Miracle-dz/UniFAR-FTUs huggingface dataset:
Extracellular Vesicles Orchestrate Immune and Tumor Interaction Networks

Simple Summary Significant strides have been made to describe the pervasive role of extracellular vesicles (EVs) in health and disease. This work provides an insightful and unifying mechanistic understanding of EVs in immunity and tumorigenesis. This is achieved by dissecting the role of EVs within the continuum of immune cell physiology, immune–infection responses, and the immune–tumor microenvironment. Our work synthesizes important topical findings on immune EV signaling in mediating immune–tumor interaction networks. Abstract Extracellular vesicles (EVs) are emerging as potent and intricate intercellular communication networks. From their first discovery almost forty years ago, several studies have bolstered our understanding of these nano-vesicular structures. EV subpopulations are now characterized by differences in size, surface markers, cargo, and biological effects. Studies have highlighted the importance of EVs in biology and intercellular communication, particularly during immune and tumor interactions. These responses can be equally mediated at the proteomic and epigenomic levels through surface markers or nucleic acid cargo signaling, respectively. Following the exponential growth of EV studies in recent years, we herein synthesize new aspects of the emerging immune–tumor EV-based intercellular communications. We also discuss the potential role of EVs in fundamental immunological processes under physiological conditions, viral infections, and tumorigenic conditions. Finally, we provide insights on the future prospects of immune–tumor EVs and suggest potential avenues for the use of EVs in diagnostics and therapeutics.
Surface molecular motion of the monodisperse polystyrene films

Forced modulation scanning force microscopic (SFM) and lateral force microscopic (LFM) measurements of the monodisperse polystyrene (PS) films were carried out at 293 K in order to reveal surface molecular motion. Surface dynamic storage modulus, E‘, and surface loss tangent, tan δ, of the monodisperse PS films were evaluated on the basis of forced modulation SFM measurement. It was revealed that the magnitudes of surface E‘ and surface tan δ were lower and higher than those for its bulk state, respectively, in the case of the number-average molecular weight (Mn) lower than 26.6k. Based on forced modulation SFM measurements, the surface of the PS film with Mn lower than 26.6k was in a glass−rubber transition state even at 293 K, in spite of that the bulk Tg was far above 293 K. LFM measurements for the PS films revealed that the magnitude of lateral force was dependent on the scanning rate of the cantilever tip in the case of Mn lower than 40.4k. The scanning rate dependence of lateral force appeared in t.
Tackling modern‐day crises: Why understanding multilevel interconnectivity is vital

Complex crises like the coronavirus pandemic are showing us that modern societies are becoming increasingly unable to live in equilibrium with nature. These crises are the result of multiple causes, which interact at different scales and across different domains. Therefore, investigating their proximate causes is not enough to fully understand them. It is also crucial to take into account the structural factors involved. As concerns the global pandemic, I suggest four levels of analysis: (i) the surface or “proximate” level of the crisis; (ii) the human–environment–animal interface, as pointed out by the One Health approach; (iii) the broader socioeconomic context; and (iv) the deeper or worldview level. Furthermore, I argue that there is the need for a mindset shift if we want to properly trace causality. Much more attention must be given to the study of multilevel connecting patterns and nonlinear mechanisms as the producers of emergent global effects.
Development of a New Dry-Desulfurization Process by a Non-Thermal Plasma Hybrid Reactor

To find out a new dry-type desulfurization process with high efficiency and cost performance, a hybrid-type reaction process combining pulsed streamer corona plasma and TiO2 catalyst was developed in order to oxidize SO2 to SO3. Experiments of both gas-phase reaction and surface reaction were performed to elucidate oxidation characteristics. Experimental results show that the oxidation fraction of SO2 to SO3 in the gas-phase reaction is below 5% at low temperatures (under 800 K). Similarly, when using TiO2 only as catalyst and applying the pulsed streamer corona plasma, respectively, the oxidation fraction is not increased significantly. Moreover, when simply combining the gas-phase reaction and the surface reaction, the oxidation fraction can reach and maintain only about 10% below 673 K. Contrary to the above two results, the oxidation fraction could be increased significantly by adding H2O of about 0.2 vol %. Hydrogen peroxide was demonstrated to have better oxidation promotion characteristics in compa.
Identification of Circulating miR-762 as a Novel Diagnostic and Prognostic Biomarker for Non-Small Cell Lung Cancer

