bluuebunny/crossref_metadata_2025_split huggingface dataset:
ZNF32 promotes the self-renewal of colorectal cancer cells by regulating the LEPR-STAT3 signaling pathway
Authors: Li Jun , Li Xiaoan , Lan Lili , Sun Lin , Li Xuemei , Li Yaqi , Tian Yan , Zhang Tongqin , Zhou Yan , Mo Chunfen , Fu Xiangsheng 
Published: February 2022

AbstractDue to the self-renewal characteristics and tumorigenic abilities of cancer stem cells (CSCs), CSCs have been demonstrated to play vital roles in carcinogenesis and antitumor therapy. Our previous report found that Krüppel-like family members (KLFs) and zinc finger protein 32 (ZNF32) play oncogenic roles in carcinogenesis. However, the roles and mechanism of ZNF32 in CSCs are still unknown. Our study demonstrated that ZNF32 was highly expressed in colorectal CSCs, which promoted their self-renewal capacity and tumorigenicity. Overexpression of ZNF32 in colorectal cancer (CRC) cells increased their self-renewal capacity. Furthermore, we identified the leptin receptor (LEPR) as the downstream target gene of ZNF32 and verified that the ZNF32-mediated regulation of CRC self-renewal is achieved via the LEPR- signal transducer and activator of transcription 3 (STAT3) pathway. Moreover, ZNF32 regulated the expression of SOX2, a core transcription factor in stem cells. Finally, we demonstrated that ZNF32 and LEPR were positively correlated in CRC tissues. ZNF32 expression was negatively correlated with the prognosis of CRC patients. Therefore, therapeutically targeting the ZNF32-LEPR-STAT3 pathway in the clinic is tempting.
DGKZ promotes TGFβ signaling pathway and metastasis in triple-negative breast cancer by suppressing lipid raft-dependent endocytosis of TGFβR2
Authors: Zhao Yuanyuan , Sun Hefen , Li Xuan , Liu Qiqi , Liu Yang , Hou Yifeng , Jin Wei 
Published: February 2022

AbstractDiacylglycerol kinase ζ (DGKZ) is a diacylglycerol kinase that metabolizes diacylglycerol to yield phosphatidic acid, and its function in breast cancer progression remains unclear. In this study, via screening of a CRISPR-Cas9 knockout library containing lipid metabolic genes, DGKZ was identified as a potential prometastatic gene. We first confirmed that high DGKZ expression correlated with tumor progression and poor prognosis in patients. Next, knockout of DGKZ in triple-negative breast cancer cell lines were found to significantly inhibit metastatic behaviors in vitro and in vivo, whereas its overexpression increased the metastatic potential of cell lines. Mechanistic studies based on RNA sequencing and bioinformatic analysis indicated that DGKZ might regulate cell metastasis by promoting epithelial–mesenchymal transition via the transforming growth factor β (TGFβ) signaling pathway. Furthermore, we found that overexpression of DGKZ activated the TGFβ/TGFβR2/Smad3 signaling pathway by inhibiting the degradation of TGFβR2 through suppression of caveolin/lipid raft-dependent endocytosis. Moreover, the caveolin/lipid raft-dependent endocytosis of TGFβR2 was regulated by the metabolite phosphatidic acid, which might alter TGFβR2 partitioning in lipid rafts and nonlipid rafts by affecting the fluidity of the plasma membrane. These findings suggested that DGKZ is a novel promoter of metastasis and that it could be a potential prognostic indicator in patients with triple-negative breast cancer.
miR-582 negatively regulates pre-B cell proliferation and survival through targeting Hif1α and Rictor
Authors: Li Xinxin , Zhang Yufei , Zheng Minhua , Cao Xiuli , Guo Min , Gao Xiangyu , Han Hua 
Published: February 2022

