bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comp34 displays potent preclinical antitumor efficacy in triple-negative breast cancer via inhibition of NUDT3-AS4, a novel oncogenic long noncoding RNA
Authors: Hao Qiongyu , Wang Piwen , Dutta Pranabananda , Chung Seyung , Li Qun , Wang Kun , Li Jieqing , Cao Wei , Deng Wenhong , Geng Qing , Schrode Katrina , Shaheen Magda , Wu Ke , Zhu Donghui , Chen Qiao-Hong , Chen Guanglin , Elshimali Yahya , Vadgama Jay , Wu Yong 
Published: December 2020

AbstractThe abnormal PI3K/AKT/mTOR pathway is one of the most common genomic abnormalities in breast cancers including triple-negative breast cancer (TNBC), and pharmacologic inhibition of these aberrations has shown activity in TNBC patients. Here, we designed and identified a small-molecule Comp34 that suppresses both AKT and mTOR protein expression and exhibits robust cytotoxicity towards TNBC cells but not nontumorigenic normal breast epithelial cells. Mechanically, long noncoding RNA (lncRNA) AL354740.1-204 (also named as NUDT3-AS4) acts as a microRNA sponge to compete with AKT1/mTOR mRNAs for binding to miR-99s, leading to decrease in degradation of AKT1/mTOR mRNAs and subsequent increase in AKT1/mTOR protein expression. Inhibition of lncRNA-NUDT3-AS4 and suppression of the NUDT3-AS4/miR-99s association contribute to Comp34-affected biologic pathways. In addition, Comp34 alone is effective in cells with secondary resistance to rapamycin, the best-known inhibitor of mTOR, and displays a greater in vivo antitumor efficacy and lower toxicity than rapamycin in TNBC xenografted models. In conclusion, NUDT3-AS4 may play a proproliferative role in TNBC and be considered a relevant therapeutic target, and Comp34 presents promising activity as a single agent to inhibit TNBC through regulation of NUDT3-AS4 and miR-99s.
mtDNA-STING pathway promotes necroptosis-dependent enterocyte injury in intestinal ischemia reperfusion
Authors: Zhang Xufei , Wu Jie , Liu Qinjie , Li Xuanheng , Li Sicheng , Chen Jun , Hong Zhiwu , Wu Xiuwen , Zhao Yun , Ren Jianan 
Published: December 2020

AbstractIntestinal ischemia reperfusion (I/R) injury is the important pathogenesis for acute intestinal barrier disruption. The STING signaling is associated with gut homeostasis and barrier integrity. However, the biological function and regulation of STING signaling in intestinal I/R injury are not yet fully understood. As the ligand of STING signaling, the mitochondrial DNA (mtDNA) has been found to be associated with necroptosis. It still remains unknown whether mtDNA-STING signaling triggers intestinal necroptosis in intestinal I/R injury. We found that circulating RIPK3 was significantly increased and had a positive correlation with markers of enterocyte injury in critically ill patients with intestinal injury. Moreover, the levels of circulating mtDNA were also associated with the levels of circulating RIPK3. To explore the relationship between mtDNA and intestinal necroptosis, mice were treated with the intraperitoneal injection of mtDNA, and necroptosis signaling was remarkably activated and the inhibition of necroptosis alleviated mtDNA-induced intestinal injury. Furthermore, STING knockout mice showed an alleviated intestinal necroptosis. In intestinal I/R injury, mtDNA was released from IECs and necroptosis was also triggered, companied with a significant decrease of RIPK3 in the intestine. STING knockout mice markedly attenuated intestinal necroptosis and intestinal I/R injury. Finally, we found that mtDNA-mediated STING signaling triggered necroptosis through synergistic IFN and TNF-α signaling in primary IECs. Our results indicated that mtDNA-STING signaling can contribute to intestinal I/R injury by promoting IEC necroptosis. STING-mediated both IFN and TNF-α signaling can trigger intestinal nercroptosis.
Loss of the tumor suppressor BTG3 drives a pro-angiogenic tumor microenvironment through HIF-1 activation
Authors: Cheng Yu-Che , Chiang Hsin-Yi , Cheng Shang-Jung , Chang Hung-Wei , Li Yi-Ju , Shieh Sheau-Yann 
Published: December 2020

