bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glutathione prevents high glucose-induced pancreatic fibrosis by suppressing pancreatic stellate cell activation via the ROS/TGFβ/SMAD pathway
Authors: Zhang Jitai , Bai Juan , Zhou Qian , Hu Yuxin , Wang Qian , Yang Lanting , Chen Huamin , An Hui , Zhou Chuanzan , Wang Yongyu , Chen Xiufang , Li Ming 
Published: May 2022

AbstractThe activation of pancreatic stellate cells (PSCs) is the key mechanism of pancreatic fibrosis, which can lead to β-cell failure. Oxidative stress is an important risk factor for PSC activation. There is no direct evidence proving if administration of glutathione can inhibit fibrosis and β-cell failure. To explore the role of glutathione in pancreatic fibrosis and β-cell failure induced by hyperglycaemia, we established a rat model of pancreatic fibrosis and β-cell failure. The model was founded through long-term oscillating glucose (LOsG) intake and the setup of a sham group and a glutathione intervention group. In vitro, rat PSCs were treated with low glucose, high glucose, or high glucose plus glutathione to explore the mechanism of high glucose-induced PSC activation and the downstream effects of glutathione. Compared with sham rats, LOsG-treated rats had higher reactive oxygen species (ROS) levels in peripheral leukocytes and pancreatic tissue while TGFβ signalling was upregulated. In addition, as the number of PSCs and pancreatic fibrosis increased, β-cell function was significantly impaired. Glutathione evidently inhibited the upregulation of TGFβ signalling and several unfavourable outcomes caused by LOsG. In vitro treatment of high glucose for 72 h resulted in higher ROS accumulation and potentiated TGFβ pathway activation in PSCs. PSCs showed myofibroblast phenotype transformation with upregulation of α-SMA expression and increased cell proliferation and migration. Treatment with either glutathione or TGFβ pathway inhibitors alleviated these changes. Together, our findings suggest that glutathione can inhibit PSC activation-induced pancreatic fibrosis via blocking ROS/TGFβ/SMAD signalling in vivo and in vitro.
Fluorescence microscopic visualization of functionalized hydrogels
Authors: Zhong Jinpan , Zhao Tianyi , Liu Mingjie 
Published: May 2022

AbstractFunctionalized hydrogels play an important part in chemistry, biology, and material science due to their unique microstructures. Characterization of these microstructures is the fundamental issue to improve the optical, mechanical, and biochemical performance of functionalized hydrogels. With the rapid development of fluorescence microscopy, a growing number of researchers have attempted to utilize this easily operated, noninvasive, and high-contrast technique to visualize the fine microstructure of hydrogels. Integration of a confocal system into fluorescence microscopy allows the sectioning and reconstruction of 3D hydrogel networks. The live recording function offers in situ and real-time images of dynamic behaviors within hydrogels. The development of super-resolution fluorescence microscopy has significantly promoted imaging quality from the submicron scale to the nanoscale. Based on these spectacular achievements, we reviewed the recent advances in fluorescence microscopic visualization of internal morphologies, mechanical properties, and dynamic structural changes. The scope of this review is to provide inspiration for researchers in chemistry, material science, and biology to study and fabricate functionalized hydrogels with the assistance of fluorescence microscopic visualization.
Mechanically resilient integrated electronics realized using interconnected 2D gold-nanosheet elastomeric electrodes
Authors: Heo Seojun , Jeong Seongsik , Kim Kyeong-Hwan , Kim Hae-Jin 
Published: May 2022

