bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liproxstatin-1 attenuates unilateral ureteral obstruction-induced renal fibrosis by inhibiting renal tubular epithelial cells ferroptosis
Authors: Zhang Bo , Chen Xiang , Ru Feng , Gan Yu , Li Bingsheng , Xia Weiping , Dai Guoyu , He Yao , Chen Zhi 
Published: September 2021

AbstractRenal fibrosis is a common pathological process that occurs with diverse etiologies in chronic kidney disease. However, its regulatory mechanisms have not yet been fully elucidated. Ferroptosis is a form of non-apoptotic regulated cell death driven by iron-dependent lipid peroxidation. It is currently unknown whether ferroptosis is initiated during unilateral ureteral obstruction (UUO)-induced renal fibrosis and its role has not been determined. In this study, we demonstrated that ureteral obstruction induced ferroptosis in renal tubular epithelial cells (TECs) in vivo. The ferroptosis inhibitor liproxstatin-1 (Lip-1) reduced iron deposition, cell death, lipid peroxidation, and inhibited the downregulation of GPX4 expression induced by UUO, ultimately inhibiting ferroptosis in TECs. We found that Lip-1 significantly attenuated UUO-induced morphological and pathological changes and collagen deposition of renal fibrosis in mice. In addition, Lip-1 attenuated the expression of profibrotic factors in the UUO model. In vitro, we used RSL3 treatment and knocked down of GPX4 level by RNAi in HK2 cells to induce ferroptosis. Our results indicated HK2 cells secreted various profibrotic factors during ferroptosis. Lip-1 was able to inhibit ferroptosis and thereby inhibit the secretion of the profibrotic factors during the process. Incubation of kidney fibroblasts with culture medium from RSL3-induced HK2 cells promoted fibroblast proliferation and activation, whereas Lip-1 impeded the profibrotic effects. Our study found that Lip-1 may relieve renal fibrosis by inhibiting ferroptosis in TECs. Mechanistically, Lip-1 could reduce the activation of surrounding fibroblasts by inhibiting the paracrine of profibrotic factors in HK2 cells. Lip-1 may potentially be used as a therapeutic approach for the treatment of UUO-induced renal fibrosis.
EMP3 negatively modulates breast cancer cell DNA replication, DNA damage repair, and stem-like properties
Authors: Zhou Kailing , Sun Yu , Dong Dan , Zhao Chenghai , Wang Wei 
Published: September 2021

AbstractEnhanced DNA damage repair capacity attenuates cell killing of DNA-damaging chemotherapeutic agents. In silico analysis showed that epithelial membrane protein 3 (EMP3) is associated with favorable survival, and negatively regulates cell cycle S-phase. Consistently, loss and gain of function studies demonstrated that EMP3 inhibits breast cancer cell S-phage entry, DNA replication, DNA damage repair, and stem-like properties. Moreover, EMP3 blocks Akt-mTOR signaling activation and induces autophagy. EMP3 negatively modulates BRCA1 and RAD51 expression, indicating EMP3 suppresses homologous recombination repair of DNA double-strand breaks. Accordingly, EMP3 sensitizes breast cancer cells to the DNA-damaging drug Adriamycin. EMP3 downregulates YTHDC1, a RNA-binding protein involved in m6a modification, which at least in part mediates the effects of EMP3 on breast cancer cells. Taken together, these data indicate that EMP3 is a putative tumor suppressor in breast cancer, and EMP3 downregulation may be responsible for breast cancer chemoresistance.
Adipocytes disrupt the translational programme of acute lymphoblastic leukaemia to favour tumour survival and persistence
Authors: Heydt Q. , Xintaropoulou C. , Clear A. , Austin M. , Pislariu I. , Miraki-Moud F. , Cutillas P. , Korfi K. , Calaminici M. , Cawthorn W. , Suchacki K. , Nagano A. , Gribben J. G. , Smith M. , Cavenagh J. D. , Oakervee H. , Castleton A. , Taussig D. , Peck B. , Wilczynska A. , McNaughton L. , Bonnet D. , Mardakheh F. , Patel B. 
Published: September 2021

