Miracle-dz/UniFAR-FTUs huggingface dataset:
Spatial frequency and valence interact in complex emotion perception

ABSTRACT Research on spatial frequency contributions to facial emotion identification has largely focused on basic emotions. The present experiment characterised spatial frequency contributions to decoding complex emotions, which can be less visible and intense than basic emotions. We investigated the effects of spatial frequency, expression valence and perceptually available features (full face or eyes only) on decoding accuracy. We observed main effects of all factors, with better performance for high (relative to low) spatial frequency, for positive (relative to negative) emotions and for full face (relative to eyes only) conditions. We also observed an interaction of all factors. The high spatial frequency advantage in decoding accuracy was eliminated only for full faces expressing more positive complex emotions. These findings suggest advantages from high spatial frequency content in accurately decoding complex emotions may attenuate when positive complex emotions are decoded from the spatial frequency content of a broader constellation of features.
Expression of LINC01606 in multiple myeloma and its effect on cell invasion and migration.

Given the increasing incidence of multiple myeloma (MM) in recent years, a full understanding of its pathogenesis to find effective molecular markers carries huge implications for future clinical diagnosis and treatment of MM. As the research advances, accumulating studies have pointed out that long non-coding RNAs (LncRNAs) may be the key to the future diagnosis and treatment of neoplastic diseases. OBJECTIVE This study investigated the clinical implications of LncRNA LINC01606 in MM and its effects on the biological behavior of MM cells. METHODS In this prospective study, 72 patients with MM (group A) admitted between July 2014 and July 2016 and 68 healthy subjects (group B) who concurrently underwent physical examination in our hospital were included. The expression of LINC01606 in peripheral blood of patients in the two groups was detected to analyze its diagnostic and prognostic value in MM. In addition, MM cells were purchased and transfected with plasmids for mimics, inhibitors and negative control of LINC01606 and miR-579-3p respectively to detect the changes in cell proliferation, invasion and migration. RESULTS The expression of LINC01606 in group A was higher than that in group B (P<0.050). The sensitivity and specificity of peripheral blood LINC01606 in predicting MM were 85.29% and 72.39%, respectively (P<0.001). Prognostic follow-up analysis revealed higher LINC01606 levels in the dead than those in the survival. The predictive sensitivity of LINC01606 for the 3-year mortality of MM patients was 63.16%, and the specificity was 86.00% (P<0.001). Higher expression of LINC01606 indicated increased risk of 3-year mortality in patients with MM (P<0.001). Compared with LINC01606 overexpression and miR-579-3p inhibition, the proliferation, invasion and migration of cells decreased more significantly by LINC01606 inhibition and miR-579-3p overexpression (P<0.050). Dual luciferase reporter (DLR) assay confirmed the targeting relationship between LINC01606 and miR-579-3p. There was no significant difference in the activity of MM cells co-transfected with LINC01606-inhibitor and miR-579-3p-inhibitor plasmids compared with the blank group (P>0.050). CONCLUSIONS LINC01606, with a high expression profile in MM, promotes the proliferation, migration and invasion of MM cells through targeted inhibition of miR-579-3p, which may be the key to future diagnosis and treatment of MM.
RNF43 pathogenic Germline variant in a family with colorectal cancer

The role of RNF43 as a cause of an inherited predisposition to colorectal cancer (CRC) is yet to be fully explored. This report presents our findings of two individuals with CRC from a single family carrying a likely‐pathogenic inherited germline variant in RNF43. The proband (III:1) and the proband's mother (II:2) were diagnosed with mismatch repair proficient CRCs at the age of 50 years and 65 years, respectively. Both patients had BRAFV600E mutated colon tumours, indicating that the CRCs arose in sessile serrated lesions. The germline variant RNF43:c.375+1G>A was identified in both patients. RNA studies showed that this variant resulted in an aberrantly spliced transcript, which was predicted to encode RNF43:p.Ala126Ilefs*50 resulting in premature termination of protein synthesis and was classified as a likely‐pathogenic variant. Our report adds further evidence to the hereditary role of RNF43 as a tumour suppressor gene in colorectal tumorigenesis and supports the inclusion of RNF43 as a gene of interest in the investigation of CRC predispositions outside the setting of serrated polyposis.
Mode of Action of RZL-012, a New Fat-Reducing Molecule