Background: MicroRNAs (miRNAs) have been demonstrated to play critical roles in tumorigenesis of non-small cell lung cancer (NSCLC), and circulating miRNAs are a valuable source of biomarkers for the clinical management of NSCLC. The aim of this study was to determine the value of serum miR-762 as a diagnostic and prognostic biomarker for NSCLC. Methods: We examined circulating miR-762 expression in 148 NSCLC patients and 60 healthy individuals using the quantitative real-time polymerase chain reaction (qRT-PCR). The effect of miR-762 downregulation on the proliferative capacity of NSCLC cells were also explored. Results: The serum miR-762 levels were significantly upregulated in NSCLC patients compared to the healthy individuals. Receiver operating characteristics (ROC) curve analysis revealed that circulating miR-762, carcinoembryonic antigen (CEA), CYFRA21-1 and a combination of these 3 biomarkers yield the areas under the curve (AUC) of 0.874, 0.826, 0.41 and 0.969, respectively. Interestingly, circulating miR-762 identified the NSCLC patients at the clinical stage I from healthy controls with an AUC value of 0.920. In addition, serum miR-762 expression was significantly correlated with clinical stage, lymph node metastasis, histological grade and gefitinib-resistance. The survival analysis showed that NSCLC patients in the high serum miR-762 group suffered worse overall survival and relapse-free survival than those in the low serum miR-762 group. The multivariate Cox proportional hazards regression analysis revealed high circulating miR-762 was an independent unfavorable prognostic factor. Downregulation of miR-762 significantly suppressed the proliferative capacity of NSCLC cells in vitro, and bioinformatic analysis of the potential downstream targets of miR-762 identified many important cancer-associated pathways. Conclusions: In conclusion, serum miR-762 might serve as a promising diagnostic and prognostic biomarker for the NSCLC.
Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation

Donor-specific anti-human leukocyte antigen antibodies (DSA) are controversially discussed in the context of liver transplantation (LT). We investigated the relationship between the presence of DSA and the outcome after LT. All the LTs performed at our center between 1 January 2008 and 31 December 2015 were examined. Recipients < 18 years, living donor-, combined, high-urgency-, and re-transplantations were excluded. Out of 510 LTs, 113 DSA-positive cases were propensity score-matched with DSA-negative cases based on the components of the Balance of Risk score. One-, three-, and five-year survival after LT were 74.3% in DSA-positive vs. 84.8% (p = 0.053) in DSA-negative recipients, 71.8% vs. 71.5% (p = 0.821), and 69.3% vs. 64.9% (p = 0.818), respectively. Rejection therapy was more often applied to DSA-positive recipients (n = 77 (68.1%) vs. 37 (32.7%) in the control group, p < 0.001). At one year after LT, 9.7% of DSA-positive patients died due to sepsis compared to 1.8% in the DSA-negative group (p = 0.046). The remaining causes of death were comparable in both groups (cardiovascular 6.2% vs. 8.0%; p = 0.692; hepatic 3.5% vs. 2.7%, p = 0.788; malignancy 3.5% vs. 2.7%, p = 0.788). DSA seem to have an indirect effect on the outcome of adult LTs, impacting decision-making in post-transplant immunosuppression and rejection therapies and ultimately increasing mortality due to infectious complications.
AtINO80 represses photomorphogenesis by modulating nucleosome density and H2A.Z incorporation in light-related genes

Significance INO80 is an evolutionarily conserved protein in eukaryotes. Mutations of INO80 cause growth arrest and embryo mortality in fruit flies and mice, which limits the investigation of INO80 biological functions during morphogenesis of multicellular organisms. Here, we show that AtINO80 interconnects with a light signaling pathway in Arabidopsis plants. Our characterization of atino80 mutants uncovers critical roles of INO80 in nucleosome density and H2A.Z incorporation during plant photomorphogenesis. Photomorphogenesis is a critical developmental process bridging light-regulated transcriptional reprogramming with morphological changes in organisms. Strikingly, the chromatin-based transcriptional control of photomorphogenesis remains poorly understood. Here, we show that the Arabidopsis (Arabidopsis thaliana) ortholog of ATP-dependent chromatin-remodeling factor AtINO80 represses plant photomorphogenesis. Loss of AtINO80 inhibited hypocotyl cell elongation and caused anthocyanin accumulation. Both light-induced genes and dark-induced genes were affected in the atino80 mutant. Genome-wide occupancy of the H2A.Z histone variant and levels of histone H3 were reduced in atino80. In particular, AtINO80 bound the gene body of ELONGATED HYPOCOTYL 5 (HY5), resulting in lower chromatin incorporations of H2A.Z and H3 at HY5 in atino80. Genetic analysis revealed that AtINO80 acts in a phytochrome B- and HY5-dependent manner in the regulation of photomorphogenesis. Together, our study elucidates a mechanism wherein AtINO80 modulates nucleosome density and H2A.Z incorporation and represses the transcription of light-related genes, such as HY5, to fine tune plant photomorphogenesis.
Mistrust and negative self‐esteem: Two paths from attachment styles to paranoia

