Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of Small-Molecule Bioactive Constituents from the Leaves of Vaccinium bracteatum Confirms It as a Potential Functional Food with Health Benefits

The health benefits of Vaccinium bracteatum are well recorded in ancient Chinese medical books and were also demonstrated by modern researches. However, the relationship between its beneficial functions and specific chemical constituents has not been fully characterized. This study investigated the bioactive small-molecule constituents in the leaves of V. bracteatum, which afforded 32 compounds including ten new ones (1–9) and ten pairs of enantiomers (9–18). Their structures with absolute configurations were elucidated by spectroscopic methods, especially nuclear magnetic resonance (NMR) and electronic circular dichroism (ECD) analyses, with 1–4 bearing a novel revolving-door shaped scaffold. While half-compounds exhibited decent antioxidant activity by scavenging 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals, all except 19 and 20 exerted significant capturing activity against diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) radicals. In addition, the new iridoids 1, 5, 6, and 7 exerted apparent neuroprotective activity toward PC12 cells, with 1 being comparable to the positive control, and selective compounds also displayed anti-diabetic and anti-inflammatory properties by inhibiting α-glucosidase and NO production, respectively. The current work revealed that the bioactive small-molecule constituents could be closely related to the functional food property of the title species.
Odontocete spatial patterns and temporal drivers of detection at sites in the Hawaiian islands

Abstract Successful conservation and management of marine top predators rely on detailed documentation of spatiotemporal behavior. For cetacean species, this information is key to defining stocks, habitat use, and mitigating harmful interactions. Research focused on this goal is employing methodologies such as visual observations, tag data, and passive acoustic monitoring (PAM) data. However, many studies are temporally limited or focus on only one or few species. In this study, we make use of an existing long‐term (2009–2019), labeled PAM data set to examine spatiotemporal patterning of at least 10 odontocete (toothed whale) species in the Hawaiian Islands using compositional analyses and modeling techniques. Species composition differs among considered sites, and this difference is robust to seasonal movement patterns. Temporally, hour of day was the most significant predictor of detection across species and sites, followed by season, though patterns differed among species. We describe long‐term trends in species detection at one site and note that they are markedly similar for many species. These trends may be related to long‐term, underlying oceanographic cycles that will be the focus of future study. We demonstrate the variability of temporal patterns even at relatively close sites, which may imply that wide‐ranging models of species presence are missing key fine‐scale movement patterns. Documented seasonal differences in detection also highlights the importance of considering season in survey design both regionally and elsewhere. We emphasize the utility of long‐term, continuous monitoring in highlighting temporal patterns that may relate to underlying climatic states and help us predict responses to climate change. We conclude that long‐term PAM records are a valuable resource for documenting spatiotemporal patterns and can contribute many insights into the lives of top predators, even in highly studied regions such as the Hawaiian Islands.
Increasing Dosage of Leucovorin Results in Pharmacokinetic and Gene Expression Differences When Administered as Two-Hour Infusion or Bolus Injection to Patients with Colon Cancer

