Miracle-dz/UniFAR-FTUs huggingface dataset:
NSP4 and ORF9b of SARS-CoV-2 Induce Pro-Inflammatory Mitochondrial DNA Release in Inner Membrane-Derived Vesicles

Circulating cell-free mitochondrial DNA (cf-mtDNA) has been found in the plasma of severely ill COVID-19 patients and is now known as a strong predictor of mortality. However, the underlying mechanism of mtDNA release is unexplored. Here, we show a novel mechanism of SARS-CoV-2-mediated pro-inflammatory/pro-apoptotic mtDNA release and a rational therapeutic stem cell-based approach to mitigate these effects. We systematically screened the effects of 29 SARS-CoV-2 proteins on mitochondrial damage and cell death and found that NSP4 and ORF9b caused extensive mitochondrial structural changes, outer membrane macropore formation, and the release of inner membrane vesicles loaded with mtDNA. The macropore-forming ability of NSP4 was mediated through its interaction with BCL2 antagonist/killer (BAK), whereas ORF9b was found to inhibit the anti-apoptotic member of the BCL2 family protein myeloid cell leukemia-1 (MCL1) and induce inner membrane vesicle formation containing mtDNA. Knockdown of BAK and/or overexpression of MCL1 significantly reversed SARS-CoV-2-mediated mitochondrial damage. Therapeutically, we engineered human mesenchymal stem cells (MSCs) with a simultaneous knockdown of BAK and overexpression of MCL1 (MSCshBAK+MCL1) and named these cells IMAT-MSCs (intercellular mitochondrial transfer-assisted therapeutic MSCs). Upon co-culture with SARS-CoV-2-infected or NSP4/ORF9b-transduced airway epithelial cells, IMAT-MSCs displayed functional intercellular mitochondrial transfer (IMT) via tunneling nanotubes (TNTs). The mitochondrial donation by IMAT-MSCs attenuated the pro-inflammatory and pro-apoptotic mtDNA release from co-cultured epithelial cells. Our findings thus provide a new mechanistic basis for SARS-CoV-2-induced cell death and a novel therapeutic approach to engineering MSCs for the treatment of COVID-19.
Screening of Pandemic Response Box Library Reveals the High Activity of Olorofim against Pathogenic Sporothrix Species

The increase in the prevalence and severity of fungal infections and the resistance to available antifungals highlights the imperative need for novel therapeutics and the search for new targets. High-content screening of libraries containing hundreds of compounds is a powerful strategy for searching for new drug candidates. In this study, we screened the Pandemic Response Box library (Medicines for Malaria Venture) of 400 diverse molecules against the Sporothrix pathogenic species. The initial screen identified twenty-four candidates that inhibited the growth of Sporothrix brasiliensis by more than 80%. Some of these compounds are known to display antifungal activity, including olorofim (MMV1782354), a new antifungal drug. Olorofim inhibited and killed the yeasts of S. brasiliensis, S. schenckii, and S. globosa at concentrations lower than itraconazole, and it also showed antibiofilm activity. According to the results obtained by fluorimetry, electron microscopy, and particle characterization analyses, we observed that olorofim induced profound alterations on the cell surface and cell cycle arrest in S. brasiliensis yeasts. We also verified that these morphophysiological alterations impaired their ability to adhere to keratinocytes in vitro. Our results indicate that olorofim is a promising new antifungal against sporotrichosis agents.
Tissue Rigidity Increased during Carcinogenesis of NTCU-Induced Lung Squamous Cell Carcinoma In Vivo

Increased tissue rigidity is an emerging hallmark of cancer as it plays a critical role in promoting cancer growth. However, the field lacks a defined characterization of tissue rigidity in dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) in vivo. Pre-malignant and malignant lung SCC was developed in BALB/c mice using N-nitroso-tris-chloroethylurea (NTCU). Picro sirius red staining and atomic force microscopy were performed to measure collagen content and collagen (diameter and rigidity), respectively. Then, the expression of tenascin C (TNC) protein was determined using immunohistochemistry staining. Briefly, all tissue rigidity parameters were found to be increased in the Cancer group as compared with the Vehicle group. Importantly, collagen content (33.63 ± 2.39%) and TNC expression (7.97 ± 2.04%) were found to be significantly higher (p < 0.05) in the Malignant Cancer group, as compared with the collagen content (18.08 ± 1.75%) and TNC expression (0.45 ± 0.53%) in the Pre-malignant Cancer group, indicating increased tissue rigidity during carcinogenesis of lung SCC. Overall, tissue rigidity of lung SCC was suggested to be increased during carcinogenesis as indicated by the overexpression of collagen and TNC protein, which may warrant further research as novel therapeutic targets to treat lung SCC effectively.
Sucrose Preference Test as a Measure of Anhedonic Behavior in a Chronic Unpredictable Mild Stress Model of Depression: Outstanding Issues