AbstractWith the growing interest in wearable devices in recent decades, considerable effort has been devoted to developing mechanical elastomeric devices such as sensors, transistors, logic circuits, and integrated circuits. To successfully implement elastomeric devices subjected to large mechanical deformations or stretching, all the components, including conductors, semiconductors, and dielectrics, must have high stability and mechanical sustainability. Elastomeric conductors, which exhibit excellent electrical performances under mechanical deformations, are key components of elastomeric devices. Herein, we prepared fully elastomeric electrodes based on interconnected 2D gold nanosheets (AuNSs) to develop mechanically resilient integrated electronics. The AuNS elastomeric electrodes exhibited a sheet resistance of less than 2 Ω/sq under 50% stretching and sustained 100,000 stretching–releasing cycles. These electrodes with a dedicated design were used in combination with elastomeric semiconductors of P3HT nanofibrils in the PDMS elastomer (P3NF/PDMS) and an ion gel as a dielectric to realize elastomeric transistors, inverters, and NOR and NAND logic gates. Additionally, an elastomeric 8 × 8 transistor array that can sustain various types of mechanical stimuli was successfully demonstrated. Furthermore, the elastomeric electronic devices implemented on a soft robot showed no interfering performances during robot gripping motion. The proposed framework is expected to aid in the rapid development and broaden the application scope of soft electronics.
Genomic prediction of cotton fibre quality and yield traits using Bayesian regression methods
Authors: Li Zitong , Liu Shiming , Conaty Warren , Zhu Qian-Hao , Moncuquet Philippe , Stiller Warwick , Wilson Iain 
Published: May 2022

AbstractGenomic selection or genomic prediction (GP) has increasingly become an important molecular breeding technology for crop improvement. GP aims to utilise genome-wide marker data to predict genomic breeding value for traits of economic importance. Though GP studies have been widely conducted in various crop species such as wheat and maize, its application in cotton, an essential renewable textile fibre crop, is still significantly underdeveloped. We aim to develop a new GP-based breeding system that can improve the efficiency of our cotton breeding program. This article presents a GP study on cotton fibre quality and yield traits using 1385 breeding lines from the Commonwealth Scientific and Industrial Research Organisation (CSIRO, Australia) cotton breeding program which were genotyped using a high-density SNP chip that generated 12,296 informative SNPs. The aim of this study was twofold: (1) to identify the models and data sources (i.e. genomic and pedigree) that produce the highest prediction accuracies; and (2) to assess the effectiveness of GP as a selection tool in the CSIRO cotton breeding program. The prediction analyses were conducted under various scenarios using different Bayesian predictive models. Results highlighted that the model combining genomic and pedigree information resulted in the best cross validated prediction accuracies: 0.76 for fibre length, 0.65 for fibre strength, and 0.64 for lint yield. Overall, this work represents the largest scale genomic selection studies based on cotton breeding trial data. Prediction accuracies reported in our study indicate the potential of GP as a breeding tool for cotton. The study highlighted the importance of incorporating pedigree and environmental factors in GP models to optimise the prediction performance.
Transmon platform for quantum computing challenged by chaotic fluctuations
Authors: Berke Christoph , Varvelis Evangelos , Trebst Simon , Altland Alexander , DiVincenzo David P. 
Published: May 2022

AbstractFrom the perspective of many-body physics, the transmon qubit architectures currently developed for quantum computing are systems of coupled nonlinear quantum resonators. A certain amount of intentional frequency detuning (‘disorder’) is crucially required to protect individual qubit states against the destabilizing effects of nonlinear resonator coupling. Here we investigate the stability of this variant of a many-body localized phase for system parameters relevant to current quantum processors developed by the IBM, Delft, and Google consortia, considering the cases of natural or engineered disorder. Applying three independent diagnostics of localization theory — a Kullback–Leibler analysis of spectral statistics, statistics of many-body wave functions (inverse participation ratios), and a Walsh transform of the many-body spectrum — we find that some of these computing platforms are dangerously close to a phase of uncontrollable chaotic fluctuations.
Competition contributes to both warm and cool range edges
Authors: Lyu Shengman , Alexander Jake M. 
Published: May 2022

AbstractCompetition plays an important role in shaping species’ spatial distributions. However, it remains unclear where and how competition regulates species’ range limits. In a field experiment with plants originating from low and high elevations and conducted across an elevation gradient in the Swiss Alps, we find that both lowland and highland species can better persist in the presence of competition within, rather than beyond, their elevation ranges. These findings suggest that competition helps set both lower and upper elevation range limits of these species. Furthermore, the reduced ability of pairs of lowland or highland species to coexist beyond their range edges is mainly driven by diminishing niche differences; changes in both niche differences and relative fitness differences drive weakening competitive dominance of lowland over highland species with increasing elevation. These results highlight the need to account for competitive interactions and investigate underlying coexistence mechanisms to understand current and future species distributions.
Ataluren binds to multiple protein synthesis apparatus sites and competitively inhibits release factor-dependent termination
Authors: Huang Shijie , Bhattacharya Arpan , Ghelfi Mikel D. , Li Hong , Fritsch Clark , Chenoweth David M. , Goldman Yale E. , Cooperman Barry S. 
Published: May 2022

