bluuebunny/crossref_metadata_2025 huggingface dataset:
DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5
Authors: Wang Liang , Tang Liang , Xu Ruijun , Ma Junpeng , Tian Kaibing , Liu Yanbin , Lu Yanghu , Wu Zhen , Zhu Xiaodong
Published: July 2021

Chordoma is a rare bone malignancy with a high rate of local recurrence and distant metastasis. Although DEP domain-containing protein 1B (DEPDC1B) is implicated in a variety of malignancies, its relationship with chordoma is unclear. In this study, the biological role and molecular mechanism of DEPDC1B in chordoma were explored. The function of DEPDC1B in chordoma cells was clarified through loss-of-function assays in vitro and in vivo. Furthermore, molecular mechanism of DEPDC1B in chordoma cells was recognized by RNA sequencing and Co-Immunoprecipitation (Co-IP) assay. The malignant behaviors of DEPDC1B knockdown chordoma cells was significantly inhibited, which was characterized by reduced proliferation, enhanced apoptosis, and hindered migration. Consistently, decreased expression of DEPDC1B suppressed tumor growth in xenograft mice. Mechanically, DEPDC1B affected the ubiquitination of baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) through ubiquitin-conjugating enzyme E2T (UBE2T). Simultaneous downregulation of BIRC5 and DEPDC1B may exacerbate the inhibitory effects of chordoma. Moreover, BIRC5 overexpression reduced the inhibitory effects of DEPDC1B knockdown in chordoma cells. In conclusion, DEPDC1B regulates the progression of human chordoma through UBE2T-mediated ubiquitination of BIRC5, suggesting that it may be a promising candidate target with potential therapeutic value.
Alternative splicing of mRNA in colorectal cancer: new strategies for tumor diagnosis and treatment
Authors: Chen Yanyan , Huang Mengxi , Liu Xiaolong , Huang Yadi , Liu Chao , Zhu Jialong , Fu Gongbo , Lei Zengjie , Chu Xiaoyuan
Published: July 2021

Alternative splicing (AS) is an important event that contributes to posttranscriptional gene regulation. This process leads to several mature transcript variants with diverse physiological functions. Indeed, disruption of various aspects of this multistep process, such as cis- or trans- factor alteration, promotes the progression of colorectal cancer. Therefore, targeting some specific processes of AS may be an effective therapeutic strategy for treating cancer. Here, we provide an overview of the AS events related to colorectal cancer based on research done in the past 5 years. We focus on the mechanisms and functions of variant products of AS that are relevant to malignant hallmarks, with an emphasis on variants with clinical significance. In addition, novel strategies for exploiting the therapeutic value of AS events are discussed.
Hippo-YAP/MCP-1 mediated tubular maladaptive repair promote inflammation in renal failed recovery after ischemic AKI
Authors: Zheng Zhihuang , Li Chuanlei , Shao Guangze , Li Jinqing , Xu Kexin , Zhao Zhonghua , Zhang Zhigang , Liu Jun , Wu Huijuan
Published: July 2021

Acute kidney injury (AKI) is associated with significant morbidity and its chronic inflammation contributes to subsequent chronic kidney disease (CKD) development. Yes-associated protein (YAP), the major transcriptional coactivator of the Hippo pathway, has been shown associated with chronic inflammation, but its role and mechanism in AKI-CKD transition remain unclear. Here we aimed to investigate the role of YAP in AKI-induced chronic inflammation. Renal ischemia/reperfusion (I/R) was used to induce a mouse model of AKI-CKD transition. We used verteporfin (VP), a pharmacological inhibitor of YAP, to treat post-IRI mice for a period, and evaluated the influence of YAP inhibition on long-term outcomes of AKI. In our results, severe IRI led to maladaptive tubular repair, macrophages infiltration, and progressive fibrosis. Following AKI, the Hippo pathway was found significantly altered with YAP persistent activation. Besides, tubular YAP activation was associated with the maladaptive repair, also correlated with interstitial macrophage infiltration. Monocyte chemoattractant protein 1 (MCP-1) was found notably upregulated with YAP activation. Of note, pharmacological inhibition of YAP in vivo attenuated renal inflammation, including macrophage infiltration and MCP-1 overexpression. Consistently, in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) induced YAP activation and MCP-1 overproduction whereas these could be inhibited by VP. In addition, we modulated YAP activity by RNA interference, which further confirmed YAP activation enhances MCP-1 expression. Together, we concluded tubular YAP activation with maladaptive repair exacerbates renal inflammation probably via promoting MCP-1 production, which contributes to AKI-CKD transition.
RETRACTED ARTICLE: AKT3-mediated IWS1 phosphorylation promotes the proliferation of EGFR-mutant lung adenocarcinomas through cell cycle-regulated U2AF2 RNA splicing
Authors: Laliotis Georgios I. , Chavdoula Evangelia , Paraskevopoulou Maria D. , Kaba Abdul , La Ferlita Alessandro , Singh Satishkumar , Anastas Vollter , Nair Keith A. , Orlacchio Arturo , Taraslia Vasiliki , Vlachos Ioannis , Capece Marina , Hatzigeorgiou Artemis , Palmieri Dario , Tsatsanis Christos , Alaimo Salvatore , Sehgal Lalit , Carbone David P. , Coppola Vincenzo , Tsichlis Philip N.
Published: July 2021