Objectives Paranoia is known to be associated with insecure attachment, with negative self‐esteem as a mediator, but this pathway is insufficient to explain the paranoid individual’s beliefs about malevolent others. Mistrust is a likely additional factor as it is a core feature of paranoid thinking also associated with insecure attachment styles. In this study, we tested whether mistrust – operationalized as judgements about the trustworthiness of unfamiliar faces – constitutes a second pathway from insecure attachment to paranoia. Design The design of the study was cross‐sectional. Methods A nationally representative British sample of 1,508 participants aged 18–86, 50.8% female, recruited through the survey company Qualtrics, completed measurements of attachment style, negative self‐esteem, and paranoid beliefs. Usable data were obtained from 1,121 participants. Participants were asked to make trustworthiness judgements about computer‐generated faces, and their outcomes were analysed by conducting signal detection analysis, which provided measures of bias (the tendency to assume untrustworthiness in conditions of uncertainty) and sensitivity (accuracy in distinguish between trustworthy and untrustworthy faces). Results Results using structural equation modelling revealed a good model fit (RMSEA = .071, 95% CI: 0.067–0.075, SRMR = .045, CFI = .93, TLI = .92). We observed indirect effects through bias towards mistrust both for the relationship between attachment anxiety and avoidance (β = .003, 95% CI: 0.001–0.005,p < .001) and attachment anxiety and paranoia (β = .003, 95% CI 0.002–0.006, p < .001). We observed an indirect effect through negative self‐esteem only for the relationship between attachment anxiety and paranoia (β = .064, 95% CI: 0.053–0.077, p < .001). Trust judgements and negative self‐esteem were not associated with each other. Conclusions We find that a bias towards mistrust is associated with greater paranoia. We also find indirect effects through bias towards mistrust between attachment styles and paranoia. Finally, we reaffirm the strong indirect effect through negative self‐esteem between attachment anxiety and paranoia. Limitations of the study are discussed. Practitioner points When working with individuals suffering from paranoia, clinicians should consider not only explicit, deliberative cognitive processes of the kind addressed in cognitive behaviour therapy (e.g. cognitive restructuring) but also the way in which their patients make perceptual judgements (e.g., their immediate reactions on encountering new people) and consider interventions targeted at these judgements, for example, bias modification training. Assessment and clinical interventions for people should consider the role of trust judgements and the way in which they combine with low self‐esteem to provoke paranoid beliefs. Psychological interventions targeting paranoid beliefs should focus on both attachment anxiety and attachment avoidance.
Muscle-Specific Deletion of Toll-like Receptor 4 Impairs Metabolic Adaptation to Wheel Running in Mice

