bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients
Authors: Wu Ping-Hsun , Lin Yi-Ting , Chiu Yi-Wen , Baldanzi Gabriel , Huang Jiun-Chi , Liang Shih-Shin , Lee Su-Chu , Chen Szu-Chia , Hsu Ya-Ling , Kuo Mei-Chuan , Hwang Shang-Jyh
Published: February 2021

Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C–C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.
Precision analysis model and experimentation of vision reconstruction with two cameras and 3D orientation reference
Authors: Chen Rong , Chen Fang , Xu Guan , Li Xiaotao , Shen Hui , Yuan Jing
Published: February 2021

Active vision reconstruction is widely used in industrial manufacturing and three-dimensional inspection. The reconstruction accuracy is an important problem to be investigated for the inspection process. The paper conducts an analysis study of the reconstruction error for the vision reconstruction with a planar laser, two cameras and a 3D orientation board. The variation principles of the spatial coordinates caused by the variations of the extrinsic parameters of the cameras, intrinsic parameters of the internal camera, and image coordinate points of the internal camera, are modeled and analyzed in this paper. The analysis is also proved by the verification experiments, which provides the application potential for other active-vision-based reconstructions.
Pigeons show how meta-control enables decision-making in an ambiguous world
Authors: Manns Martina , Otto Tobias , Salm Laurenz
Published: February 2021

In situations where the left and right brain sides receive conflicting information that leads to incompatible response options, the brain requires efficient problem-solving mechanisms. This problem is particularly significant in lateralized brains, in which the hemispheres differ in encoding strategies or attention focus and hence, consider different information for decision-making. Meta-control, in which one hemisphere dominates ambiguous decisions, can be a mechanism that ensures fast behavioral reactions. We therefore confronted pigeons with a task in which two stimulus classes were brought into conflict. To this end, we trained pigeons simultaneously on two categories (cats or dogs) whereby each hemisphere learnt only one of the categories respectively. After learning, the birds were confronted with stimulus pairs that combined a picture with a cat (positive for one hemisphere) and a picture with a dog (positive for the other hemisphere). Pecking responses indicated the hemisphere dominating response selection. Pigeons displayed individual meta-control despite equal categorization performances of both brain hemispheres. This means that hemispheric dominance only emerged in interhemispheric conflict situations. The analysis of response latencies indicate that conflict decisions relied on intrahemispheric processes. Interhemispheric components played a role for more complex decisions. This flexibility could be a crucial building block for the evolutionary success of a lateralized brain.
Dicke and Fano-Andreev reflections in a triple quantum-dot system
Authors: González I. A. , Pacheco M. , Calle A. M. , Siqueira E. C. , Orellana P. A.
Published: February 2021

This article studies quantum interference effects and their influence on the electronic transport through a parallel triple quantum-dot system coupled to normal and superconducting leads in the linear response and non-equilibrium regime. We model the system by a triple impurity Anderson Hamiltonian including the Coulomb intra-dot correlations in all quantum-dots. Using the non-equilibrium Green’s function formalism, we calculate the Andreev conductance and the transmittance for energies within the superconductor gap. Our results show that the Andreev reflection spectra, both in the presence and absence of Coulomb interaction, reveal Fano and Dicke-like resonances in analogy to the Fano and Dicke effects in atomic physics. As one of the main results, we obtain that the charge shows abrupt changes due to the Dicke effect.
Transition from unclassified Ktedonobacterales to Actinobacteria during amorphous silica precipitation in a quartzite cave environment
Authors: Ghezzi D. , Sauro F. , Columbu A. , Carbone C. , Hong P.-Y. , Vergara F. , De Waele J. , Cappelletti M.
Published: February 2021

The orthoquartzite Imawarì Yeuta cave hosts exceptional silica speleothems and represents a unique model system to study the geomicrobiology associated to silica amorphization processes under aphotic and stable physical–chemical conditions. In this study, three consecutive evolution steps in the formation of a peculiar blackish coralloid silica speleothem were studied using a combination of morphological, mineralogical/elemental and microbiological analyses. Microbial communities were characterized using Illumina sequencing of 16S rRNA gene and clone library analysis of carbon monoxide dehydrogenase (coxL) and hydrogenase (hypD) genes involved in atmospheric trace gases utilization. The first stage of the silica amorphization process was dominated by members of a still undescribed microbial lineage belonging to the Ktedonobacterales order, probably involved in the pioneering colonization of quartzitic environments. Actinobacteria of the Pseudonocardiaceae and Acidothermaceae families dominated the intermediate amorphous silica speleothem and the final coralloid silica speleothem, respectively. The atmospheric trace gases oxidizers mostly corresponded to the main bacterial taxa present in each speleothem stage. These results provide novel understanding of the microbial community structure accompanying amorphization processes and of coxL and hypD gene expression possibly driving atmospheric trace gases metabolism in dark oligotrophic caves.
Exploring the predictive value of lesion topology on motor function outcomes in a porcine ischemic stroke model
Authors: Scheulin Kelly M. , Jurgielewicz Brian J. , Spellicy Samantha E. , Waters Elizabeth S. , Baker Emily W. , Kinder Holly A. , Simchick Gregory A. , Sneed Sydney E. , Grimes Janet A. , Zhao Qun , Stice Steven L. , West Franklin D.
Published: February 2021