Despite numerous studies on the neurobiology of depression, the etiological and pathophysiological mechanisms of this disorder remain poorly understood. A large number of animal models and tests to evaluate depressive-like behavior have been developed. Chronic unpredictable mild stress (CUMS) is the most common and frequently used model of depression, and the sucrose preference test (SPT) is one of the most common tests for assessing anhedonia. However, not all laboratories can reproduce the main effects of CUMS, especially when this refers to a decrease in sucrose preference. It is also unknown how the state of anhedonia, assessed by the SPT, relates to the state of anhedonia in patients with depression. We analyzed the literature available in the PubMed database using keywords relevant to the topic of this narrative review. We hypothesize that the poor reproducibility of the CUMS model may be due to differences in sucrose consumption, which may be influenced by such factors as differences in sucrose preference concentration threshold, water and food deprivation, and differences in animals’ susceptibility to stress. We also believe that comparisons between animal and human states of anhedonia should be made with caution because there are many inconsistencies between the two, including in assessment methods. We also tried to offer some recommendations that should improve the reproducibility of the CUMS model and provide a framework for future research.
The evolution of interacting spiral galaxy NGC 5194

NGC 5194 (M51a) is a grand-design spiral galaxy and undergoing interactions with its companion. Here, we focus on investigating main properties of its star formation history (SFH) by constructing a simple evolution model, which assumes that the disc builds up gradually by cold gas infall and the gas infall rate can be parameterizedly described by a Gaussian form. By comparing model predictions with the observed data, we discuss the probable range for free parameter in the model and then know more about the main properties of the evolution and SFH of M51a. We find that the model predictions are very sensitive to the free parameter and the model adopting a constant infall-peak time t(p) = 7.0 Gyr can reproduce most of the observed constraints of M51a. Although our model does not assume the gas infall time-scale of the inner disc is shorter than that of the outer disc, our model predictions still show that the disc of M51a forms inside-out. We find that the mean stellar age of M51a is younger than that of the Milky Way, but older than that of the gas-rich disc galaxy UGC 8802. In this paper, we also introduce a 'toy' model to allow an additional cold gas infall occurred recently to imitate the influence of the interaction between M51a and its companion. Our results show that the current molecular gas surface density, the star formation rate and the UV-band surface brightness are important quantities to trace the effects of recent interaction on galactic star formation process.
SIMULTANEOUS MULTIWAVELENGTH OBSERVATION OF Mkn 501 IN A LOW STATE IN 2006

We present results of the multiwavelength campaign on the TeV blazar Mkn 501 performed in 2006 July, including MAGIC for the very-high-energy (VHE) γ-ray band and Suzaku for the X-ray band. A VHE γ-ray signal was clearly detected with an average flux above 200 GeV of ∼20% of the Crab Nebula flux, which indicates a low state of source activity in this energy range. No significant variability has been found during the campaign. The VHE γ-ray spectrum can be described by a simple power law from 80 GeV to 2 TeV with a photon index of 2.8 ± 0.1, which corresponds to one of the steepest photon indices observed in this energy range so far for this object. The X-ray spectrum covers a wide range from 0.6 to 40 keV, and is well described by a broken power law, with photon indices of 2.257 ± 0.004 and 2.420 ± 0.012 below and above the break energy of 3.24+0.13−0.12 keV. No apparent high-energy cut-off is seen above the break energy. Although an increase of the flux of about 50% is observed in the X-ray band within the observation, the data indicate a consistently low state of activity for this source. Time-resolved spectra show an evidence for spectral hardening with a flux level. A homogeneous one-zone synchrotron self-Compton (SSC) model can adequately describe the spectral energy distribution (SED) from the X-ray to the VHE γ-ray bands with a magnetic field intensity B = 0.313 G and a Doppler beaming factor δ = 20, which are similar to the values in the past multiwavelength campaigns in high states. Based on our SSC parameters derived for the low state, we are able to reproduce the SED of the high state by just changing the Lorentz factor of the electrons corresponding to the break energy in the primary electron spectrum. This suggests that the variation of the injected electron population in the jet is responsible for the observed low–high state variation of the SED.
XX. CoRoT-20b: A very high density, high eccentricity transiting giant planet