AbstractB cell development in bone marrow (BM) is a multi-staged process involving pro-B, pre-B, immature B, and mature B cells, among which pre-B cells undergo vigorous proliferation, differentiation, apoptosis, and gene rearrangement. While several signaling pathways participate in pre-B cell development have been clarified, detailed intrinsic mechanisms regulating pre-B cell proliferation and survival have not been fully understood. In the current study, we report that miR-582 regulates pre-B cell proliferation and survival. miR-582 is enriched in pre-B cells. Deletion of miR-582 in mice expanded the BM pre-B cell population in a cell-autonomous manner as shown by competitive BM transplantation. We show that forced miR-582 overexpression inhibited pre-B cell proliferation and survival, whereas downregulation of miR-582 by siRNA significantly promoted pre-B cell proliferation and survival in vitro. We identified that Hif1α and Rictor are authentic targets of miR-582 in pre-B cells as shown by reporter assays. Moreover, miR-582 overexpression reduced the expression of Hif1α and its downstream molecule Glut1, as well as Rictor and mTORC2 activity as shown by attenuated AKT and FoxO1 phosphorylation, while miR-582 knockdown showed opposite effects. miR-582 knockdown-induced increases in pre-B proliferation and survival was abrogated by Hif1α and Rictor inhibitors. Together, miR-582 functions as a negative regulator of pre-B cell proliferation and survival by simultaneously targeting Hif1α and mTORC2 signaling that regulates metabolism in early B cell development.
cFLIP downregulation is an early event required for endoplasmic reticulum stress-induced apoptosis in tumor cells
Authors: Mora-Molina Rocío , Stöhr Daniela , Rehm Markus , López-Rivas Abelardo 
Published: February 2022

AbstractProtein misfolding or unfolding and the resulting endoplasmic reticulum (ER) stress frequently occur in highly proliferative tumors. How tumor cells escape cell death by apoptosis after chronic ER stress remains poorly understood. We have investigated in both two-dimensional (2D) cultures and multicellular tumor spheroids (MCTSs) the role of caspase-8 inhibitor cFLIP as a regulator of the balance between apoptosis and survival in colon cancer cells undergoing ER stress. We report that downregulation of cFLIP proteins levels is an early event upon treatment of 2D cultures of colon cancer cells with ER stress inducers, preceding TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2) upregulation, caspase-8 activation, and apoptosis. Maintaining high cFLIP levels during ER stress by ectopic expression of cFLIP markedly inhibits ER stress-induced caspase-8 activation and apoptosis. Conversely, cFLIP knockdown by RNA interference significantly accelerates caspase-8 activation and apoptosis upon ER stress. Despite activation of the proapoptotic PERK branch of the unfolded protein response (UPR) and upregulation of TRAIL-R2, MCTSs are markedly more resistant to ER stress than 2D cultures of tumor cells. Resistance of MCTSs to ER stress-induced apoptosis correlates with sustained cFLIPLexpression. Interestingly, resistance to ER stress-induced apoptosis is abolished in MCTSs generated from cFLIPLknockdown tumor cells. Overall, our results suggest that controlling cFLIP levels in tumors is an adaptive strategy to prevent tumor cell’s demise in the unfavorable conditions of the tumor microenvironment.
TNF antagonist sensitizes synovial fibroblasts to ferroptotic cell death in collagen-induced arthritis mouse models
Authors: Wu Jiao , Feng Zhuan , Chen Liang , Li Yong , Bian Huijie , Geng Jiejie , Zheng Zhao-Hui , Fu Xianghui , Pei Zhuo , Qin Yifei , Yang Liu , Zhao Yilin , Wang Ke , Chen Ruo , He Qian , Nan Gang , Jiang Xuejun , Chen Zhi-Nan , Zhu Ping 
Published: February 2022