AbstractB-cell translocation gene 3 (BTG3) is a member of the antiproliferative BTG gene family and is a downstream target of p53. Here, we show that senescence triggered by BTG3 depletion was accompanied by a secretome enriched with cytokines, growth factors, and matrix-remodeling enzymes, which could promote angiogenesis and cell scattering in vitro. We present evidence that at least part of these activities can be explained by elevated HIF-1α activity. Mechanistically, the BTG3 C-terminal domain competes with the coactivator p300 for binding the HIF-1α transactivation domain. The angiogenic promoting effect of BTG3 knockdown was largely diminished upon co-depletion of HIF-1α, indicating that HIF-1α is a major downstream target of BTG3 in the control of angiogenesis. In vivo, ectopic expression of BTG3 suppresses angiogenesis in xenograft tumors; and syngenic tumor growth and metastasis were enhanced in Btg3-null mice. Moreover, analysis of clinical datasets revealed that a higher BTG3/VEGFA expression ratio correlates with improved patient survival in a number of cancer types. Taken together, our findings highlight the non-autonomous regulation of tumor microenvironment by BTG3 while suppressing tumor progression.
SEMG1/2 augment energy metabolism of tumor cells
Authors: Shuvalov Oleg , Kizenko Alyona , Petukhov Alexey , Fedorova Olga , Daks Alexandra , Bottrill Andrew , Snezhkina Anastasiya V. , Kudryavtseva Anna V. , Barlev Nikolai 
Published: December 2020

AbstractSEMG1 and SEMG2 genes belong to the family of cancer-testis antigens (CTAs), whose expression normally is restricted to male germ cells but is often restored in various malignancies. High levels of SEMG1 and SEMG2 expression are detected in prostate, renal, and lung cancer as well as hemoblastosis. However, the functional importance of both SEMGs proteins in human neoplasms is still largely unknown. In this study, by using a combination of the bioinformatics and various cellular and molecular assays, we have demonstrated that SEMG1 and SEMG2 are frequently expressed in lung cancer clinical samples and cancer cell lines of different origins and are negatively associated with the survival rate of cancer patients. Using the pull-down assay followed by LC-MS/MS mass-spectrometry, we have identified 119 proteins associated with SEMG1 and SEMG2. Among the SEMGs interacting proteins we noticed two critical glycolytic enzymes-pyruvate kinase M2 (PKM2) and lactate dehydrogenase A (LDHA). Importantly, we showed that SEMGs increased the protein level and activity of both PKM2 and LDHA. Further, both SEMGs increased the membrane mitochondrial potential (MMP), glycolysis, respiration, and ROS production in several cancer cell lines. Taken together, these data provide first evidence that SEMGs can up-regulate the energy metabolism of cancer cells, exemplifying their oncogenic features.
Importance of tailoring lattice strain in halide perovskite crystals
Authors: Kim Hui-Seon , Park Nam-Gyu 
Published: December 2020

AbstractIn this review paper, the residual strain of a polycrystalline halide perovskite film is systematically studied based on its structural inhomogeneity, which is closely correlated to the local carrier dynamics caused by a modulated electronic band structure. Long-range collective strain ordering is responsible for the overall structural properties, consequently determining the optoelectronic properties of the perovskite film. Notably, the perovskite phase stability is strongly affected by the internal strain, favoring a lower energy state. The important parameters affecting the residual strain in a real perovskite film, ranging from thermal stress to lattice mismatch and compositional inhomogeneity, are subsequently introduced along with their impacts on the optoelectronic properties and/or the stability of the crystals.
SLAMF7 and IL-6R define distinct cytotoxic versus helper memory CD8+ T cells
Authors: Loyal Lucie , Warth Sarah , Jürchott Karsten , Mölder Felix , Nikolaou Christos , Babel Nina , Nienen Mikalai , Durlanik Sibel , Stark Regina , Kruse Beate , Frentsch Marco , Sabat Robert , Wolk Kerstin , Thiel Andreas 
Published: December 2020

AbstractThe prevailing ‘division of labor’ concept in cellular immunity is that CD8+ T cells primarily utilize cytotoxic functions to kill target cells, while CD4+ T cells exert helper/inducer functions. Multiple subsets of CD4+ memory T cells have been characterized by distinct chemokine receptor expression. Here, we demonstrate that analogous CD8+ memory T-cell subsets exist, characterized by identical chemokine receptor expression signatures and controlled by similar generic programs. Among them, Tc2, Tc17 and Tc22 cells, in contrast to Tc1 and Tc17 + 1 cells, express IL-6R but not SLAMF7, completely lack cytotoxicity and instead display helper functions including CD40L expression. CD8+ helper T cells exhibit a unique TCR repertoire, express genes related to skin resident memory T cells (TRM) and are altered in the inflammatory skin disease psoriasis. Our findings reveal that the conventional view of CD4+ and CD8+ T cell capabilities and functions in human health and disease needs to be revised.
One-dimensional confinement and width-dependent bandgap formation in epitaxial graphene nanoribbons
Authors: Karakachian Hrag , Nguyen T. T. Nhung , Aprojanz Johannes , Zakharov Alexei A. , Yakimova Rositsa , Rosenzweig Philipp , Polley Craig M. , Balasubramanian Thiagarajan , Tegenkamp Christoph , Power Stephen R. , Starke Ulrich 
Published: December 2020