We report the discovery by the CoRoT space mission of a new giant planet, CoRoT-20b. The planet has a mass of 4.24 +/- 0.23 MJ and a radius of 0.84 +/- 0.04 RJ. With a mean density of 8.87 +/- 1.10 g/cm^3, it is among the most compact planets known so far. Evolution models for the planet suggest a mass of heavy elements of the order of 800 ME if embedded in a central core, requiring a revision either of the planet formation models or of planet evolution and structure models. We note however that smaller amounts of heavy elements are expected from more realistic models in which they are mixed throughout the envelope. The planet orbits a G-type star with an orbital period of 9.24 days and an eccentricity of 0.56. The star's projected rotational velocity is vsini = 4.5 +/- 1.0 km/s, corresponding to a spin period of 11.5 +/- 3.1 days if its axis of rotation is perpendicular to the orbital plane. In the framework of Darwinian theories and neglecting stellar magnetic breaking, we calculate the tidal evolution of the system and show that CoRoT-20b is presently one of the very few Darwin-stable planets that is evolving towards a triple synchronous state with equality of the orbital, planetary and stellar spin periods.
Buoyancy and g-modes in young superfluid neutron stars

We consider the local dynamics of a realistic neutron star core, including composition gradients, superfluidity and thermal effects. The main focus is on the gravity g-modes, which are supported by composition stratification and thermal gradients. We derive the equations that govern this problem in full detail, paying particular attention to the input that needs to be provided through the equation of state and distinguishing between normal and superfluid regions. The analysis highlights a number of key issues that should be kept in mind whenever equation of state data is compiled from nuclear physics for use in neutron star calculations. We provide explicit results for a particular stellar model and a specific nucleonic equation of state, making use of cooling simulations to show how the local wave spectrum evolves as the star ages. Our results show that the composition gradient is effectively dominated by the muons whenever they are present. When the star cools below the superfluid transition, the support for g-modes at lower densities (where there are no muons) is entirely thermal. We confirm the recent suggestion that the g-modes in this region may be unstable, but our results indicate that this instability will be weak and would only be present for a brief period of the star’s life. Our analysis accounts for the presence of thermal excitations encoded in entrainment between the entropy and the superfluid component. Finally, we discuss the complete spectrum, including the normal sound waves and, in superfluid regions, the second sound
Asymptotic periodicity of densities and ergodic properties for nonsingular systems

Each one dimensional piecewise smooth expanding transformation T on a finite interval has the following ergodic property (A), which is the result of Li and Yorke [11] and Wagner [15], (see also Morita [13]). In one dimensional case m denotes the Lebesgue measure. (A) There exists a sequence of m-absolutely continuous T-invariant probability measures {y>i,-">Hi} with Lt:= supp\i{ for i= I,---,/, which has the following properties. (1) fii(Li)=lfori=l,. ~,l. (2) (T, /Zj) is ergodic for i = 1,••-,/. (3) m(LfnL,.) = 0 i / i # j . (4) T-^ ^ L( m-a.e. for i = I , , / . (5) If rj is an m-absolutely continuous T-invariant probability measure, rj can be written as a convex combination of /xf's. (6) Put C= Un°°=o{*; T"(x)*UU^}> then m(C) = 0. (7) For i= l , • • • , / , there exists a collection of sets L£1,---,Lfr(f) with the following properties: (a)Li = [j^1Lij. (b) m(Lij(]Lik) = 0 ifj^k. (c) T-(LiJ+1) ID Ltj m-a.e. for j = l,--. ,r(0 1, and T " 1 ^ ) => LUr{i) m — a.e. (d) (T, |iy) is exact, where fitj = r (0 '^ | L i . . On the other hand, Lasota, Li and Yorke [8] pointed out that the behavior of the Frobenius-Perron operator P associated with T is asymptotically periodic. Namely it has the following property (B). (B) There exists a sequence of densities gi,--,gr and a sequence of bounded linear functional X1,-",Xr such that
Thermal Casimir effect for neutrino and electromagnetic fields in the closed Friedmann cosmological model

