Miracle-dz/UniFAR-FTUs huggingface dataset:
X-Raying the Ultraluminous Infrared Starburst Galaxy and Broad Absorption Line QSO Markarian 231 with Chandra

With 40 ks of Chandra ACIS-S3 exposure, new information on both the starburst and QSO components of the X-ray emission of Markarian 231, an ultraluminous infrared galaxy and broad absorption line QSO, has been obtained. The bulk of the X-ray luminosity is emitted from an unresolved nuclear point source, and the spectrum is remarkably hard, with the majority of the flux emitted above 2 keV. Most notably, significant nuclear variability (a decrease of ~45% in approximately 6 hr) at energies above 2 keV indicates that Chandra has probed within light-hours of the central black hole. Although we concur with Maloney & Reynolds that the direct continuum is not observed, this variability coupled with the 188 eV upper limit on the equivalent width of the Fe Kα emission line argues against the reflection-dominated model put forth by these authors based on their ASCA data. Instead, we favor a model in which a small, Compton-thick absorber blocks the direct X-rays, and only indirect, scattered X-rays from multiple lines of sight can reach the observer. Extended soft, thermal emission encompasses the optical extent of the galaxy and exhibits resolved structure. An off-nuclear X-ray source with a 0.35-8.0 keV luminosity of LX = 7 × 1039 ergs s-1, consistent with the ultraluminous X-ray sources in other nearby starbursts, is detected. We also present an unpublished Faint Object Spectrograph spectrum from the Hubble Space Telescope archive showing the broad C IV absorption.
Functional characterization of cannabidiol effect on the serotonergic neurons of the dorsal raphe nucleus in rat brain slices

Cannabidiol (CBD), the main non-psychoactive cannabinoid found in the cannabis plant, elicits several pharmacological effects via the 5-HT1A receptor. The dorsal raphe nucleus (DRN) is the main serotonergic cluster in the brain that expresses the 5-HT1A receptor. To date, the effect of CBD on the neuronal activity of DRN 5-HT cells and its interaction with somatodendritic 5-HT1A autoreceptors have not been characterized. Our aim was to study the effect of CBD on the firing activity of DRN 5-HT cells and the 5-HT1A autoreceptor activation by electrophysiological and calcium imaging techniques in male Sprague–Dawley rat brain slices. Perfusion with CBD (30 μM, 10 min) did not significantly change the firing rate of DRN 5-HT cells or the inhibitory effect of 5-HT (50–100 μM, 1 min). However, in the presence of CBD (30 μM, 10 min), the inhibitory effects of 8-OH-DPAT (10 nM) and ipsapirone (100 nM) were reduced by 66% and 53%, respectively. CBD failed to reverse ipsapirone-induced inhibition, whereas perfusion with the 5-HT1A receptor antagonist WAY100635 (30 nM) completely restored by 97.05 ± 14.63% the firing activity of 5-HT cells. Administration of AM251 (1 µM), MDL100907 (30 nM), or picrotoxin (20 μM) did not change the blockade produced by CBD (30 μM) on ipsapirone-induced inhibition. Our study also shows that CBD failed to modify the KCl (15 mM, 4 min)-evoked increase in [Ca2+]i or the inhibitory effect of ipsapirone (1 μM, 4 min) on KCl-evoked [Ca2+]i. In conclusion, CBD does not activate 5-HT1A autoreceptors, but it hindered the inhibitory effect produced by selective 5-HT1A receptor agonists on the firing activity of DRN 5-HT cells through a mechanism that does not involve CB1, 5-HT2A, or GABAA receptors. Our data support a negative allosteric modulation of DRN somatodendritic 5-HT1A receptor by CBD.
Coordinate regulation of methanol utilization pathway genes of Komagataella phaffii by transcription factors and chromatin modifiers