Simple Summary 5-fluorouracil (5-FU) is the drug used in almost all chemotherapy regimens for colorectal cancer. To potentiate the drug effect, 5-FU is most often combined with the folate leucovorin (LV). Although 5-FU dosage to some extent is individualized, LV dosage is not. To address the issues of LV dosage and administration this randomized pharmacokinetic study was performed comparing different LV dosages as well as infusion and bolus injection administration regimens. Folate concentrations in blood, tumor, mucosa and resection margins were analyzed as was tissue gene expression. In conclusion, different metabolic mechanisms appear to be induced when LV is administered as two-hour infusion or bolus injection, respectively. To achieve maximal inhibition of the 5-FU target enzyme thymidylate synthase (TS), an excess of the polyglutamated folate metabolite methylenetetrahydrofolate (MeTHF) is needed. Regarding polyglutamation, our results points in favor of the bolus regimen. These results could be used to optimize the effect of 5-FU. Abstract The combination of 5-fluorouracil (5-FU) and leucovorin (LV) forms the chemotherapy backbone for patients with colorectal cancer. However, the LV administration is often standardized and not based on robust scientific data. To address these issues, a randomized pharmacokinetics study was performed in patients with colon cancer. Thirty patients were enrolled, receiving 60, 200 or 500 mg/m2 LV as a single two-hour infusion. Blood, tumor, mucosa, and resection margin biopsies were collected. Folate concentrations were analyzed with LC-MS/MS and gene expression with qPCR. Data from a previous study where patients received LV as bolus injections were used as comparison. Saturation of methylenetetrahydrofolate (MeTHF) and tetrahydrofolate (THF) levels was seen after two-hour infusion and polyglutamated MeTHF + THF levels in tumors decreased with increasing LV dosage. The decrease was associated with decreased FPGS and increased GGH expression, which was not observed after LV bolus injection. In the bolus group, results indicate activation of a metabolic switch possibly promoting TYMS inhibition in response to 5-FU. Different metabolic mechanisms appear to be induced when LV is administered as infusion and bolus injection. Since maximal inhibition of TYMS by the 5-FU metabolite 5-fluoro-2′-deoxyuridine 5′-monophosphate (FdUMP) requires excess polyglutamated MeTHF, the results point in favor of the bolus regimen.
The Pan-STARRS Synthetic Solar System Model: A Tool for Testing and Efficiency Determination of the Moving Object Processing System

We present here the Pan-STARRS Moving Object Processing System (MOPS) Synthetic Solar System Model (S3M), the first-ever attempt at building a comprehensive flux-limited model of the major small-body populations in the solar system. The goal of the S3M is to provide a valuable tool in the design and testing of the MOPS software, and will be used in the monitoring of the upcoming Pan-STARRS 1 all-sky survey, which started science operations during late spring of 2010. The model is composed of synthetic populations of near-Earth objects (NEOs with a subpopulation of Earth impactors), the main-belt asteroids (MBAs), Jovian Trojans, Centaurs, trans-Neptunian objects (classical, resonant, and scattered trans-Neptunian objects [TNOs]), Jupiter-family comets (JFCs), long-period comets (LPCs), and interstellar comets. The model reasonably reproduces the true populations to a minimum of V = 24.5, corresponding to approximately the expected limiting magnitude for Pan-STARRS’s ability to detect moving objects. The NEO synthetic population has been extended to H < 25 (corresponding to objects of about 50 m in diameter), allowing for close flybys of the Earth to be modeled.
Chloroplast phylogenomics and the taxonomy of Saxifraga section Ciliatae (Saxifragaceae)

Abstract Comprising ca. 200 species, Saxifraga sect. Ciliatae is the most species‐rich section of Saxifraga s.str. , whose center of diversity is in the Tibeto‐Himalayan region. The infra‐sectional classification of sect. Ciliatae is still in debate due to the high level of species richness, as well as remarkable variations of habitat, morphology, physiology and life cycles. Subdivisions of this section proposed in various taxonomic systems have not been adequately tested in previous phylogenetic studies, partly due to low taxonomic sampling density, but also to the use of few DNA markers. In order to achieve a more robust infra‐sectional classification of sect. Ciliatae, complete chloroplast genomes of 94 taxa from this section were analyzed, of which 93 were newly sequenced, assembled and annotated. The length of the 94 plastomes of sect. Ciliatae taxa range from 143,479 to 159,938 bp, encoding 75 to 79 unique protein‐coding genes (PCGs). Analyses of the 94 plastomes revealed high conservation in structural organization, gene arrangement, and gene content. Gene loss and changes of IR boundaries were detected but in extremely low frequency. The molecular phylogenetic tree from concatenated PCGs and complete chloroplast genome sequences exhibited high resolution and support values and confirms that sect. Ciliatae is monophyletic. Three well‐supported clades were revealed within the section that agree relatively well with the subsectional taxonomy of Gornall (1987), but some minor modifications should be made. Firstly, the monotypic subsection Cinerascentes should be abandoned and its constituent species, S. cinerascens, assigned to subsect. Gemmiparae. Secondly, subsections Rosulares and Serpyllifoliae should be merged and become subsect. Rosulares. Section Ciliatae thus comprises: subsect. Hirculoideae Engl. & Irmsch. ; subsect. Rosulares Gornall; subsect. Gemmiparae Engl. & Irmsch. ; subsect. Flagellares (C. B. Clarke) Engl. & Irmsch. and subsect. Hemisphaericae (Engl. & Irmsch.) Gornall.
High-Phosphate-Stimulated Macrophage-Derived Exosomes Promote Vascular Calcification via let-7b-5p/TGFBR1 Axis in Chronic Kidney Disease