AKT-phosphorylated IWS1 regulates alternative RNA splicing via a pathway that is active in lung cancer. RNA-seq studies in lung adenocarcinoma cells lacking phosphorylated IWS1, identified a exon 2-deficientU2AF2splice variant. Here, we show that exon 2 inclusion in theU2AF2mRNA is a cell cycle-dependent process that is regulated by LEDGF/SRSF1 splicing complexes, whose assembly is controlled by the IWS1 phosphorylation-dependent deposition of histone H3K36me3 marks in the body of target genes. The exon 2-deficientU2AF2mRNA encodes a Serine-Arginine-Rich (RS) domain-deficient U2AF65, which is defective inCDCA5pre-mRNA processing. This results in downregulation of theCDCA5-encoded protein Sororin, a phosphorylation target and regulator of ERK, G2/M arrest and impaired cell proliferation and tumor growth. Analysis of human lung adenocarcinomas, confirmed activation of the pathway inEGFR-mutant tumors and showed that pathway activity correlates with tumor stage, histologic grade, metastasis, relapse after treatment, and poor prognosis.
PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma
Authors: Giuliani Virginia , Miller Meredith A. , Liu Chiu-Yi , Hartono Stella R. , Class Caleb A. , Bristow Christopher A. , Suzuki Erika , Sanz Lionel A. , Gao Guang , Gay Jason P. , Feng Ningping , Rose Johnathon L. , Tomihara Hideo , Daniele Joseph R. , Peoples Michael D. , Bardenhagen Jennifer P. , Geck Do Mary K. , Chang Qing E. , Vangamudi Bhavatarini , Vellano Christopher , Ying Haoqiang , Deem Angela K. , Do Kim-Anh , Genovese Giannicola , Marszalek Joseph R. , Kovacs Jeffrey J. , Kim Michael , Fleming Jason B. , Guccione Ernesto , Viale Andrea , Maitra Anirban , Emilia Di Francesco M. , Yap Timothy A. , Jones Philip , Draetta Giulio , Carugo Alessandro , Chedin Frederic , Heffernan Timothy P.
Published: July 2021

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.

Statement of significance

PDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.
Skeletal stem and progenitor cells maintain cranial suture patency and prevent craniosynostosis
Authors: Menon Siddharth , Salhotra Ankit , Shailendra Siny , Tevlin Ruth , Ransom Ryan C. , Januszyk Michael , Chan Charles K. F. , Behr Björn , Wan Derrick C. , Longaker Michael T. , Quarto Natalina
Published: July 2021

Cranial sutures are major growth centers for the calvarial vault, and their premature fusion leads to a pathologic condition called craniosynostosis. This study investigates whether skeletal stem/progenitor cells are resident in the cranial sutures. Prospective isolation by FACS identifies this population with a significant difference in spatio-temporal representation between fusing versus patent sutures. Transcriptomic analysis highlights a distinct signature in cells derived from the physiological closing PF suture, and scRNA sequencing identifies transcriptional heterogeneity among sutures. Wnt-signaling activation increases skeletal stem/progenitor cells in sutures, whereas its inhibition decreases. CrossingAxin2LacZ/+mouse, endowing enhanced Wnt activation, to aTwist1+/−mouse model of coronal craniosynostosis enriches skeletal stem/progenitor cells in sutures restoring patency. Co-transplantation of these cells with Wnt3a prevents resynostosis following suturectomy inTwist1+/−mice. Our study reveals that decrease and/or imbalance of skeletal stem/progenitor cells representation within sutures may underlie craniosynostosis. These findings have translational implications toward therapeutic approaches for craniosynostosis.
Quasi-equilibrium phase coexistence in single component supercritical fluids
Authors: Lee Seungtaek , Lee Juho , Kim Yeonguk , Jeong Seokyong , Kim Dong Eon , Yun Gunsu
Published: July 2021

In their supercritical state simple fluids are generally thought to assume a homogeneous phase throughout all combinations of pressures and temperatures, although various response functions or transport properties may exhibit anomalous behavior, characterizing a state point as either more gas-like or liquid-like, respectively. While a large body of results has been compiled in the last two decades regarding the details of the supercritical phase in thermodynamic equilibrium, far less studies have been dedicated to out-of-equilibrium situations that nevertheless occur along with the handling of substances such as carbon dioxide or Argon. Here we consider successive compression-expansion cycles of equal amounts of Argon injected into a high-pressure chamber, traversing the critical pressure at two times the critical temperature. Due to expansion cooling, the fluid temporarily becomes sub-critical, and light scattering experiments show the formation of sub-micron-sized droplets and nanometer-scale clusters, both of which are distinct from spontaneous density fluctuations of the supercritical background and persist for a surprisingly long time. A kinetic rate model of the exchange of liquid droplets with the smaller clusters can explain this behavior. Our results indicate non-equilibrium aspects of supercritical fluids that may prove important for their processing in industrial applications.
Mobility patterns are associated with experienced income segregation in large US cities
Authors: Moro Esteban , Calacci Dan , Dong Xiaowen , Pentland Alex
Published: July 2021

