chan Johnny C. L. , Shi Mingyuan , Yang Chi , Zhao Siyu , Xu Ying , Chen Junming , Du Ling , Wu Jie , Ye Jiaxin , Xing Rui , Wang Huimei , Liu Lu 
Published: January 2024

AbstractThe increase in intense tropical cyclone (TC) activity across the western North Pacific (WNP) has often been attributed to a warming ocean. However, it is essential to recognize that the tropical WNP region already boasts high temperatures, and a marginal increase in oceanic warmth due to global warming does not exert a significant impact on the potential for TCs to intensify. Here we report that the weakened vertical wind shear is the primary driver behind the escalating trend in TC intensity within the summer monsoon trough of the tropical WNP, while local ocean surface and subsurface thermodynamic factors play a minor role. Through observational diagnoses and numerical simulations, we establish that this weakening of the vertical wind shear is very likely due to the increase in temperature of the Tibetan Plateau. With further warming of the Tibetan Plateau under the Representative Concentration Pathway 4.5 scenario, the projected TCs will likely become stronger.
MADS1-regulated lemma and awn development benefits barley yield
Authors: Zhang Yueya , Shen Chaoqun , Li Gang , Shi Jin , Yuan Yajing , Ye Lingzhen , Song Qingfeng , Shi Jianxin , Zhang Dabing 
Published: January 2024

AbstractFloral organ shape and size in cereal crops can affect grain size and yield, so genes that regulate their development are promising breeding targets. The lemma, which protects inner floral organs, can physically constrain grain growth; while the awn, a needle-like extension of the lemma, creates photosynthate to developing grain. Although several genes and modules controlling grain size and awn/lemma growth in rice have been characterized, these processes, and the relationships between them, are not well understood for barley and wheat. Here, we demonstrate that the barley E-class gene HvMADS1 positively regulates awn length and lemma width, affecting grain size and weight. Cytological data indicates that HvMADS1 promotes awn and lemma growth by promoting cell proliferation, while multi-omics data reveals that HvMADS1 target genes are associated with cell cycle, phytohormone signaling, and developmental processes. We define two potential targets of HvMADS1 regulation, HvSHI and HvDL, whose knockout mutants mimic awn and/or lemma phenotypes of mads1 mutants. Additionally, we demonstrate that HvMADS1 interacts with APETALA2 (A-class) to synergistically activate downstream genes in awn/lemma development in barley. Notably, we find that MADS1 function remains conserved in wheat, promoting cell proliferation to increase awn length. These findings extend our understanding of MADS1 function in floral organ development and provide insights for Triticeae crop improvement strategies.
Nuclear Hsp104 safeguards the dormant translation machinery during quiescence
Authors: Kohler Verena , Kohler Andreas , Berglund Lisa Larsson , Hao Xinxin , Gersing Sarah , Imhof Axel , Nyström Thomas , Höög Johanna L. , Ott Martin , Andréasson Claes , Büttner Sabrina 
Published: January 2024

AbstractThe resilience of cellular proteostasis declines with age, which drives protein aggregation and compromises viability. The nucleus has emerged as a key quality control compartment that handles misfolded proteins produced by the cytosolic protein biosynthesis system. Here, we find that age-associated metabolic cues target the yeast protein disaggregase Hsp104 to the nucleus to maintain a functional nuclear proteome during quiescence. The switch to respiratory metabolism and the accompanying decrease in translation rates direct cytosolic Hsp104 to the nucleus to interact with latent translation initiation factor eIF2 and to suppress protein aggregation. Hindering Hsp104 from entering the nucleus in quiescent cells results in delayed re-entry into the cell cycle due to compromised resumption of protein synthesis. In sum, we report that cytosolic-nuclear partitioning of the Hsp104 disaggregase is a critical mechanism to protect the latent protein synthesis machinery during quiescence in yeast, ensuring the rapid restart of translation once nutrients are replenished.
Radiomic tractometry reveals tract-specific imaging biomarkers in white matter
Authors: Neher Peter , Hirjak Dusan , Maier-Hein Klaus 
Published: January 2024

AbstractTract-specific microstructural analysis of the brain’s white matter (WM) using diffusion MRI has been a driver for neuroscientific discovery with a wide range of applications. Tractometry enables localized tissue analysis along tracts but relies on bare summary statistics and reduces complex image information along a tract to few scalar values, and so may miss valuable information. This hampers the applicability of tractometry for predictive modelling. Radiomics is a promising method based on the analysis of numerous quantitative image features beyond what can be visually perceived, but has not yet been used for tract-specific analysis of white matter. Here we introduce radiomic tractometry (RadTract) and show that introducing rich radiomics-based feature sets into the world of tractometry enables improved predictive modelling while retaining the localization capability of tractometry. We demonstrate its value in a series of clinical populations, showcasing its performance in diagnosing disease subgroups in different datasets, as well as estimation of demographic and clinical parameters. We propose that RadTract could spark the establishment of a new generation of tract-specific imaging biomarkers with benefits for a range of applications from basic neuroscience to medical research.
A weakly solvating electrolyte towards practical rechargeable aqueous zinc-ion batteries
Authors: Shi Xin , Xie Jinhao , Wang Jin , Xie Shilei , Yang Zujin , Lu Xihong 
Published: January 2024

AbstractStructure deterioration and side reaction, which originated from the solvated H2O, are the main constraints for the practical deployment of both cathode and anode in aqueous Zn-ion batteries. Here we formulate a weakly solvating electrolyte to reduce the solvating power of H2O and strengthen the coordination competitiveness of SO42− to Zn2+ over H2O. Experiment results and theoretical simulations demonstrate that the water-poor solvation structure of Zn2+ is achieved, which can (i) substantially eliminate solvated-H2O-mediated undesirable side reactions on the Zn anode. (ii) boost the desolvation kinetics of Zn2+ and suppress Zn dendrite growth as well as structure aberration of the cathode. Remarkably, the synergy of these two factors enables long-life full cells including Zn/NaV3O8·1.5H2O, Zn/MnO2 and Zn/CoFe(CN)6 cells. More importantly, practical rechargeable AA-type Zn/NVO cells are assembled, which present a capacity of 101.7 mAh and stability of 96.1% capacity retention after 30 cycles at 0.66 C.
Multiresistance states in ferro- and antiferroelectric trilayer boron nitride
Authors: Lv Ming , Wang Jiulong , Tian Ming , Wan Neng , Tong Wenyi , Duan Chungang , Xue Jiamin 
Published: January 2024

AbstractStacking two atomic layers together can induce interlayer (sliding) ferroelectricity that is absent in their naturally occurring crystal forms. With the flexibility of two-dimensional materials, more layers could be assembled to give rise to even richer polarization states. Here, we show that three-layer boron nitride can host ferro- and antiferroelectric domains in the same sample. When used as a tunneling junction, the polarization of these domains could be switched in a layer-by-layer procedure, producing multiple resistance states. Theoretical investigation reveals an important role played by the interaction between the trilayer boron nitride and graphene substrate. These findings reveal the great potential and unique properties of 2D sliding ferroelectric materials.