AbstractThe specific niche adaptations that facilitate primary disease and Acute Lymphoblastic Leukaemia (ALL) survival after induction chemotherapy remain unclear. Here, we show that Bone Marrow (BM) adipocytes dynamically evolve during ALL pathogenesis and therapy, transitioning from cellular depletion in the primary leukaemia niche to a fully reconstituted state upon remission induction. Functionally, adipocyte niches elicit a fate switch in ALL cells towards slow-proliferation and cellular quiescence, highlighting the critical contribution of the adipocyte dynamic to disease establishment and chemotherapy resistance. Mechanistically, adipocyte niche interaction targets posttranscriptional networks and suppresses protein biosynthesis in ALL cells. Treatment with general control nonderepressible 2 inhibitor (GCN2ib) alleviates adipocyte-mediated translational repression and rescues ALL cell quiescence thereby significantly reducing the cytoprotective effect of adipocytes against chemotherapy and other extrinsic stressors. These data establish how adipocyte driven restrictions of the ALL proteome benefit ALL tumours, preventing their elimination, and suggest ways to manipulate adipocyte-mediated ALL resistance.
A physicochemical orthophosphate cycle via a kinetically stable thermodynamically activated intermediate enables mild prebiotic phosphorylations
Authors: Maguire Oliver R. , Smokers Iris B. A. , Huck Wilhelm T. S. 
Published: September 2021

AbstractThe incorporation of orthophosphate from scarce geochemical sources into the organic compounds essential for life under mild conditions is a fundamental challenge for prebiotic chemistry. Here we report a prebiotic system capable of overcoming this challenge by taking inspiration from extant life’s recycling of orthophosphate via its conversion into kinetically stable thermodynamically activated (KSTA) nucleotide triphosphates (e.g. ATP). We separate the activation of orthophosphate from its transfer to organic compounds by, crucially, first accumulating a KSTA phosphoramidate. We use cyanate to activate orthophosphate in aqueous solution under mild conditions and then react it with imidazole to accumulate the KSTA imidazole phosphate. In a paste, imidazole phosphate phosphorylates all the essential building blocks of life. Integration of this chemistry into a wet/dry cycle enables the continuous recycling of orthophosphate and the accretion of phosphorylated compounds. This system functions even at low reagent concentrations due to solutes concentrating during evaporation. Our system demonstrates a general strategy for how to maximise the usage of scarce resources based upon cycles which accumulate and then release activated intermediates.
A CRISPR/Cas9 genetically engineered organoid biobank reveals essential host factors for coronaviruses
Authors: Beumer Joep , Geurts Maarten H. , Lamers Mart M. , Puschhof Jens , Zhang Jingshu , van der Vaart Jelte , Mykytyn Anna Z. , Breugem Tim I. , Riesebosch Samra , Schipper Debby , van den Doel Petra B. , de Lau Wim , Pleguezuelos-Manzano Cayetano , Busslinger Georg , Haagmans Bart L. , Clevers Hans 
Published: September 2021

AbstractRapid identification of host genes essential for virus replication may expedite the generation of therapeutic interventions. Genetic screens are often performed in transformed cell lines that poorly represent viral target cells in vivo, leading to discoveries that may not be translated to the clinic. Intestinal organoids are increasingly used to model human disease and are amenable to genetic engineering. To discern which host factors are reliable anti-coronavirus therapeutic targets, we generate mutant clonal IOs for 19 host genes previously implicated in coronavirus biology. We verify ACE2 and DPP4 as entry receptors for SARS-CoV/SARS-CoV-2 and MERS-CoV respectively. SARS-CoV-2 replication in IOs does not require the endosomal Cathepsin B/L proteases, but specifically depends on the cell surface protease TMPRSS2. Other TMPRSS family members were not essential. The newly emerging coronavirus variant B.1.1.7, as well as SARS-CoV and MERS-CoV similarly depended on TMPRSS2. These findings underscore the relevance of non-transformed human models for coronavirus research, identify TMPRSS2 as an attractive pan-coronavirus therapeutic target, and demonstrate that an organoid knockout biobank is a valuable tool to investigate the biology of current and future emerging coronaviruses.
Structure of human cytomegalovirus virion reveals host tRNA binding to capsid-associated tegument protein pp150
Authors: Liu Yun-Tao , Strugatsky David , Liu Wei , Zhou Z. Hong 
Published: September 2021