AbstractThe ability to define an off state in logic electronics is the key ingredient that is impossible to fulfill using a conventional pristine graphene layer, due to the absence of an electronic bandgap. For years, this property has been the missing element for incorporating graphene into next-generation field effect transistors. In this work, we grow high-quality armchair graphene nanoribbons on the sidewalls of 6H-SiC mesa structures. Angle-resolved photoelectron spectroscopy (ARPES) and scanning tunneling spectroscopy measurements reveal the development of a width-dependent semiconducting gap driven by quantum confinement effects. Furthermore, ARPES demonstrates an ideal one-dimensional electronic behavior that is realized in a graphene-based environment, consisting of well-resolved subbands, dispersing and non-dispersing along and across the ribbons respectively. Our experimental findings, coupled with theoretical tight-binding calculations, set the grounds for a deeper exploration of quantum confinement phenomena and may open intriguing avenues for new low-power electronics.
Direct observation of the formation and stabilization of metallic nanoparticles on carbon supports
Authors: Huang Zhennan , Yao Yonggang , Pang Zhenqian , Yuan Yifei , Li Tangyuan , He Kun , Hu Xiaobing , Cheng Jian , Yao Wentao , Liu Yuzi , Nie Anmin , Sharifi-Asl Soroosh , Cheng Meng , Song Boao , Amine Khalil , Lu Jun , Li Teng , Hu Liangbing , Shahbazian-Yassar Reza 
Published: December 2020

AbstractDirect formation of ultra-small nanoparticles on carbon supports by rapid high temperature synthesis method offers new opportunities for scalable nanomanufacturing and the synthesis of stable multi-elemental nanoparticles. However, the underlying mechanisms affecting the dispersion and stability of nanoparticles on the supports during high temperature processing remain enigmatic. In this work, we report the observation of metallic nanoparticles formation and stabilization on carbon supports through in situ Joule heating method. We find that the formation of metallic nanoparticles is associated with the simultaneous phase transition of amorphous carbon to a highly defective turbostratic graphite (T-graphite). Molecular dynamic (MD) simulations suggest that the defective T-graphite provide numerous nucleation sites for the nanoparticles to form. Furthermore, the nanoparticles partially intercalate and take root on edge planes, leading to high binding energy on support. This interaction between nanoparticles and T-graphite substrate strengthens the anchoring and provides excellent thermal stability to the nanoparticles. These findings provide mechanistic understanding of rapid high temperature synthesis of metal nanoparticles on carbon supports and the origin of their stability.
Ferroptotic damage promotes pancreatic tumorigenesis through a TMEM173/STING-dependent DNA sensor pathway
Authors: Dai Enyong , Han Leng , Liu Jiao , Xie Yangchun , Zeh Herbert J. , Kang Rui , Bai Lulu , Tang Daolin 
Published: December 2020

AbstractFerroptosis is a more recently recognized form of cell death that relies on iron-mediated oxidative damage. Here, we evaluate the impact of high-iron diets or depletion of Gpx4, an antioxidant enzyme reported as an important ferroptosis suppressor, in the pancreas of mice with cerulean- or L-arginine-induced pancreatitis, and in an oncogenic Kras murine model of spontaneous pancreatic ductal adenocarcinoma (PDAC). We find that either high-iron diets or Gpx4 depletion promotes 8-OHG release and thus activates the TMEM173/STING-dependent DNA sensor pathway, which results in macrophage infiltration and activation during Kras-driven PDAC in mice. Consequently, the administration of liproxstatin-1 (a ferroptosis inhibitor), clophosome-mediated macrophage depletion, or pharmacological and genetic inhibition of the 8-OHG-TMEM173 pathway suppresses Kras-driven pancreatic tumorigenesis in mice. GPX4 is also a prognostic marker in patients with PDAC. These findings provide pathological and mechanistic insights into ferroptotic damage in PDAC tumorigenesis in mice.
D-mannose suppresses macrophage IL-1β production
Authors: Torretta Simone , Scagliola Alessandra , Ricci Luisa , Mainini Francesco , Di Marco Sabrina , Cuccovillo Ivan , Kajaste-Rudnitski Anna , Sumpton David , Ryan Kevin M. , Cardaci Simone 
Published: December 2020