AbstractGenetic diseases are often caused by nonsense mutations, but only one TRID (translation readthrough inducing drug), ataluren, has been approved for clinical use. Ataluren inhibits release factor complex (RFC) termination activity, while not affecting productive binding of near-cognate ternary complex (TC, aa-tRNA.eEF1A.GTP). Here we use photoaffinity labeling to identify two sites of ataluren binding within rRNA, proximal to the decoding center (DC) and the peptidyl transfer center (PTC) of the ribosome, which are directly responsible for ataluren inhibition of termination activity. A third site, within the RFC, has as yet unclear functional consequences. Using single molecule and ensemble fluorescence assays we also demonstrate that termination proceeds via rapid RFC-dependent hydrolysis of peptidyl-tRNA followed by slow release of peptide and tRNA from the ribosome. Ataluren is an apparent competitive inhibitor of productive RFC binding, acting at or before the hydrolysis step. We propose that designing more potent TRIDs which retain ataluren’s low toxicity should target areas of the RFC binding site proximal to the DC and PTC which do not overlap the TC binding site.
Distinctive molecular features of regenerative stem cells in the damaged male germline
Authors: La Hue M. , Liao Jinyue , Legrand Julien M. D. , Rossello Fernando J. , Chan Ai-Leen , Vaghjiani Vijesh , Cain Jason E. , Papa Antonella , Lee Tin Lap , Hobbs Robin M. 
Published: May 2022

AbstractMaintenance of male fertility requires spermatogonial stem cells (SSCs) that self-renew and generate differentiating germ cells for production of spermatozoa. Germline cells are sensitive to genotoxic drugs and patients receiving chemotherapy can become infertile. SSCs surviving treatment mediate germline recovery but pathways driving SSC regenerative responses remain poorly understood. Using models of chemotherapy-induced germline damage and recovery, here we identify unique molecular features of regenerative SSCs and characterise changes in composition of the undifferentiated spermatogonial pool during germline recovery by single-cell analysis. Increased mitotic activity of SSCs mediating regeneration is accompanied by alterations in growth factor signalling including PI3K/AKT and mTORC1 pathways. While sustained mTORC1 signalling is detrimental for SSC maintenance, transient mTORC1 activation is critical for the regenerative response. Concerted inhibition of growth factor signalling disrupts core features of the regenerative state and limits germline recovery. We also demonstrate that the FOXM1 transcription factor is a target of growth factor signalling in undifferentiated spermatogonia and provide evidence for a role in regeneration. Our data confirm dynamic changes in SSC functional properties following damage and support an essential role for microenvironmental growth factors in promoting a regenerative state.
Dynamic magnetic field alignment and polarized emission of semiconductor nanoplatelets in a liquid crystal polymer
Authors: Kim Dahin , Ndaya Dennis , Bosire Reuben , Masese Francis K. , Li Weixingyue , Thompson Sarah M. , Kagan Cherie R. , Murray Christopher B. , Kasi Rajeswari M. , Osuji Chinedum O. 
Published: May 2022

