Miracle-dz/UniFAR-FTUs huggingface dataset:
Chromomycin A5 induces bona fide immunogenic cell death in melanoma

Purpose Some first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Tumor cells undergoing ICD function as a vaccine, releasing damage-associated molecular patterns (DAMPs), which act as adjuvants, and neoantigens of the tumor are recognized as antigens. ICD induction is rare, however it yields better and long-lasting antitumor responses to chemotherapy. Advanced metastatic melanoma (AMM) is incurable for more than half of patients. The discovery of ICD inducers against AMM is an interesting drug discovery strategy with high translational potential. Here we evaluated ICD induction of four highly cytotoxic chromomycins A (CA5-8). Methods ICD features and DAMPs were evaluated using several in vitro techniques with metastatic melanoma cell line (B16-F10) exposed to chromomcins A5-8 such as flow cytometry, western blot, RT-PCR and luminescence. Additionally in vivo vaccination assays with CA5-treated cells in a syngeneic murine model (C57Bl/6) were performed to confirm ICD evaluating the immune cells activation and their antitumor activity. Results B16-F10 treated with CA5-8 and doxorubicin exhibited ICD features such as autophagy and apoptosis, externalization of calreticulin, and releasing of HMGB1. However, CA5-treated cells had the best profile, also inducing ATP release, ERp57 externalization, phosphorylation of eIF2α and altering expression of transcription of genes related to autophagy, endoplasmic reticulum stress, and apoptosis. Bona fide ICD induction by CA5 was confirmed by vaccination of C57BL/6 mice with CA5-treated cells which activated antigen-presenting cells and T lymphocytes and stimulated antitumor activity. Conclusion CA5 induces bona fide immunogenic cell death on melanoma.
Identification of six hub genes and two key pathways in two rat renal fibrosis models based on bioinformatics and RNA-seq transcriptome analyses

Renal fibrosis (RF) is the common pathological manifestation and central treatment target of multiple chronic kidney diseases with high morbidity and mortality. Currently, the molecular mechanisms underlying RF remain poorly understood, and exploration of RF-related hub targets and pathways is urgently needed. In this study, two classical RF rat models (adenine and UUO) were established and evaluated by HE, Masson and immunohistochemical staining. To clear molecular mechanisms of RF, differentially expressed genes (DEGs) were identified using RNA-Seq analysis, hub targets and pathways were screened by bioinformatics (functional enrichment analyses, PPI network, and co-expression analysis), the screening results were verified by qRT-PCR, and potential drugs of RF were predicted by network pharmacology and molecular docking. The results illustrated that renal structures were severely damaged and fibrotic in adenine- and UUO-induced models, as evidenced by collagen deposition, enhanced expressions of biomarkers (TGF-β1 and α-SMA), reduction of E-cadherin biomarker, and severe renal function changes (significantly decreased UTP, CREA, Ccr, and ALB levels and increased UUN and BUN levels), etc. 1189 and 1253 RF-related DEGs were screened in the adenine and UUO models, respectively. Two key pathways (AGE-RAGE and NOD-like receptor) and their hub targets (Tgfb1, Col1a1, Nlrc4, Casp4, Trpm2, and Il18) were identified by PPI networks, co-expressed relationships, and qRT-PCR verification. Furthermore, various reported herbal ingredients (curcumin, resveratrol, honokiol, etc.) were considered as important drug candidates due to the strong binding affinity with these hub targets. Overall, this study mainly identified two key RF-related pathways (AGE-RAGE and NOD-like receptor), screened hub targets (Tgfb1, Col1a1, Nlrc4, Casp4, Trpm2, and Il18) that involved inflammation, ECM formation, myofibroblasts generation, and pyroptosis, etc., and provided referable drug candidates (curcumin, resveratrol, honokiol, etc.) in basic research and clinical treatment of RF.
STRONG [O iii] OBJECTS AMONG SDSS BROAD-LINE ACTIVE GALAXIES

