bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long non-coding RNA HOTAIR knockdown enhances radiosensitivity through regulating microRNA-93/ATG12 axis in colorectal cancer
Authors: Liu Yingqiang , Chen Xijuan , Chen Xiling , Liu Junqi , Gu Hao , Fan Ruitai , Ge Hong 
Published: March 2020

AbstractColorectal cancer (CRC) is a global healthcare problem. Radioresistance is a huge setback for CRC radiotherapy. In this text, the roles and molecular mechanisms of long non-coding RNA HOTAIR in CRC tumorigenesis and radioresistance were further investigated. ATG12 mRNA, HOTAIR, and microRNA-93 (miR-93) levels were measured by quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay. Protein levels of LC3 I, LC3 II, p62, ATG12, cleaved caspase 3, Bax, and Bcl-2 were detected by western blotting assay in cells and were examined by immunohistochemistry (IHC) assay in tissues. Cell survival fractions, viability, and apoptotic rates were determined by clonogenic survival assay, CCK-8 assay, and flow cytometry analysis, respectively. The relationships of HOTAIR, miR-93, and ATG12 were tested by bioinformatics analysis and luciferase reporter assay. Mouse xenograft tumor models were established to investigate the influence of HOTAIR knockdown on CRC radioresistance in vivo. We found that HOTAIR expression was markedly upregulated in plasma from CRC patients after radiotherapy and CRC cells after irradiation. HOTAIR knockdown, miR-93 overexpression, or ATG12 silencing weakened cell viability, induced cell apoptosis, inhibited cell autophagy, and enhanced cell radiosensitivity in CRC. HOTAIR exerted its functions by downregulating miR-93. Moreover, HOTAIR functioned as a molecular sponge of miR-93 to regulate ATG12 expression. ATG12 protein expression was markedly upregulated and associated with miR-93 and HOTAIR expression in CRC tissues. Furthermore, HOTAIR knockdown enhanced radiosensitivity of CRC xenograft tumors by regulating miR-93/ATG12 axis. In conclusion, HOTAIR knockdown potentiated radiosensitivity through regulating miR-93/ATG12 axis in CRC, further elucidating the roles and molecular basis of HOTAIR in CRC radioresistance.
Metformin inhibits IL-1β secretion via impairment of NLRP3 inflammasome in keratinocytes: implications for preventing the development of psoriasis
Authors: Tsuji Gaku , Hashimoto-Hachiya Akiko , Yen Vu Hai , Takemura Masaki , Yumine Ayako , Furue Kazuhisa , Furue Masutaka , Nakahara Takeshi 
Published: March 2020

AbstractPsoriasis is a systemic inflammatory disease significantly associated with comorbidities including type 2 diabetes mellitus (T2DM). Metformin is utilized as a first-line agent for treating T2DM. Although metformin reportedly inhibits mature IL-1β secretion via NLRP3 inflammasome in macrophages of T2DM patients, it remains unclear whether it affects skin inflammation in psoriasis. To test this, we analysed normal human epidermal keratinocytes (NHEKs), a major skin component, stimulated with the key mediators of psoriasis development, TNF-α and IL-17A. This stimulation induced the upregulation of pro-IL-1β mRNA and protein levels, and subsequently mature IL-1β secretion, which was inhibited by metformin treatment. To further reveal the mechanism involved, we examined how metformin treatment affected NLRP3 inflammasome activated by TNF-α and IL-17A stimulation. We found that this treatment downregulated caspase-1 expression, a key mediator of NLRP3 inflammasome. Furthermore, inhibitors of AMPK and SIRT1 abrogated the downregulation of caspase-1 induced by metformin treatment, indicating that AMPK and SIRT1 are essential for the inhibitory effect on NLRP3 inflammasome in NHEKs. As IL-1β stimulation induced upregulation of IL-36γ, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels in NHEKs, we examined whether metformin treatment affects such gene expression. Metformin treatment inhibited upregulation of IL-36γ, CXCL1, CXCL2, CCL20, S100A7, S100A8 and S100A9 mRNA and protein levels induced by TNF-α and IL-17A stimulation. Finally, we examined whether metformin administration affected psoriasis development in an imiquimod-induced mouse psoriasis model. Oral metformin treatment significantly decreased ear thickness, epidermal hyperplasia and inflammatory cell infiltration. A cytokine profile in the epidermis under metformin treatment showed that IL-1β, Cxcl1, Cxcl2, S100a7, S100a8 and S100A9 mRNA levels were downregulated compared with control levels. These results indicate that metformin administration prevented psoriasis development in vivo. Collectively, our findings suggest that metformin-mediated anti-psoriatic effects on the skin have the potential for treating psoriasis in T2DM patients.
Targeting immunometabolism as an anti-inflammatory strategy
Authors: Pålsson-McDermott Eva M. , O’Neill Luke A. J. 
Published: March 2020