AbstractReconfigurable arrays of 2D nanomaterials are essential for the realization of switchable and intelligent material systems. Using liquid crystals (LCs) as a medium represents a promising approach, in principle, to enable such control. In practice, however, this approach is hampered by the difficulty of achieving stable dispersions of nanomaterials. Here, we report on good dispersions of pristine CdSe nanoplatelets (NPLs) in LCs, and reversible, rapid control of their alignment and associated anisotropic photoluminescence, using a magnetic field. We reveal that dispersion stability is greatly enhanced using polymeric, rather than small molecule, LCs and is considerably greater in the smectic phases of the resulting systems relative to the nematic phases. Aligned composites exhibit highly polarized emission that is readily manipulated by field-realignment. Such dynamic alignment of optically-active 2D nanomaterials may enable the development of programmable materials for photonic applications and the methodology can guide designs for anisotropic nanomaterial composites for a broad set of related nanomaterials.
Genetic diversity of SARS-CoV-2 infections in Ghana from 2020-2021
Authors: Morang’a Collins M. , Ngoi Joyce M. , Gyamfi Jones , Amuzu Dominic S. Y. , Nuertey Benjamin D. , Soglo Philip M. , Appiah Vincent , Asante Ivy A. , Owusu-Oduro Paul , Armoo Samuel , Adu-Gyasi Dennis , Amoako Nicholas , Oliver-Commey Joseph , Owusu Michael , Sylverken Augustina , Fenteng Edward D. , M’cormack Violette V. , Tei-Maya Frederick , Quansah Evelyn B. , Ayivor-Djanie Reuben , Amoako Enock K. , Ogbe Isaac T. , Yemi Bright K. , Osei-Wusu Israel , Mettle Deborah N. A. , Saiid Samirah , Tapela Kesego , Dzabeng Francis , Magnussen Vanessa , Quaye Jerry , Opurum Precious C. , Carr Rosina A. , Ababio Patrick T. , Abass Abdul-Karim , Akoriyea Samuel K. , Amoako Emmanuella , Kumi-Ansah Frederick , Boakye Oliver D. , Mibut Dam K. , Odoom Theophilus , Ofori-Boadu Lawrence , Allegye-Cudjoe Emmanuel , Dassah Sylvester , Asoala Victor , Asante Kwaku P. , Phillips Richard O. , Osei-Atweneboana Mike Y. , Gyapong John O. , Kuma-Aboagye Patrick , Ampofo William K. , Duedu Kwabena O. , Ndam Nicaise T. , Bediako Yaw , Quashie Peter K. , Amenga-Etego Lucas N. , Awandare Gordon A. 
Published: May 2022

AbstractThe COVID-19 pandemic is one of the fastest evolving pandemics in recent history. As such, the SARS-CoV-2 viral evolution needs to be continuously tracked. This study sequenced 1123 SARS-CoV-2 genomes from patient isolates (121 from arriving travellers and 1002 from communities) to track the molecular evolution and spatio-temporal dynamics of the SARS-CoV-2 variants in Ghana. The data show that initial local transmission was dominated by B.1.1 lineage, but the second wave was overwhelmingly driven by the Alpha variant. Subsequently, an unheralded variant under monitoring, B.1.1.318, dominated transmission from April to June 2021 before being displaced by Delta variants, which were introduced into community transmission in May 2021. Mutational analysis indicated that variants that took hold in Ghana harboured transmission enhancing and immune escape spike substitutions. The observed rapid viral evolution demonstrates the potential for emergence of novel variants with greater mutational fitness as observed in other parts of the world.
Preventing erosion of X-chromosome inactivation in human embryonic stem cells
Authors: Cloutier Marissa , Kumar Surinder , Buttigieg Emily , Keller Laura , Lee Brandon , Williams Aaron , Mojica-Perez Sandra , Erliandri Indri , Rocha Andre Monteiro Da , Cadigan Kenneth , Smith Gary D. , Kalantry Sundeep 
Published: May 2022

AbstractX-chromosome inactivation is a paradigm of epigenetic transcriptional regulation. Female human embryonic stem cells (hESCs) often undergo erosion of X-inactivation upon prolonged culture. Here, we investigate the sources of X-inactivation instability by deriving new primed pluripotent hESC lines. We find that culture media composition dramatically influenced the expression of XIST lncRNA, a key regulator of X-inactivation. hESCs cultured in a defined xenofree medium stably maintained XIST RNA expression and coating, whereas hESCs cultured in the widely used mTeSR1 medium lost XIST RNA expression. We pinpointed lithium chloride in mTeSR1 as a cause of XIST RNA loss. The addition of lithium chloride or inhibitors of GSK-3 proteins that are targeted by lithium to the defined hESC culture medium impeded XIST RNA expression. GSK-3 inhibition in differentiating female mouse embryonic stem cells and epiblast stem cells also resulted in a loss of XIST RNA expression. Together, these data may reconcile observed variations in X-inactivation in hESCs and inform the faithful culture of pluripotent stem cells.
Fibronectin binding protein B binds to loricrin and promotes corneocyte adhesion by Staphylococcus aureus
Authors: da Costa Thaina M. , Viljoen Albertus , Towell Aisling M. , Dufrêne Yves F. , Geoghegan Joan A. 
Published: May 2022

