Miracle-dz/UniFAR-FTUs huggingface dataset:
CD11c+ B Cells Are Mainly Memory Cells, Precursors of Antibody Secreting Cells in Healthy Donors

CD11c+ B cells have been reported to be increased in autoimmune diseases, but they are detected in the blood of healthy individuals as well. We aimed to characterize CD11c+ B cells from healthy donors by flow cytometry, microarray analysis, and in vitro functional assays. Here, we report that CD11c+ B cells are a distinct subpopulation of B cells, enriched in the memory subpopulation even if their phenotype is heterogeneous, with overexpression of genes involved in B-cell activation and differentiation as well as in antigen presentation. Upon activation, CD11c+ B cells can differentiate into antibody-secreting cells, and CD11c could be upregulated in CD11c− B cells by B-cell receptor activation. Finally, we show that patients with pemphigus, an autoimmune disease mediated by B cells, have a decreased frequency of CD11c+ B cell after treatment, relative to baseline. Our findings show that CD11c+ B cells are mainly memory B cells prone to differentiate into antibody secreting cells that accumulate with age, independently of gender.
Inhibitor 9 Combined With Androgen Deprivation Therapy or Chemotherapy Delays the Malignant Behavior of Castration-Resistant Prostate Cancer Through K-Ras/PLCε/PKCε Signaling Pathway

Castration-resistant prostate cancer (CRPC) is a progressed stage of prostate cancer, which requires better understanding of the mechanisms and remains an unmet clinical need. As a common oncogene, K-Ras is associated with malignant behavior in different types of tumors but its role in CRPC is unknown. The present study aims to find the mechanism of K-Ras in CRPC and whether it can be used as a crucial molecule for the treatment of CRPC. For this purpose, tissue samples from primary prostate cancer (PPC) and CRPC patients were analyzed by immunohistochemistry and the data showed that K-Ras was elevated in CRPC. More importantly, higher K-Ras expression was related to a shorter recurrence-free survival time in patients with CRPC. In addition, K-Ras promoted the invasion, migration, and drug resistance of CRPC cells by activation of PLCε/PKCε signaling pathway. Meanwhile, the inhibitor of K-RasG12C mutants was able to inhibit malignant behavior of CRPC cells in vitro and in vivo. Inhibitors of K-RasG12C mutants have entered clinical trials. Taken together, the study shows that K-Ras may activate PKCε through PLCε, resulting in the alterations of malignant behavior of CRPC. Inhibitor 9, an inhibitor of the K-RasG12C mutant, has a strong anti-tumor effect in CRPC, which potentially suggests that inhibitors of this nature may serve as a promising treatment for CRPC.
Assessing Alternative Microscopy-Based Approaches to Species Abundance Description of Intertidal Diatom Communities

Diatoms usually dominate microphytobenthic biofilms in coastal and estuarine intertidal environments. Yet, functional studies on biofilms often skip species analysis because benthic diatoms are notoriously difficult to extract from sediments and challenging to identify at that taxonomic level. Valid, less time-consuming alternatives would surely be welcomed and increase the inclusion of community structure information in microphytobenthos (MPB) ecophysiological studies. Starting with an original 181-species abundances matrix (OSM), obtained during a 2-year spatial–temporal survey in a Tagus Estuary intertidal flat with contrasting sediment textures, the current study assessed the effectiveness of several approaches to species abundances analysis. The effect of excluding abundance data or rare species, the influence of taxonomic resolution, or the use of size-based metrics on biotic multivariate patterns was examined by an objective comparison that replicated these different approaches on three different levels: (1) inter-matrix correlations, (2) performance in several non-parametric multivariate analyses (ANOSIM, MDS), and (3) correlations with the environmental dataset. When compared with the OSM, all matrices had strong or very strong positive correlations. All discriminated successfully spatial patterns, separating well assemblages from sandy and muddy sediments, and all had significant correlations with the environmental dataset. Apart from the relative biovolume species matrix (BSM), only the species matrices were able to discriminate significantly temporal patterns. The exclusion of the rarest species (48% of total) had a negligible effect, with the common and original species abundances matrices having a ρ > 0.99 correlation. Of the alternative approaches to species abundances, species presence/absence and the genera abundances matrices yielded the best results overall. Genera presence/absence and the size-class matrices had intermediate performances, with the former performing comparatively poorly with regard to seasonal patterns. BSM had the lowest correlation with the environmental variable dataset (ρ = 0.598) and the worst overall performance in the other multivariate routines. This means that either a high-taxonomic resolution qualitative analysis (i.e. species presence/absence) or, in alternatively, a genus-level analysis retaining abundance data may be sufficient to describe basic spatial differences in estuarine intertidal flats. However, if seasonal variations in mudflat diatom assemblage structure are to be detected, species-level abundance data are still necessary.
Histone Deacetylase HDA9 With ABI4 Contributes to Abscisic Acid Homeostasis in Drought Stress Response