Harnessing the maximum diagnostic potential of magnetic resonance imaging (MRI) by including stroke lesion location in relation to specific structures that are associated with particular functions will likely increase the potential to predict functional deficit type, severity, and recovery in stroke patients. This exploratory study aims to identify key structures lesioned by a middle cerebral artery occlusion (MCAO) that impact stroke recovery and to strengthen the predictive capacity of neuroimaging techniques that characterize stroke outcomes in a translational porcine model. Clinically relevant MRI measures showed significant lesion volumes, midline shifts, and decreased white matter integrity post-MCAO. Using a pig brain atlas, damaged brain structures included the insular cortex, somatosensory cortices, temporal gyri, claustrum, and visual cortices, among others. MCAO resulted in severely impaired spatiotemporal gait parameters, decreased voluntary movement in open field testing, and higher modified Rankin Scale scores at acute timepoints. Pearson correlation analyses at acute timepoints between standard MRI metrics (e.g., lesion volume) and functional outcomes displayed moderate R values to functional gait outcomes. Moreover, Pearson correlation analyses showed higher R values between functional gait deficits and increased lesioning of structures associated with motor function, such as the putamen, globus pallidus, and primary somatosensory cortex. This correlation analysis approach helped identify neuroanatomical structures predictive of stroke outcomes and may lead to the translation of this topological analysis approach from preclinical stroke assessment to a clinical biomarker.
A two-herb formula inhibits hyperproliferation of rheumatoid arthritis fibroblast-like synoviocytes
Authors: Chen Ying-Jie , Liu Yu-Xi , Wu Jia-Ying , Li Chun-Yu , Tang Min-Min , Bai Lu , Fu Xiu-Qiong , Li Jun-Kui , Chou Ji-Yao , Yin Cheng-Le , Wang Ya-Ping , Bai Jing-Xuan , Wu Ying , Wang Xiao-Qi , Yu Zhi-Ling
Published: February 2021

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE’s anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug.
European cephalopods distribution under climate-change scenarios
Authors: Schickele Alexandre , Francour Patrice , Raybaud Virginie
Published: February 2021

In a context of increasing anthropogenic pressure, projecting species potential distributional shifts is of major importance for the sustainable exploitation of marine species. Despite their major economical (i.e. important fisheries) and ecological (i.e. central position in food-webs) importance, cephalopods literature rarely addresses an explicit understanding of their current distribution and the potential effect that climate change may induce in the following decades. In this study, we focus on three largely harvested and common cephalopod species in Europe:Octopus vulgaris,Sepia officinalisandLoligo vulgaris. Using a recently improved species ensemble modelling framework coupled with five atmosphere–ocean general circulation models, we modelled their contemporary and potential future distributional range over the twenty-first century. Independently of global warming scenarios, we observed a decreasing in the suitability of environmental conditions in the Mediterranean Sea and the Bay of Biscay. Conversely, we projected a rapidly increasing environmental suitability in the North, Norwegian and Baltic Seas for all species. This study is a first broad scale assessment and identification of the geographical areas, fisheries and ecosystems impacted by climate-induced changes in cephalopods distributional range.
Phosphorylation of the proline-rich domain of WAVE3 drives its oncogenic activity in breast cancer
Authors: Kansakar Urna , Wang Wei , Markovic Vesna , Sossey-Alaoui Khalid
Published: February 2021

Post-translational modification of proteins, such as tyrosine phosphorylation, plays a major role in driving the oncogenic activity of oncogenes. WAVE3 (WASF3), an adaptor and actin cytoskeleton remodeling protein, contributes to cell migration, cancer cell invasion, and metastasis. WAVE3 plays a vital role in the progression and metastasis of triple negative breast cancer (TNBC), in part through the regulation of cancer stem cells (CSCs). Several studies have shown that WAVE3 tyrosine phosphorylation is required for its oncogenic activity. Moreover, our recent study showed that the proline rich domain (PRD) of WAVE3 is required for maintenance of the CSC niche in breast cancer by regulating the nuclear translocation of the CSC-specific nuclear transcription factor YB1. Here, we show that the PRD domain of WAVE3 and its phosphorylation are essential for driving the oncogenic activity of WAVE3. We show that phosphorylation of WAVE3 PRD is essential for migration and invasion of breast cancer cells in vitro, as well as tumor growth and metastasis in vivo. Mechanistically, we show that phosphorylation of the WAVE3 PRD is essential for interaction between WAVE3 and YB1. Loss of PRD phosphorylation inhibits such interaction and the YB1-mediated activation of expression of CSC markers, as well as the WAVE3 mediated activation of EMT. Together, our study identifies a novel role of WAVE3 and its PRD domain in the regulation of the invasion metastasis cascade in BC that is independent of the known function of WAVE3 as an actin cytoskeleton remodeling protein through the WAVE regulatory complex (WRC).
Highlighting the potential utility of MBP crystallization chaperone for Arabidopsis BIL1/BZR1 transcription factor-DNA complex
Authors: Nosaki Shohei , Terada Tohru , Nakamura Akira , Hirabayashi Kei , Xu Yuqun , Bui Thi Bao Chau , Nakano Takeshi , Tanokura Masaru , Miyakawa Takuya
Published: February 2021