Although macrophage infiltration has been proven to increase calcified artery media in chronic kidney disease (CKD) patients, the mechanism by which macrophages are involved in vascular calcification (VC) progression remains unclear. Taking advantage of miRNA-seq, RNA-seq, dual-luciferase reporter assay, qRT-PCR, and arteries from CKD patients as well as CKD mouse models, we identified that high-phosphate-stimulated macrophage-derived exosomes (Mexo-P) suppressed let-7b-5p expression in VSMCs, which further upregulated TGFBR1. Moreover, gain-and-loss-of-function assays were used to determine the regulatory effects and downstream mechanism of let-7b-5p and TGFBR1 on VC. Mechanically, Mexo-P induced VSMC TGFBR1 upregulation by suppressing let-7b-5p, which further amplifies SMAD3/RUNX2 signaling and thereby contributes to VC. Our findings indicate that macrophage-derived exosomes promote CKD-associated VC through the let-7b-5p/TGFBR1 axis in high-phosphate conditions. Our study provides insight into macrophages associated with VC, which might be potential therapeutical targets for VC.
Association of Pulmonary Sepsis and Immune Checkpoint Inhibitors: A Pharmacovigilance Study

Simple Summary This study investigates the association of pulmonary sepsis with immune checkpoint inhibitors by conducting an analysis using data from the Food and Drug Administration pharmacovigilance database. Compared to chemotherapy or targeted therapy, a robust signal emerged for nivolumab and atezolizumab. Co-administration of immune checkpoint inhibitors and glucocorticoids or proton pump inhibitors synergistically increased the risk of pulmonary sepsis. These signals should promote both prospective research and multidisciplinary proactive monitoring by healthcare professionals. Abstract Background: Although some sepsis cases were reported with immune checkpoint inhibitors (ICIs) in clinical trials, the link between pulmonary sepsis and ICIs remains mostly unknown. We aim to investigate the association between pulmonary sepsis and ICIs, and to describe the clinical features. Methods: A disproportionality analysis was performed using FAERS data and compared rates of pulmonary sepsis in cancer patients receiving ICIs vs. other drug regimens (such as chemotherapy and targeted therapy). Associations between ICIs and sepsis were assessed using reporting odds ratios (ROR) and information component (IC). We also detected drug interaction signals based on the Ω shrinkage measure. Age and gender distribution were compared between pulmonary sepsis and all adverse events associated with ICIs. Results: We identified 120 reports of pulmonary sepsis associated with ICIs between Q1, 2011 to Q3, 2021. A total of 82 of 120 (68.3%) patients on ICIs suffered from pulmonary sepsis and progressed to death. In addition, there is no significant difference in age and gender in the occurrence of pulmonary sepsis in cancer patients on ICIs. Overall ICIs, nivolumab, and atezolizumab still have a significant signal of pulmonary sepsis (ROR025 > 1, IC025 > 0, p < 0.001) compared with targeted therapy (such as tyrosine kinase inhibitors) or chemotherapy. Co-administration of ICIs and glucocorticoids or proton pump inhibitors synergistically increased the risk of pulmonary sepsis (Ω025 > 0). Conclusions: Our study suggested ICIs, especially nivolumab and atezolizumab, tended to increase the risk of pulmonary sepsis more than other anticancer regimens. Clinicians should be vigilant in the prevention and management of pulmonary sepsis during ICIs therapy.
Solar Flare Geometries. II. The Volume Fractal Dimension