Supplemental Digital Content is Available in the Text. BACKGROUND RZL-012 (5-[3,6-dibromo-9H-carbazol-9-yl]-N,N,N-trimethylpentan-1-aminium chloride) is a novel investigational drug injected subcutaneously into fat tissues in patients with fat-related disorders (Dercum disease) or subjects seeking aesthetic changes. OBJECTIVE Preclinical studies were undertaken to understand RZL-012's mechanism of action. MATERIALS AND METHODS The effects of RZL-012 were tested in vitro by measuring adipocyte cell killing, membrane integrity, cytosolic calcium, and mitochondrial membrane potential (MMP). In vivo studies in pigs evaluated RZL-012's adipocyte killing effect and measured pig fat thickness in the injected areas. RESULTS RZL-012 triggered adipocyte cell killing with IC50 values ranging from 25 to 106 μM. RZL-012 demonstrated initial effects on membrane integrity and calcium levels with delayed alterations in MMP. Incubation of RZL-012 with nanoghosts increased membrane permeability, culminating in full membrane destruction. Analysis of injected areas in pigs revealed liponecrosis 24 hours after dosing followed by an inflammatory response and formation of fibrotic tissue. Three months after dosing, an 18% reduction in mean fat thickness was observed in RZL-012 treated pigs. CONCLUSION RZL-012 destroys adipocytes by directly disrupting cell membrane integrity. Replacement of dead fat tissue by fibrotic tissue enables healing and causes contraction of the injected area. These effects are translated into significant reduction in fat tissue volume.
A glyoxylate-containing benzene derivative and butenolides from a marine algicolous fungus Aspergillus sp. SCSIO 41304

Abstract A new glyoxylate-containing benzene derivative, methyl 2-(4-hydroxy-3-(3′-methyl-2′-butenyl)phenyl)-2-oxoacetate (1), together with ten known compounds (2–11), were isolated from the marine algicolous fungus, Aspergillus sp. SCSIO 41304. Their planar structures and absolute configurations were elucidated by detailed NMR, MS spectroscopic analysis and comparing with literature data. Compound 1 was isolated as a new fungal secondary metabolite, possessing a methyl glyoxylate moiety R-CO-CO-OCH3, which is rare in natural sources. All the isolated compounds (1–11) were tested for their antibacterial and enzyme inhibitory activities against acetylcholinesterase (AChE) and pancreatic lipase (PL). Among these compounds, aspulvinone H (4) showed moderate inhibition against AChE and PL with IC50 values of 25.95 and 47.06 μM, respectively. Further molecular docking simulation exhibited that compound 4 could well bind to the catalytic pockets of the AChE and PL. Graphical Abstract
A Novel Method to Make Polyacrylamide Gels with Mechanical Properties Resembling those of Biological Tissues.

Studies characterizing how cells respond to the mechanical properties of their environment have been enabled by the use of soft elastomers and hydrogels as substrates for cell culture. A limitation of most such substrates is that, although their elastic properties can be accurately controlled, their viscous properties cannot, and cells respond to both elasticity and viscosity in the extracellular material to which they bind. Some approaches to endow soft substrates with viscosity as well as elasticity are based on coupling static and dynamic crosslinks in series within polymer networks or forming gels with a combination of sparse chemical crosslinks and steric entanglements. These materials form viscoelastic fluids that have revealed significant effects of viscous dissipation on cell function; however, they do not completely capture the mechanical features of soft solid tissues. In this report, we describe a method to make viscoelastic solids that more closely mimic some soft tissues using a combination of crosslinked networks and entrapped linear polymers. Both the elastic and viscous moduli of these substrates can be altered separately, and methods to attach cells to either the elastic or the viscous part of the network are described. Graphic abstract: Polyacrylamide gels with independently controlled elasticity and viscosity.
Phenotype Bias Determines How Natural RNA Structures Occupy the Morphospace of All Possible Shapes