The maltose-binding protein (MBP) fusion tag is one of the most commonly utilized crystallization chaperones for proteins of interest. Recently, this MBP-mediated crystallization technique was adapted to Arabidopsis thaliana (At) BRZ-INSENSITIVE-LONG (BIL1)/BRASSINAZOLE-RESISTANT (BZR1), a member of the plant-specific BZR TFs, and revealed the first structure of AtBIL1/BZR1 in complex with target DNA. However, it is unclear how the fused MBP affects the structural features of the AtBIL1/BZR1-DNA complex. In the present study, we highlight the potential utility of the MBP crystallization chaperone by comparing it with the crystallization of unfused AtBIL1/BZR1 in complex with DNA. Furthermore, we assessed the validity of the MBP-fused AtBIL1/BZR1-DNA structure by performing detailed dissection of crystal packings and molecular dynamics (MD) simulations with the removal of the MBP chaperone. Our MD simulations define the structural basis underlying the AtBIL1/BZR1-DNA assembly and DNA binding specificity by AtBIL1/BZR1. The methodology employed in this study, the combination of MBP-mediated crystallization and MD simulation, demonstrates promising capabilities in deciphering the protein-DNA recognition code.
Environmental enrichment influences novelty reactivity, novelty preference, and anxiety via distinct genetic mechanisms in C57BL/6J and DBA/2J mice
Authors: Dickson Price E. , Mittleman Guy
Published: February 2021

Environmental factors such as stress drive the development of drug addiction in genetically vulnerable individuals; the genes underlying this vulnerability are unknown. One strategy for uncovering these genes is to study the impact of environmental manipulation on high-throughput phenotypes that predict drug use and addiction-like behaviors. In the present study, we assessed the viability of this approach by evaluating the relative effects of environmental enrichment and isolation housing on three high-throughput phenotypes known to predict variation on distinct aspects of intravenous drug self-administration. Prior to behavioral testing, male and female C57BL/6J and DBA/2J mice (BXD founders) were housed in enrichment or isolation for ten weeks beginning at weaning. Enrichment significantly reduced novelty reactivity; this effect was significantly more robust in C57BL/6J mice relative to DBA/2J mice. Enrichment significantly reduced novelty preference; this effect was significantly dependent on novel environment characteristics and was significantly more robust in DBA/2J mice relative to C57BL/6J mice. Enrichment significantly increased anxiety; this effect was not strain-dependent. Collectively, these data indicate that (1) environmental enrichment influences novelty reactivity, novelty preference, and anxiety via distinct genetic mechanisms in mice, and (2) the BXD panel can be used to discover the genetic and epigenetic mechanisms underlying this phenomenon.
A look-ahead Monte Carlo simulation method for improving parental selection in trait introgression
Authors: Moeinizade Saba , Han Ye , Pham Hieu , Hu Guiping , Wang Lizhi
Published: February 2021

Multiple trait introgression is the process by which multiple desirable traits are converted from a donor to a recipient cultivar through backcrossing and selfing. The goal of this procedure is to recover all the attributes of the recipient cultivar, with the addition of the specified desirable traits. A crucial step in this process is the selection of parents to form new crosses. In this study, we propose a new selection approach that estimates the genetic distribution of the progeny of backcrosses after multiple generations using information of recombination events. Our objective is to select the most promising individuals for further backcrossing or selfing. To demonstrate the effectiveness of the proposed method, a case study has been conducted using maize data where our method is compared with state-of-the-art approaches. Simulation results suggest that the proposed method, look-ahead Monte Carlo, achieves higher probability of success than existing approaches. Our proposed selection method can assist breeders to efficiently design trait introgression projects.
Rare deleterious germline variants and risk of lung cancer
Authors: Liu Yanhong , Xia Jun , McKay James , Tsavachidis Spiridon , Xiao Xiangjun , Spitz Margaret R. , Cheng Chao , Byun Jinyoung , Hong Wei , Li Yafang , Zhu Dakai , Song Zhuoyi , Rosenberg Susan M. , Scheurer Michael E. , Kheradmand Farrah , Pikielny Claudio W. , Lusk Christine M. , Schwartz Ann G. , Wistuba Ignacio I. , Cho Michael H. , Silverman Edwin K. , Bailey-Wilson Joan , Pinney Susan M. , Anderson Marshall , Kupert Elena , Gaba Colette , Mandal Diptasri , You Ming , de Andrade Mariza , Yang Ping , Liloglou Triantafillos , Davies Michael P. A. , Lissowska Jolanta , Swiatkowska Beata , Zaridze David , Mukeria Anush , Janout Vladimir , Holcatova Ivana , Mates Dana , Stojsic Jelena , Scelo Ghislaine , Brennan Paul , Liu Geoffrey , Field John K. , Hung Rayjean J. , Christiani David C. , Amos Christopher I.
Published: February 2021