AbstractD-mannose is a monosaccharide approximately a hundred times less abundant than glucose in human blood. Previous studies demonstrated that supraphysiological levels of D-mannose inhibit tumour growth and stimulate regulatory T cell differentiation. It is not known whether D-mannose metabolism affects the function of non-proliferative cells, such as inflammatory macrophages. Here, we show that D-mannose suppresses LPS-induced macrophage activation by impairing IL-1β production. In vivo, mannose administration improves survival in a mouse model of LPS-induced endotoxemia as well as decreases progression in a mouse model of DSS-induced colitis. Phosphomannose isomerase controls response of LPS-activated macrophages to D-mannose, which impairs glucose metabolism by raising intracellular mannose-6-phosphate levels. Such alterations result in the suppression of succinate-mediated HIF-1α activation, imposing a consequent reduction of LPS-induced Il1b expression. Disclosing an unrecognized metabolic hijack of macrophage activation, our study points towards safe D-mannose utilization as an effective intervention against inflammatory conditions.
A partially self-regenerating synthetic cell
Authors: Lavickova Barbora , Laohakunakorn Nadanai , Maerkl Sebastian J. 
Published: December 2020

AbstractSelf-regeneration is a fundamental function of all living systems. Here we demonstrate partial molecular self-regeneration in a synthetic cell. By implementing a minimal transcription-translation system within microfluidic reactors, the system is able to regenerate essential protein components from DNA templates and sustain synthesis activity for over a day. By quantitating genotype-phenotype relationships combined with computational modeling we find that minimizing resource competition and optimizing resource allocation are both critically important for achieving robust system function. With this understanding, we achieve simultaneous regeneration of multiple proteins by determining the required DNA ratios necessary for sustained self-regeneration. This work introduces a conceptual and experimental framework for the development of a self-replicating synthetic cell.
Aberrant interaction of FUS with the U1 snRNA provides a molecular mechanism of FUS induced amyotrophic lateral sclerosis
Authors: Jutzi Daniel , Campagne Sébastien , Schmidt Ralf , Reber Stefan , Mechtersheimer Jonas , Gypas Foivos , Schweingruber Christoph , Colombo Martino , von Schroetter Christine , Loughlin Fionna E. , Devoy Anny , Hedlund Eva , Zavolan Mihaela , Allain Frédéric H.-T. , Ruepp Marc-David 
Published: December 2020

AbstractMutations in the RNA-binding protein Fused in Sarcoma (FUS) cause early-onset amyotrophic lateral sclerosis (ALS). However, a detailed understanding of central RNA targets of FUS and their implications for disease remain elusive. Here, we use a unique blend of crosslinking and immunoprecipitation (CLIP) and NMR spectroscopy to identify and characterise physiological and pathological RNA targets of FUS. We find that U1 snRNA is the primary RNA target of FUS via its interaction with stem-loop 3 and provide atomic details of this RNA-mediated mode of interaction with the U1 snRNP. Furthermore, we show that ALS-associated FUS aberrantly contacts U1 snRNA at the Sm site with its zinc finger and traps snRNP biogenesis intermediates in human and murine motor neurons. Altogether, we present molecular insights into a FUS toxic gain-of-function involving direct and aberrant RNA-binding and strengthen the link between two motor neuron diseases, ALS and spinal muscular atrophy (SMA).
Depth-dependent valence stratification driven by oxygen redox in lithium-rich layered oxide
Authors: Zhang Jin , Wang Qinchao , Li Shaofeng , Jiang Zhisen , Tan Sha , Wang Xuelong , Zhang Kai , Yuan Qingxi , Lee Sang-Jun , Titus Charles J. , Irwin Kent D. , Nordlund Dennis , Lee Jun-Sik , Pianetta Piero , Yu Xiqian , Xiao Xianghui , Yang Xiao-Qing , Hu Enyuan , Liu Yijin 
Published: December 2020

