Miracle-dz/UniFAR-FTUs huggingface dataset:
Roles of Non-Coding RNAs in Response to Nitrogen Availability in Plants

Nitrogen (N) is an essential nutrient for plant growth and development; therefore, N deficiency is a major limiting factor in crop production. Plants have evolved mechanisms to cope with N deficiency, and the role of protein-coding genes in these mechanisms has been well studied. In the last decades, regulatory non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), small interfering RNAs (siRNAs), and long ncRNAs (lncRNAs), have emerged as important regulators of gene expression in diverse biological processes. Recent advances in technologies for transcriptome analysis have enabled identification of N-responsive ncRNAs on a genome-wide scale. Characterization of these ncRNAs is expected to improve our understanding of the gene regulatory mechanisms of N response. In this review, we highlight recent progress in identification and characterization of N-responsive ncRNAs in Arabidopsis thaliana and several other plant species including maize, rice, and Populus.
Social-Aware Pedestrian Trajectory Prediction via States Refinement LSTM

In the task of pedestrian trajectory prediction, social interaction could be one of the most complicated factors since it is difficult to be interpreted through simple rules. Recent studies have shown a great ability of LSTM networks in learning social behaviors from datasets, e.g., introducing LSTM hidden states of the neighbors at the last time step into LSTM recursion. However, those methods depend on previous neighboring features which lead to a delayed observation. In this paper, we propose a data-driven states refinement LSTM network (SR-LSTM) to enable the utilization of the current intention of neighbors through a message passing framework. Moreover, the model performs in the form of self-updating by jointly refining the current states of all participants, rather than an input-output mechanism served by feature concatenation. In the process of states refinement, a social-aware information selection module consisting of an element-wise motion gate and a pedestrian-wise attention is designed to serve as the guidance of the message passing process. Considering the pedestrian walking space as a graph where each pedestrian is a node and each pedestrian pair with an edge, spatial-edge LSTMs are further exploited to enhance the model capacity, where two kinds of LSTMs interact with each other so that states of them are interactively refined. Experimental results on four widely used pedestrian trajectory datasets, ETH, UCY, PWPD, and NYGC demonstrate the effectiveness of the proposed model.
Silicon-Based Ag Dendritic Nanoforests for Light-Assisted Bacterial Inhibition

Silver dendritic nanoforests (Ag-DNFs) on silicon (Ag-DNFs/Si) were synthesized through the fluoride-assisted Galvanic replacement reaction (FAGRR) method. The synthesized Ag-DNFs/Si were characterized by scanning electron microscopy, energy-dispersive X-ray spectrometry, inductively coupled plasma mass spectrometry (ICP-MS), reflection absorbance spectrometry, surface-enhanced Raman scattering spectrometry, and X-ray diffractometry. The Ag+ concentration in ICP-MS measurements indicated 1.033 mg/cm2 of deposited Ag synthesized for 200 min on Si substrate. The optical absorbance spectra indicated the induced surface plasmon resonance of Ag DNFs increased with the thickness of the Ag DNFs layer. Surface-enhanced Raman scattering measurement and a light-to-heat energy conversion test presented the superior plasmonic response of Ag-DNFs/Si for advanced applications. The Ag-DNFs/Si substrate exhibited high antibacterial activity against Escherichia coli and Staphylococcus aureus. The large surface area of the dense crystal Ag DNFs layer resulted in high antibacterial efficiency. The plasmonic response in the metal–crystal Ag DNFs under external light illumination can supply energy to enhance bacterial inhibition. High-efficiency plasmonic heating by the dense Ag DNFs can lead to localized bacterial inhibition. Thus, the Ag-DNFs/Si substrate has excellent potential for antibacterial applications.
Structure of the helicase core of Werner helicase, a key target in microsatellite instability cancers

WRN is a key drug target for cancers with microsatellite instability. A crystal structure of the helicase domain of WRN identifies its unique features and provides a basis for structure-guided design of inhibitors. Loss of WRN, a DNA repair helicase, was identified as a strong vulnerability of microsatellite instable (MSI) cancers, making WRN a promising drug target. We show that ATP binding and hydrolysis are required for genome integrity and viability of MSI cancer cells. We report a 2.2-Å crystal structure of the WRN helicase core (517–1,093), comprising the two helicase subdomains and winged helix domain but not the HRDC domain or nuclease domains. The structure highlights unusual features. First, an atypical mode of nucleotide binding that results in unusual relative positioning of the two helicase subdomains. Second, an additional β-hairpin in the second helicase subdomain and an unusual helical hairpin in the Zn2+ binding domain. Modelling of the WRN helicase in complex with DNA suggests roles for these features in the binding of alternative DNA structures. NMR analysis shows a weak interaction between the HRDC domain and the helicase core, indicating a possible biological role for this association. Together, this study will facilitate the structure-based development of inhibitors against WRN helicase.
Predictors of Functional Outcome After Microfracture Treatment of Cartilage Defects of the Knee.