Traditional understanding of urban income segregation is largely based on static coarse-grained residential patterns. However, these do not capture the income segregation experience implied by the rich social interactions that happen in places that may relate to individual choices, opportunities, and mobility behavior. Using a large-scale high-resolution mobility data set of 4.5 million mobile phone users and 1.1 million places in 11 large American cities, we show that income segregation experienced in places and by individuals can differ greatly even within close spatial proximity. To further understand these fine-grained income segregation patterns, we introduce a Schelling extension of a well-known mobility model, and show that experienced income segregation is associated with an individual’s tendency to explore new places (place exploration) as well as places with visitors from different income groups (social exploration). Interestingly, while the latter is more strongly associated with demographic characteristics, the former is more strongly associated with mobility behavioral variables. Our results suggest that mobility behavior plays an important role in experienced income segregation of individuals. To measure this form of income segregation, urban researchers should take into account mobility behavior and not only residential patterns.
Badland landscape response to individual geomorphic events
Authors: Yang Ci-Jian , Turowski Jens M. , Hovius Niels , Lin Jiun-Chuan , Chang Kuo-Jen
Published: July 2021

Landscapes form by the erosion and deposition of sediment, driven by tectonic and climatic forcing. The principal geomorphic processes of badland – landsliding, debris flow and runoff erosion – are similar to those in full scale mountain topography, but operate faster. Here, we show that in the badlands of SW Taiwan, individual rainfall events cause quantifiable landscape change, distinct for the type of rainfall. Typhoon rain reduced hillslope gradients, while lower-intensity precipitation either steepened or flattened the landscape, depending on its initial topography. The steep topography observed in our first survey is inconsistent with the effects of any of the rainfall events. We suggest that it is due to the 2016 Mw 6.4 Meinong earthquake. The observed pattern in the badlands was mirrored in the response of the Taiwan mountain topography to typhoon Morakot in 2009, confirming that badlands offer special opportunities to quantify natural landscape dynamics on observational time scales.
A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial
Authors: Folegatti Pedro M. , Harrison Kate , Preciado-Llanes Lorena , Lopez Fernando Ramos , Bittaye Mustapha , Kim Young Chan , Flaxman Amy , Bellamy Duncan , Makinson Rebecca , Sheridan Jonathan , Azar Sasha R. , Campos Rafael Kroon , Tilley Mark , Tran Nguyen , Jenkin Daniel , Poulton Ian , Lawrie Alison , Roberts Rachel , Berrie Eleanor , Rossi Shannan L. , Hill Adrian , Ewer Katie J. , Reyes-Sandoval Arturo
Published: July 2021

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.
Exites in Cambrian arthropods and homology of arthropod limb branches
Authors: Liu Yu , Edgecombe Gregory D. , Schmidt Michel , Bond Andrew D. , Melzer Roland R. , Zhai Dayou , Mai Huijuan , Zhang Maoyin , Hou Xianguang
Published: July 2021

The last common ancestor of all living arthropods had biramous postantennal appendages, with an endopodite and exopodite branching off the limb base. Morphological evidence for homology of these rami between crustaceans and chelicerates has, however, been challenged by data from clonal composition and from knockout of leg patterning genes. Cambrian arthropod fossils have been cited as providing support for competing hypotheses about biramy but have shed little light on additional lateral outgrowths, known as exites. Here we draw on microtomographic imaging of the Cambrian great-appendage arthropodLeanchoiliato reveal a previously undetected exite at the base of most appendages, composed of overlapping lamellae. A morphologically similar, and we infer homologous, exite is documented in the same position in members of the trilobite-allied Artiopoda. This early Cambrian exite morphology supplements an emerging picture from gene expression that exites may have a deeper origin in arthropod phylogeny than has been appreciated.
Engineering polar vortex from topologically trivial domain architecture
Authors: Tan Congbing , Dong Yongqi , Sun Yuanwei , Liu Chang , Chen Pan , Zhong Xiangli , Zhu Ruixue , Liu Mingwei , Zhang Jingmin , Wang Jinbin , Liu Kaihui , Bai Xuedong , Yu Dapeng , Ouyang Xiaoping , Wang Jie , Gao Peng , Luo Zhenlin , Li Jiangyu
Published: July 2021

Topologically nontrivial polar structures are not only attractive for high-density data storage, but also for ultralow power microelectronics thanks to their exotic negative capacitance. The vast majority of polar structures emerging naturally in ferroelectrics, however, are topologically trivial, and there are enormous interests in artificially engineered polar structures possessing nontrivial topology. Here we demonstrate reconstruction of topologically trivial strip-like domain architecture into arrays of polar vortex in (PbTiO3)10/(SrTiO3)10 superlattice, accomplished by fabricating a cross-sectional lamella from the superlattice film. Using a combination of techniques for polarization mapping, atomic imaging, and three-dimensional structure visualization supported by phase field simulations, we reveal that the reconstruction relieves biaxial epitaxial strain in thin film into a uniaxial one in lamella, changing the subtle electrostatic and elastostatic energetics and providing the driving force for the polar vortex formation. The work establishes a realistic strategy for engineering polar topologies in otherwise ordinary ferroelectric superlattices.
Cryo-EM structure of mycobacterial cytochrome bd reveals two oxygen access channels
Authors: Wang Weiwei , Gao Yan , Tang Yanting , Zhou Xiaoting , Lai Yuezheng , Zhou Shan , Zhang Yuying , Yang Xiuna , Liu Fengjiang , Guddat Luke W. , Wang Quan , Rao Zihe , Gong Hongri
Published: July 2021