The methylotrophic yeast Komagataella phaffii (a.k.a. Pichia pastoris) harbors a methanol utilization (MUT) pathway, enabling it to utilize methanol as the sole source of carbon. The nexus between transcription factors such as Mxr1p and Trm1p and chromatin-modifying enzymes in the regulation of genes of MUT pathway has not been well studied in K. phaffii. Using transcriptomics, we demonstrate that Gcn5, a histone acetyltransferase, and Gal83, one of the beta subunits of nuclear-localized SNF1 (sucrose non-fermenting 1) kinase complex are essential for the transcriptional regulation by the zinc finger transcription factors Mxr1p and Trm1p. We conclude that interactions among Gcn5, Snf1, Mxr1p, and Trm1p play a critical role in the transcriptional regulation of genes of MUT pathway of K. phaffii.
Why did they get in trouble? The influence of firm characteristics and institutional distance on Chinese firms’ foreign market entry attempt

Despite the rich body of research on the outward foreign direct investment (OFDI) by Chinese multinationals, little attention has been given to the fact that China’s OFDI is facing a high failure rate even in their initial attempt to enter a foreign market. Grounded on institutional theory, this study provides a nuanced view of the expansion dynamic of Chinese multinational firms overseas using a unique dataset that contains both successful and troubled Chinese foreign market entry attempts between 2018 and 2021. We find that at the firm level, state-owned firms are more likely to face difficulties when trying to enter a new market compared to their private counterparts. Firms’ corporate social responsibility (CSR) reporting reduces the chance of failure. These effects are conditioned on the political, economic, and cultural distances between the home and host counties.
Editorial: Recent advances in the ecology and evolution of the Bathyergidae

COPYRIGHT © 2022 Braude, Holtze, Bennett and Begall. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Recent advances in the ecology and evolution of the Bathyergidae
Unpacking the effects of personality traits on algorithmic awareness: The mediating role of previous knowledge and moderating role of internet use

The COVID-19 pandemic has accelerated the integration of algorithms in online platforms to facilitate people’s work and life. Algorithms are increasingly being utilized to tailor the selection and presentation of online content. Users’ awareness of algorithmic curation influences their ability to properly calibrate their reception of online content and interact with it accordingly. However, there has been a lack of research exploring the factors that contribute to users’ algorithmic awareness, especially in the roles of personality traits. In this study, we explore the influence of Big Five personality traits on internet users’ algorithmic awareness of online content and examine the mediating effect of previous knowledge and moderating effect of breadth of internet use in in China during the pandemic era. We adapted the 13-item Algorithmic Media Content Awareness Scale (AMCA-scale) to survey users’ algorithmic awareness of online content in four dimensions. Our data were collected using a survey of a random sample of internet users in China (n = 885). The results of this study supported the moderated mediation model of open-mindedness, previous knowledge, breadth of internet use, and algorithmic awareness. The breadth of internet use was found to be a negative moderator between previous knowledge and algorithmic awareness.
Protein-protein interaction-based high throughput screening for adenylyl cyclase 1 inhibitors: Design, implementation, and discovery of a novel chemotype

Genetic and preclinical studies have implicated adenylyl cyclase 1 (AC1) as a potential target for the treatment of chronic inflammatory pain. AC1 activity is increased following inflammatory pain stimuli and AC1 knockout mice show a marked reduction in responses to inflammatory pain. Previous drug discovery efforts have centered around the inhibition of AC1 activity in cell-based assays. In the present study, we used an in vitro approach focused on inhibition of the protein-protein interaction (PPI) between Ca2+/calmodulin (CaM) and AC1, an interaction that is required for activation of AC1. We developed a novel fluorescence polarization (FP) assay focused on the PPI between an AC1 peptide and CaM and used this assay to screen over 23,000 compounds for inhibitors of the AC1-CaM PPI. Next, we used a cellular NanoBiT assay to validate 21 FP hits for inhibition of the AC1-CaM PPI in a cellular context with full-length proteins. Based on efficacy, potency, and selectivity for AC1, hits 12, 13, 15, 18, 20, and 21 were prioritized. We then tested these compounds for inhibition of AC1 activity in cyclic AMP (cAMP) accumulation assays, using HEK293 cells stably expressing AC1. Hit 15 contained a dithiophene scaffold and was of particular interest because it shared structural similarities with our recently reported benzamide series of AC1 inhibitors. We next tested a small set of 13 compounds containing the dithiophene scaffold for structure-activity relationship studies. Although many compounds were non-selective, we observed trends for tuning AC1/AC8 selectivity based on heterocycle type and substituents. Having an ethyl on the central thiophene caused the scaffold to be more selective for AC8. Cyclization of the alkyl substituent fused to the thiophene significantly reduced activity and also shifted selectivity toward AC8. Notably, combining the fused cyclohexane-thiophene ring system with a morpholine heterocycle significantly increased potency at both AC1 and AC8. Through designing a novel FP screen and NanoBiT assay, and evaluating hits in cAMP accumulation assays, we have discovered a novel, potent, dithiophene scaffold for inhibition of the AC1- and AC8-CaM PPI. We also report the most potent fully efficacious inhibitor of AC8 activity known to-date.
COVID-19: The effects of perceived organizational justice, job engagement, and perceived job alternatives on turnover intention among frontline nurses