Supplemental digital content is available in the text. ABSTRACT Purpose Toll-like receptor 4 (TLR4) is an inflammatory receptor expressed ubiquitously in immune cells as well as skeletal muscle and other metabolic tissues. Skeletal muscle develops favorable inflammation-mediated metabolic adaptations from exercise training. Multiple inflammatory myokines, downstream from TLR4, are proposed links to the metabolic benefits of exercise. In addition, activation of TLR4 alters skeletal muscle substrate preference. The role of skeletal muscle TLR4 (mTLR4) in exercise metabolism has not previously been investigated. Herein, we aimed to specifically test the significance of mTLR4 to exercise-induced metabolic adaptations. Methods We developed a novel muscle-specific TLR4 knockout (mTLR4−/−) mouse model on C57BL/6J background. Male mTLR4−/− mice and wild-type (WT) littermates were compared under sedentary (SED) and voluntary wheel running (WR) conditions for 4 wk. Results mTLR4 deletion revealed marked reductions in downstream interleukin-1 receptor-associated kinase-4 (IRAK4) phosphorylation. In addition, the disruption of mTLR4 signaling prominently blunted the metabolic adaptations in WR-mTLR4−/− mice as opposed to substantial improvements exhibited by the WT counterparts. Voluntary WR in WT mice, relative to SED, resulted in significant increases in skeletal muscle fatty acid oxidation, glucose oxidation, and associated mitochondrial enzyme activities, all of which were not significantly changed in mTLR4−/− mice. Conclusions This study introduces a novel mTLR4−/− mouse model and identifies mTLR4 as an immunomodulatory effector of exercise-induced metabolic adaptations in skeletal muscle.
Engaging endogenous opioid circuits in pain affective processes

The pervasive use of opioid compounds for pain relief is rooted in their utility as one of the most effective therapeutic strategies for providing analgesia. While the detrimental side effects of these compounds have significantly contributed to the current opioid epidemic, opioids still provide millions of patients with reprieve from the relentless and agonizing experience of pain. The human experience of pain has long recognized the perceived unpleasantness entangled with a unique sensation that is immediate and identifiable from the first‐person subjective vantage point as “painful. ” From this phenomenological perspective, how is it that opioids interfere with pain perception? Evidence from human lesion, neuroimaging, and preclinical functional neuroanatomy approaches is sculpting the view that opioids predominately alleviate the affective or inferential appraisal of nociceptive neural information. Thus, opioids weaken pain‐associated unpleasantness rather than modulate perceived sensory qualities. Here, we discuss the historical theories of pain to demonstrate how modern neuroscience is revisiting these ideas to deconstruct the brain mechanisms driving the emergence of aversive pain perceptions. We further detail how targeting opioidergic signaling within affective or emotional brain circuits remains a strong avenue for developing targeted pharmacological and gene‐therapy analgesic treatments that might reduce the dependence on current clinical opioid options.
Determination of total cadmium in calcareous soils by extraction using aliquat‐336 and 3‐heptan‐one after aqua regia digestion

Abstract Measurement of total soil cadmium (Cd) is difficult due to calcium (Ca) and other chemicals which cause high background absorbance when trace levels of Cd are to be determined. When soil Cd is low, even use of deuterium background correction with flame atomic absorption spectroscopy (AAS) cannot provide accurate Cd results. Use of furnace atomic absorption with method of standard additions can circumvent these interferences, but the cost and time required are substantial. We desired a more rapid, convenient, and reliable alternative to extraction using dithizone and back‐extraction into acid, or to ammonium pyrollidinedithiocarbamate (APDC) which does not require close pH adjustment nor have many sources of potantial contamination. We evaluated analysis of these complex soil extracts with the method of Viets (1978) which extracts metals from 1N acid solutions using Aliquat‐336 in methylisobutyl‐ketone (MIBK). We tested the use of the less toxic and less water soluble 3‐heptanone as an organic sol.
Comprehensive characterization of dihydrofolate reductase‐mediated gene amplification for the establishment of recombinant human embryonic kidney 293 cells producing monoclonal antibodies

Human embryonic kidney 293 (HEK293) cells with glycosylation machinery have emerged as an alternative host cell line for stable expression of therapeutic glycoproteins. To characterize dihydrofolate reductase/methotrexate (DHFR/MTX)‐mediated gene amplification in HEK293 cells, an expression vector containing dhfr and monoclonal antibody (mAb) gene was transfected into dhfr‐deficient HEK293 cells generated by knocking out dhfr and dhfrl1 in HEK293E cells. Due to the improved selection stringency, mAb‐producing parental cell pools could be generated in the absence of MTX. When subjected to stepwise selection for increasing MTX concentrations such as 1, 10, and 100 nM, there was an increase in the specific mAb productivity (qmAb) of the parental cell pool upon DHFR/MTX‐mediated gene amplification. High producing (HP) clones with a qmAb of more than 2‐fold of the corresponding cell pool could be obtained using the limiting dilution method. The qmAb of most HP clones obtained from cell pools at elevated MTX concentrations significantly decreased during long‐term culture (3 months) in the absence of selection pressure. However, some HP clones could maintain high qmAb during long‐term culture. Taken together, a stable HP recombinant HEK293 cell line can be established using DHFR/MTX‐mediated gene amplification together with dhfr− HEK293 host cells.
Role of lncRNA FTX in invasion, metastasis, and epithelial-mesenchymal transition of endometrial stromal cells caused by endometriosis by regulating the PI3K/Akt signaling pathway