AbstractUnder the Baltimore nucleic acid-based virus classification scheme, the herpesvirus human cytomegalovirus (HCMV) is a Class I virus, meaning that it contains a double-stranded DNA genome—and no RNA. Here, we report sub-particle cryoEM reconstructions of HCMV virions at 2.9 Å resolution revealing structures resembling non-coding transfer RNAs (tRNAs) associated with the virion’s capsid-bound tegument protein, pp150. Through deep sequencing, we show that these RNA sequences match human tRNAs, and we built atomic models using the most abundant tRNA species. Based on our models, tRNA recruitment is mediated by the electrostatic interactions between tRNA phosphate groups and the helix-loop-helix motif of HCMV pp150. The specificity of these interactions may explain the absence of such tRNA densities in murine cytomegalovirus and other human herpesviruses.
Structural insight into the mechanism of energy transfer in cyanobacterial phycobilisomes
Authors: Zheng Lvqin , Zheng Zhenggao , Li Xiying , Wang Guopeng , Zhang Kun , Wei Peijun , Zhao Jindong , Gao Ning 
Published: September 2021

AbstractPhycobilisomes (PBS) are the major light-harvesting machineries for photosynthesis in cyanobacteria and red algae and they have a hierarchical structure of a core and peripheral rods, with both consisting of phycobiliproteins and linker proteins. Here we report the cryo-EM structures of PBS from two cyanobacterial species, Anabaena 7120 and Synechococcus 7002. Both PBS are hemidiscoidal in shape and share a common triangular core structure. While the Anabaena PBS has two additional hexamers in the core linked by the 4th linker domain of ApcE (LCM). The PBS structures predict that, compared with the PBS from red algae, the cyanobacterial PBS could have more direct routes for energy transfer to ApcD. Structure-based systematic mutagenesis analysis of the chromophore environment of ApcD and ApcF subunits reveals that aromatic residues are critical to excitation energy transfer (EET). The structures also suggest that the linker protein could actively participate in the process of EET in both rods and the cores. These results provide insights into the organization of chromophores and the mechanisms of EET within cyanobacterial PBS.
Atomic-scale imaging of CH3NH3PbI3 structure and its decomposition pathway
Authors: Chen Shulin , Wu Changwei , Han Bo , Liu Zhetong , Mi Zhou , Hao Weizhong , Zhao Jinjin , Wang Xiao , Zhang Qing , Liu Kaihui , Qi Junlei , Cao Jian , Feng Jicai , Yu Dapeng , Li Jiangyu , Gao Peng 
Published: September 2021

AbstractUnderstanding the atomic structure and structural instability of organic-inorganic hybrid perovskites is the key to appreciate their remarkable photoelectric properties and understand failure mechanism. Here, using low-dose imaging technique by direct-detection electron-counting camera in a transmission electron microscope, we investigate the atomic structure and decomposition pathway of CH3NH3PbI3 (MAPbI3) at the atomic scale. We successfully image the atomic structure of perovskite in real space under ultra-low electron dose condition, and observe a two-step decomposition process, i.e., initial loss of MA+ followed by the collapse of perovskite structure into 6H-PbI2 with their critical threshold doses also determined. Interestingly, an intermediate phase (MA0.5PbI3) with locally ordered vacancies can robustly exist before perovskite collapses, enlightening strategies for prevention and recovery of perovskite structure during the degradation. Associated with the structure evolution, the bandgap gradually increases from ~1.6 eV to ~2.1 eV. In addition, it is found that C-N bonds can be readily destroyed under irradiation, releasing NH3 and HI and leaving hydrocarbons. These findings enhance our understanding of the photoelectric properties and failure mechanism of MAPbI3, providing potential strategies into material optimization.
Argininosuccinate lyase is a metabolic vulnerability in breast development and cancer
Authors: Karvelsson Sigurdur Trausti , Wang Qiong , Hilmarsdottir Bylgja , Sigurdsson Arnar , Moestue Siver Andreas , Mælandsmo Gunhild Mari , Halldorsson Skarphedinn , Gudmundsson Steinn , Rolfsson Ottar 
Published: September 2021