We present the results of a spectral principal component analysis on 9046 broad-line active galactic nuclei from the Sloan Digital Sky Survey. We examine correlations between spectral regions within various eigenspectra (e.g., between Fe ii strength and Hβ width) and confirm that the same trends are apparent in spectral measurements, as validation of our technique. Because we found that our sample had a large range in the equivalent width of [O iii] λ5007, we divided the data into three subsets based on [O iii] strength. Of these, only in the sample with the weakest equivalent width of [O iii] were we able to recover the known correlation between [O iii] strength and full width at half maximum of Hβ and their anticorrelation with Fe ii strength. At the low luminosities considered here (L5100 Å of 1042–1046 erg s−1), interpretation of the principal components is considerably complicated particularly because of the wide range in [O iii] equivalent width. We speculate that variations in the covering factor are responsible for this wide range in [O iii] strength.
Association analysis of rice resistance genes and blast fungal avirulence genes for effective breeding resistance cultivars

Utilization of rice blast-resistance (R) genes is the most economical and environmentally friendly method to control blast disease. However, rice varieties with R genes influence the outcome of genetic architectures of Magnaporthe oryzae (M. oryzae), and mutations in avirulence (AVR) genes of M. oryzae may cause dysfunction of the corresponding R genes in rice varieties. Although monitoring and characterizing rice R genes and pathogen AVR genes in field populations may facilitate the implementation of effective R genes, little is known about the changes of R genes over time and their ultimate impact on pathogen AVR genes. In this study, 117 main cultivated rice varieties over the past five decades and 35 M. oryzae isolates collected from those diseased plants were analyzed by PCR using gene-specific markers of the nine R genes and six primer pairs targeting the coding sequence or promoter of AVR genes, respectively. The R genes Pigm, Pi9, Pi2, Piz-t, Pi-ta, Pik, Pi1, Pikp, and Pikm were identified in 5, 0, 1, 4, 18, 0, 2, 1, and 0 cultivars, respectively. Significantly, none of these R genes had significant changes that correlated to their application periods of time. Among the four identified AVR genes, AVR-Pik had the highest amplification frequency (97.14%) followed by AVR-Pita (51.43%) and AVR-Pi9 (48.57%); AVR-Piz-t had the lowest frequency (28.57%). All these AVR genes except AVR-Pi9 had 1–2 variants. Inoculation mono-genic lines contained functional genes of Pi2/9 and Pik loci with 14 representative isolates from those 35 ones revealed that the presence of certain AVR-Piz-t, AVR-Pita variants, and AVR-Pik-E + AVR-Pik-D in M. oryzae populations, and these variants negated the ability of the corresponding R genes to confer resistance. Importantly, Pi2, Pi9, and Pigm conferred broad-spectrum resistance to these local isolates. These findings reveal that the complex genetic basis of M. oryzae and some effective blast R genes should be considered in future rice blast-resistance breeding programs.
Constraining the growth of perturbations with lensing of supernovae

A recently proposed technique allows one to constrain both the background and perturbation cosmological parameters through the distribution function of supernova Ia apparent magnitudes. Here we extend this technique to alternative cosmological scenarios, in which the growth of structure does not follow the CDM prescription. We apply the method first to the supernova data provided by the JLA catalog combined with redshift distortion data and with low-redshift cluster data and show that although the supernovae alone are not very constraining, they help in reducing the confidence regions. Then we apply our method to future data from LSST and from a survey that approximates the Euclid satellite mission. In this case we show that the combined data are nicely complementary and can constrain the normalization 8 and the growth rate index to within 0.6% and 7%, respectively. In particular, the LSST supernova catalog is forecast to give the constraint ( 8/0.83) 6.7 = 0.55 ± 0.1. We also report on constraints relative to a step-wise parametrization of the growth rate of structures. These results show that supernova lensing serves as a good cross-check on the measurement of perturbation parameters from more standard techniques.
Biological relevance of ZNF224 expression in chronic lymphocytic leukemia and its implication IN NF-kB pathway regulation