Based on the area fractal dimension D2 of solar flares measured in Paper I, we carry out modeling of the three-dimensional (3D) flare volume here and derive an analytical relation between the volume fractal scaling V(L) ∝ LD3 and the area fractal scaling A(L) ∝ LD2. The 3D volume model captures a flare arcade with a variable number of flare loops; its fractal structure is not isotropic, but consists of aligned one-dimensional substructures. The geometry of the arcade model has three free parameters and makes some simplifying assumptions, such as semicircular loops, east-west orientation, location near the equator, and no magnetic shear. The analytical model predicts the scaling of the area filling factor qA(nloop) and volumetric filling factor qV(nloop) as a function of the number of loops nloop, and allows one to predict the volume filling factor qV(qA) and volume fractal dimension D3(D2) from the observationally measured parameters qA and D2. We also corroborate the analytical model with numerical simulations. We apply this fractal model to the 20 flares analyzed in Paper I and find maximum volume filling factors with a median range of qV ≈ 0.03–0.08 (assuming solid filling for loop widths of ≲1 Mm). The fractal nature of the flare volume has important consequences for correcting electron densities determined from flare volume emission measures and density-dependent physical quantities, such as the thermal energy or radiative cooling time. The fractal scaling has also far-reaching consequences for frequency distributions and scaling laws of solar and stellar flares.
Comparison of Safety of RADial comPRESSion Devices: A Multi-Center Trial of Patent Hemostasis following Percutaneous Coronary Intervention from Conventional Radial Access (RAD-PRESS Trial)

Although radial access is the current gold standard for the implementation of percutaneous coronary interventions (PCI), post-procedural radial compression devices are seldom compared with each other in terms of safety or efficacy. Our group aimed to compare a cost effective and potentially green method to dedicated radial compression devices, with respect to access site complications combined in a device oriented complex endpoint (DOCE), freedom from which served as our primary endpoint. Patients undergoing PCI were randomized to receive either the cost effective or a dedicated device, either of which were removed using patent hemostasis. Twenty-four hours after the procedure, radial artery ultrasonography was performed to evaluate the access site. The primary endpoint was assessed using a non-inferiority framework with a non-inferiority margin of five percentage points, which was considered as the least clinically meaningful difference. The cost-effective technique and the dedicated devices were associated with a comparably low rate of complications (freedom from DOCE: 83.3% vs. 70.8%, absolute risk difference: 12.5%, one-sided 95% confidence interval (CI): 1.11%). Composition of the DOCE (i.e., no complication, hematoma, pseudoaneurysm, and radial artery occlusion) and compression time were also assessed in superiority tests as secondary endpoints. Both the cost-effective technique and the dedicated devices were associated with comparably low rates of complications: p = 0.1289. All radial compression devices performed similarly when considering the time to complete removal of the respective device (120.0 (inter-quartile range: 100.0–142.5) for the vial vs. 120.0 (inter-quartile range: 110.0–180) for the dedicated device arm, with a median difference of [95% CI]: 7.0 [−23.11 to 2.00] min, p = 0.2816). In conclusion, our cost-effective method was found to be non-inferior to the dedicated devices with respect to safety, therefore it is a safe alternative to dedicated radial compression devices, as well as seeming to be similarly effective.
Harsh nutritional environment has positive and negative consequences for family living in a burying beetle

Abstract Harsh environmental conditions in form of low food availability for both offspring and parents alike can affect breeding behavior and success. There has been evidence that food scarce environments can induce competition between family members, and this might be intensified when parents are caring as a pair and not alone. On the other hand, it is possible that a harsh, food‐poor environment could also promote cooperative behaviors within a family, leading, for example, to a higher breeding success of pairs than of single parents. We studied the influence of a harsh nutritional environment on the fitness outcome of family living in the burying beetle Nicrophorus vespilloides. These beetles use vertebrate carcasses for reproduction. We manipulated food availability on two levels: before and during breeding. We then compared the effect of these manipulations in broods with either single females or biparentally breeding males and females. We show that pairs of beetles that experienced a food‐poor environment before breeding consumed a higher quantity of the carcass than well‐fed pairs or single females. Nevertheless, they were more successful in raising a brood with higher larval survival compared to pairs that did not experience a food shortage before breeding. We also show that food availability during breeding and social condition had independent effects on the mass of the broods raised, with lighter broods in biparental families than in uniparental ones and on smaller carcasses. Our study thus indicates that a harsh nutritional environment can increase both cooperative as well as competitive interactions between family members. Moreover, our results suggest that it can either hamper or drive the formation of a family because parents choose to restrain reproductive investment in a current brood or are encouraged to breed in a food‐poor environment, depending on former experiences and their own nutritional status.
Properties of Tropical Convection Observed by Millimeter-Wave Radar Systems