Cytochromes bd are ubiquitous amongst prokaryotes including many human-pathogenic bacteria. Such complexes are targets for the development of antimicrobial drugs. However, an understanding of the relationship between the structure and functional mechanisms of these oxidases is incomplete. Here, we have determined the 2.8 Å structure of Mycobacterium smegmatis cytochrome bd by single-particle cryo-electron microscopy. This bd oxidase consists of two subunits CydA and CydB, that adopt a pseudo two-fold symmetrical arrangement. The structural topology of its Q-loop domain, whose function is to bind the substrate, quinol, is significantly different compared to the C-terminal region reported for cytochromes bd from Geobacillus thermodenitrificans (G. th) and Escherichia coli (E. coli). In addition, we have identified two potential oxygen access channels in the structure and shown that similar tunnels also exist in G. th and E. coli cytochromes bd. This study provides insights to develop a framework for the rational design of antituberculosis compounds that block the oxygen access channels of this oxidase.
Plasmodium falciparum transcription in different clinical presentations of malaria associates with circulation time of infected erythrocytes
Authors: Thomson-Luque Richard , Votborg-Novél Lasse , Ndovie Wanangwa , Andrade Carolina M. , Niangaly Moussa , Attipa Charalampos , Lima Nathalia F. , Coulibaly Drissa , Doumtabe Didier , Guindo Bouréima , Tangara Bourama , Maiga Fayçal , Kone Abdoulaye Kassoum , Traore Karim , Kayentao Kassoum , Ongoiba Aissata , Doumbo Safiatou , Thera Mahamadou A. , Traoré Boubacar , Seydel Karl , Osório Nuno S. , Portugal Silvia
Published: July 2021

Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one or more severe malaria symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions have yet been drawn. Here, we apply a series of bioinformatic approaches based on P. falciparum’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to publicly available transcriptomes of parasites obtained from malaria cases of differing clinical severity across multiple studies. Our analysis shows that within each IDC, the circulation time of infected erythrocytes without sequestering to endothelial cells decreases with increasing parasitaemia or disease severity. Accordingly, we find that the size of circulating infected erythrocytes is inversely related to parasite density and disease severity. We propose that enhanced adhesiveness of infected erythrocytes leads to a rapid increase in parasite burden, promoting higher parasitaemia and increased disease severity.
Modelling a multiplex brain network by local transfer entropy
Authors: Parente Fabrizio , Colosimo Alfredo
Published: July 2021

This paper deals with the information transfer mechanisms underlying causal relations between brain regions under resting condition. fMRI images of a large set of healthy individuals from the 1000 Functional Connectomes Beijing Zang dataset have been considered and the causal information transfer among brain regions studied using Transfer Entropy concepts. Thus, we explored the influence of a set of states in two given regions at time t (At Bt.) over the state of one of them at a following time step (Bt+1) and could observe a series of time-dependent events corresponding to four kinds of interactions, or causal rules, pointing to (de)activation and turn off mechanisms and sharing some features with positive and negative functional connectivity. The functional architecture emerging from such rules was modelled by a directional multilayer network based upon four interaction matrices and a set of indexes describing the effects of the network structure in several dynamical processes. The statistical significance of the models produced by our approach was checked within the used database of homogeneous subjects and predicts a successful extension, in due course, to detect differences among clinical conditions and cognitive states.
Sublinear domination and core–periphery networks
Authors: Papachristou Marios
Published: July 2021

In this paper we devise a generative random network model with core–periphery properties whose core nodes act as sublinear dominators, that is, if the network has n nodes, the core has size o(n) and dominates the entire network. We show that instances generated by this model exhibit power law degree distributions, and incorporates small-world phenomena. We also fit our model in a variety of real-world networks.
Antagonist effects of grain boundaries between the trapping process and the fast diffusion path in nickel bicrystals
Authors: Li J. , Hallil A. , Metsue A. , Oudriss A. , Bouhattate J. , Feaugas X.
Published: July 2021

Hydrogen-grain-boundaries interactions and their role in intergranular fracture are well accepted as one of the key features in understanding hydrogen embrittlement in a large variety of common engineer situations. These interactions implicate some fundamental processes classified as segregation, trapping and diffusion of the solute which can be studied as a function of grain boundary configuration. In the present study, we carried out an extensive analysis of four grain-boundaries based on the complementary of atomistic calculations and experimental data. We demonstrate that elastic deformation has an important contribution on the segregation energy which cannot be simply reduced to a volume change and need to consider the deviatoric part of strain. Additionally, some significant configurations of the segregation energy depend on the long-range elastic distortion and allows to rationalize the elastic contribution in three terms. By investigating the different energy barriers involved to reach all the segregation sites, the antagonist impact of grain boundaries on hydrogen diffusion and trapping process was elucidated. The segregation energy and migration energy are two fundamental parameters in order to classify the grain-boundaries as a trapping location or short circuit for diffusion.
Brain-dead and coma patients exhibit different serum metabolic profiles: preliminary investigation of a novel diagnostic approach in neurocritical care
Authors: Dawiskiba Tomasz , Wojtowicz Wojciech , Qasem Badr , Łukaszewski Marceli , Mielko Karolina Anna , Dawiskiba Agnieszka , Banasik Mirosław , Skóra Jan Paweł , Janczak Dariusz , Młynarz Piotr
Published: July 2021