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease, whose presentation and clinical course are highly variable. Identification of novel prognostic factors may contribute to improving the CLL classification and providing indications for treatment options. The zinc finger protein ZNF224 plays a key role in cell transformation, through the control of apoptotic and survival pathways. In this study, we evaluated the potential application of ZNF224 as a novel marker of CLL progression and therapy responsiveness. To this aim, we analyzed ZNF224 expression levels in B lymphocytes from CLL patients at different stages of the disease and in patients showing different treatment outcomes. The expression of ZNF224 was significantly increased in disease progression and dramatically decreased in patients in complete remission after chemotherapy. Gene expression correlation analysis performed on datasets of CLL patients revealed that ZNF224 expression was well correlated with that of some prognostic and predictive markers. Moreover, bioinformatic analysis coupled ZNF224 to NF-κB pathway, and experimental data demonstrated that RNA interference of ZNF224 reduced the activity of the NF-κB survival pathway in CLL cells. Consistently with a pro-survival role, ZNF224 knockdown raised spontaneous and drug-induced apoptosis and inhibited the proliferation of peripheral blood mononuclear cells from CLL patients. Our findings provide evidence for the involvement of ZNF224 in the survival of CLL cells via NF-κB pathway modulation, and also suggest ZNF224 as a prognostic and predictive molecular marker of CLL disease.
The effect of neoadjuvant chemotherapy on the tumor immune microenvironment in gastrointestinal tumors

In recent years, numerous studies have demonstrated that the tumor immune microenvironment (TIME) is capable of regulating the growth of tumors, and tumor-infiltrating immune cells in the TIME can affect the prognosis and treatment responses of patients. Consequently, therapies targeting these immune cells have emerged as important antitumor treatments. As a crucial componet of the perioperative treatment of malignant tumors, neoadjuvant chemotherapy (NACT) can improve the surgical resection rate and prognosis of patients and is a suitable clinical model to evaluate the effect of chemotherapy on the TIME. To provide a rationale for developing valid combinational therapies, this review summarizes the impact of NACT on the TIME, the relationship between tumor-infiltrating immune cells and treatment responses of patients, and the prognostic value of these infiltrating immune cells.
First-in-man application of Liwen RF™ ablation system in the treatment of drug-resistant hypertrophic obstructive cardiomyopathy

Objectives This study sought to evaluate the clinical applicability of the Liwen Liu RF™ ablation system for percutaneous intramyocardial septal radiofrequency ablation (PIMSRA). Background Data on new cardiac radiofrequency ablation devices for the treatment of hypertrophic obstructive cardiomyopathy (HOCM) are limited. Materials and methods From July 2019 to July 2020, a total of 68 patients with drug-resistant HOCM, who underwent PIMSRA with the Liwen RF™ ablation system, which has an ablation electrode of stepless adjustable length, were prospectively enrolled. Safety endpoints included, amongst others, the occurrence of pericardial effusion and/or hemorrhage, cardiac arrhythmias, device failure and procedural death. The reduction in left ventricular outflow tract (LVOT) gradients at 12 months follow-up were used as a surrogate marker for device efficacy. Results All procedures were technically successful. The total energy output time of the system was 75.8 (IQR: 30.0) min, and the average power was 43.61 ± 13.34 watts. No ablation system error occurred. The incidence of pericardial effusion or hemorrhage, transient arrhythmia and resuscitation was 8.8, 39.7, and 1.5% during procedure, respectively. None of the patients died. During 30-day follow-up, there were no complications with the exception of a pericardial effusion in one patient (1.5%). No further complications were reported after 30 days. The patients’ resting [baseline: 75 (IQR: 48) vs. 12-months: 12 (IQR: 19) mmHg, p < 0.001] and provoked [baseline: 122 (IQR: 53) vs. 12-months: 41 (IQR: 59) mmHg, p < 0.001] LVOT gradients decreased significantly during follow-up. Conclusion In this study, we demonstrate the safety and feasibility of the Liwen RF™ ablation system to treat HOCM. The system allows for significant and sustainable LVOT gradient reduction during 12-months of follow-up. Hence, the Liwen RF™ ablation system is a promising new device that has the potential to become an alternative to existing septal reduction concepts in HOCM patients.
A 6-day high-intensity interval microcycle improves indicators of endurance performance in elite cross-country skiers