Drought stress, a major environmental factor, significantly affects plant growth and reproduction. Plants have evolved complex molecular mechanisms to tolerate drought stress. In this study, we investigated the function of the Arabidopsis thaliana RPD3-type HISTONE DEACETYLASE 9 (HDA9) in response to drought stress. The loss-of-function mutants hda9-1 and hda9-2 were insensitive to abscisic acid (ABA) and sensitive to drought stress. The ABA content in the hda9-1 mutant was reduced in wild type (WT) plant. Most histone deacetylases in animals and plants form complexes with other chromatin-remodeling components, such as transcription factors. In this study, we found that HDA9 interacts with the ABA INSENSITIVE 4 (ABI4) transcription factor using a yeast two-hybrid assay and coimmunoprecipitation. The expression of CYP707A1 and CYP707A2, which encode (+)-ABA 8′-hydroxylases, key enzymes in ABA catabolic pathways, was highly induced in hda9-1, hda9-2, abi4, and hda9-1 abi4 mutants upon drought stress. Chromatin immunoprecipitation and quantitative PCR showed that the HDA9 and ABI4 complex repressed the expression of CYP707A1 and CYP707A2 by directly binding to their promoters in response to drought stress. Taken together, these data suggest that HDA9 and ABI4 form a repressive complex to regulate the expression of CYP707A1 and CYP707A2 in response to drought stress in Arabidopsis.
HIF-1 Has a Central Role in Caenorhabditis elegans Organismal Response to Selenium

Selenium is a trace element for most organisms; its deficiency and excess are detrimental. Selenium beneficial effects are mainly due to the role of the 21st genetically encoded amino acid selenocysteine (Sec). Selenium also exerts Sec-independent beneficial effects. Its harmful effects are thought to be mainly due to non-specific incorporation in protein synthesis. Yet the selenium response in animals is poorly understood. In Caenorhabditis elegans, Sec is genetically incorporated into a single selenoprotein. Similar to mammals, a 20-fold excess of the optimal selenium requirement is harmful. Sodium selenite (Na2SeO3) excess causes development retardation, impaired growth, and neurodegeneration of motor neurons. To study the organismal response to selenium we performed a genetic screen for C. elegans mutants that are resistant to selenite. We isolated non-sense and missense egl-9/EGLN mutants that confer robust resistance to selenium. In contrast, hif-1/HIF null mutant was highly sensitive to selenium, establishing a role for this transcription factor in the selenium response. We showed that EGL-9 regulates HIF-1 activity through VHL-1, and identified CYSL-1 as a key sensor that transduces the selenium signal. Finally, we showed that the key enzymes involved in sulfide and sulfite stress (sulfide quinone oxidoreductase and sulfite oxidase) are not required for selenium resistance. In contrast, knockout strains in the persulfide dioxygenase ETHE-1 and the sulfurtransferase MPST-7 affect the organismal response to selenium. In sum, our results identified a transcriptional pathway as well as enzymes possibly involved in the organismal selenium response.
Metabolomic Diversity and Identification of Antibacterial Activities of Bacteria Isolated From Marine Sediments in Hawai’i and Puerto Rico