There is a clear difference between severe brain damage and brain death. However, in clinical practice, the differentiation of these states can be challenging. Currently, there are no laboratory tools that facilitate brain death diagnosis. The aim of our study was to evaluate the utility of serum metabolomic analysis in differentiating coma patients (CP) from individuals with brain death (BD). Serum samples were collected from 23 adult individuals with established diagnosis of brain death and 24 patients in coma with Glasgow Coma Scale 3 or 4, with no other clinical symptoms of brain death for at least 7 days after sample collection. Serum metabolomic profiles were investigated using proton nuclear magnetic resonance (NMR) spectroscopy. The results obtained were examined by univariate and multivariate data analysis (PCA, PLS-DA, and OPLS-DA). Metabolic profiling allowed us to quantify 43 resonance signals, of which 34 were identified. Multivariate statistical modeling revealed a highly significant separation between coma patients and brain-dead individuals, as well as strong predictive potential. The findings not only highlight the potential of the metabolomic approach for distinguishing patients in coma from those in the state of brain death but also may provide an understanding of the pathogenic mechanisms underlying these conditions.
A neural pathomics framework for classifying colorectal cancer histopathology images based on wavelet multi-scale texture analysis
Authors: Trivizakis Eleftherios , Ioannidis Georgios S. , Souglakos Ioannis , Karantanas Apostolos H. , Tzardi Maria , Marias Kostas
Published: July 2021

Colorectal cancer (CRC) constitutes the third most commonly diagnosed cancer in males and the second in females. Precise histopathological classification of CRC tissue pathology is the cornerstone not only for diagnosis but also for patients’ management decision making. An automated system able to accurately classify different CRC tissue regions may increase diagnostic precision and alleviate clinical workload. However, tissue classification is a challenging task due to the variability in morphological and textural characteristics present in histopathology images. In this study, an artificial neural network was trained to classify between eight classes of CRC tissue image patches derived from a public dataset with 5000 CRC histopathology image tiles. A total of 532 multi-level pathomics features examined at different scales were extracted by visual descriptors such as local binary patterns, wavelet transforms and Gabor filters. An exhaustive evaluation involving a variety of wavelet families and parameters was performed in order to shed light on the impact of scale on pathomics based CRC tissue differentiation. Our model achieved a performance accuracy of 95.3% with tenfold cross validation demonstrating superior performance compared to 87.4% reported in recent studies. Furthermore, we experimentally showed that the first and the second levels of the wavelet approximations can be used without compromising classification performance.
High-resolution model of Arabidopsis Photosystem II reveals the structural consequences of digitonin-extraction
Authors: Graça André T. , Hall Michael , Persson Karina , Schröder Wolfgang P.
Published: July 2021

In higher plants, the photosynthetic process is performed and regulated by Photosystem II (PSII). Arabidopsis thaliana was the first higher plant with a fully sequenced genome, conferring it the status of a model organism; nonetheless, a high-resolution structure of its Photosystem II is missing. We present the first Cryo-EM high-resolution structure of Arabidopsis PSII supercomplex with average resolution of 2.79 Å, an important model for future PSII studies. The digitonin extracted PSII complexes demonstrate the importance of: the LHG2630-lipid-headgroup in the trimerization of the light-harvesting complex II; the stabilization of the PsbJ subunit and the CP43-loop E by DGD520-lipid; the choice of detergent for the integrity of membrane protein complexes. Furthermore, our data shows at the anticipated Mn4CaO5-site a single metal ion density as a reminiscent early stage of Photosystem II photoactivation.
Earthworms drastically change fungal and bacterial communities during vermicomposting of sewage sludge
Authors: Domínguez Jorge , Aira Manuel , Crandall Keith A. , Pérez-Losada Marcos
Published: July 2021

Wastewater treatment plants produce hundreds of million tons of sewage sludge every year all over the world. Vermicomposting is well established worldwide and has been successful at processing sewage sludge, which can contribute to alleviate the severe environmental problems caused by its disposal. Here, we utilized 16S and ITS rRNA high-throughput sequencing to characterize bacterial and fungal community composition and structure during the gut- and cast-associated processes (GAP and CAP, respectively) of vermicomposting of sewage sludge. Bacterial and fungal communities of earthworm casts were mainly composed of microbial taxa not found in the sewage sludge; thus most of the bacterial (96%) and fungal (91%) taxa in the sewage sludge were eliminated during vermicomposting, mainly through the GAP. Upon completion of GAP and during CAP, modified microbial communities undergo a succession process leading to more diverse microbiotas than those found in sewage sludge. Consequently, bacterial and fungal community composition changed significantly during vermicomposting. Vermicomposting of sewage resulted in a stable and rich microbial community with potential biostimulant properties that may aid plant growth. Our results support the use of vermicompost derived from sewage sludge for sustainable agricultural practices, if heavy metals or other pollutants are under legislation limits or adequately treated.
Manually scanned single fiber optical coherence tomography for skin cancer characterization
Authors: Chuchvara Nadiya , Rao Babar , Liu Xuan
Published: July 2021