AbstractThe growing field of immunometabolism has taught us how metabolic cellular reactions and processes not only provide a means to generate ATP and biosynthetic precursors, but are also a way of controlling immunity and inflammation. Metabolic reprogramming of immune cells is essential for both inflammatory as well as anti-inflammatory responses. Four anti-inflammatory therapies, DMF, Metformin, Methotrexate and Rapamycin all work by affecting metabolism and/or regulating or mimicking endogenous metabolites with anti-inflammatory effects. Evidence is emerging for the targeting of specific metabolic events as a strategy to limit inflammation in different contexts. Here we discuss these recent developments and speculate on the prospect of targeting immunometabolism in the effort to develop novel anti-inflammatory therapeutics. As accumulating evidence for roles of an intricate and elaborate network of metabolic processes, including lipid, amino acid and nucleotide metabolism provides key focal points for developing new therapies, we here turn our attention to glycolysis and the TCA cycle to provide examples of how metabolic intermediates and enzymes can provide potential novel therapeutic targets.
The discovery of dynamic chiral anomaly in a Weyl semimetal NbAs
Authors: Yuan Xiang , Zhang Cheng , Zhang Yi , Yan Zhongbo , Lyu Tairu , Zhang Mengyao , Li Zhilin , Song Chaoyu , Zhao Minhao , Leng Pengliang , Ozerov Mykhaylo , Chen Xiaolong , Wang Nanlin , Shi Yi , Yan Hugen , Xiu Faxian 
Published: March 2020

AbstractThe experimental discovery of Weyl semimetals offers unprecedented opportunities to study Weyl physics in condensed matters. Unique electromagnetic response of Weyl semimetals such as chiral magnetic effect has been observed and presented by the axial θ E · B term in electromagnetic Lagrangian (E and B are the electric and magnetic field, respectively). But till now, the experimental progress in this direction in Weyl semimetals is restricted to the DC regime. Here we report experimental access to the dynamic regime in Weyl semimetal NbAs by combining the internal deformation potential of coupled phonons with applied static magnetic field. While the dynamic E · B field is realized, it produces an anomalous phonon activity with a characteristic angle-dependence. Our results provide an effective approach to achieve the dynamic regime beyond the widely-investigated DC limit which enables the coupling between the Weyl fermions and the electromagnetic wave for further study of novel light-matter interactions in Weyl semimetals.
Resolving dynamics and function of transient states in single enzyme molecules
Authors: Sanabria Hugo , Rodnin Dmitro , Hemmen Katherina , Peulen Thomas-Otavio , Felekyan Suren , Fleissner Mark R. , Dimura Mykola , Koberling Felix , Kühnemuth Ralf , Hubbell Wayne , Gohlke Holger , Seidel Claus A. M. 
Published: March 2020