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04–75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71–8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3′ UTR (OR 4.33, 95%CI 2.03–9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73–11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33–5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.
A mode-balanced reconfigurable logic gate built in a van der Waals strata
Authors: Cao Wei , Chu Jae Hwan , Parto Kamyar , Banerjee Kaustav
Published: February 2021

Two-dimensional (2D) semiconducting materials, in particular transition-metal dichalcogenides, have emerged as the preferred channel materials for sub-5 nm field-effect transistors (FETs). However, the lack of practical doping techniques for these materials poses a significant challenge to designing complementary logic gates containing both n- and p-type FETs. Although electrical tuning of the polarity of 2D-FETs can potentially circumvent this problem, such devices suffer from the lack of balanced n- and p-mode transistor performance, forming one of the most enigmatic challenges of the reconfigurable 2D-FET technology. Here we provide a solution to this dilemma by judicious use of van der Waals (vdW) materials consisting of conductors, dielectrics and semiconductors forming a 50 nm thin quantum engineered strata that can guarantee a purely vdW-type interlayer interaction, which faithfully preserves the mid-gap contact design and thereby achieves an intrinsically mode-balanced and fully reconfigurable all-2D logic gate. The intrinsically mode-balanced gate eliminates the need for transistor sizing and allows post-fabrication reconfigurability to the transistor operation mode, simultaneously allowing an ultra-compact footprint and increased circuit functionality, which can be potentially exploited to build more area-efficient and low-cost integrated electronics for the internet of things (IoT) paradigm.
Randomized controlled study using text messages to help connect new medicaid beneficiaries to primary care
Authors: Levine David M. , Kakani Pragya , Mehrotra Ateev
Published: February 2021

Accessing primary care is often difficult for newly insured Medicaid beneficiaries. Tailored text messages may help patients navigate the health system and initiate care with a primary care physician. We conducted a randomized controlled trial of tailored text messages with newly enrolled Medicaid managed care beneficiaries. Text messages included education about the importance of primary care, reminders to obtain an appointment, and resources to help schedule an appointment. Within 120 days of enrollment, we examined completion of at least one primary care visit and use of the emergency department. Within 1 year of enrollment, we examined diagnosis of a chronic disease, receipt of preventive care, and use of the emergency department. 8432 beneficiaries (4201 texting group; 4231 control group) were randomized; mean age was 37 years and 24% were White. In the texting group, 31% engaged with text messages. In the texting vs control group after 120 days, there were no differences in having one or more primary care visits (44.9% vs. 45.2%; difference, −0.27%; p = 0.802) or emergency department use (16.2% vs. 16.0%; difference, 0.23%; p = 0.771). After 1 year, there were no differences in diagnosis of a chronic disease (29.0% vs. 27.8%; difference, 1.2%; p = 0.213) or appropriate preventive care (for example, diabetes screening: 14.1% vs. 13.4%; difference, 0.69%; p = 0.357), but emergency department use (32.7% vs. 30.2%; difference, 2.5%; p = 0.014) was greater in the texting group. Tailored text messages were ineffective in helping new Medicaid beneficiaries visit primary care within 120 days.
Recalibration of deep learning models for abnormality detection in smartphone-captured chest radiograph
Authors: Kuo Po-Chih , Tsai Cheng Che , López Diego M. , Karargyris Alexandros , Pollard Tom J. , Johnson Alistair E. W. , Celi Leo Anthony
Published: February 2021

Image-based teleconsultation using smartphones has become increasingly popular. In parallel, deep learning algorithms have been developed to detect radiological findings in chest X-rays (CXRs). However, the feasibility of using smartphones to automate this process has yet to be evaluated. This study developed a recalibration method to build deep learning models to detect radiological findings on CXR photographs. Two publicly available databases (MIMIC-CXR and CheXpert) were used to build the models, and four derivative datasets containing 6453 CXR photographs were collected to evaluate model performance. After recalibration, the model achieved areas under the receiver operating characteristic curve of 0.80 (95% confidence interval: 0.78–0.82), 0.88 (0.86–0.90), 0.81 (0.79–0.84), 0.79 (0.77–0.81), 0.84 (0.80–0.88), and 0.90 (0.88–0.92), respectively, for detecting cardiomegaly, edema, consolidation, atelectasis, pneumothorax, and pleural effusion. The recalibration strategy, respectively, recovered 84.9%, 83.5%, 53.2%, 57.8%, 69.9%, and 83.0% of performance losses of the uncalibrated model. We conclude that the recalibration method can transfer models from digital CXRs to CXR photographs, which is expected to help physicians’ clinical works.
Intertissue small RNA communication mediates the acquisition and inheritance of hormesis in Caenorhabditis elegans
Authors: Okabe Emiko , Uno Masaharu , Kishimoto Saya , Nishida Eisuke
Published: February 2021