Nurses’ turnover intention has become a concern for medical institutions because nurses are more needed than ever under the prevalence of COVID-19. This research sought to investigate the effects of the four dimensions of organizational justice on COVID-19 frontline nurses’ turnover intention through the mediating role of job engagement. We also tested the extent to which perceived job alternatives could moderate the relationship between job engagement and turnover intention. This descriptive cross-sectional study used an online survey to collect data from 650 frontline nurses working in appointed hospitals in Jiangsu province, China. Hierarchical regression was used to analyze the hypothesized relationships. Findings revealed that all organizational justice components significantly influenced job engagement and turnover intention. Job engagement also significantly affected nurses’ turnover intention and mediated the relationships between organizational justice components and turnover intention. Besides, perceived job alternatives moderated the relationships between job engagement and turnover intention. The implications of this study include demonstrating that healthcare authorities should respect human rights through effective organizational justice as this approach could encourage nurses to appreciate their job and be more devoted to staying and achieving their institutional duties, especially under challenging circumstances.
Pancreatic injury following immune checkpoint inhibitors: A systematic review and meta-analysis

Background: Pancreatic injury (pancreatitis, amylase/lipase elevation) is a rare adverse event of immune checkpoint inhibitors (ICIs). With the high number of clinical studies on ICIs, the incidence and characteristics of associated pancreatic injury (PI) need to be reevaluated. Methods: A systematic review and meta-analysis was conducted to assess the incidence of PI in cancer patients who received ICIs in randomized controlled trials (RCTs). PubMed, Embase, the ASCO, ESMO, and AACR conference proceedings before 1 April 2022, were investigated for relevant research. Results: 50 RCTs involving 35,223 patients were included. The incidence of ICIs-PI was 2.22% (95% CI = 1.94%–2.53%). The incidence of PI was 3.76% (95% CI = 1.84–7.67%) when combining two ICIs, which was higher than single ICIs [2.25% (95% CI = 1.91–2.65%)]. The ICIs were ranked from high to low based on PI incidence: PD-L1 inhibitors 3.01% (95% CI = 1.86–4.87%), CTLA-4 inhibitors 2.92% (95% CI = 0.99–8.65%) and PD-1 Inhibitor 2% (95% CI = 1.67–2.39%). The ICI with the highest rate of PI was pembrolizumab 7.23. % (95% CI = 1.69–30.89%). In addition, the incidence of severe ICIs-PI was 2.08% (95% CI = 1.76–2.46%); and the incidence of severe PI was 2.32% (95% CI = 1.76–3.06%) when combining two ICIs, which was higher than single ICI [1.95% (95% CI = 1.58–2.41%)]. The ICIs were ranked from high to low according to the incidence of severe PI: PD-L1 inhibitors 3.1% (95% CI = 1.7–5.64%), CTLA-4 inhibitors 2.69% (95% CI = 0.76–9.49%), PD-1 inhibitors 1.80% (95% CI = 1.41–2.29%). Conclusion: Treatment with multiple ICIs result in a higher incidence of PI compared to single ICIs, irrespective of the grade of pancreatic injury. The incidence of PI caused by PD-L1 inhibitors is higher than that of CTLA-4 inhibitors and PD-1 Inhibitor, and Pembrolizumab has the highest rate of ICIs-PI. Although the incidence of ICIs-PI is not high, they are usually severe (≥ grade 3 events).
Phenotypic prevalence of obesity and metabolic syndrome among an underdiagnosed and underscreened population of over 50 million children and adults