Optical coherence tomography (OCT) is a cross-sectional imaging modality based on low coherence light interferometry. Within dermatology, it has found applications for in vivo diagnostic imaging purposes, as well as to guide Mohs micrographic surgery (MMS), due to its ability to visualize skin morphology up to several millimeters in depth. However, standard OCT probes have a large footprint and capture an extended area of the skin, making it difficult to precisely pinpoint clinically relevant location being imaged. Mohs surgeons stand to benefit from a handheld in vivo imaging device that can accurately trace surgical margins. In this study, we demonstrate the use of a single fiber OCT (sfOCT) instrument. Our imaging system features a miniature common path single fiber probe, and a novel speckle decorrelation technique that generates distortion free 2D images from manual scanning.By manually moving the single-fiber probe across the region of interest, the user can perform a lateral OCT scan while visualizing the location of the probe during data acquisition. Using the sfOCT, we have identified normal skin morphology, qualitatively correlated features of basal cell carcinoma and squamous cell carcinoma with histopathology, and quantified the disruption of the dermo-epidermal junction OCT pattern in skin tumors—each demonstrating the potential of utilizing sfOCT to differentiate tumor from normal skin. Using this imaging tool, a Mohs surgeon can enhance determination of surgical margins for the first stage of MMS, potentially decreasing the time and number of stages required for complete tumor removal.
Dynamic changes in mitochondrial 3D structure during folliculogenesis and luteal formation in the goat large luteal cell lineage
Authors: Jiang Yi-Fan , Yu Pin-Huan , Budi Yovita Permata , Chiu Chih-Hsien , Fu Chi-Yu
Published: July 2021

In mammalian ovaries, mitochondria are integral sites of energy production and steroidogenesis. While shifts in cellular activities and steroidogenesis are well characterized during the differentiation of large luteal cells in folliculogenesis and luteal formation, mitochondrial dynamics during this process have not been previously evaluated. In this study, we collected ovaries containing primordial follicles, mature follicles, corpus hemorrhagicum, or corpus luteum from goats at specific times in the estrous cycle. Enzyme histochemistry, ultrastructural observations, and 3D structural analysis of serial sections of mitochondria revealed that branched mitochondrial networks were predominant in follicles, while spherical and tubular mitochondria were typical in large luteal cells. Furthermore, the average mitochondrial diameter and volume increased from folliculogenesis to luteal formation. In primordial follicles, the signals of cytochrome c oxidase and ATP synthase were undetectable in most cells, and the large luteal cells from the corpus hemorrhagicum also showed low enzyme signals and content when compared with granulosa cells in mature follicles or large luteal cells from the corpus luteum. Our findings suggest that the mitochondrial enlargement could be an event during folliculogenesis and luteal formation, while the modulation of mitochondrial morphology and respiratory enzyme expressions may be related to tissue remodeling during luteal formation.
Acetate sensing by GPR43 alarms neutrophils and protects from severe sepsis
Authors: Schlatterer Katja , Beck Christian , Schoppmeier Ulrich , Peschel Andreas , Kretschmer Dorothee
Published: July 2021

Bacterial sepsis is a major cause of mortality resulting from inadequate immune responses to systemic infection. Effective immunomodulatory approaches are urgently needed but it has remained elusive, which targets might be suitable for intervention. Increased expression of the G-protein-coupled receptor GPR43, which is known to govern intestinal responses to acetate, has been associated with sepsis patient survival but the mechanisms behind this observation have remained unclear. We show that elevated serum acetate concentrations prime neutrophils in a GPR43-dependent fashion, leading to enhanced neutrophil chemotaxis, oxidative burst, cytokine release and upregulation of phagocytic receptors. Consequently, acetate priming improved the capacity of human neutrophils to eliminate methicillin-resistant Staphylococcus aureus. Acetate administration increased mouse serum acetate concentrations and primed neutrophils. Notably, it rescued wild-type mice from severe S. aureus sepsis and reduced bacterial numbers in peripheral organs by several magnitudes. Acetate treatment improved the sepsis course even when applied several hours after onset of the infection, which recommends GPR43 as a potential target for sepsis therapy. Our study indicates that the severity of sepsis depends on transient neutrophil priming by appropriate blood acetate concentrations. Therapeutic interventions based on GPR43 stimulation could become valuable strategies for reducing sepsis-associated morbidity and mortality.
Force-mediated molecule release from double network hydrogels
Authors: Jayathilaka Pavithra Bhakthi , Molley Thomas Gregory , Huang Yuwan , Islam Md Shariful , Buche Michael Robert , Silberstein Meredith Natania , Kruzic Jamie Joseph , Kilian Kristopher Alan
Published: July 2021

Mechanochemical release of molecules through a retro Diels–Alder reaction is demonstrated within double network hydrogels.
From water-rich to oil-rich gelled non-toxic microemulsions
Authors: Peng Ke , Preisig Natalie , Sottmann Thomas , Stubenrauch Cosima
Published: July 2021

Gelled non-toxic microemulsions have great potential in transdermal drug delivery: the microemulsion provides optimum solubilization for drugs and promotes drug permeation through skin barrier, while the gel network provides mechanical stability.
Non-Arrhenius kinetics and slowed-diffusion mechanism of molecular aggregation of a rhodamine dye on colloidal particles
Authors: Šimonová Baranyaiová Tímea , Mészáros Róbert , Sebechlebská Táňa , Bujdák Juraj
Published: July 2021