Purpose The aim of this study was to compare the effects of a 6-day high-intensity interval (HIT) block [BLOCK, n = 12, maximal oxygen uptake (V̇O2max = 69. 6 ± 4.3 mL·min−1·kg−1)] with a time-matched period with usual training (CON, n = 12, V̇O2max = 69.2 ± 4.2 mL·min−1·kg−1) in well-trained cross-country (XC) skiers on physiological determinants and indicators of endurance performance. Furthermore, the study aimed to investigate the acute physiological responses, including time ≥90% of V̇O2max, and its associated reliability during repeated HIT sessions in the HIT microcycle. Methods Before the 6-day HIT block and following 5 days of recovery after the HIT block, both groups were tested on indicators of endurance performance. To quantify time ≥90% of V̇O2max during interval sessions in the HIT block, V̇O2 measurements were performed on the 1st, 2nd, and last HIT session in BLOCK. Results BLOCK had a larger improvement than CON in maximal 1-min velocity achieved during the V̇O2max test (3.1 ± 3.1% vs. 1.2 ± 1.6%, respectively; p = 0.010) and velocity corresponding to 4 mmol·L−1 blood lactate (3.2 ± 2.9% vs. 0.6 ± 2.1%, respectively; p = 0.024). During submaximal exercise, BLOCK displayed a larger reduction in respiratory exchange ratio, blood lactate concentration, heart rate, and rate of perceived exertion (p < 0.05) and a tendency towards less energy expenditure compared to CON (p = 0.073). The ICC of time ≥90% V̇O2max in the present study was 0.57, which indicates moderate reliability. Conclusions In well-trained XC skiers, BLOCK induced superior changes in indicators of endurance performance compared with CON, while time ≥90% of V̇O2max during the HIT sessions in the 6-day block had a moderate reliability.
Scalar Wigner theory for polarized light in nonlinear Kerr media

A scalar Wigner distribution function for describing polarized light is proposed in analogy with the treatment of spin variables in quantum kinetic theory. The formalism is applied to the propagation of circularly polarized light in nonlinear Kerr media, and an extended phase-space evolution equation is derived along with invariant quantities. The formalism is additionally used to analyze the modulational instability
PROBING EXPLOSION GEOMETRY OF CORE-COLLAPSE SUPERNOVAE WITH LIGHT CURVES OF THE SHOCK BREAKOUT

We investigate effects of aspherical energy deposition in core-collapse supernovae (CCSNe) on the light curve of the supernova shock breakout. We performed two-dimensional hydrodynamical calculations of an aspherical supernova explosion to obtain the time when a shock wave generated in the stellar interior reaches the stellar surface in each radial direction. Using results of the calculations, light curves during the shock breakout are derived in an approximate way. We show that the light curve during the shock breakout can be a strong indicator of aspherical properties of CCSNe.
Anticancer regimens containing third generation taxanes SB-T-121605 and SB-T-121606 are highly effective in resistant ovarian carcinoma model