AbstractWe use a hybrid fluorescence spectroscopic toolkit to monitor T4 Lysozyme (T4L) in action by unraveling the kinetic and dynamic interplay of the conformational states. In particular, by combining single-molecule and ensemble multiparameter fluorescence detection, EPR spectroscopy, mutagenesis, and FRET-positioning and screening, and other biochemical and biophysical tools, we characterize three short-lived conformational states over the ns-ms timescale. The use of 33 FRET-derived distance sets, to screen available T4L structures, reveal that T4L in solution mainly adopts the known open and closed states in exchange at 4 µs. A newly found minor state, undisclosed by, at present, more than 500 crystal structures of T4L and sampled at 230 µs, may be actively involved in the product release step in catalysis. The presented fluorescence spectroscopic toolkit will likely accelerate the development of dynamic structural biology by identifying transient conformational states that are highly abundant in biology and critical in enzymatic reactions.
Structural evolution at the oxidative and reductive limits in the first electrochemical cycle of Li1.2Ni0.13Mn0.54Co0.13O2
Authors: Yin Wei , Grimaud Alexis , Rousse Gwenaelle , Abakumov Artem M. , Senyshyn Anatoliy , Zhang Leiting , Trabesinger Sigita , Iadecola Antonella , Foix Dominique , Giaume Domitille , Tarascon Jean-Marie 
Published: March 2020

AbstractHigh-energy-density lithium-rich materials are of significant interest for advanced lithium-ion batteries, provided that several roadblocks, such as voltage fade and poor energy efficiency are removed. However, this remains challenging as their functioning mechanisms during first cycle are not fully understood. Here we enlarge the cycling potential window for Li1.2Ni0.13Mn0.54Co0.13O2 electrode, identifying novel structural evolution mechanism involving a structurally-densified single-phase A’ formed under harsh oxidizing conditions throughout the crystallites and not only at the surface, in contrast to previous beliefs. We also recover a majority of first-cycle capacity loss by applying a constant-voltage step on discharge. Using highly reducing conditions we obtain additional capacity via a new low-potential P” phase, which is involved into triggering oxygen redox on charge. Altogether, these results provide deeper insights into the structural-composition evolution of Li1.2Ni0.13Mn0.54Co0.13O2 and will help to find measures to cure voltage fade and improve energy efficiency in this class of material.
Transposon age and non-CG methylation
Authors: Wang Zhengming , Baulcombe David C. 
Published: March 2020

AbstractSilencing of transposable elements (TEs) is established by small RNA-directed DNA methylation (RdDM). Maintenance of silencing is then based on a combination of RdDM and RNA-independent mechanisms involving DNA methyltransferase MET1 and chromodomain DNA methyltransferases (CMTs). Involvement of RdDM, according to this model should decrease with TE age but here we show a different pattern in tomato and Arabidopsis. In these species the CMTs silence long terminal repeat (LTR) transposons in the distal chromatin that are younger than those affected by RdDM. To account for these findings we propose that, after establishment of primary RdDM as in the original model, there is an RNA-independent maintenance phase involving CMTs followed by secondary RdDM. This progression of epigenetic silencing in the gene-rich distal chromatin is likely to influence the transcriptome either in cis or in trans depending on whether the mechanisms are RNA-dependent or -independent.
Two distinct modes of DNMT1 recruitment ensure stable maintenance DNA methylation
Authors: Nishiyama Atsuya , Mulholland Christopher B. , Bultmann Sebastian , Kori Satomi , Endo Akinori , Saeki Yasushi , Qin Weihua , Trummer Carina , Chiba Yoshie , Yokoyama Haruka , Kumamoto Soichiro , Kawakami Toru , Hojo Hironobu , Nagae Genta , Aburatani Hiroyuki , Tanaka Keiji , Arita Kyohei , Leonhardt Heinrich , Nakanishi Makoto 
Published: March 2020