AbstractLithium-rich nickel-manganese-cobalt (LirNMC) layered material is a promising cathode for lithium-ion batteries thanks to its large energy density enabled by coexisting cation and anion redox activities. It however suffers from a voltage decay upon cycling, urging for an in-depth understanding of the particle-level structure and chemical complexity. In this work, we investigate the Li1.2Ni0.13Mn0.54Co0.13O2 particles morphologically, compositionally, and chemically in three-dimensions. While the composition is generally uniform throughout the particle, the charging induces a strong depth dependency in transition metal valence. Such a valence stratification phenomenon is attributed to the nature of oxygen redox which is very likely mostly associated with Mn. The depth-dependent chemistry could be modulated by the particles’ core-multi-shell morphology, suggesting a structural-chemical interplay. These findings highlight the possibility of introducing a chemical gradient to address the oxygen-loss-induced voltage fade in LirNMC layered materials.
Receptor-targeted engineered probiotics mitigate lethal Listeria infection
Authors: Drolia Rishi , Amalaradjou Mary Anne Roshni , Ryan Valerie , Tenguria Shivendra , Liu Dongqi , Bai Xingjian , Xu Luping , Singh Atul K. , Cox Abigail D. , Bernal-Crespo Victor , Schaber James A. , Applegate Bruce M. , Vemulapalli Ramesh , Bhunia Arun K. 
Published: December 2020

AbstractProbiotic bacteria reduce the intestinal colonization of pathogens. Yet, their use in preventing fatal infection caused by foodborne Listeria monocytogenes (Lm), is inconsistent. Here, we bioengineered Lactobacillusprobiotics (BLP) to express the Listeria adhesion protein (LAP) from a non-pathogenic Listeria (L. innocua) and a pathogenic Listeria (Lm) on the surface of Lactobacillus casei. The BLP strains colonize the intestine, reduce Lm mucosal colonization and systemic dissemination, and protect mice from lethal infection. The BLP competitively excludes Lm by occupying the surface presented LAP receptor, heat shock protein 60 and ameliorates the Lm-induced intestinal barrier dysfunction by blocking the nuclear factor-κB and myosin light chain kinase-mediated redistribution of the major epithelial junctional proteins. Additionally, the BLP increases intestinal immunomodulatory functions by recruiting FOXP3+T cells, CD11c+ dendritic cells and natural killer cells. Engineering a probiotic strain with an adhesion protein from a non-pathogenic bacterium provides a new paradigm to exclude pathogens and amplify their inherent health benefits.
A social engineering model for poverty alleviation
Authors: Chattopadhyay Amit K. , Kumar T. Krishna , Rice Iain 
Published: December 2020

AbstractPoverty, the quintessential denominator of a developing nation, has been traditionally defined against an arbitrary poverty line; individuals (or countries) below this line are deemed poor and those above it, not so! This has two pitfalls. First, absolute reliance on a single poverty line, based on basic food consumption, and not on total consumption distribution, is only a partial poverty index at best. Second, a single expense descriptor is an exogenous quantity that does not evolve from income-expenditure statistics. Using extensive income-expenditure statistics from India, here we show how a self-consistent endogenous poverty line can be derived from an agent-based stochastic model of market exchange, combining all expenditure modes (basic food, other food and non-food), whose parameters are probabilistically estimated using advanced Machine Learning tools. Our mathematical study establishes a consumption based poverty measure that combines labor, commodity, and asset market outcomes, delivering an excellent tool for economic policy formulation.
The erosion of biodiversity and biomass in the Atlantic Forest biodiversity hotspot
Authors: de Lima Renato A. F. , Oliveira Alexandre A. , Pitta Gregory R. , de Gasper André L. , Vibrans Alexander C. , Chave Jérôme , ter Steege Hans , Prado Paulo I. 
Published: December 2020

AbstractTropical forests are being deforested worldwide, and the remaining fragments are suffering from biomass and biodiversity erosion. Quantifying this erosion is challenging because ground data on tropical biodiversity and biomass are often sparse. Here, we use an unprecedented dataset of 1819 field surveys covering the entire Atlantic Forest biodiversity hotspot. We show that 83−85% of the surveys presented losses in forest biomass and tree species richness, functional traits, and conservation value. On average, forest fragments have 25−32% less biomass, 23−31% fewer species, and 33, 36, and 42% fewer individuals of late-successional, large-seeded, and endemic species, respectively. Biodiversity and biomass erosion are lower inside strictly protected conservation units, particularly in large ones. We estimate that biomass erosion across the Atlantic Forest remnants is equivalent to the loss of 55−70 thousand km2of forests or US$2.3−2.6 billion in carbon credits. These figures have direct implications on mechanisms of climate change mitigation.