The formation of dye molecular aggregates takes place through two parallel diffusion processes: by intermittent lateral diffusion of dye cations and by their inter-particle diffusion initiated by the collisions between the colloidal particles.
14-Electron Rh and Ir silylphosphine complexes and their catalytic activity in alkene functionalization with hydrosilanes
Authors: Abeynayake Niroshani S. , Zamora-Moreno Julio , Gorla Saidulu , Donnadieu Bruno , Muñoz-Hernández Miguel A. , Montiel-Palma Virginia
Published: July 2021

14-electron Rh and Ir species as robust catalysts for silicon functionalization.
Synthesis and evaluation of the anticancer activity of [Pt(diimine)(N,N-dibutyl-N′-acylthiourea)]+ complexes
Authors: Peega Tebogo , Magwaza Rachael N. , Harmse Leonie , Kotzé Izak A.
Published: July 2021

A series of platinum(ii) diimine acylthiourea complexes are reported with potent in vitro activity against two lung cancer cell lines (A549 and H1975) and a colorectal cancer cell line (HT-29) by inducing cell death by both apoptosis and paraptosis.
Alternative ball-milling synthesis of vanadium-substituted polyoxometalates as catalysts for the aerobic cleavage of C–C and C–O bonds
Authors: Al-Hussaini Louay , Valange Sabine , Gálvez Maria Elena , Launay Franck
Published: July 2021

Ball-milling-based synthesis of vanadium-substituted phosphomolybdic acid enables energy saving while improving the yield and providing active catalysts for aerobic oxidative cleavage.
Breaking the symmetry: C1-salans with (N–H) backbones
Authors: Devonport Jack , Spencer John , Kostakis George E.
Published: July 2021

We disclose a synthetic route that providess an unprecedented library of C1 salan ligands endowed with (N–H) backbones, previously limited to N-methylated backbones.
Metal specificity of the Ni(ii) and Zn(ii) binding sites of the N-terminal and G-domain of E. coli HypB
Authors: Hecel Aleksandra , Kola Arian , Valensin Daniela , Kozlowski Henryk , Rowinska-Zyrek Magdalena
Published: July 2021

HypB is one of the chaperones required for proper nickel insertion into [NiFe]-hydrogenase.
Make it stereoscopic: interfacial design for full-temperature adaptive flexible zinc–air batteries
Authors: Pei Zengxia , Ding Luyao , Wang Cheng , Meng Qiangqiang , Yuan Ziwen , Zhou Zheng , Zhao Shenlong , Chen Yuan
Published: July 2021

A flexible zinc–air battery fabricated from a stereoscopic air-cathode and a rationalized polyelectrolyte affords excellent electrochemical performances with flexibility in a broad temperature range of −30 to 80 °C.
Potential prebiotic properties of exopolysaccharides produced by a novelLactobacillusstrain,Lactobacillus pentosusYY-112
Authors: Wang Mingzhe , Zhou Wanyi , Yang Ying , Xing Jianrong , Xu Xiaodan , Lin Yuqing
Published: July 2021

EPSs produced byLactobacillus pentosusYY-112 were promising for development into prebiotics with potential health benefits.
Visible-light-driven radical 1,3-addition of selenosulfonates to vinyldiazo compounds
Authors: Li Weiyu , Zhou Lei
Published: July 2021

A visible-light driven 1,3-selenosulfonylation of vinyldiazo compounds with selenosulfonates provided γ-seleno allylic sulfones in good yields. Control experiments showed that the 1,3-addition proceededviaa radical-chain propagation process.
Characterization of laser-induced breakdown spectroscopy on tungsten at variable ablation angles using a coaxial system in a vacuum
Authors: Wu Huace , Li Cong , Wu Ding , Liu Jiamin , He Zhonglin , Li Qianhui , Yuan Shu , Cui Xiaoqian , Hai Ran , Ding Hongbin
Published: July 2021

In this work, a LIBS system with a coaxial collection configuration based on the linear array fiber bundle is developed to investigate the features of laser-induced tungsten (W) plasma spectra at variable LAAs under vacuum conditions.
A novel strategy for direct elemental determination using laser-induced breakdown spectroscopy: fluence calibration
Authors: Machado Raquel C. , Babos Diego Victor , Andrade Daniel F. , Pereira-Filho Edenir Rodrigues
Published: July 2021

Fluence calibration is a novel nontraditional calibration method for LIBS analysis which requires only one standard and two fluence values to build a linear model and allows faster and simpler pellet preparation, acquisition and data treatment.
Construction of S-doped MgO coupled with g-C3N4 nanocomposites with enhanced photocatalytic activity under visible light irradiation
Authors: Chen Yuwei , Jiang Yongfeng , Chen Bingyan , Ye Fanglong , Duan Huaqiang , Cui Haoyu
Published: July 2021

In the present work, a series of photocatalysts in which S-MgO (SM) was coupled with g-C3N4 (CN) were synthesized and characterized in detail using various characterization techniques.
Nanocomplex made up of antimicrobial metallo-supramolecules and model biomembranes – characterization and enhanced fluorescence
Authors: Liu Chung-Hao , Wang Heng , Yang Lin , Liu Yun , Li Xiaopeng , Nieh Mu-Ping
Published: July 2021