AbstractFerroptosis is a nonapoptotic cell death process that requires cellular iron and the accumulation of lipid peroxides. In progressive rheumatoid arthritis (RA), synovial fibroblasts proliferate abnormally in the presence of reactive oxygen species (ROS) and elevated lipid oxidation. Here we show, using a collagen-induced arthritis (CIA) mouse model, that imidazole ketone erastin (IKE), a ferroptosis inducer, decreases fibroblast numbers in the synovium. Data from single-cell RNA sequencing further identify two groups of fibroblasts that have distinct susceptibility to IKE-induced ferroptosis, with the ferroptosis-resistant fibroblasts associated with an increased TNF-related transcriptome. Mechanistically, TNF signaling promotes cystine uptake and biosynthesis of glutathione (GSH) to protect fibroblasts from ferroptosis. Lastly, low dose IKE together with etanercept, a TNF antagonist, induce ferroptosis in fibroblasts and attenuate arthritis progression in the CIA model. Our results thus imply that the combination of TNF inhibitors and ferroptosis inducers may serve as a potential candidate for RA therapy.
The toposiomerase IIIalpha-RMI1-RMI2 complex orients human Bloom’s syndrome helicase for efficient disruption of D-loops
Authors: Harami Gábor M. , Pálinkás János , Seol Yeonee , Kovács Zoltán J. , Gyimesi Máté , Harami-Papp Hajnalka , Neuman Keir C. , Kovács Mihály 
Published: February 2022

AbstractHomologous recombination (HR) is a ubiquitous and efficient process that serves the repair of severe forms of DNA damage and the generation of genetic diversity during meiosis. HR can proceed via multiple pathways with different outcomes that may aid or impair genome stability and faithful inheritance, underscoring the importance of HR quality control. Human Bloom’s syndrome (BLM, RecQ family) helicase plays central roles in HR pathway selection and quality control via unexplored molecular mechanisms. Here we show that BLM’s multi-domain structural architecture supports a balance between stabilization and disruption of displacement loops (D-loops), early HR intermediates that are key targets for HR regulation. We find that this balance is markedly shifted toward efficient D-loop disruption by the presence of BLM’s interaction partners Topoisomerase IIIα-RMI1-RMI2, which have been shown to be involved in multiple steps of HR-based DNA repair. Our results point to a mechanism whereby BLM can differentially process D-loops and support HR control depending on cellular regulatory mechanisms.
Hydrodynamic manipulation of nano-objects by optically induced thermo-osmotic flows
Authors: Fränzl Martin , Cichos Frank 
Published: February 2022

AbstractManipulation of nano-objects at the microscale is of great technological importance for constructing new functional materials, manipulating tiny amounts of fluids, reconfiguring sensor systems, or detecting tiny concentrations of analytes in medical screening. Here, we show that hydrodynamic boundary flows enable the trapping and manipulation of nano-objects near surfaces. We trigger thermo-osmotic flows by modulating the van der Waals and double layer interactions at a gold-liquid interface with optically generated local temperature fields. The hydrodynamic flows, attractive van der Waals and repulsive double layer forces acting on the suspended nanoparticles enable precise nanoparticle positioning and guidance. A rapid multiplexing of flow fields permits the parallel manipulation of many nano-objects and the generation of complex flow fields. Our findings have direct implications for the field of plasmonic nanotweezers and other thermo-plasmonic trapping systems, paving the way for nanoscopic manipulation with boundary flows.
Highly selective cesium(I) capture under acidic conditions by a layered sulfide
Authors: Tang Jun-Hao , Jin Jian-Ce , Li Wei-An , Zeng Xi , Ma Wen , Li Ji-Long , Lv Tian-Tian , Peng Ying-Chen , Feng Mei-Ling , Huang Xiao-Ying 
Published: February 2022

AbstractRadiocesium remediation is desirable for ecological protection, human health and sustainable development of nuclear energy. Effective capture of Cs+ from acidic solutions is still challenging, mainly due to the low stability of the adsorbing materials and the competitive adsorption of protons. Herein, the rapid and highly selective capture of Cs+ from strongly acidic solutions is achieved by a robust K+-directed layered metal sulfide KInSnS4 (InSnS-1) that exhibits excellent acid and radiation resistance. InSnS-1 possesses high adsorption capacity for Cs+ and can serve as the stationary phase in ion exchange columns to effectively remove Cs+ from neutral and acidic solutions. The adsorption of Cs+ and H3O+ is monitored by single-crystal structure analysis, and thus the underlying mechanism of selective Cs+ capture from acidic solutions is elucidated at the molecular level.
Reversible transition between the polar and antipolar phases and its implications for wake-up and fatigue in HfO2-based ferroelectric thin film
Authors: Cheng Yan , Gao Zhaomeng , Ye Kun Hee , Park Hyeon Woo , Zheng Yonghui , Zheng Yunzhe , Gao Jianfeng , Park Min Hyuk , Choi Jung-Hae , Xue Kan-Hao , Hwang Cheol Seong , Lyu Hangbing 
Published: February 2022