INTRODUCTION Microfracture (MFx) is a widely used technique in the treatment of articular cartilage defects of the knee. The objective of this study was to determine the prognostic factors of functional outcomes after MFx treatment of knee cartilage defects ≤ 4 cm2. MATERIALS AND METHODS Forty-eight patients who were to be treated by MFx for knee cartilage defects ≤ 4 cm2 were prospectively included. The mean follow-up was 5.7 years (3.7-9.5). Demographics, sport practiced, time from diagnosis to surgery and associated lesions were collected. The cartilage defect was graded according to the ICRS classification. The MOCART score was calculated from a one-year MRI. The subjective VAS and IKDC scores were collected preoperatively and at the latest follow-up. Prognostic factors were determined using univariate and multivariate regression analyses incorporating pre-, peri- and postoperative clinical and radiological criteria. The dependent variable was defined as the difference between the pre- and post-operative clinical scores (dIKDC and dVAS). RESULTS The mean size of the cartilage defect was 1.8 cm2 (0.8-4). At the last follow-up, the VAS and IKDC scores were significantly improved compared to the pre-operative period (p<0.01). The average MOCART score on the one-year MRI was 50 (20-70). Three patients (6 %) who demonstrated filling defects on MRI and debilitating pain required surgical re-intervention. The factors that impacted the functional outcome as reflected by the VAS and IKDC scores were age, BMI, time from diagnosis to surgery, size of the lesion and the MOCART score. CONCLUSION This study demonstrates that MFx is a successful first-line treatment option for small articular cartilage defects (≤ 4 cm2) of the knee and provides good function and pain relief in the mid-term. The predictors of poor functional outcomes were older age, higher BMI, longer time from diagnosis to surgery, larger lesion size and lower MOCART score.
Cannabidiol and Vitamin D3 Impact on Osteogenic Differentiation of Human Dental Mesenchymal Stem Cells

Background and objective: The aim of the present study was to establish a new differentiation protocol using cannabidiol (CBD) and vitamin D3 (Vit. D3) for a better and faster osteogenic differentiation of dental tissue derived mesenchymal stem cells (MSCs). Materials and methods: MSCs were harvested from dental follicle (DFSCs), dental pulp (DPSCs), and apical papilla (APSCs) of an impacted third molar of a 17-year old patient. The stem cells were isolated and characterized using flow cytometry; reverse transcription polymerase chain reaction (RT-PCR); and osteogenic, chondrogenic, and adipogenic differentiation. The effects of CBD and Vit. D3 on osteogenic differentiation of dental-derived stem cell were evaluated in terms of viability/metabolic activity by alamar test, expression of collagen1A, osteopontin (OP), osteocalcin (OC), and osteonectin genes and by quantification of calcium deposits by alizarin red assay. Results: Stem cell characterization revealed more typical stemness characteristics for DFSCs and DPSCs and atypical morphology and markers expression for APSCs, a phenotype that was confirmed by differences in multipotential ability. The RT-PCR quantification of bone matrix proteins expression revealed a different behavior for each cell type, APSCs having the best response for CBD. DPSCs showed the best osteogenic potential when treated with Vit. D3. Cultivation of DFSC in standard stem cell conditions induced the highest expression of osteogenic genes, suggesting the spontaneous differentiation capacity of these cells. Regarding mineralization, alizarin red assay indicated that DFSCs and APSCs were the most responsive to low doses of CBD and Vit. D3. DPSCs had the lowest mineralization levels, with a slightly better response to Vit. D3. Conclusions: This study provides evidence that DFSCs, DPSCs, and APSCs respond differently to osteoinduction stimuli and that CBD and Vit. D3 can enhance osteogenic differentiation of these types of cells under certain conditions and doses.
A Modified Recommended Food Score Is Inversely Associated with High Blood Pressure in Korean Adults