We calculate the total internal energy, total energy density and pressure, and the free energy for the neutrino and electromagnetic fields in Einstein and closed Friedmann cosmological models. The Casimir contributions to all these quantities are separated. The asymptotic expressions for both the total internal energy and free energy, and for the Casimir contributions to them are found in the limiting cases of low and high temperatures. It is shown that the neutrino field does not possess a classical limit at high temperature. As for the electromagnetic field, we demonstrate that the total internal energy has the classical contribution and the Casimir internal energy goes to the classical limit at high temperature. The respective Casimir free energy contains both linear and logarithmic terms with respect to the temperature. The total and Casimir entropies for the neutrino and electromagnetic fields at low temperature are also calculated and shown to be in agreement with the Nernst heat theorem.
Performance of Purple rice cultivar under different hill density

Purple rice has become a fascinating source of nutritional value among healthy cereal grains. A field experiment was conducted at Bangladesh Agricultural University during the Rabi season (February to May) of 2021 to evaluate the effect of number of seedlings/hill on growth, yield attributes and yield of Purple rice. Three seedling densities, viz. 1, 2 and 3 seedlings/hill, and three rice cultivars, viz. Purple rice, Pahari rice and a check BRRI dhan67 were experimental treatments and the experiment was laid out in a split-plot design with three replications. Results revealed that seedling number/hill had significant effects on the growth, yield and yield attributes of rice cultivars. The tallest plant (136.31 cm) was observed from the transplanting of 1 seedling/hill followed by 2 seedlings/hill (133.35 cm) in Pahari rice. The maximum values of the number of effective tillers (13.47; Purple rice), flag leaf length and width (41.36 and 1.24 cm; Pahari rice) were recorded from the treatment 2 seedlings/hill. The longest panicle (26.58 cm; Pahari rice) was observed in 1 seedling/hill, statistically, a similar value was found with 2 seedlings/hill (24.44 cm). Among rice cultivars, BRRI dhan67 produced the heaviest grains (1000-seed weight 23.96 g) with 2 seedlings/hill and maximum grain yield (6.35 t/ha) with 1 seedling/hill. Single seedling/hill was found to be the best management practice to get a higher yield per unit area for Purple rice and other rice cultivars also.
The Effects of Multilevel Orientations on Frontline Deliberate Learning

The study proposes a frontline deliberate learning (FDL) process involving knowledge generation, knowledge articulation, and knowledge codification, which enable organizations to capture knowledge embedded in the frontlines. It examines the antecedent effects of three orientations (i.e., performance, learning, and customer orientation) at both the individual dispositional level and strategic business unit (SBU) level on frontline deliberate learning. The proposed model was tested using survey data from multiple respondents from the healthcare industry. The results indicate that knowledge articulation plays a mediating role in the influence of knowledge generation on knowledge codification. Individual performance, learning, and customer orientation primarily affect knowledge generation. However, these three orientations at the unit level have different effects on knowledge articulation and the unit level’s codification.
Assessment of Lipid Quality in Commercial Omega-3 Supplements Sold in the French Market

Supplementation of omega-3 fatty acids is considered a valuable strategy to supply the low intake of these fatty acids. Thus, the safety of the supplements is an important milestone. Because of that, we analyzed 20 unflavored supplements sold in the French market for fatty acid and triglyceride composition, for EPA and DHA, and for tocol content, as well as for oxidative status. This study found that only 2.5% of the supplements did not meet their label claims for omega-3 content. TAG analysis showed high variability among the triglyceride distribution, and the same trend was also noticed for the tocol content; in fact, a high variability of the distribution of the six tocols (four tocopherols and two tocotrienols) was found among the samples. Of the tested products, all of them complied with peroxide value, p-anisidine value, and Totox values established by the Global Organization for EPA and DHA Omega-3s (GOED) and were not oxidized.
Effective Isolation of Fault-Correlated Variables via Statistical and Mutation Analysis