Morphospaces representations of phenotypic characteristics are often populated unevenly, leaving large parts unoccupied. Such patterns are typically ascribed to contingency, or else to natural selection disfavouring certain parts of the morphospace. The extent to which developmental bias, the tendency of certain phenotypes to preferentially appear as potential variation, also explains these patterns is hotly debated. Here we demonstrate quantitatively that developmental bias is the primary explanation for the occupation of the morphospace of RNA secondary structure (SS) shapes. Upon random mutations, some RNA SS shapes (the frequent ones) are much more likely to appear than others. By using the RNAshapes method to define coarse-grained SS classes, we can directly compare the frequencies that non-coding RNA SS shapes appear in the RNAcentral database to frequencies obtained upon random sampling of sequences. We show that: a) Only the most frequent structures appear in nature; the vast majority of possible structures in the morphospace have not yet been explored. b) Remarkably small numbers of random sequences are needed to produce all the RNA SS shapes found in nature so far. c) Perhaps most surprisingly, the natural frequencies are accurately predicted, over several orders of magnitude in variation, by the likelihood that structures appear upon uniform random sampling of sequences. The ultimate cause of these patterns is not natural selection, but rather strong phenotype bias in the RNA genotype-phenotype map, a type of developmental bias or “findability constraint”, which limits evolutionary dynamics to a hugely reduced subset of structures that are easy to “find”.
Dual-stimuli-responsive TiOx/DOX nanodrug system for lung cancer synergistic therapy

Biological applications of nanosheets are rapidly increasing currently, which introduces new possibilities to improve the efficacy of cancer chemotherapy and radiotherapy. Herein, we designed and synthesized a novel nano-drug system, doxorubicin (DOX) loaded titanium peroxide (TiOx) nanosheets, toward the synergistic treatment of lung cancer. The precursor of TiO2 nanosheets with high specific surface area was synthesized by a modified hydrothermal process using the polymer P123 as a soft template to control the shape. TiOx nanosheets were obtained by oxidizing TiO2 nanosheets with H2O2. The anti-cancer drug DOX was effectively loaded on the surface of TiOx nanosheets. Generation of reactive oxygen species, including H2O2, ·OH and ·O2−, was promoted from TiOx nanosheets under X-ray irradiation, which is effective for cancer radiotherapy and drug release in cancer cells. In this way, chemotherapy and radiotherapy were combined effectively for the synergistic therapy of cancers. Our results reinforce the DOX loaded TiOx nanosheets as a pH sensitive and X-ray controlled dual-stimuli-responsive drug release system. The cytotoxicity, cellular uptake, and intracellular location of the formulations were evaluated in the A549 human non-small cell lung cancer cell line. Our results showed that TiOx/DOX complexes exhibited a greater cytotoxicity toward A549 cells than free DOX. This work demonstrates that the therapeutic efficacy of DOX-loaded TiOx nanosheets is strongly dependent on their loading mode and the chemotherapeutic and radiotherapy effect is improved under X-ray illumination, which provides a significant breakthrough for future applications of TiOx as a light activated drug carrier in cancer chemotherapy and radiotherapy.
Forebrain Architecture and Development in Cyclostomes, with Reference to the Early Morphology and Evolution of the Vertebrate Head

The vertebrate head and brain are characterized by highly complex morphological patterns. The forebrain, the most anterior division of the brain, is subdivided into the diencephalon, hypothalamus, and telencephalon from the neuromeric subdivision into prosomeres. Importantly, the telencephalon contains the cerebral cortex, which plays a key role in higher order cognitive functions in humans. To elucidate the evolution of the forebrain regionalization, comparative analyses of the brain development between extant jawed and jawless vertebrates are crucial. Cyclostomes – lampreys and hagfishes – are the only extant jawless vertebrates, and diverged from jawed vertebrates (gnathostomes) over 500 million years ago. Previous developmental studies on the cyclostome brain were conducted mainly in lampreys because hagfish embryos were rarely available. Although still scarce, the recent availability of hagfish embryos has propelled comparative studies of brain development and gene expression. By integrating findings with those of cyclostomes and fossil jawless vertebrates, we can depict the morphology, developmental mechanism, and even the evolutionary path of the brain of the last common ancestor of vertebrates. In this review, we summarize the development of the forebrain in cyclostomes and suggest what evolutionary changes each cyclostome lineage underwent during brain evolution. In addition, together with recent advances in the head morphology in fossil vertebrates revealed by CT scanning technology, we discuss how the evolution of craniofacial morphology and the changes of the developmental mechanism of the forebrain towards crown gnathostomes are causally related.
The CD200/CD200R mechanism in mesenchymal stem cells' regulation of dendritic cells.