AbstractColonisation of humans by Staphylococcus aureus is a major risk factor for infection, yet the bacterial and host factors involved are not fully understood. The first step during skin colonisation is adhesion of the bacteria to corneocytes in the stratum corneum where the cornified envelope protein loricrin is the main ligand for S. aureus. Here we report a novel loricrin-binding protein of S. aureus, the cell wall-anchored fibronectin binding protein B (FnBPB). Single-molecule force spectroscopy revealed both weak and ultra-strong (2 nN) binding of FnBPB to loricrin and that mechanical stress enhanced the strength of these bonds. Treatment with a peptide derived from fibrinogen decreased the frequency of strong interactions, suggesting that both ligands bind to overlapping sites within FnBPB. Finally, we show that FnBPB promotes adhesion to human corneocytes by binding strongly to loricrin, highlighting the relevance of this interaction to skin colonisation.
Rationally engineering santalene synthase to readjust the component ratio of sandalwood oil
Authors: Zha Wenlong , Zhang Fan , Shao Jiaqi , Ma Xingmei , Zhu Jianxun , Sun Pinghua , Wu Ruibo , Zi Jiachen 
Published: May 2022

AbstractPlant essential oils (PEOs) are widely used in cosmetic and nutraceutical industries. The component ratios of PEOs determine their qualities. Controlling the component ratios is challenging in construction of PEO biotechnological platforms. Here, we explore the catalytic reaction pathways of both product-promiscuous and product-specific santalene synthases (i.e., SaSSy and SanSyn) by multiscale simulations. F441 of SanSyn is found as a key residue restricting the conformational dynamics of the intermediates, and thereby the direct deprotonation by the general base T298 dominantly produce α-santalene. The subsequent mutagenesis of this plastic residue leads to generation of a mutant enzyme SanSynF441V which can produce both α- and β-santalenes. Through metabolic engineering efforts, the santalene/santalol titer reaches 704.2 mg/L and the component ratio well matches the ISO 3518:2002 standard. This study represents a paradigm of constructing biotechnological platforms of PEOs with desirable component ratios by the combination of metabolic and enzymatic engineering.
Network pharmacology of iridoid glycosides from Eucommia ulmoides Oliver against osteoporosis
Authors: Wang Ting , Fan Liming , Feng Shuai , Ding Xinli , An Xinxin , Chen Jiahuan , Wang Minjuan , Zhai Xifeng , Li Yang 
Published: May 2022

AbstractEucommia ulmoides Oliver is one of the commonly used traditional Chinese medicines for the treatment of osteoporosis, and iridoid glycosides are considered to be its active ingredients against osteoporosis. This study aims to clarify the chemical components and molecular mechanism of iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis by integrating network pharmacology and molecular simulations. The active iridoid glycosides and their potential targets were retrieved from text mining as well as Swiss Target Prediction, TargetNet database, and STITCH databases. At the same time, DisGeNET, GeneCards, and Therapeutic Target Database were used to search for the targets associated with osteoporosis. A protein–protein interaction network was built to analyze the interactions between targets. Then, DAVID bioinformatics resources and R 3.6.3 project were used to carry out Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Moreover, interactions between active compounds and potential targets were investigated through molecular docking, molecular dynamic simulation, and binding free energy analysis. The results showed that a total of 12 iridoid glycosides were identified as the active iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis. Among them, aucubin, reptoside, geniposide and ajugoside were the core compounds. The enrichment analysis suggested iridoid glycosides of Eucommia ulmoides Oliver prevented osteoporosis mainly through PI3K-Akt signaling pathway, MAPK signaling pathway and Estrogen signaling pathway. Molecular docking results indicated that the 12 iridoid glycosides had good binding ability with 25 hub target proteins, which played a critical role in the treatment of osteoporosis. Molecular dynamic and molecular mechanics Poisson–Boltzmann surface area results revealed these compounds showed stable binding to the active sites of the target proteins during the simulations. In conclusion, our research demonstrated that iridoid glycosides of Eucommia ulmoides Oliver in the treatment of osteoporosis involved a multi-component, multi-target and multi-pathway mechanism, which provided new suggestions and theoretical support for treating osteoporosis.