Environmental conditions can cause phenotypic changes, part of which can be inherited by subsequent generations via soma-to-germline communication. However, the signaling molecules or pathways that mediate intertissue communication remain unclear. Here, we show that intertissue small RNA communication systems play a key role in the acquisition and inheritance of hormesis effects – stress-induced stress resistance – in Caenorhabditis elegans. The miRNA-processing enzyme DRSH-1 is involved in both the acquisition and the inheritance of hormesis, whereas worm-specific Argonaute (WAGO) proteins, which function with endo-siRNAs, are involved only in its inheritance. Further analyses demonstrate that the miRNA production system in the neuron and the small RNA transport machinery in the intestine are both essential for its acquisition and that both the transport of small RNAs in the germline and the germline Argonaute HRDE-1 complex are required for its inheritance. Our results thus demonstrate that overlapping and distinct roles of small RNA systems in the acquisition and inheritance of hormesis effects.
Biocompatible nucleus-targeted graphene quantum dots for selective killing of cancer cells via DNA damage
Authors: Qi Lei , Pan Tonghe , Ou Liling , Ye Zhiqiang , Yu Chunlei , Bao Bijun , Wu Zixia , Cao Dayong , Dai Liming
Published: February 2021

Graphene quantum dots (GQDs) are nano-sized graphene slices. With their small size, lamellar and aromatic-ring structure, GQDs tend to enter into the cell nucleus and interfere with DNA activity. Thus, GQD alone is expected to be an anticancer reagent. Herein, we developed GQDs that suppress the growth of tumor by selectively damaging the DNA of cancer cells. The amine-functionalized GQDs were modified with nucleus targeting TAT peptides (TAT-NGs) and further grafted with cancer-cell-targeting folic acid (FA) modified PEG via disulfide linkage (FAPEG-TNGs). The resulting FAPEG-TNGs exhibited good biocompatibility, nucleus uptake, and cancer cell targeting. They adsorb on DNA via the π–π and electrostatic interactions, which induce the DNA damage, the upregulation of the cell apoptosis related proteins, and the suppression of cancer cell growth, ultimately. This work presents a rational design of GQDs that induce the DNA damage to realize high therapeutic performance, leading to a distinct chemotherapy strategy for targeted tumor therapy.
CASSPER is a semantic segmentation-based particle picking algorithm for single-particle cryo-electron microscopy
Authors: George Blesson , Assaiya Anshul , Roy Robin J. , Kembhavi Ajit , Chauhan Radha , Paul Geetha , Kumar Janesh , Philip Ninan S.
Published: February 2021

Particle identification and selection, which is a prerequisite for high-resolution structure determination of biological macromolecules via single-particle cryo-electron microscopy poses a major bottleneck for automating the steps of structure determination. Here, we present a generalized deep learning tool, CASSPER, for the automated detection and isolation of protein particles in transmission microscope images. This deep learning tool uses Semantic Segmentation and a collection of visually prepared training samples to capture the differences in the transmission intensities of protein, ice, carbon, and other impurities found in the micrograph. CASSPER is a semantic segmentation based method that does pixel-level classification and completely eliminates the need for manual particle picking. Integration of Contrast Limited Adaptive Histogram Equalization (CLAHE) in CASSPER enables high-fidelity particle detection in micrographs with variable ice thickness and contrast. A generalized CASSPER model works with high efficiency on unseen datasets and can potentially pick particles on-the-fly, enabling data processing automation.
A high-throughput Galectin-9 imaging assay for quantifying nanoparticle uptake, endosomal escape and functional RNA delivery
Authors: Munson Michael J. , O’Driscoll Gwen , Silva Andreia M. , Lázaro-Ibáñez Elisa , Gallud Audrey , Wilson John T. , Collén Anna , Esbjörner Elin K. , Sabirsh Alan
Published: February 2021

RNA-based therapies have great potential to treat many undruggable human diseases. However, their efficacy, in particular for mRNA, remains hampered by poor cellular delivery and limited endosomal escape. Development and optimisation of delivery vectors, such as lipid nanoparticles (LNPs), are impeded by limited screening methods to probe the intracellular processing of LNPs in sufficient detail. We have developed a high-throughput imaging-based endosomal escape assay utilising a Galectin-9 reporter and fluorescently labelled mRNA to probe correlations between nanoparticle-mediated uptake, endosomal escape frequency, and mRNA translation. Furthermore, this assay has been integrated within a screening platform for optimisation of lipid nanoparticle formulations. We show that Galectin-9 recruitment is a robust, quantitative reporter of endosomal escape events induced by different mRNA delivery nanoparticles and small molecules. We identify nanoparticles with superior escape properties and demonstrate cell line variances in endosomal escape response, highlighting the need for fine-tuning of delivery formulations for specific applications.
High-throughput behavioral screen in C. elegans reveals Parkinson’s disease drug candidates
Authors: Sohrabi Salman , Mor Danielle E. , Kaletsky Rachel , Keyes William , Murphy Coleen T.
Published: February 2021

We recently linked branched-chain amino acid transferase 1 (BCAT1) dysfunction with the movement disorder Parkinson’s disease (PD), and found that RNAi-mediated knockdown of neuronal bcat-1 in C. elegans causes abnormal spasm-like ‘curling’ behavior with age. Here we report the development of a machine learning-based workflow and its application to the discovery of potentially new therapeutics for PD. In addition to simplifying quantification and maintaining a low data overhead, our simple segment-train-quantify platform enables fully automated scoring of image stills upon training of a convolutional neural network. We have trained a highly reliable neural network for the detection and classification of worm postures in order to carry out high-throughput curling analysis without the need for user intervention or post-inspection. In a proof-of-concept screen of 50 FDA-approved drugs, enasidenib, ethosuximide, metformin, and nitisinone were identified as candidates for potential late-in-life intervention in PD. These findings point to the utility of our high-throughput platform for automated scoring of worm postures and in particular, the discovery of potential candidate treatments for PD.
Zn2+-dependent DNAzymes that cleave all combinations of ribonucleotides
Authors: Inomata Rika , Zhao Jing , Miyagishi Makoto
Published: February 2021