Background: Metabolic syndrome is a phenotypic condition associated with a variety of genotypes. Studies of rare genotypes can be made more difficult by clinical underscreening of the population for the phenotypic traits that define metabolic syndrome to clinicians. Studies have demonstrated underdiagnosis of pediatric obesity, as well as reduced rates of pediatric screening for obesity related conditions, including conditions leading to a diagnosis of metabolic syndrome. If true, there may be a significant underdiagnosis of metabolic syndrome among the pediatric population compared to the adult population. Methods: Using Epic’s Cosmos Data Network aggregated, de-identified patient data collected from healthcare organizations using the Epic electronic health record (EHR), we examined obesity and metabolic syndrome rates among adult and pediatric patients. We also examined screening rates for obesity related conditions and metabolic syndrome among adult and pediatric patients across the United States. We also sought to compare rates between subgroups within the population including age, sex, and race. Results: In our population, 45% of adults and 27% of pediatric population were obese by age and gender specific BMI criteria. 38% of the obese adult population had an ICD-10 code associated with the diagnosis vs. 52% of the pediatric population. Of adults meeting obesity criteria, 36% had results for appropriate, guideline-based blood laboratory testing for insulin resistance, 40–42% for dyslipidemia, and 55% for hepatic steatosis. 36% of obese adult patients had none of the recommended blood laboratory testing. 31% of the adult population met diagnostic criteria for metabolic syndrome. Of pediatric patients meeting obesity criteria, 27% had results for appropriate blood laboratory testing for insulin resistance, 28% for dyslipidemia, and 33% for hepatic steatosis. 59% of obese pediatric patients had none of the recommended blood laboratory testing. 3% of the pediatric population met criteria for diagnosis of metabolic syndrome. Discussion: This study represents one of the largest multicenter national cohorts assembled for studying metabolic syndrome (over 50 million patients) and demonstrates the power of emerging aggregated EHR tools for research. Although obesity is better diagnosed in pediatric patients than in adult patients, significantly lower screening rates for obesity related conditions occurred in pediatric patients compared to adults. Statistically significant, but clinically negligible differences in screening rates were found by race and gender. These results support smaller prior studies that suggest that obesity is under-diagnosed and obesity related conditions underscreened in pediatric and adult populations, and additionally suggests underdiagnosis of metabolic syndrome among United States pediatric and adult patients.
RAB20 deficiency promotes the development of silicosis via NLRP3 inflammasome

Silicosis is a worldwide serious occupational disease that is caused by inhalation of silica crystals. However, little is known about the pathogenesis mechanism of silicosis. We performed single-cell sequencing in bronchoalveolar lavage fluid (BALF) from mine workers with silicosis and their co-workers who did not develop silicosis, and found that the RAB20 deficiency in monocytes/macrophages was strongly linked to the development of silicosis. In the silicosis murine model, RAB20 knockout markedly enhanced the silica crystal-induced pulmonary interstitial fibrosis and respiratory dysfunction. Moreover, this process is strongly accompanied by IL-1β release and NLRP3 activation. In vitro, RAB20 knockout macrophages aggravated the crystalline silica-induced IL-1β release and NLRP3 inflammasome activation partly by increased ratio of crystalline silica/phagosomal areas/volumes to induce lysosomal injury. Thus, these findings provide novel molecular insights into the intricate mechanisms underlying lysosomal protein RAB20 that are necessary for environmental irritant-mediated innate immunity, and shed light on the future development of novel therapy target for the prevention of silicosis.
Why are bleeding trauma patients still dying? Towards a systems hypothesis of trauma