AbstractStable inheritance of DNA methylation is critical for maintaining differentiated phenotypes in multicellular organisms. We have recently identified dual mono-ubiquitylation of histone H3 (H3Ub2) by UHRF1 as an essential mechanism to recruit DNMT1 to chromatin. Here, we show that PCNA-associated factor 15 (PAF15) undergoes UHRF1-dependent dual mono-ubiquitylation (PAF15Ub2) on chromatin in a DNA replication-coupled manner. This event will, in turn, recruit DNMT1. During early S-phase, UHRF1 preferentially ubiquitylates PAF15, whereas H3Ub2 predominates during late S-phase. H3Ub2 is enhanced under PAF15 compromised conditions, suggesting that H3Ub2 serves as a backup for PAF15Ub2. In mouse ES cells, loss of PAF15Ub2 results in DNA hypomethylation at early replicating domains. Together, our results suggest that there are two distinct mechanisms underlying replication timing-dependent recruitment of DNMT1 through PAF15Ub2 and H3Ub2, both of which are prerequisite for high fidelity DNA methylation inheritance.
Oxide-ion conduction in the Dion–Jacobson phase CsBi2Ti2NbO10−δ
Authors: Zhang Wenrui , Fujii Kotaro , Niwa Eiki , Hagihala Masato , Kamiyama Takashi , Yashima Masatomo 
Published: March 2020

AbstractOxide-ion conductors have found applications in various electrochemical devices, such as solid-oxide fuel cells, gas sensors, and separation membranes. Dion–Jacobson phases are known for their rich magnetic and electrical properties; however, there have been no reports on oxide-ion conduction in this family of materials. Here, for the first time to the best of our knowledge, we show the observation of fast oxygen anionic conducting behavior in CsBi2Ti2NbO10−δ. The bulk ionic conductivity of this Dion–Jacobson phase is 8.9 × 10−2 S cm−1 at 1073 K, a level that is higher than that of the conventional yttria-stabilized zirconia. The oxygen ion transport is attributable to the large anisotropic thermal motions of oxygen atoms, the presence of oxygen vacancies, and the formation of oxide-ion conducting layers in the crystal structure. The present finding of high oxide-ion conductivity in rare-earth-free CsBi2Ti2NbO10−δ suggests the potential of Dion–Jacobson phases as a platform to identify superior oxide-ion conductors.
A fluoroxalate cathode material for potassium-ion batteries with ultra-long cyclability
Authors: Ji Bifa , Yao Wenjiao , Zheng Yongping , Kidkhunthod Pinit , Zhou Xiaolong , Tunmee Sarayut , Sattayaporn Suchinda , Cheng Hui-Ming , He Haiyan , Tang Yongbing 
Published: March 2020

AbstractPotassium-ion batteries are a compelling technology for large scale energy storage due to their low-cost and good rate performance. However, the development of potassium-ion batteries remains in its infancy, mainly hindered by the lack of suitable cathode materials. Here we show that a previously known frustrated magnet, KFeC2O4F, could serve as a stable cathode for potassium ion storage, delivering a discharge capacity of ~112 mAh g−1 at 0.2 A g−1 and 94% capacity retention after 2000 cycles. The unprecedented cycling stability is attributed to the rigid framework and the presence of three channels that allow for minimized volume fluctuation when Fe2+/Fe3+ redox reaction occurs. Further, pairing this KFeC2O4F cathode with a soft carbon anode yields a potassium-ion full cell with an energy density of ~235 Wh kg−1, impressive rate performance and negligible capacity decay within 200 cycles. This work sheds light on the development of low-cost and high-performance K-based energy storage devices.
Electron transport chain activity is a predictor and target for venetoclax sensitivity in multiple myeloma
Authors: Bajpai Richa , Sharma Aditi , Achreja Abhinav , Edgar Claudia L. , Wei Changyong , Siddiqa Arusha A. , Gupta Vikas A. , Matulis Shannon M. , McBrayer Samuel K. , Mittal Anjali , Rupji Manali , Barwick Benjamin G. , Lonial Sagar , Nooka Ajay K. , Boise Lawrence H. , Nagrath Deepak , Shanmugam Mala 
Published: March 2020