It is a widely-adopted strategy for developers to monitor the values of program variables when debugging in practice. In particular, developers often set breakpoints at specific locations or execute the program step by step in the debugging mode to inspect if abnormal values or status will be observed for concerned variables. Such a practical debugging strategy can facilitate developers in understanding and localizing the target fault. This study aims to identify suspicious program variables of a given fault (i.e., denoted as <italic>fault-correlated variables</italic>) automatically, thus facilitating the debugging activities for developers. To the best of our knowledge, this is the finest granularity in fault localization (FL) so far, which can address the limitations of being coarse-grained as faced by existing FL techniques. However, isolating fault-correlated variables precisely is challenging since there are usually substantially different variables used or defined in a program, and plenty of them are in the same basic block which cannot be well discriminated from each other since they will be either executed or not against the given test suite. To address such challenges, this study presents <monospace>I</monospace>soVar, a two-phase model to isolate fault-correlated variables. Specifically, <monospace>I</monospace>soVar first performs statistical analysis based on <italic>variable execution matrices</italic>, which is a novel concept proposed in this study, to identify a set of suspicious variables. It then observes the impacts of those variables on the program dynamically after applying subtle mutations at the bytecode level, to further isolate fault-correlated variables. Extensive experiments on Defects4J and Bears demonstrate that <monospace>I</monospace>soVar can outperform state-of-the-art techniques significantly (<inline-formula><tex-math notation="LaTeX">$13.0\%$</tex-math><alternatives><mml:math><mml:mrow><mml:mn>13</mml:mn><mml:mo>.</mml:mo><mml:mn>0</mml:mn><mml:mo>%</mml:mo></mml:mrow></mml:math><inline-graphic xlink:href="wen-ieq1-3209590.gif"/></alternatives></inline-formula> for MAP and <inline-formula><tex-math notation="LaTeX">$19.3\%$</tex-math><alternatives><mml:math><mml:mrow><mml:mn>19</mml:mn><mml:mo>.</mml:mo><mml:mn>3</mml:mn><mml:mo>%</mml:mo></mml:mrow></mml:math><inline-graphic xlink:href="wen-ieq2-3209590.gif"/></alternatives></inline-formula> for MRR). More importantly, we incorporated <monospace>I</monospace>soVar into 11 existing FL techniques as well as 14 automated program repair techniques, and found that <monospace>I</monospace>soVar can significantly boost their performance.
Stochastically Flipping Labels of Discriminator’s Outputs for Training Generative Adversarial Networks

Generative Adversarial Networks (GANs) play the adversarial game between two neural networks: the generator and the discriminator. Many studies treat the discriminator’s outputs as an implicit posterior distribution prior to the input image distribution. Thus, increasing the discriminator’s output dimensions can represent richer information than a single output dimension of the discriminator. However, increasing the output dimensions will lead to a very strong discriminator, which can easily surpass the generator and break the balance of adversarial learning. Solving such conflict and elevating the generation quality of GANs remains challenging. Hence, we propose a simple yet effective method to solve this conflict problem based on a stochastic selecting method by extending the flipped and non-flipped non-saturating losses in BipGAN. We organized our experiments based on the famous BigGAN and StyleGAN models for comparison. Our experiments successfully validated our approach to strengthening the generation quality within limited output dimensions via several standard evaluation metrics and real-world datasets and achieved competitive results in the Human face generation task.
Risk Analysis of Thyroid Cancer in China: A Spatial Analysis

Thyroid cancer (TC) is the fastest growing cancer in China and has lots of influencing factors which can be intervened to reduce its incidence. In this article, we aimed to identify the risk factors of TC. The regional TC data in 2016 were obtained from the China Cancer Registry Annual Report published by the National Cancer Center (NCC). Univariate correlation analysis and generalized linear Poisson regression analysis were used to determine risk factors for morbidity of TC from the provincial and prefecture levels. High urbanization rate (UR) (RR = 1.109, 95%CI: 1.084, 1.135), high GDP per capita (PGDP) (RR = 1.013, 95%CI: 1.007, 1.018), high aquatic products (RR = 1.047, 95%CI: 1.020, 1.075) and dry and fresh fruit consumption (RR = 1.024, 95%CI: 1.007, 1.040) can increase TC incidence. Therefore, high PGDP, high UR, high aquatic products and dry and fresh fruit consumption were all risk factors for TC incidence. Our results may be helpful for providing analytical ideas and methodological references for the regionalized prevention and control of TC in a targeted manner.