Although several DNAzymes are known, their utility is limited by a narrow range of substrate specificity. Here, we report the isolation of two zinc-dependent DNAzymes, ZincDz1 and ZincDz2, which exhibit compact catalytic core sequences with highly versatile hydrolysis activity. They were selected through in vitro selection followed by deep sequencing analysis. Despite their sequence similarity, each DNAzyme showed different Zn2+-concentration and pH-dependent reaction profiles, and cleaved the target RNA sequences at different sites. Using various substrate RNA sequences, we found that the cleavage sequence specificity of ZincDz2 and its highly active mutant ZincDz2-v2 to be 5′-rN↓rNrPu-3′. Furthermore, we demonstrated that the designed ZincDz2 could cut microRNA miR-155 at three different sites. These DNAzymes could be useful in a broad range of applications in the fields of medicine and biotechnology.
Structure–function studies of ultrahigh molecular weight isoprenes provide key insights into their biosynthesis
Authors: Kajiura Hiroyuki , Yoshizawa Takuya , Tokumoto Yuji , Suzuki Nobuaki , Takeno Shinya , Takeno Kanokwan Jumtee , Yamashita Takuya , Tanaka Shun-ichi , Kaneko Yoshinobu , Fujiyama Kazuhito , Matsumura Hiroyoshi , Nakazawa Yoshihisa
Published: February 2021

Some plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms—EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants.
A hexokinase isoenzyme switch in human liver cancer cells promotes lipogenesis and enhances innate immunity
Authors: Perrin-Cocon Laure , Vidalain Pierre-Olivier , Jacquemin Clémence , Aublin-Gex Anne , Olmstead Keedrian , Panthu Baptiste , Rautureau Gilles Jeans Philippe , André Patrice , Nyczka Piotr , Hütt Marc-Thorsten , Amoedo Nivea , Rossignol Rodrigue , Filipp Fabian Volker , Lotteau Vincent , Diaz Olivier
Published: February 2021

During the cancerous transformation of normal hepatocytes into hepatocellular carcinoma (HCC), the enzyme catalyzing the first rate-limiting step of glycolysis, namely the glucokinase (GCK), is replaced by the higher affinity isoenzyme, hexokinase 2 (HK2). Here, we show that in HCC tumors the highest expression level of HK2 is inversely correlated to GCK expression, and is associated to poor prognosis for patient survival. To further explore functional consequences of the GCK-to-HK2 isoenzyme switch occurring during carcinogenesis, HK2 was knocked-out in the HCC cell line Huh7 and replaced by GCK, to generate the Huh7-GCK+/HK2− cell line. HK2 knockdown and GCK expression rewired central carbon metabolism, stimulated mitochondrial respiration and restored essential metabolic functions of normal hepatocytes such as lipogenesis, VLDL secretion, glycogen storage. It also reactivated innate immune responses and sensitivity to natural killer cells, showing that consequences of the HK switch extend beyond metabolic reprogramming.
Gravitational wave detectors with broadband high frequency sensitivity
Authors: Page Michael A. , Goryachev Maxim , Miao Haixing , Chen Yanbei , Ma Yiqiu , Mason David , Rossi Massimiliano , Blair Carl D. , Ju Li , Blair David G. , Schliesser Albert , Tobar Michael E. , Zhao Chunnong
Published: February 2021

Gravitational waves from the neutron star coalescence GW170817 were observed from the inspiral, but not the high frequency postmerger nuclear matter motion. Optomechanical white light signal recycling has been proposed for achieving broadband sensitivity in gravitational wave detectors, but has been reliant on development of suitable ultra-low loss mechanical components. Here we show demonstrated optomechanical resonators that meet loss requirements for a white light signal recycling interferometer with strain sensitivity below 10−24 Hz−1/2 at a few kHz. Experimental data for two resonators are combined with analytic models of interferometers similar to LIGO to demonstrate enhancement across a broader band of frequencies versus dual-recycled Fabry-Perot Michelson detectors. Candidate resonators are a silicon nitride membrane acoustically isolated by a phononic crystal, and a single-crystal quartz acoustic cavity. Optical power requirements favour the membrane resonator, while thermal noise performance favours the quartz resonator. Both could be implemented as add-on components to existing detectors.
Quantum simulation of parity–time symmetry breaking with a superconducting quantum processor
Authors: Dogra Shruti , Melnikov Artem A. , Paraoanu Gheorghe Sorin
Published: February 2021