Antimicrobial 3-D supramolecular hexagonal prisms can be entrapped by lipid discoidal bicelles, forming a well-defined nanocomplex. Such a nanocomplex emits the three-fold intensity compared to its solution form, making it a candidate for theranostic applications.
Recent advances in the synthesis of pyrrolo[1,2-a]indoles and their derivatives
Authors: Shelke Yogesh G. , Hande Pankaj E. , Gharpure Santosh J.
Published: July 2021

This review focuses on recent developments in the synthesis of pyrrolo[1,2-a]indole derivatives. The mechanism, factors affecting the yield and selectivity of the product, and application to the synthesis of bioactive molecules are explained.
Facile preparation of a polysilsesquioxane sheet with a three-dimensional structure
Authors: Li Meng , Hao Bin , Zhang Linsheng , Li Hui , Lv Peng , Yue Xiu , Yasin Akram , Ma Peng-Cheng
Published: July 2021

A polysilsesquioxane (PSQ) sheet with novel three-dimensional networks was reported. The formation of the unique structure was mainly dominated by the alkyl long-chain in the silane.
Steric shelter-free cobalt nanoparticle-based high-sensitive biomimetic superoxide anion sensor
Authors: Zou Zhuo , Shi Zhuan Zhuan , Yuan Cheng Song , Tang Chu Yue , Wu Chao , Liang Tao Tao , Tang Kang Lai , Chen Hong , Bin Yang Hong , Li Chang Ming
Published: July 2021

Here, unique cobalt nanoparticles were deposited on nitrogen-doped graphene as an enzyme-free biomimetic sensor for superoxide anion detection with excellent selectivity, high sensitivity and a fast response.
The impact of fluence dependent 120 MeV Ag swift heavy ion irradiation on the changes in structural, electronic, and optical properties of AgInSe2 nano-crystalline thin films for optoelectronic applications
Authors: Panda R. , Khan S. A. , Singh U. P. , Naik R. , Mishra N. C.
Published: July 2021

Swift heavy ion (SHI) irradiation in thin films significantly modifies the structure and related properties in a controlled manner.
MFI zeolite-supported Ru nanoparticles for efficient conversion of pyroglutamic acid to 2-pyrrolidone
Authors: Otani Akihiro , Kuroda Masaya , Suganuma Satoshi , Tsuji Etsushi , Katada Naonobu
Published: July 2021

Ru/MFI provided high 2-pyrrolidone yield in the conversion of pyroglutamic acid through hydrogenation and decarbonylation.
On the limit of proton-coupled electronic doping in a Ti(iv)-containing MOF
Authors: Mancuso Jenna L. , Fabrizio Kevin , Brozek Carl K. , Hendon Christopher H.
Published: July 2021

Photo-promoted doping of MIL-125 is limited by the potential of MOF-bound protons exceeding the hydrogen evolution reaction.
‘Reverse biomimetic’ synthesis of l-arogenate and its stabilized analogues from l-tyrosine
Authors: Eagling Louise , Leonard Daniel J. , Schwarz Maria , Urruzuno Iñaki , Boden Grace , Wailes J. Steven , Ward John W. , Clayden Jonathan
Published: July 2021

l-Tyrosine provides a precursor for a practical synthesis of the unstable primary metabolite l-arogenate and some stabilised arogenate analogues.
High thermoelectric efficiency in electrodeposited silver selenide films: from Pourbaix diagram to a flexible thermoelectric module
Authors: Manzano Cristina V. , Llorente del Olmo Cristina , Caballero-Calero Olga , Martín-González Marisol
Published: July 2021

High thermoelectric efficient is obtained in electrodeposited silver selenide films and a unileg flexible thermoelectric module is fabricated with a maximum power density of 138.6 mW m−2 at 19 K.
The rapid and controllable fabrication of large-scale and highly ordered micro-honeycomb arrays induced by nonsolvent phase separation
Authors: Zhang Xiaoyu , Wang Shuya , Han Shengpeng , Ouyang Xiao , Ma Ning , Wei Hao , Zhang Xinyue
Published: July 2021

Structures that are highly ordered in nature show unique light propagation abilities.
Collective hydrodynamic transport of magnetic microrollers
Authors: Junot Gaspard , Cebers Andrejs , Tierno Pietro
Published: July 2021

We investigate the collective dynamics of magnetically driven microrollers that propel and assemble under the combined action of magnetism and hydrodynamics. We describe the collective mean velocity and the dynamic clustering.
Electrochemical formation and dissolution of an iodine–halide coordination solid complex in a nano-confined space
Authors: Jeon Jaehyun , Hwang Jiseon , Yang Jung Hoon , Chang Jinho
Published: July 2021

Electrochemical formation and dissolution of an iodine–halide coordination solid complex, [(I2)n·X−] (X− = Br− and I−), occurs in the nanopores of electrodes in aqueous energy storage systems. Relative to [(I2)n·I−]/I−, [(I2)n·Br−]/I− exhibits superior capacity retention.
A bioinspired solar evaporator for continuous and efficient desalination by salt dilution and secretion
Authors: Zhang Shuqian , Yuan Yang , Zhang Wang , Song Fang , Li Jinghan , Liu Qinglei , Gu Jiajun , Zhang Di
Published: July 2021

A bioinspired solar evaporator simultaneously realizes high evaporation efficiency, long-term stability and zero liquid discharge in water desalination by combining salt dilution and secretion.