AbstractEpithelial-to-mesenchymal transition (EMT) is fundamental to both normal tissue development and cancer progression. We hypothesized that EMT plasticity defines a range of metabolic phenotypes and that individual breast epithelial metabolic phenotypes are likely to fall within this phenotypic landscape. To determine EMT metabolic phenotypes, the metabolism of EMT was described within genome-scale metabolic models (GSMMs) using either transcriptomic or proteomic data from the breast epithelial EMT cell culture model D492. The ability of the different data types to describe breast epithelial metabolism was assessed using constraint-based modeling which was subsequently verified using 13C isotope tracer analysis. The application of proteomic data to GSMMs provided relatively higher accuracy in flux predictions compared to the transcriptomic data. Furthermore, the proteomic GSMMs predicted altered cholesterol metabolism and increased dependency on argininosuccinate lyase (ASL) following EMT which were confirmed in vitro using drug assays and siRNA knockdown experiments. The successful verification of the proteomic GSMMs afforded iBreast2886, a breast GSMM that encompasses the metabolic plasticity of EMT as defined by the D492 EMT cell culture model. Analysis of breast tumor proteomic data using iBreast2886 identified vulnerabilities within arginine metabolism that allowed prognostic discrimination of breast cancer patients on a subtype-specific level. Taken together, we demonstrate that the metabolic reconstruction iBreast2886 formalizes the metabolism of breast epithelial cell development and can be utilized as a tool for the functional interpretation of high throughput clinical data.
Long-term warming and nitrogen fertilization affect C-, N- and P-acquiring hydrolase and oxidase activities in winter wheat monocropping soil
Authors: Zhang Chuang , Dong Wenxu , Manevski Kiril , Hu Wenpei , Timilsina Arbindra , Chen Xiaoru , Zhang Xinyuan , Hu Chunsheng 
Published: September 2021

AbstractThe enzymatic activities and ratios are critical indicators for organic matter decomposition and provide potentially positive feedback to carbon (C) loss under global warming. For agricultural soils under climate change, the effect of long-term warming on the activities of oxidases and hydrolases targeting C, nitrogen (N) and phosphorus (P) and their ratios is unclear, as well as whether and to what extend the response is modulated by long-term fertilization. A 9-year field experiment in the North China Plain, including an untreated control, warming, N fertilization, and combined (WN) treatment plots, compared the factorial effect of warming and fertilization. Long-term warming interacted with fertilization to stimulate the highest activities of C, N, and P hydrolases. Activities of C and P hydrolase increased from 8 to 69% by N fertilization, 9 to 53% by warming, and 28 to 130% by WN treatment compared to control, whereas the activities of oxidase increased from 4 to 16% in the WN soils. Both the warming and the WN treatments significantly increased the enzymatic C:N ratio from 0.06 to 0.16 and the vector length from 0.04 to 0.12 compared to the control soil, indicating higher energy and resource limitation for the soil microorganisms. Compared to WN, the warming induced similar ratio of oxidase to C hydrolase, showing a comparable ability of different microbial communities to utilize lignin substrates. The relationship analyses showed mineralization of organic N to mediate the decomposition of lignin and enzyme ratio in the long-term warming soil, while N and P hydrolases cooperatively benefited to induce more oxidase productions in the soil subject to both warming and N fertilization. We conclude that coupled resource limitations induced microbial acclimation to long-term warming in the agricultural soils experiencing high N fertilizer inputs.
Octavinyl polyhedral oligomeric silsesquioxane on tailoring the DC electrical characteristics of polypropylene
Authors: Lin Xiaosi , Siew Wah Hoon , Liggat John , Given Martin , He Jinliang 
Published: September 2021

AbstractThis work reports the effect of octavinyl polyhedral oligomeric silsesquioxane (OvPOSS) on tuning the electrical performance of polypropylene (PP). OvPOSS with different content are introduced into PP using the solution method. The microstructural morphology, crystallinity behaviour, breakdown strength, DC conductivity, space charge formation, and trapping level distribution are measured. The results indicate that the OvPOSS nanofiller can be dispersed uniformly with a doping content of 2.0 phr or less. The DC conductivity is decreased, and the breakdown strength of OvPOSS/PP nanocomposites is significantly increased. The space charge accumulation of the OvPOSS/PP nanocomposites is significantly suppressed due to the introduction of deeper traps by the OvPOSS nanofiller. Finally, the experimental results demonstrate that the OvPOSS nanofiller can greatly increase the electrical performance of the base PP and the OvPOSS/PP nanocomposites have much potential for HVDC applications. They further demonstrate that the PP is environmental‐friendly due to its thermo‐plastic property, which can be recycled after the manufacture.
Learning compact ConvNets through filter pruning based on the saliency of a feature map
Authors: Liu Zhoufeng , Liu Xiaohui , Li Chunlei , Ding Shumin , Liao Liang 
Published: September 2021