AbstractAtomic-resolution Cs-corrected scanning transmission electron microscopy revealed local shifting of two oxygen positions (OI and OII) within the unit cells of a ferroelectric (Hf0.5Zr0.5)O2 thin film. A reversible transition between the polar Pbc21 and antipolar Pbca phases, where the crystal structures of the 180° domain wall of the Pbc21 phase and the unit cell structure of the Pbca phase were identical, was induced by applying appropriate cycling voltages. The critical field strength that determined whether the film would be woken up or fatigued was ~0.8 MV/cm, above or below which wake-up or fatigue was observed, respectively. Repeated cycling with sufficiently high voltages led to development of the interfacial nonpolar P42/nmc phase, which induced fatigue through the depolarizing field effect. The fatigued film could be rejuvenated by applying a slightly higher voltage, indicating that these transitions were reversible. These mechanisms are radically different from those of conventional ferroelectrics.
Internal Stark effect of single-molecule fluorescence
Authors: Vasilev Kirill , Doppagne Benjamin , Neuman Tomáš , Rosławska Anna , Bulou Hervé , Boeglin Alex , Scheurer Fabrice , Schull Guillaume 
Published: February 2022

AbstractThe optical properties of chromophores can be efficiently tuned by electrostatic fields generated in their close environment, a phenomenon that plays a central role for the optimization of complex functions within living organisms where it is known as internal Stark effect (ISE). Here, we realised an ISE experiment at the lowest possible scale, by monitoring the Stark shift generated by charges confined within a single chromophore on its emission energy. To this end, a scanning tunneling microscope (STM) functioning at cryogenic temperatures is used to sequentially remove the two central protons of a free-base phthalocyanine chromophore deposited on a NaCl-covered Ag(111) surface. STM-induced fluorescence measurements reveal spectral shifts that are associated to the electrostatic field generated by the internal charges remaining in the chromophores upon deprotonation.
Arabidopsis guard cell chloroplasts import cytosolic ATP for starch turnover and stomatal opening
Authors: Lim Shey-Li , Flütsch Sabrina , Liu Jinhong , Distefano Luca , Santelia Diana , Lim Boon Leong 
Published: February 2022

AbstractStomatal opening requires the provision of energy in the form of ATP for proton pumping across the guard cell (GC) plasma membrane and for associated metabolic rearrangements. The source of ATP for GCs is a matter of ongoing debate that is mainly fuelled by controversies around the ability of GC chloroplasts (GCCs) to perform photosynthesis. By imaging compartment-specific fluorescent ATP and NADPH sensor proteins in Arabidopsis, we show that GC photosynthesis is limited and mitochondria are the main source of ATP. Unlike mature mesophyll cell (MC) chloroplasts, which are impermeable to cytosolic ATP, GCCs import cytosolic ATP through NUCLEOTIDE TRANSPORTER (NTT) proteins. GCs from ntt mutants exhibit impaired abilities for starch biosynthesis and stomatal opening. Our work shows that GCs obtain ATP and carbohydrates via different routes from MCs, likely to compensate for the lower chlorophyll contents and limited photosynthesis of GCCs.
Cerebral microcirculation mapped by echo particle tracking velocimetry quantifies the intracranial pressure and detects ischemia
Authors: Zhang Zeng , Hwang Misun , Kilbaugh Todd J. , Sridharan Anush , Katz Joseph 
Published: February 2022