Hypertension is associated with an increase in cardiovascular disease and mortality. The interplay between dietary intake—especially sodium intake—and high blood pressure highlights the importance of understanding the role of eating patterns on cardiometabolic risk factors. This study investigates the relationship between a modified version of the Recommended Food Score (RFS) and hypertension in 8389 adults aged 19–64 years from the Korea National Health and Nutrition Examination Survey 2013–2015. A dish-based, semi-quantitative, 112-item food frequency questionnaire was used to assess dietary intakes. Modified RFS (mRFS) is based on the reported consumption of foods recommended in the Dietary Approaches to Stop Hypertension (DASH) diet modified for Korean foods. High blood pressure included hypertension and prehypertension, also known as stage 1 hypertension. Men and women with the highest quintile of mRFS had a 27.2% (OR: 0.728, 95% CI: 0.545–0.971, p-trend = 0.0289) and 32.9% (OR: 0.671, 95% CI: 0.519–0.867, p-trend = 0.0087) lower prevalence of high blood pressure than those with the lowest quintile of mRFS, respectively. Our finding suggests that a higher mRFS may be associated with a lower prevalence of high blood pressure among the Korean adult population.
Generation and Application of the Zebrafish heg1 Mutant as a Cardiovascular Disease Model

Cardiovascular disease (CVD) is the leading cause of global mortality, which has caused a huge burden on the quality of human life. Therefore, experimental animal models of CVD have become essential tools for analyzing the pathogenesis, developing drug screening, and testing potential therapeutic strategies. In recent decades, zebrafish has entered the field of CVD as an important model organism. HEG1, a heart development protein with EGF like domains 1, plays important roles in the development of vertebrate cardiovascular system. Loss of HEG1 will affect the stabilization of vascular endothelial cell connection and eventually lead to dilated cardiomyopathy (DCM). Here, we generated a heg1-specific knockout zebrafish line using CRISPR/Cas9 technology. Zebrafish heg1 mutant demonstrated severe cardiovascular malformations, including atrial ventricular enlargement, heart rate slowing, venous thrombosis and slow blood flow, which were similar to human heart failure and thrombosis phenotype. In addition, the expression of zebrafish cardiac and vascular markers was abnormal in heg1 mutants. In order to apply zebrafish heg1 mutant in cardiovascular drug screening, four Traditional Chinese Medicine (TCM) herbs and three Chinese herbal monomers were used to treat heg1 mutant. The pericardial area, the distance between sinus venosus and bulbus arteriosus (SV-BA), heart rate, red blood cells (RBCs) accumulation in posterior cardinal vein (PCV), and blood circulation in the tail vein were measured to evaluate the therapeutic effects of those drugs on DCM and thrombosis. Here, a new zebrafish model of DCM and thrombosis was established, which was verified to be suitable for drug screening of cardiovascular diseases. It provided an alternative method for traditional in vitro screening, and produced potential clinical related drugs in a rapid and cost-effective way.
Diversity and biomass dynamics of unicellular marine fungi during a spring phytoplankton bloom.

Microbial communities have important functions during spring phytoplankton blooms, regulating bloom dynamics and processing organic matter. Despite extensive research into such processes, an in-depth assessment of the fungal component is missing, especially for the smaller size fractions. We assessed the dynamics of unicellular mycoplankton during a spring phytoplankton bloom in the North Sea by 18S rRNA gene tag sequencing and a modified CARD-FISH protocol. Visualization and enumeration of dominant taxa revealed unique cell count patterns that varied considerably over short time scales. The Rozellomycota sensu lato (s.l.) reached a maximum of 105 cells L-1 , being comparable to freshwater counts. The abundance of Dikarya surpassed previous values by two orders of magnitude (105 cells L-1 ) and the corresponding biomass (maximum of 8.9 mg C m-3 ) was comparable to one reported for filamentous fungi with assigned ecological importance. Our results show that unicellular fungi are an abundant and, based on high cellular ribosome content and fast dynamics, active part of coastal microbial communities. The known ecology of the visualized taxa and the observed dynamics suggest the existence of different ecological niches that link primary and secondary food chains, highlighting the importance of unicellular fungi in food web structures and carbon transfer. This article is protected by copyright. All rights reserved.
GEF-H1 Is Required for Colchicine Inhibition of Neutrophil Rolling and Recruitment in Mouse Models of Gout