Over the years, many explanations have been put forward to explain early and late deaths following hemorrhagic trauma. Most include single-event, sequential contributions from sympathetic hyperactivity, endotheliopathy, trauma-induced coagulopathy (TIC), hyperinflammation, immune dysfunction, ATP deficit and multiple organ failure (MOF). We view early and late deaths as a systems failure, not as a series of manifestations that occur over time. The traditional approach appears to be a by-product of last century’s highly reductionist, single-nodal thinking, which also extends to patient management, drug treatment and drug design. Current practices appear to focus more on alleviating symptoms rather than addressing the underlying problem. In this review, we discuss the importance of the system, and focus on the brain’s “privilege” status to control secondary injury processes. Loss of status from blood brain barrier damage may be responsible for poor outcomes. We present a unified Systems Hypothesis Of Trauma (SHOT) which involves: 1) CNS-cardiovascular coupling, 2) Endothelial-glycocalyx health, and 3) Mitochondrial integrity. If central control of cardiovascular coupling is maintained, we hypothesize that the endothelium will be protected, mitochondrial energetics will be maintained, and immune dysregulation, inflammation, TIC and MOF will be minimized. Another overlooked contributor to early and late deaths following hemorrhagic trauma is from the trauma of emergent surgery itself. This adds further stress to central control of secondary injury processes. New point-of-care drug therapies are required to switch the body’s genomic and proteomic programs from an injury phenotype to a survival phenotype. Currently, no drug therapy exists that targets the whole system following major trauma.
Investigation of the transability of dietary small non-coding RNAs to animals

Our daily diet not only provides essential nutrients needed for survival and growth but also supplies bioactive ingredients to promote health and prevent disease. Recent studies have shown that exogenous microRNAs (miRNAs), xenomiRs, may enter the consumer’s body through dietary intake and regulate gene expression. This fascinating phenomenon suggests that xenomiRs can act as a new class of bioactive substances associated with mammalian systems. In contrast, several studies have failed to detect xenomiRs in consumers and reported that the observed diet-derived miRNAs in the previous studies can be related to the false positive effects of experiments. This discrepancy can be attributed to the potential artifacts related to the process of experiments, small sample size, and inefficient bioinformatics pipeline. Since this hypothesis is not generally accepted yet, more studies are required. Here, a stringent and reliable bioinformatics pipeline was used to analyze 133 miRNA sequencing data from seven different studies to investigate this phenomenon. Generally, our results do not support the transfer of diet-derived miRNAs into the animal/human tissues in every situation. Briefly, xenomiRs were absent from most samples, and also, their expressions were very low in the samples where they were present, which is unlikely to be sufficient to regulate cell transcripts. Furthermore, this study showed that the possibility of miRNAs being absorbed through animals’ diets and thus influencing gene expression during specific periods of biological development is not inconceivable. In this context, our results were in agreement with the theory of the transfer of small RNAs under certain conditions and periods as xenomiRs were found in colostrum which may modulate infants’ immune systems via post-transcriptional regulation. These findings provide evidence for the selective absorption of diet-derived small RNAs, which need to be investigated in future studies to shed light on the mechanisms underlying the transference of diet-derived miRNAs.
Terahertz reconfigurable dielectric metasurface hybridized with vanadium dioxide for two-dimensional multichannel multiplexing

The metasurface hybridized with vanadium dioxide (VO2) can be dynamically tuned, which has attracted enormous attention in recent years and orbital angular momentum (OAM) multiplexing based on metasurfaces has shown promising prospects in terahertz communications. However, existing research on VO2 metasurface focuses on the metallic metasurface. The dielectric VO2 metasurface used for OAM multiplexing is rarely reported to the present. This paper proposed a terahertz reconfigurable dielectric metasurface hybridized with VO2 for two-dimensional multichannel multiplexing combing with spatial and frequency domains. The metasurface works in both reflection and transmission modes and simultaneously the polarization control and operating frequency band regulation can be realized by switching the VO2 from the metallic state to the insulator state. For the reflective or transmissive metasurface, when 4×M-channel (M is a positive integer) off-axis plane waves are incident on the metasurface, the co-polarization reflected or cross-polarization transmitted waves are transformed into 4×M-channel orthogonal on-axis beams with topological or frequency orthogonality. A metasurface composed of 14 × 14 unit cells is designed for verification. The simulated result shows that two-dimensional 12-channel multiplexing combing with OAM and frequency by the designed metasurface can be realized on the reflection and transmission modes in two different frequency bands. The proposed metasurface has great potential in terahertz communications.