OBJECTIVE To investigate the CD200/CD200R pathway mechanism in mesenchymal stem cells' (MSC) regulation of dendritic cells (DC) (MSc). METHODS We collected marrow samples from 40 patients admitted to our hospital from January 2018 to December 2019. The bone marrow MSCs were cultivated, and the peripheral blood mononuclear cells (PBMC) and peripheral blood DC were isolated to establish an in vitro immune response model. The expressions of the CD200 molecule on the surface of MSC were measured. Anti-CD200 blocking antibodies were added to the culture system to observe the effect of the PBMC differentiation and the immature DC (imDC) to mature DC (mDC). Then the impact of the different positive rates of CD200 in the same MSC on imDC maturity was measured. RESULTS After adding mitogen pHA, the IL-4, IL-10, and TNF-α secretions were increased (all P<0.05), and the OD value of the PBMC+pHA group was higher than it was in the PBMC group. After stimulated by pHA, the CD200 of the MSC group was higher than it was in the MSC+PBMC group (P<0.05). The MSC+PBMC group co-culture inhibited the development of imDC to mDC. Adding anti-CD200 antibodies to the MSC+PBMC co-culture system, MSC could still inhibit the differentiation of PBMC to imDC, and MSC had a significant inhibition effect on imDC to mDC maturation (P=0.006). The addition of MSC reduces the maturation markers on the surface of mDC (P<0.05). The addition of MSC inhibited the ability of mDC to stimulate PBMC (POD<0.05) and decreased the IL-12 (PIL-12<0.05) levels. The addition of the anti-CD200 antibody increased the proliferation ability of mDC to stimulate PBMC (POD<0.05), and it also increased the IL-12 levels in mDC (PIL-12<0.05). The expression of the DC mature immune phenotype in the CD200 high expression group was weak (PCD83, CD86<0.05). CONCLUSION The mechanism by which MSC inhibits DC may be achieved through the CD200/CD200R pathway, and the CD200/CD200R pathway mainly acts on the process from imDC to mDC.
Effect of Adjusted Antiplatelet Therapy on Preventing Ischemic Events After Stenting for Intracranial Aneurysms

Supplemental Digital Content is available in the text. Background and Purpose: This study tests whether patients with unruptured intracranial aneurysm who underwent stent placement benefitted from platelet function monitoring–guided adjustment of antiplatelet therapy. Methods: We conducted a randomized, open-label, parallel group, assessor-blinded trial. Patients with unruptured intracranial aneurysm who underwent stent placement were assigned in a 1:1 ratio to receive either drug adjustment (patients who had high on-treatment platelet reactivity to antiplatelet therapy on the basis of platelet function monitoring [monitoring group]) or conventional therapy (without monitoring and drug adjustment [conventional group]). The second monitoring was performed 14 days after randomization in patients with drug adjustment. The primary outcome was the composite frequency of ischemic stroke, transient ischemic attack, stent thrombosis, urgent revascularization, and cerebrovascular death within 7 days after stent implantation. The safety outcome was the composite frequency of major, minor, or minimal bleeding within 1 month after stent implantation. Results: In total, 314 patients were included (n=157 per group). The primary combined outcome occurred in 19 patients (12.1%) in the conventional group and 8 patients (5.1%) in the monitoring group (hazard ratio, 0.39 [95% CI, 0.17–0.92]; P=0.03). Ischemic stroke occurred at a lower frequency in the monitoring group compared with that in the conventional group (4.5% versus 12.1%; hazard ratio, 0.34 [95% CI, 0.14–0.83]; P=0.01), which drove the overall primary combined outcome. The safety outcome occurred in the monitoring group (7.0%) and in the conventional group (1.9%; hazard ratio, 3.87 [95% CI, 1.06–14.14]; P=0.03). A significant difference was observed in the frequency of minor or minimal bleeding events between the two groups (monitoring group versus conventional group, 6.4% versus 1.3%; P=0.02) but not in the frequency of major bleeding events between the two groups. Conclusions: Platelet function monitoring–guided antiplatelet therapy reduces thromboembolic events in patients with unruptured intracranial aneurysm after stent placement, significantly enhancing minor or minimal bleeding events but not major bleeding events. Registration: URL: https://www.clinicaltrials. gov; Unique identifier: NCT03989557.
Protecting Young Agricultural Workers: The Development of an Online Supervisor Training