Abstract This paper describes the results of analysis of over 825 000 profiles of millimeter-wave radar (MWR) reflectivities primarily collected by zenith-pointing surface radars observing tropical convection associated with various phases of activity of the large-scale tropical circulation. The data principally analyzed in this paper come from surface observations obtained at the Atmospheric Radiation Measurement Manus site during active and break episodes of the Madden–Julian oscillation (MJO) and from observations collected from a shipborne radar during an active phase of the monsoon over the Indian Ocean during the Joint Air–Sea Monsoon Interaction Experiment. It was shown, for example, in a histogram regime analysis that the MWR data produce statistics on convection regimes similar in most respects to the analogous regime analysis of the Tropical Rainfall Measuring Mission radar–radiometer observations. Attenuation of the surface MWRs by heavy precipitation, however, incorrectly shifts a small fracti.
miR-146a, miR-221, and miR-155 are Involved in Inflammatory Immune Response in Severe COVID-19 Patients

COVID-19 infection triggered a global public health crisis during the 2020–2022 period, and it is still evolving. This highly transmissible respiratory disease can cause mild symptoms up to severe pneumonia with potentially fatal respiratory failure. In this cross-sectional study, 41 PCR-positive patients for SARS-CoV-2 and 42 healthy controls were recruited during the first wave of the pandemic in Mexico. The plasmatic expression of five circulating miRNAs involved in inflammatory and pathological host immune responses was assessed using RT-qPCR (Reverse Transcription quantitative Polymerase Chain Reaction). Compared with controls, a significant upregulation of miR-146a, miR-155, and miR-221 was observed; miR-146a had a positive correlation with absolute neutrophil count and levels of brain natriuretic propeptide (proBNP), and miR-221 had a positive correlation with ferritin and a negative correlation with total cholesterol. We found here that CDKN1B gen is a shared target of miR-146a, miR-221-3p, and miR-155-5p, paving the way for therapeutic interventions in severe COVID-19 patients. The ROC curve built with adjusted variables (miR-146a, miR-221-3p, miR-155-5p, age, and male sex) to differentiate individuals with severe COVID-19 showed an AUC of 0.95. The dysregulation of circulating miRNAs provides new insights into the underlying immunological mechanisms, and their possible use as biomarkers to discriminate against patients with severe COVID-19. Functional analysis showed that most enriched pathways were significantly associated with processes related to cell proliferation and immune responses (innate and adaptive). Twelve of the predicted gene targets have been validated in plasma/serum, reflecting their potential use as predictive prognosis biomarkers.
Amplitude distribution of shot noise

A shot noise, I(t), is a superposition of impulses occurring at random Poisson distributed times …, t −1 , t 0 , t 1 , t 2 , …. In the simplest case, if the impulses all have the same shape F(t), then $I(t)=\sum{\limits_{i}}F(t-t_i)$ . We study, in this and more general cases, the distribution function $Q(I)=Pr\[I(t)\ \leqq\ I\]$ . One of our results is an integral equation for Q(I). This yields explicit expressions for Q(I) in a number of cases, including F(t) = e−t; it also permits a computational technique which is applied to F(t) = e−t sin ωt for >> 1.
Age of Cosmic-Ray Protons Computed Using Simple Configurations of the Galactic Magnetic Field

The influence of various magnetic field structures of the Galactic disk on some fundamental properties of cosmic-ray protons has been investigated with a simulation program, which generates cosmic-ray trajectories in the disk volume. The regular component of the Galactic magnetic field has been approximated by three different geometrical configurations (circular, elliptical, and spiral). Ages, residence times, and grammages of cosmic protons in various conditions are calculated and discussed. These calculations indicate that the proton age is strongly influenced by the magnetic field configuration but weakly affected by the field strength. The age of cosmic-ray protons in the spiral field turns out to be 6.7 × 106 yr, and the corresponding matter thickness 12 g cm-2.