AbstractThe BCL-2 antagonist venetoclax is highly effective in multiple myeloma (MM) patients exhibiting the 11;14 translocation, the mechanistic basis of which is unknown. In evaluating cellular energetics and metabolism of t(11;14) and non-t(11;14) MM, we determine that venetoclax-sensitive myeloma has reduced mitochondrial respiration. Consistent with this, low electron transport chain (ETC) Complex I and Complex II activities correlate with venetoclax sensitivity. Inhibition of Complex I, using IACS-010759, an orally bioavailable Complex I inhibitor in clinical trials, as well as succinate ubiquinone reductase (SQR) activity of Complex II, using thenoyltrifluoroacetone (TTFA) or introduction of SDHC R72C mutant, independently sensitize resistant MM to venetoclax. We demonstrate that ETC inhibition increases BCL-2 dependence and the ‘primed’ state via the ATF4-BIM/NOXA axis. Further, SQR activity correlates with venetoclax sensitivity in patient samples irrespective of t(11;14) status. Use of SQR activity in a functional-biomarker informed manner may better select for MM patients responsive to venetoclax therapy.
Climate adaptation by crop migration
Authors: Sloat Lindsey L. , Davis Steven J. , Gerber James S. , Moore Frances C. , Ray Deepak K. , West Paul C. , Mueller Nathaniel D. 
Published: March 2020

AbstractMany studies have estimated the adverse effects of climate change on crop yields, however, this literature almost universally assumes a constant geographic distribution of crops in the future. Movement of growing areas to limit exposure to adverse climate conditions has been discussed as a theoretical adaptive response but has not previously been quantified or demonstrated at a global scale. Here, we assess how changes in rainfed crop area have already mediated growing season temperature trends for rainfed maize, wheat, rice, and soybean using spatially-explicit climate and crop area data from 1973 to 2012. Our results suggest that the most damaging impacts of warming on rainfed maize, wheat, and rice have been substantially moderated by the migration of these crops over time and the expansion of irrigation. However, continued migration may incur substantial environmental costs and will depend on socio-economic and political factors in addition to land suitability and climate.
Ultra-high open-circuit voltage of tin perovskite solar cells via an electron transporting layer design
Authors: Jiang Xianyuan , Wang Fei , Wei Qi , Li Hansheng , Shang Yuequn , Zhou Wenjia , Wang Cheng , Cheng Peihong , Chen Qi , Chen Liwei , Ning Zhijun 
Published: March 2020

AbstractTin perovskite is rising as a promising candidate to address the toxicity and theoretical efficiency limitation of lead perovskite. However, the voltage and efficiency of tin perovskite solar cells are much lower than lead counterparts. Herein, indene-C60 bisadduct with higher energy level is utilized as an electron transporting material for tin perovskite solar cells. It suppresses carrier concentration increase caused by remote doping, which significantly reduces interface carriers recombination. Moreover, indene-C60 bisadduct increases the maximum attainable photovoltage of the device. As a result, the use of indene-C60 bisadduct brings unprecedentedly high voltage of 0.94 V, which is over 50% higher than that of 0.6 V for device based on [6,6]-phenyl-C61-butyric acid methyl ester. The device shows a record power conversion efficiency of 12.4% reproduced in an accredited independent photovoltaic testing lab.
DJ-1 suppresses ferroptosis through preserving the activity of S-adenosyl homocysteine hydrolase
Authors: Cao Ji , Chen Xiaobing , Jiang Li , Lu Bin , Yuan Meng , Zhu Difeng , Zhu Hong , He Qiaojun , Yang Bo , Ying Meidan 
Published: March 2020