Antibiotic resistance is a growing concern worldwide and consequently metabolomic tools are being applied increasingly in efforts aimed at identifying new antimicrobial compounds. Marine bacteria-derived compounds have shown great promise in this area. A metabolomics-based study was undertaken to study the diversity of secondary metabolites from marine sediment bacteria isolated from different locations of Hawai’i and Puerto Rico. This effort included characterizing the biodiversity in the sediment samples and searching for antibacterial activity and associated compounds. Bacterial strains were isolated using several different nutrient agars and culture conditions. DNA sequencing (16s rDNA) was used for phylogenetic characterization. Antibacterial activity was assessed against antibiotic-resistant strains of Escherichia coli, Salmonella enterica, Acinetobacter baumannii, Staphylococcus aureus, and Enterococcus faecalis. Ethyl acetate extracted bacterial secondary metabolites were measured by ultra-performance liquid chromatography-mass spectrometry, processed in Progenesis QI and further analyzed by partial least squares-discriminant analysis using MetaboAnalyst 3. Among the strains (n = 143) that were isolated from these two geographical areas and tested for antibiotic activity, 19 exhibited antibacterial activity against at least one antibiotic-resistant human pathogen. One strain from Hawai’i possessed broad-spectrum activity against all five pathogens. Metabolite profiles were diverse and separated the strains into two clusters in PCA analysis that mirrored geographical origin of the isolated strains. A diversity of bacteria and potential antibacterial compounds were observed in this study. Marine environments represent an opportunity to discover a rich diversity of antibacterial compounds for which resistance mechanisms may be uncommon in human pathogens.
Metabolic Profiling Reveals an Abnormal Pattern of Serum Fatty Acids in MRL/lpr Mice Under Treatment With Prednisone

Glucocorticoids (GCs) are commonly used to treat systemic lupus erythematosus (SLE). Unfortunately, excessive GCs can induce many side effects associated with disordered fatty acid (FA) metabolism. Although an increased level of total FA has been found after GCs treatment, it is not clear whether all FA species increased or only certain FA species were altered. A gas chromatography–mass spectrometry-based FA profiling approach was performed to reveal the alterations of FA species in SLE model mice (MRL/lpr) after treatment with 5 mg/kg of prednisone. The study showed a distinct FA profile in MRL/lpr mice compared to the controls, mainly manifested by elevated polyunsaturated FAs (arachidonate, docosahexaenoate, etc.), which are related to the inflammatory state; and altered (product FA/precursor FA) ratios representing the estimated activities of FA desaturase and elongase (higher activities of multiple elongases, △4 desaturase, △5 desaturase, △6 desaturase, and lower activity of △8 desaturase). Treatment with 5 mg/kg of prednisone decreased the total level of n-6 polyunsaturated FA in MRL/lpr mice; in particular, the level of arachidonate and estimated activity of △5 desaturase were reduced to the control level. Moreover, prednisone induced additional perturbations in FAs, including not only saturated FAs, but also monounsaturated FAs and n-3 polyunsaturated FAs, indicating that there was a strong effect of prednisone on FA metabolism. These results may be valuable for further studies of the side effects of GCs treatment.
The Impact of Perceived Etiology, Treatment Type, and Wording of Treatment Information on the Assessment of Gastritis Treatments

How patients assess the suitability of a certain therapy for treating a disease depends on a variety of influencing factors. Three key factors are people's subjective perceptions of a disease, the type of treatment, and the kind of communication used to convey information. The study presented here was a randomized controlled experiment in which we examined these three factors. We used a mixed design where we manipulated perceived etiology of gastritis (biopsychosocial vs. biomedical) as a between-group factor, and treatment type (behavioral vs. pharmacological) and wording of treatment information (holistic vs. scientific) as within-group factors. We found that gastritis treatments that matched the perceived etiology of the illness were assessed to be more effective. Moreover, treatments that matched the perceived etiology enhanced participants' intention to undergo the treatment themselves and their willingness to recommend it to a person close to them. Finally, participants' intention to undergo the treatment was also enhanced when the wording of the treatment information matched the perceived etiology. We discuss the implications of our findings in terms of health communication and patient education.
Integrative Analysis of Sirtuins and Their Prognostic Significance in Clear Cell Renal Cell Carcinoma