The observation of genuine quantum effects in systems governed by non-Hermitian Hamiltonians has been an outstanding challenge in the field. Here we simulate the evolution under such Hamiltonians in the quantum regime on a superconducting quantum processor by using a dilation procedure involving an ancillary qubit. We observe the parity–time ($${\mathcal{PT}}$$
PT
)-symmetry breaking phase transition at the exceptional points, obtain the critical exponent, and show that this transition is associated with a loss of state distinguishability. In a two-qubit setting, we show that the entanglement can be modified by local operations.
A miniaturized giant magnetic resistance system for quantitative detection of methamphetamine
Authors: Yang Guopan , Cheng Kunxue , Chu Zhengkang , Ren Chunhui , Fu Yusheng , Guo Jinhong
Published: February 2021

A giant magnetic resistance system is developed which uses a signal detection unit, an external interference cancellation method, and a weak-signal waveform reconstruction method to achieve quantitative detection of methamphetamine.
Is the H4 histone tail intrinsically disordered or intrinsically multifunctional?
Authors: Röder Konstantin
Published: February 2021

While the H4 histone tail exhibits a large structural variance associated with disorder, the energy landscape shows a high level of topographic order. This result opens a new perspective on how we interpret disorder.
Evaluation of the in vitro effects of the increasing inclusion levels of yeast β-glucan, a casein hydrolysate and its 5 kDa retentate on selected bacterial populations and strains commonly found in the gastrointestinal tract of pigs
Authors: Venardou Brigkita , O'Doherty John V. , McDonnell Mary J. , Mukhopadhya Anindya , Kiely Claire , Ryan Marion T. , Sweeney Torres
Published: February 2021

The 5 kDa retentate of a casein hydrolysate exhibited an in vitro prebiotic activity.
Flexible on-site halogenation paired with hydrogenation using halide electrolysis
Authors: Shang Xiao , Liu Xuan , Sun Yujie
Published: February 2021

Simultaneous organic halogenation coupled with hydrogenation are realized by on-site electrochemical production of halogen and hydrogen gases.
Response of G protein-coupled receptor CED-1 in germline to polystyrene nanoparticles inCaenorhabditis elegans
Authors: Yang Yunhan , Dong Wenting , Wu Qiuli , Wang Dayong
Published: February 2021

A GPCR CED-1-mediated signaling cascade in the germline was identified for the control of the response to nanoplastic exposure.
Microfluidic synthesis of quantum dots and their applications in bio-sensing and bio-imaging
Authors: Cheng Yu , Ling Si Da , Geng Yuhao , Wang Yundong , Xu Jianhong
Published: February 2021

Biosensing and bioimaging of organisms or molecules allows for the study of physiological processes or the diagnosis of diseases. QDs are promising optical detectors and microfluidic technology is one promising path for their industrial production.
Tumor-targeted gene therapy with lipid nanoparticles inhibits tumor-associated adipocytes and remodels the immunosuppressive tumor microenvironment in triple-negative breast cancer
Authors: Liu Yun , Tiruthani Karthik , Wang Menglin , Zhou Xuefei , Qiu Nasha , Xiong Yang , Pecot Chad V. , Liu Rihe , Huang Leaf
Published: February 2021

In breast cancer model, we identified C–C Motif Chemokine Ligand 2 (CCL2) as the key mediator which is secreted by tumor associated adipocytes, and developed targeted lipid-protamine-DNA (LPD) nanoparticles to locally “trap” CCL2 to ameliorate the immunosuppressive tumor microenvironment.
Micro–nanoarchitectures of electrodeposited Ni–ITO nanocomposites on copper foil as electrocatalysts for the oxygen evolution reaction
Authors: Sivasakthi P. , Sangaranarayanan M. V. , Gurumallesh Prabu H.
Published: February 2021

A simple conventional three electrodes system was used for the preparation of Ni and Ni–ITO nanocomposites as an electrocatalyst for oxygen evolution reaction.
Reply to the ‘Comment on “Size dependence of bubble wetting on surfaces: breakdown of contact angle match between small sized bubbles and droplets”’ by A. I. Rusanov, D. V. Tatyanenko and A. K. Shchekin, Nanoscale, 2020, DOI:10.1039/D0NR00232A
Authors: Zhang Hongguang , Zhang Xianren
Published: February 2021

In this Reply, we clarify the rationale behind our conclusions and point out that in their derivation Rusanov et al. failed to consider the difference between bubbles and droplets.
Analyzing mechanisms in Co(i) redox catalysis using a pattern recognition platform
Authors: Tang Tianhua , Sandford Christopher , Minteer Shelley D. , Sigman Matthew S.
Published: February 2021

Through kinetic studies combining electroanalytical techniques with multivariable linear-regression (MLR) analysis, a pattern recognition platform is established to determine the electron-transfer mechanism (inner-sphere or outer-sphere) of an electrochemical reduction of benzyl bromides, mediated by different cobalt complexes.
Single crystal of two-dimensional mixed-halide copper-based perovskites with reversible thermochromism
Authors: Elattar Amr , Suzuki Hiroo , Mishima Ryuji , Nakao Kodai , Ota Hiromi , Nishikawa Takeshi , Inoue Hirotaka , Kyaw Aung Ko Ko , Hayashi Yasuhiko
Published: February 2021