AbstractWith the performance increase of convolutional neural network (CNN), the disadvantages of CNN's high storage and high power consumption are followed. Among the methods mentioned in various literature, filter pruning is a crucial method for constructing lightweight networks. However, the current filter pruning method is still challenged by complicated processes and training inefficiency. This paper proposes an effective filter pruning method, which uses the saliency of the feature map (SFM), i.e. information entropy, as a theoretical guide for whether the filter is essential. The pruning principle use here is that the filter with a weak saliency feature map in the early stage will not significantly improve the final accuracy. Thus, one can efficiently prune the non‐salient feature map with a smaller information entropy and the corresponding filter. Besides, an over‐parameterized convolution method is employed to improve the pruned model's accuracy without increasing parameter at inference time. Experimental results show that without introducing any additional constraints, the effectiveness of this method in FLOPs and parameters reduction with similar accuracy has advanced the state‐of‐the‐art. For example, on CIFAR‐10, the pruned VGG‐16 achieves only a small loss of 0.39% in Top‐1 accuracy with a factor of 83.3% parameters, and 66.7% FLOPs reductions. On ImageNet‐100, the pruned ResNet‐50 achieves only a small accuracy degradation of 0.76% in Top‐1 accuracy with a factor of 61.19% parameters, and 62.98% FLOPs reductions.
The BER performance of a FSO system with polar codes under weak turbulence
Authors: Mohan Nithin , Ghassemlooy Zabih , Li Emma , Abadi Mojtaba Mansour , Zvanovec Stanislav , Hudson Ralph , Htay Zun 
Published: September 2021

AbstractThe key challenge in free space optical (FSO) communications is combating turbulence‐induced fading. As the channel fading in FSO is quasi‐static, the transmission parameters such as the code rates, transmit power and modulation schemes can be modified with respect to the channel state information transmitted via the feedback path. As a result, adaptive channel coding is considered as one of the practical approaches to improve the FSO link performance. In this study, the FSO system with polar codes is investigated and its performance is analysed by determining the optimum code‐rate required to achieve a bit error rate of 10−9 under weak turbulence. It is shown that, using Monte‐Carlo simulations for the scintillation indices of 0.12 and 0.2, the successive cancelation list (SCL) decoder offers coding gains of 2.5 and 0.3 dB, respectively, as compared with SC decoder, and for the scintillation index of 0.31, the SC decoder offers a coding gain of 2.5 dB compared to that of the SCL decoder for the code rate.
How Selection Over Time Contributes to the Inconsistency of the Association Between Sex/Gender and Cognitive Decline Across Cognitive Aging Cohorts
Authors: Rouanet Anaïs , Avila-Rieger Justina , Dugravot Aline , Lespinasse Jérémie , Stuckwisch Rachel , Merrick Richard , Anderson Emma , Long Leann , Helmer Catherine , Jacqmin-Gadda Hélène , Dufouil Carole , Judd Suzanne , Manly Jennifer , Sabia Séverine , Gross Alden , Proust-Lima Cécile 
Published: September 2021

Abstract
The association between sex/gender and aging-related cognitive decline remains poorly understood because of inconsistencies in findings. Such heterogeneity could be attributable to the cognitive functions studied and study population characteristics, but also to differential selection by dropout and death between men and women. We aimed to evaluate the impact of selection by dropout and death on the association between sex/gender and cognitive decline. We first compared the statistical methods most frequently used for longitudinal data, targeting either population estimands (marginal models fitted by generalized estimating equations) or subject-specific estimands (mixed/joint models fitted by likelihood maximization) in 8 studies of aging: 6 population-based studies (the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) Study (1996–2009), Personnes Âgées QUID (PAQUID; 1988–2014), the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study (2003–2016), the Three-City Study (Bordeaux only; 1999–2016), the Washington Heights-Inwood Community Aging Project (WHICAP; 1992–2017), and the Whitehall II Study (2007–2016)) and 2 clinic-based studies (the Alzheimer’s Disease Neuroimaging Initiative (ADNI; 2004–2017) and a nationwide French cohort study, MEMENTO (2011–2016)). We illustrate differences in the estimands of the association between sex/gender and cognitive decline in selected examples and highlight the critical role of differential selection by dropout and death. Using the same estimand, we then contrast the sex/gender–cognitive decline associations across cohorts and cognitive measures suggesting a residual differential sex/gender association depending on the targeted cognitive measure (memory or animal fluency) and the initial cohort selection. We recommend focusing on subject-specific estimands in the living population for assessing sex/gender differences while handling differential selection over time.