AbstractAffecting 1.1‰ of infants, hydrocephalus involves abnormal accumulation of cerebrospinal fluid, resulting in elevated intracranial pressure (ICP). It is the leading cause for brain surgery in newborns, often causing long-term neurologic disabilities or even death. Since conventional invasive ICP monitoring is risky, early neurosurgical interventions could benefit from noninvasive techniques. Here we use clinical contrast-enhanced ultrasound (CEUS) imaging and intravascular microbubble tracking algorithms to map the cerebral blood flow in hydrocephalic pediatric porcine models. Regional microvascular perfusions are quantified by the cerebral microcirculation (CMC) parameter, which accounts for the concentration of micro-vessels and flow velocity in them. Combining CMC with hemodynamic parameters yields functional relationships between cortical micro-perfusion and ICP, with correlation coefficients exceeding 0.85. For cerebral ischemia cases, the nondimensionalized cortical micro-perfusion decreases by an order of magnitude when ICP exceeds 50% of the MAP. These findings suggest that CEUS-based CMC measurement is a plausible noninvasive method for assessing the ICP and detecting ischemia.
Circadian lipid and hepatic protein rhythms shift with a phase response curve different than melatonin
Authors: Kent Brianne A. , Rahman Shadab A. , St. Hilaire Melissa A. , Grant Leilah K. , Rüger Melanie , Czeisler Charles A. , Lockley Steven W. 
Published: February 2022

AbstractWhile studies suggest that light and feeding patterns can reset circadian rhythms in various metabolites, whether these shifts follow a predictable pattern is unknown. We describe the first phase response curves (PRC) for lipids and hepatic proteins in response to combined light and food stimuli. The timing of plasma rhythms was assessed by constant routine before and after exposure to a combined 6.5-hour blue light exposure and standard meal schedule, which was systematically varied by ~20° between individuals. We find that the rhythms shift according to a PRC, with generally greater shifts for lipids and liver proteins than for melatonin. PRC timing varies relative to the stimulus, with albumin and triglyceride PRCs peaking at a time similar to melatonin whereas the cholesterol and high-density lipoprotein PRCs are offset by ~12 h. These data have important implications for treating circadian misalignment in shiftworkers who consume meals and are exposed to light around the clock.
Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
Authors: Singh Dhiraj K. , Aladyeva Ekaterina , Das Shibali , Singh Bindu , Esaulova Ekaterina , Swain Amanda , Ahmed Mushtaq , Cole Journey , Moodley Chivonne , Mehra Smriti , Schlesinger Larry S. , Artyomov Maxim N. , Khader Shabaana A. , Kaushal Deepak 
Published: February 2022

AbstractEmergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi; peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR+CD68+CD163+SIGLEC1+macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor SARS-CoV-2 while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery.
The IGFBP3/TMEM219 pathway regulates beta cell homeostasis
Authors: D’Addio Francesca , Maestroni Anna , Assi Emma , Ben Nasr Moufida , Amabile Giovanni , Usuelli Vera , Loretelli Cristian , Bertuzzi Federico , Antonioli Barbara , Cardarelli Francesco , El Essawy Basset , Solini Anna , Gerling Ivan C. , Bianchi Cristina , Becchi Gabriella , Mazzucchelli Serena , Corradi Domenico , Fadini Gian Paolo , Foschi Diego , Markmann James F. , Orsi Emanuela , Škrha Jan , Camboni Maria Gabriella , Abdi Reza , James Shapiro A. M. , Folli Franco , Ludvigsson Johnny , Del Prato Stefano , Zuccotti Gianvincenzo , Fiorina Paolo 
Published: February 2022

AbstractLoss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients’ cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes.
Biophysical properties at patch scale shape the metabolism of biofilm landscapes
Authors: Depetris Anna , Tagliavini Giorgia , Peter Hannes , Kühl Michael , Holzner Markus , Battin Tom J. 
Published: February 2022

AbstractPhototrophic biofilms form complex spatial patterns in streams and rivers, yet, how community patchiness, structure and function are coupled and contribute to larger-scale metabolism remains unkown. Here, we combined optical coherence tomography with automated O2 microprofiling and amplicon sequencing in a flume experiment to show how distinct community patches interact with the hydraulic environment and how this affects the internal distribution of oxygen. We used numerical simulations to derive rates of community photosynthetic activity and respiration at the patch scale and use the obtained parameter to upscale from individual patches to the larger biofilm landscape. Our biofilm landscape approach revealed evidence of parallels in the structure-function coupling between phototrophic biofilms and their streambed habitat.