Key Points Colchicine induces a neutrophil contractile response in a GEF-H1–dependent manner. Colchicine induces GEF-H1–dependent inhibition of neutrophil rolling and adhesion. GEF-H1 is required for colchicine inhibition of neutrophil response to MSU in vivo. Gout is a painful arthritic inflammatory disease caused by buildup of monosodium urate (MSU) crystals in the joints. Colchicine, a microtubule-depolymerizing agent that is used in prophylaxis and treatment of acute gout flare, alleviates the painful inflammatory response to MSU crystals. Using i.p. and intra-articular mouse models of gout-like inflammation, we found that GEF-H1/GEF-H1/AHRGEF2, a microtubule-associated Rho-GEF, was necessary for the inhibitory effect of colchicine on neutrophil recruitment. GEF-H1 was required for neutrophil polarization in response to colchicine, characterized by uropod formation, accumulation of F-actin and myosin L chain at the leading edge, and accumulation of phosphorylated myosin L chain, flotillin-2, and P-selectin glycoprotein ligand-1 (PSGL-1) in the uropod. Wild-type neutrophils that were pre-exposed to colchicine failed to roll or accumulate on activated endothelial monolayers, whereas GEF-H1 knockout (GEF-H1−/−) neutrophils were unaffected by treatment with colchicine. In vivo, colchicine blocked MSU-induced recruitment of neutrophils to the peritoneum and the synovium in wild-type mice, but not in GEF-H1−/− mice. Inhibition of macrophage IL-1β production by colchicine was independent of GEF-H1, supporting a neutrophil-intrinsic mode of action. Our results suggest that the anti-inflammatory effects of colchicine in acute gout-like inflammation can be accounted for by inhibition of neutrophil-rolling interactions with the inflamed vasculature and occurs through GEF-H1–dependent neutrophil stimulation by colchicine. These results contribute to our understanding of the therapeutic action of colchicine, and could inform the application of this drug in other conditions.
Epigenetic regulation of cancer stem cell formation and maintenance

Cancerous tumours contain a rare subset of cells with stem‐like properties that are termed cancer stem cells (CSCs). CSCs are defined by their ability to divide both symmetrically and asymmetrically, to initiate new tumour growth and to tolerate the foreign niches required for metastatic dissemination. Accumulating evidence suggests that tumours arise from cells with stem‐like properties, the generation of CSCs is therefore likely to be an initiatory event in carcinogenesis. Furthermore, CSCs in established tumours exist in a dynamic and plastic state, with nonstem tumour cells thought to be capable of de‐differentiation to CSCs. The regulation of the CSC state both during tumour initiation and within established tumours is a desirable therapeutic target and is mediated by epigenetic factors. In this review, we will explore the epigenetic parallels between induced pluripotency and the generation of CSCs, and discuss how the epigenetic regulation of CSCs opens up novel opportunities for therapeutic intervention.
Topical Capsaicin for the Treatment of Neuropathic Pain.

Neuropathic pain (NP) is an egregious problem worldwide. Due to the side effects of the oral drug, drugs delivered directly to the affected area of pain is preferred. Capsaicin, a chemical compound isolated from chili peppers, is employed as an analgesic in topical ointments and dermal patches to alleviate pain. To systematically review of capsaicin's functions on NP, we collected the articles in PUBMED published in the last ten years. 108 articles were selected among 265 after filtering through the inclusion and exclusion criteria. The data and knowledge currently existing for capsaicin treatment in NP are summarized. This review indicates that capsaicin represents an effective improvement within the treatment of NP without affecting the motor and the large nerve fibers involved in sensory function. Transient receptor potential channel vanilloid-receptor type 1 (TRPV1), is the capsaicin receptor, that is expressed on central and peripheral terminals of a sensitive primary nerve cell. Topical capsaicin encompasses a sensible safety profile and efficaciousness in reducing NP. Therefore, studies over the last ten years suggest that capsaicin might be a potential drug for the treatment of NP.
Etude par résonance magnétique nucléaire de macromolécules biologiques : structure, dynamique et interactions : application à une protéine de liaison aux odeurs