Background Studies have considered long non-coding RNA 5 prime to Xist (lncRNA FTX) a key lncRNA for normal uterine development, but it has not been reported whether lncRNA FTX is involved in regulating the development of endometriosis (EMs). The aim of the present study was to explore the effect and mechanism of long non-coding RNA 5 prime to Xist (lncRNA FTX) on the invasion, metastasis, and epithelial-mesenchymal transition (EMT) of endometrial stromal cells (ESCs) caused by EMs. Methods Ectopic or normal endometrial tissues were collected from 38 patients with EMs, who were diagnosed and operated on at Beijing Tongren Hospital from June 2018 to December 2019, and 20 healthy volunteers with normal endometria. The expression of lncRNA FTX in both groups was detected by quantitative reverse transcription polymerase chain reaction. Ectopic endometrial stromal cells (EESC) and ESC from patients with EMs and healthy volunteers were separated and cultured, and the expression of lncRNA FTX in the cells was detected. The expression of lncRNA FTX in EESC was overexpressed or interfered. Proliferation, invasion, and migration was detected by Cell Counting Kit-8, transwell assay, and scratch assay. Apoptosis and cell cycle were detected by flow cytometry. EMT-related protein and PI3K/Akt signaling pathway-related protein expressions were detected by Western blot. Results LncRNA FTX was underexpressed in endometrial tissues and EESC from patients with EMs. The overexpression of lncRNA FTX could significantly inhibit the proliferation, invasion, and migration of EESC, but promoted apoptosis and cell cycle arrest in the G0/G1 phase. The overexpression of lncRNA FTX significantly increased the expression of EMT-related protein, E-cadherin, and decreased the protein expression of vimentin, N-cadherin, and zinc finger E-box binding homeobox 1. In addition, the overexpression of lncRNA FTX could decrease the expression of p-PI3K/PI3K and p-Akt/Akt. Interfering with the expression of lncRNA FTX had the opposite result. Conclusions The overexpression of lncRNA FTX could decrease the invasion, metastasis, and EMT of ESC caused by EMs by inhibiting the activity of the PI3K/Akt signaling pathway.
Targeted disruption of the histone lysine 79 methyltransferase Dot1L in nephron progenitors causes congenital renal dysplasia

ABSTRACT The epigenetic regulator Dot1, the only known histone H3K79 methyltransferase, has a conserved role in organismal development and homoeostasis. In yeast, Dot1 is required for telomeric silencing and genomic integrity. In Drosophila, Dot1 (Grappa) regulates homoeotic gene expression. Dysregulation of DOT1L (human homologue of Dot1) causes leukaemia and is implicated in dilated cardiomyopathy. In mice, germline disruption of Dot1L and loss of H3K79me2 disrupt vascular and haematopoietic development. Targeted inactivation of Dot1L in principal cells of the mature collecting duct affects terminal differentiation and cell type patterning. However, the role of H3K79 methylation in mammalian tissue development has been questioned, as it is dispensable in the intestinal epithelium, a rapidly proliferating tissue. Here, we used lineage-specific Cre recombinase to delineate the role of Dot1L methyltransferase activity in the mouse metanephric kidney, an organ that develops via interactions between ureteric epithelial (Hoxb7) and mesenchymal (Six2) cell lineages. The results demonstrate that Dot1LHoxb7 is dispensable for ureteric bud branching morphogenesis. In contrast, Dot1LSix2 is critical for the maintenance and differentiation of Six2+ progenitors into epithelial nephrons. Dot1LSix2 mutant kidneys exhibit congenital nephron deficit and cystic dysplastic kidney disease. Molecular analysis implicates defects in key renal developmental regulators, such as Lhx1, Pax2 and Notch. We conclude that the developmental functions of Dot1L-H3K79 methylation in the kidney are lineage-restricted. The link between H3K79me and renal developmental pathways reaffirms the importance of chromatin-based mechanisms in organogenesis.