Facile synthesis of single crystal of two-dimensional mixed-halide copper-based perovskites with tunable band gaps and their capability of exfoliation and reversible thermochromism.
Highly active g-C3N4photocatalysts modified with transition metal cobalt for hydrogen evolution
Authors: Xie Juan , Wang Chenjie , Chen Ning , Chen Weifeng , Xu Jiake , Bai Penghui , Liu Biao , Zhang Lei , Wang Hu
Published: February 2021

The Co atoms form the unique Co–Nxstructure in Co/CN, which act as the electron transport highway. The Co/CN system simultaneously achieves high light harvesting abilities, resulting in the high photocatalytic performance for water reduction.
Ternary organic solar cells with 16.88% efficiency enabled by a twisted perylene diimide derivative to enhance the open-circuit voltage
Authors: Ni Ming-Yang , Leng Shi-Feng , Liu Heng , Yang Yan-Kang , Li Qian-Hui , Sheng Chun-Qi , Lu Xinhui , Liu Feng , Wan Jun-Hua
Published: February 2021

A coronene-cored perylene diimide twisted tetramer was developed as an acceptor additive to increase the Voc values of PM6:Y6 blend-based OSCs.
Development of a piperazinyl-NBD-based fluorescent probe and its dual-channel detection for hydrogen sulfide
Authors: Pei Shizeng , Li Jiale , Zhang Caihong , Liang Wenting , Zhang Guomei , Shi Lihong , Wang Wen , Shuang Shaomin , Dong Chuan
Published: February 2021

To selectively detect H2S, a novel dual-channel fluorescence probe, triphenylamine piperazine NBD (TPA-Pz-NBD), was developed based on the thiolysis reaction of NBD amine.
Nanosilver-loaded PMMA bone cement doped with different bioactive glasses – evaluation of cytocompatibility, antibacterial activity, and mechanical properties
Authors: Wekwejt M. , Chen S. , Kaczmarek-Szczepańska B. , Nadolska M. , Łukowicz K. , Pałubicka A. , Michno A. , Osyczka A. M. , Michálek M. , Zieliński A.
Published: February 2021

Nanosilver-loaded PMMA bone cement doped with bioactive glasses is a novel cement developed as a replacement for conventional cements.
Correction: Small-molecule-based human genome G4 profiling reveals potential gene regulation activity
Authors: Zeng Weiwu , Wu Fan , Liu Chaoxing , Yang Yan , Wang Bingyao , Yuan Yushu , Wang Jiaqi , Chen Yuqi , Fu Boshi , Wu Zhiguo , Zhou Xiang
Published: February 2021

Correction for ‘Small-molecule-based human genome G4 profiling reveals potential gene regulation activity’ by Weiwu Zeng et al., Chem. Commun., 2019, 55, 2269–2272, DOI: 10.1039/C8CC10052G.
Correction: Fast prediction of oxygen reduction reaction activity on carbon nanotubes with a localized geometric descriptor
Authors: Yang Kunran , Zaffran Jeremie , Yang Bo
Published: February 2021

Correction for ‘Fast prediction of oxygen reduction reaction activity on carbon nanotubes with a localized geometric descriptor’ by Kunran Yang et al., Phys. Chem. Chem. Phys., 2020, 22, 890–895, DOI: 10.1039/C9CP04885E.
Correction: The development of a full range analytical interatomic potential
Authors: Sheng X. W. , Tang K. T.
Published: February 2021

Correction for ‘The development of a full range analytical interatomic potential’ by X. W. Sheng et al., Phys. Chem. Chem. Phys., 2021, DOI: 10.1039/d0cp04083e.
Fabrication of ring oscillators using organic molecules of phenacene and perylenedicarboximide
Authors: Fioravanti Niko , Pierantoni Luca , Mencarelli Davide , Turchetti Claudio , Hamao Shino , Okamoto Hideki , Goto Hidenori , Eguchi Ritsuko , Fujiwara Akihiko , Kubozono Yoshihiro
Published: February 2021

A ring oscillator consisting of p-channel and n-channel organic FETs.
Correction: Investigation of plasma metabolomics and neurotransmitter dysfunction in the process of Alzheimer’s disease rat induced by amyloid beta 25-35
Authors: Wei Mengying , Liu Yuanyuan , Pi Zifeng , Yue Kexin , Li Shizhe , Hu Mingxin , Liu Zhiqiang , Song Fengrui , Liu Zhongying
Published: February 2021

Correction for ‘Investigation of plasma metabolomics and neurotransmitter dysfunction in the process of Alzheimer’s disease rat induced by amyloid beta 25-35’ by Mengying Wei et al., RSC Adv., 2019, 9, 18308–18319. DOI: 10.1039/C9RA00302A.
Coupling molecular rigidity and flexibility on fused backbones for NIR-II photothermal conversion
Authors: He Yonglin , Liao Hailiang , Lyu Shanzhi , Xu Xiao-Qi , Li Zhengke , McCulloch Iain , Yue Wan , Wang Yapei
Published: February 2021

Low bandgap and large deformation generally conflict each other. This work couples molecular rigidity and flexibility by intramolecular hydrogen bonds and double bonds to achieve NIR-II light absorption and reinforced internal conversion at the same time.