Sirtuins, class III histone deacetylases, are involved in multiple biological processes in cancer initiation and progression. However, the diverse expression patterns and prognostic values of sirtuins in cancers have yet to be elucidated. In this study, we first evaluated the expression and prognostic values of sirtuins in multiple cancer cohorts using publicly available TCGA pan-cancer datasets. Pan-cancer survival analysis indicated that 6 out of 7 sirtuin family members were significant associated with prognosis of clear cell renal cell carcinoma (KIRC) patients. SIRT1, SIRT3, SIRT4, and SIRT5 were associated with favorable prognosis of KIRC patients, while SIRT6 and SIRT7 were associated with unfavorable prognosis. The expression levels of SIRT4 and SIRT5 in KIRC tissues were lower than that in normal tissues, while SIRT6 and SIRT7 were higher in KIRC tissues. The expression levels of SIRT1, SIRT3, SIRT5, SIRT6, and SIRT7 were significantly correlated with tumor stage and histological grade. DNA methylation may contribute to the dysregulation of sirtuins. Finally, GSEA was conducted to predict the potential functions of sirtuins in KIRC. Our results may provide novel insights for the development of sirtuins-based cancer therapy in KIRC.
The Optimal Outcome of Suppressing Ewing Sarcoma Growth in vivo With Biocompatible Bioengineered miR-34a-5p Prodrug

Being the second most common type of primary bone malignancy in children and adolescents, Ewing Sarcoma (ES) encounters the dilemma of low survival rate with a lack of effective treatments. As an emerging approach to combat cancer, RNA therapeutics may expand the range of druggable targets. Since the genome-derived oncolytic microRNA-34a (miR-34a) is down-regulated in ES, restoration of miR-34a-5p expression or function represents a new therapeutic strategy which is, however, limited to the use of chemically-engineered miRNA mimics. Very recently we have developed a novel bioengineering technology using a stable non-coding RNA carrier (nCAR) to achieve high-yield production of biocompatible miRNA prodrugs, which is a great addition to current tools for the assessment of RNA therapeutics. Herein, for the first time, we investigated the biochemical pharmacology of bioengineered miR-34a-5p prodrug (nCAR/miR-34a-5p) in the control of ES using human ES cells and xenograft mouse models. The bioengineered nCAR/miR-34a-5p was precisely processed to mature miR-34a-5p in ES cells and subsequently suppressed cell proliferation, attributable to the enhancement of apoptosis and induction of G2 cell cycle arrest through downregulation of SIRT-1, BCL-2 and CDK6 protein levels. Furthermore, systemic administration of nCAR/miR-34a-5p dramatically suppressed the ES xenograft tumor growth in vivo while showing biocompatibility. In addition, the antitumor effect of bioengineered nCAR/miR-34a-5p was associated with a lower degree of tumoral cell proliferation and greater extent of apoptosis. These findings demonstrate the efficacy of bioengineered miR-34a-5p prodrug for the treatment of ES and support the development of miRNA therapeutics using biocompatible bioengineered miRNA prodrugs.
Energy Saving at Work: Exploring the Role of Social Norms, Perceived Control and Ascribed Responsibility in Different Office Layouts

Reducing energy consumption in office buildings is critical for improving energy efficiency and decarbonization at the large scale. This study (N = 854) investigated the influence of social-psychological factors on energy-saving intention and behaviors in single-person versus shared offices based on the extend model of Theory of Planned Behavior (TPB). We found that ascription of responsibility, a variable added to the TPB, is the strongest predictor of energy-saving intentions for both single-person and shared offices. Interestingly, while injunctive norms are an important predictor of behavioral intention for single-person offices, descriptive norms are an important one for shared offices. Energy-saving intention mediates the influences of the aforementioned variables on energy-saving behaviors. Contrary to our hypotheses, perceived control over energy-saving and perceived ease of access to building control features have no direct impacts on energy-saving behaviors in single-person offices, while they have impacts on energy-saving behaviors in shared offices. This study provides useful insights for building designers and occupant behavior and energy modeling researchers.
Exploring the Use of Meditation as a Valuable Tool to Counteract Sedentariness