AbstractFerroptosis is a newly characterized form of regulated cell death mediated by iron-dependent accumulation of lipid reactive oxygen species and holds great potential for cancer therapy. However, the molecular mechanisms underlying ferroptosis remain largely elusive. In this study, we define an integrative role of DJ-1 in ferroptosis. Inhibition of DJ-1 potently enhances the sensitivity of tumor cells to ferroptosis inducers both in vitro and in vivo. Metabolic analysis and metabolite rescue assay reveal that DJ-1 depletion inhibits the transsulfuration pathway by disrupting the formation of the S-adenosyl homocysteine hydrolase tetramer and impairing its activity. Consequently, more ferroptosis is induced when homocysteine generation is decreased, which might be the only source of glutathione biosynthesis when cystine uptake is blocked. Thus, our findings show that DJ-1 determines the response of cancer cells to ferroptosis, and highlight a candidate therapeutic target to potentially improve the effect of ferroptosis-based antitumor therapy.
Repetition enhancement to voice identities in the dog brain
Authors: Boros Marianna , Gábor Anna , Szabó Dóra , Bozsik Anett , Gácsi Márta , Szalay Ferenc , Faragó Tamás , Andics Attila 
Published: March 2020

AbstractIn the human speech signal, cues of speech sounds and voice identities are conflated, but they are processed separately in the human brain. The processing of speech sounds and voice identities is typically performed by non-primary auditory regions in humans and non-human primates. Additionally, these processes exhibit functional asymmetry in humans, indicating the involvement of distinct mechanisms. Behavioural studies indicate analogue side biases in dogs, but neural evidence for this functional dissociation is missing. In two experiments, using an fMRI adaptation paradigm, we presented awake dogs with natural human speech that either varied in segmental (change in speech sound) or suprasegmental (change in voice identity) content. In auditory regions, we found a repetition enhancement effect for voice identity processing in a secondary auditory region – the caudal ectosylvian gyrus. The same region did not show repetition effects for speech sounds, nor did the primary auditory cortex exhibit sensitivity to changes either in the segmental or in the suprasegmental content. Furthermore, we did not find evidence for functional asymmetry neither in the processing of speech sounds or voice identities. Our results in dogs corroborate former human and non-human primate evidence on the role of secondary auditory regions in the processing of suprasegmental cues, suggesting similar neural sensitivity to the identity of the vocalizer across the mammalian order.
Tibial subchondral trabecular bone micromechanical and microarchitectural properties are affected by alignment and osteoarthritis stage
Authors: Renault Jean-Baptiste , Carmona Maximiliano , Tzioupis Chris , Ollivier Matthieu , Argenson Jean-Noël , Parratte Sébastien , Chabrand Patrick 
Published: March 2020

AbstractAt advanced knee osteoarthritis (OA) stages subchondral trabecular bone (STB) is altered. Lower limb alignment plays a role in OA progression and modify the macroscopic loading of the medial and lateral condyles of the tibial plateau. How the properties of the STB relate to alignment and OA stage is not well defined. OA stage (KL scores 2–4) and alignment (HKA from 17° Varus to 8° Valgus) of 30 patients were measured and their tibial plateau were collected after total knee arthroplasty. STB tissue elastic modulus, bone volume fraction (BV/TV) and trabecula thickness (Tb.Th) were evaluated with nanoindentation and µCT scans (8.1 µm voxel-size) of medial and lateral samples of each plateau. HKA and KL scores were statistically significantly associated with STB elastic modulus, BV/TV and Tb.Th. Medial to lateral BV/TV ratio correlated with HKA angle (R = −0.53, p = 0.016), revealing a higher ratio for varus than valgus subjects. STB properties showed lower values for KL stage 4 patients. Tissue elastic modulus ratios and BV.TV ratios were strongly correlated (R = 0.81, p < 0.001). Results showed that both micromechanical and microarchitectural properties of STB are affected by macroscopic loading at late stage knee OA. For the first time, a strong association between tissue stiffness and quantity of OA STB was demonstrated.