ASP2 est une proteine de 123 acides amines liant les odeurs (Odorant-Binding Protein). Elle est sans doute impliquee dans la premiere etape du processus de reconnaissance des odeurs chez l'abeille domestique au niveau de la lymphe sensillaire. Le present travail de these a permis, par resonance magnetique nucleaire, d'elucider la structure ainsi que de sonder la dynamique du squelette d'ASP2 en complexe avec le TSP (trimethylesilyle propionate-d4). A l'exception du segment D30-S45, la structure d'ASP2, monomerique, est bien definie (rmsd<1A). Quatre helices alpha1 et alpha4, alpha5, alpha6 antiparalleles forment un faisceau convergent. L'extremite ouverte du faisceau est fermee par l'helice alpha3. L'arrangement de ces cinq helices cree une poche essentiellement hydrophobe et faiblement polaire. Le segment D30-S45 presente une dynamique originale expliquant sa mauvaise definition dans la structure : le segment D30 a A38 est en echange conformationnel sur la gamme de la milliseconde tandis que la region A37 a S45 contient des mouvements importants dans la gamme pico-nanoseconde. L'apoproteine est presente sous deux formes en equilibre lent et de conformations tres similaires a celle du complexe. Les populations respectives dependent du pH. Lors de la fixation du ligand, une seule des conformations est selectionnee. L'IBMP (2-isobutyle- 3-methoxy-pyrazine) se fixe au sein de la poche hydrophobe de deux orientations, tete-beches, avec des affinites comparables. De plus, la poche hydrophobe d'ASP2 s'adapte a la taille du ligand. L'implication fonctionnelle de ces resultats est discutee.
Assessing the Robustness of a Factory Amid the COVID-19 Pandemic: A Fuzzy Collaborative Intelligence Approach

The COVID-19 pandemic has affected the operations of factories worldwide. However, the impact of the COVID-19 pandemic on different factories is not the same. In other words, the robustness of factories to the COVID-19 pandemic varies. To explore this topic, this study proposes a fuzzy collaborative intelligence approach to assess the robustness of a factory to the COVID-19 pandemic. In the proposed methodology, first, a number of experts apply a fuzzy collaborative intelligence approach to jointly evaluate the relative priorities of factors that affect the robustness of a factory to the COVID-19 pandemic. Subsequently, based on the evaluated relative priorities, a fuzzy weighted average method is applied to assess the robustness of a factory to the COVID-19 pandemic. The assessment result can be compared with that of another factory using a fuzzy technique for order preference by similarity to ideal solution. The proposed methodology has been applied to assess the robustness of a wafer fabrication factory in Taiwan to the COVID-19 pandemic.
Outcomes of conventionally-treated systemic sclerosis patients eligible for autologous haematopoietic stem cell transplantation.

OBJECTIVES Autologous haematopoietic stem cell transplantation (HSCT) has exhibited superior efficacy compared to conventional immunosuppressives in rapidly progressive diffuse systemic sclerosis (SSc) patients, albeit still of limited availability. We examined disease outcomes of conventionally-treated real-world inception patients eligible for HSCT, according to HSCT criteria used in the ASTIS and SCOT randomised trials, and compared them to the outcomes of participants in these trials. METHODS Overall and event-free survival rates in our inception cohort were analysed at 4.5 and 7 years after HSCT criteria fulfilment and compared to those reported in HSCT and control arms of ASTIS and SCOT. RESULTS Forty-five of our 142 inception cohort patients fulfilled HSCT criteria within 4 years from disease onset and had comparable baseline characteristics to SCOT/ASTIS patients. Four patients underwent HSCT. The remaining 41 were treated with conventional DMARDs: cyclophosphamide (n=24), mycophenolate mofetil (n=17), rituximab (n=2), tocilizumab (n=3), methotrexate (n=6) or combinations and their 10-year survival was 56% vs. 76% in those with diffuse SSc not fulfilling HSCT criteria. Their survival rates at the time endpoints of SCOT and ASTIS (4.5 and 7 years, respectively) were comparable to the conventionally-treated SCOT/ASTIS control groups. Extrapolating from SCOT/ASTIS results, if all our patients had undergone HSCT promptly, their overall and event-free survival rates could have increased from 73/51% to 83/72% at 4.5 years, and from 63/39% to 76/72% at 7 years, respectively. CONCLUSIONS Wider availability and physician's early acknowledgement and referral of eligible patients for HSCT could significantly improve disease outcomes of rapidly progressive diffuse SSc patients.