ABSTRACT Adolescents and young adults working in agriculture are at greater risk of injury. We describe the development of an online safety and health training for people who hire, teach, or supervise young agricultural workers. The online training targeted specific skills supervisors can use to effectively supervise, train, and communicate with young workers about health and safety hazards that impact injury risk. Consistent with NIOSH’s evidence-based Total Worker Health® approach, the training integrated safety and health promotion and was also informed by behavioral change theories. An iterative approach was used to develop and evaluate the training. A content review provided feedback on topics and organization of material. Safety and health experts assessed the revised training content and rated the training topics on clarity, accuracy, and completeness. Finally, a pilot study with employers and health and safety professionals was used to evaluate the training materials. The content review suggested ways to reorganize the material to improve flow and reduce redundancy. Ratings of clarity, accuracy, and completeness were high, ranging from 5 to 7 (mean ratings from 5.8 to 7.0) on a scale of 1 (“does not do this at all”) to 7 (“does this very well”). The pilot study led to changes in wording and items used to assess knowledge. A theoretically-informed approach was used to develop an online supervisor training to increase awareness and build skills. An iterative process that included expert review, evaluation of learning competencies, and a pilot study with the end-users is described.
Effect of Glycyrrhiza uralensis against ulcerative colitis through regulating the signaling pathway of FXR/P-gp.

OBJECTIVE Ulcerative colitis (UC) is a moderate to severe inflammatory bowel disease, with a characteristic inflammatory response. Chinese herbal medicine can play a role in UC treatment. Herein, we aimed to investigate the function of Glycyrrhiza uralensis in UC treatment and the underlying mechanism. METHODS After establishing an animal model of UC, different agents of kuijieguanchang prescription, Glycyrrhiza uralensis, mesalazine, and GW4064 were administrated to mice. The apoptosis rate was measured by TUNEL assay, and the expression of different biomarkers was tested by western blot and qPCR. RESULTS Glycyrrhiza uralensis could regulate apoptosis of intestinal mucosal cells, through regulating the expression of apoptosis-related proteins and protective proteins of intestinal mucosa. The administration of Glycyrrhiza uralensis could greatly enhance the expression of muc1, muc3, and the pro-apoptotic protein, BAX. The proteins involved in malignancy from UC, such as Bcl-2 and fgf-15, were dramatically downregulated after using the Glycyrrhiza uralensis. Moreover, it was illustrated that Glycyrrhiza uralensis acted against UC by activating the signaling of P-gp through upregualting its expression. The upregulation of FGFR4, SHP, and P-gp in liver conferred protective function in UC. CONCLUSION Glycyrrhiza uralensis could regulate apoptosis of intestinal mucosal cells, through regulating the expression of apoptosis-related proteins and protective proteins of intestinal mucosa. The results provide novel options for UC treatment, as well as a rationale for pharmacology of Chinese traditional medicine, that is favorable for use of herbal medicine.
A review of the toxicology of oil in vertebrates: what we have learned following the Deepwater Horizon oil spill

ABSTRACT In the wake of the Deepwater Horizon (DWH) oil spill, a number of government agencies, academic institutions, consultants, and nonprofit organizations conducted lab- and field-based research to understand the toxic effects of the oil. Lab testing was performed with a variety of fish, birds, turtles, and vertebrate cell lines (as well as invertebrates); field biologists conducted observations on fish, birds, turtles, and marine mammals; and epidemiologists carried out observational studies in humans. Eight years after the spill, scientists and resource managers held a workshop to summarize the similarities and differences in the effects of DWH oil on vertebrate taxa and to identify remaining gaps in our understanding of oil toxicity in wildlife and humans, building upon the cross-taxonomic synthesis initiated during the Natural Resource Damage Assessment. Across the studies, consistency was found in the types of toxic response observed in the different organisms. Impairment of stress responses and adrenal gland function, cardiotoxicity, immune system dysfunction, disruption of blood cells and their function, effects on locomotion, and oxidative damage were observed across taxa. This consistency suggests conservation in the mechanisms of action and disease pathogenesis. From a toxicological perspective, a logical progression of impacts was noted: from molecular and cellular effects that manifest as organ dysfunction, to systemic effects that compromise fitness, growth, reproductive potential, and survival. From a clinical perspective, adverse health effects from DWH oil spill exposure formed a suite of signs/symptomatic responses that at the highest doses/concentrations resulted in multi-organ system failure.