Some forms of meditation have been recently proposed as effective tools to facilitate the handling of undesired thoughts and reappraisal of negative emotions that commonly arise during exercise-related situations. The effects of meditation-based interventions on psychological responses could also be used as a means by which to increase exercise adherence and counteract the detrimental consequences of sedentariness. In the present article, we briefly describe the effects of meditation on physical activity and related factors. We also propose a theoretical model as a means by which to further understanding of the effects of meditation on psychological, psychophysical, and psychophysiological responses during exercise. The results of very recent studies in the realms of cognitive and affective psychology are promising. The putative psychological mechanisms underlying the effects of meditation on exercise appear to be associated with the interpretation of interoceptive and exteroceptive sensory signals. This is primarily due to the fact that meditation influences the cerebral processing of physical sensations, emotions, and thoughts. In such instances, the bodily and perceptual responses that are commonly reported during exercise might be assuaged during the practice of meditation. It also appears that conscious presence and self-compassion function as an emotional backdrop against which more complex behaviors can be forged. In such instances, re-engagement to physical activity programs can be more effectively achieved through the implementation of holistic methods to treat the body and mind. The comments provided in the present paper might have very important implications for exercise adherence and the treatment of hypokinetic diseases.
Sequestration of Exogenous Volatiles by Plant Cuticular Waxes as a Mechanism of Passive Associational Resistance: A Proof of Concept

Numerous plant-derived volatile organic compounds (VOCs) induce the expression of resistance-related genes and thereby cause an “associational resistance” in neighbouring plants. However, VOCs can also be sequestered by plant cuticular waxes. In case that they maintain their biological activity, such sequestered VOCs could generate a “passive” associational resistance that is independent of any gene expression in the receiver. As a proof of concept, we used major components of the cuticular wax layers of the tree, Parkinsonia praecox, and conidia of Colletotrichum lindemuthianum, a fungal pathogen that has not been reported to infect P. praecox. Wax layers were re-constituted on glass slides and exposed to each of 20 pure VOCs for 1 d and then to ambient air for 1 d or 15 d. Gas chromatography-mass spectrometry (GC-MS) analyses showed that all 20 VOCs were sequestered by the re-constituted wax layers. Exposure to 18 of the VOCs significantly inhibited the germination of C. lindemuthianum conidia on these wax layers after 1 day of exposure to ambient air. Four of the VOCs: 4Z-heptenol, farnesene, limonene, and 2E-decenal, inhibited germination rates to less than 25% of the controls. After 15 d, all VOCs were still detectable, although at strongly reduced concentrations, and no significant inhibition of conidial germination could be detected anymore. Exogenous VOCs can be sequestered by the components of plant cuticular waxes and maintain their biological activity, at least over a certain time span: an effect that could generate a transient “passive associational resistance” to pathogens.
Predicting or Pretending: Artificial Intelligence for Protein-Ligand Interactions Lack of Sufficiently Large and Unbiased Datasets

Predicting protein-ligand interactions using artificial intelligence (AI) models has attracted great interest in recent years. However, data-driven AI models unequivocally suffer from a lack of sufficiently large and unbiased datasets. Here, we systematically investigated the data biases on the PDBbind and DUD-E datasets. We examined the model performance of atomic convolutional neural network (ACNN) on the PDBbind core set and achieved a Pearson R2 of 0.73 between experimental and predicted binding affinities. Strikingly, the ACNN models did not require learning the essential protein-ligand interactions in complex structures and achieved similar performance even on datasets containing only ligand structures or only protein structures, while data splitting based on similarity clustering (protein sequence or ligand scaffold) significantly reduced the model performance. We also identified the property and topology biases in the DUD-E dataset which led to the artificially increased enrichment performance of virtual screening. The property bias in DUD-E was reduced by enforcing the more stringent ligand property matching rules, while the topology bias still exists due to the use of molecular fingerprint similarity as a decoy selection criterion. Therefore, we believe that sufficiently large and unbiased datasets are desirable for training robust AI models to accurately predict protein-ligand interactions.