Taxanes are widely used in the treatment of ovarian carcinomas. One of the main problems with conventional taxanes is the risk of development of multidrug resistance. New-generation synthetic experimental taxoids (Stony Brook Taxanes; SB-T) have shown promising effects against various resistant tumor models. The aim of our study was to compare the in vitro efficacy, intracellular content, and in vivo antitumor effect of clinically used paclitaxel (PTX) and SB-Ts from the previously tested second (SB-T-1214, SB-T-1216) and the newly synthesized third (SB-T-121402, SB-T-121605, and SB-T-121606) generation in PTX resistant ovarian carcinoma cells NCI/ADR-RES. The efficacy of the new SB-Ts was up to 50-times higher compared to PTX in NCI/ADR-RES cells in vitro. SB-T-121605 and SB-T-121606 induced cell cycle arrest in the G2/M phase much more effectively and their intracellular content was 10–15-times higher, when compared to PTX. Incorporation of SB-T-121605 and SB-T-121606 into therapeutic regimens containing PTX were effective in suppressing tumor growth in vivo in NCI/ADR-RES based mice xenografts at small doses (≤3 mg/kg), where their adverse effects were eliminated. In conclusion, new SB-T-121605 and SB-T-121606 analogs are promising candidates for the next phase of preclinical testing of their combination therapy with conventional taxanes in resistant ovarian carcinomas.
CCD photometric investigation of a W UMa-Type binary GSC 0763–0572

A photometric solution of an A-type W UMa binary, GSC 0763–0572, is examined with a revised orbital period. The overcontact degree is found to be f = 40.66%, with a low mass ratio of q = 0.2554. The result demonstrates an unambiguous increase in the orbital period with a relative period change of ΔP/P = +5.69 × 10−7 d yr−1. This indicates that GSC 0763–0572 is undergoing a process of mass transfer from the secondary component to the primary one with a rate of relative mass change of Δm1/m = +5.18 × 10−8 yr−1, for a conservative model of mass transfer. We find that GSC 0763–0572 might transform into a rapidly rotating star, if total spin angular momentum increases until it is greater than one-third of the orbital angular momentum, without breaking the contact configuration.
CENTRAL DARK MATTER TRENDS IN EARLY-TYPE GALAXIES FROM STRONG LENSING, DYNAMICS, AND STELLAR POPULATIONS

We analyze the correlations between central dark matter (DM) content of early-type galaxies and their sizes and ages, using a sample of intermediate-redshift (z ∼ 0.2) gravitational lenses from the SLACS survey, and by comparing them to a larger sample of z ∼ 0 galaxies. We decompose the deprojected galaxy masses into DM and stellar components using combinations of strong lensing, stellar dynamics, and stellar populations modeling. For a given stellar mass, we find that for galaxies with larger sizes, the DM fraction increases and the mean DM density decreases, consistently with the cuspy halos expected in cosmological formation scenarios. The DM fraction also decreases with stellar age, which can be partially explained by the inverse correlation between size and age. The residual trend may point to systematic dependencies on formation epoch of halo contraction or stellar initial mass functions. These results are in agreement with recent findings based on local galaxies by Napolitano et al. and suggest negligible evidence of galaxy evolution over the last ∼2.5 Gyr other than passive stellar aging.
Association of ultracold double-species bosonic molecules

We report on the creation of heterospecies bosonic molecules, associated from an ultracold Bose-Bose mixture of 41K and 87Rb, by using a resonantly modulated magnetic field close to two Feshbach resonances. We measure the binding energy of the weakly bound molecular states versus the Feshbach field and compare our results to theoretical predictions. We observe the broadening and asymmetry of the association spectrum due to thermal distribution of the atoms, and a frequency shift occurring when the binding energy depends nonlinearly on the Feshbach field. A simple model is developed to quantitatively describe the association process. Our work marks an important step forward in the experimental route towards Bose-Einstein condensates of dipolar molecules.
Juvenile hormone modulates hydrocarbon expression and reproduction in the german wasp Vespula germanica

Juvenile hormone (JH) affects multiple physiological traits in insects. In social insects, besides development, JH has been demonstrated to influence caste determination and the production of chemical compounds. In social wasps, JH triggers behavioral maturation, gonadotropic effects, and hydrocarbon modulation. Here, we investigated whether JH displays the same function in fertility and fertility cue production in females of the German wasp Vespula germanica, previously shown in the related species Vespula vulgaris. By experimentally treating workers with JH-analog, an anti-JH, and acetone solvent control, we tested whether JH modulates the cuticular chemical expression (CHCs), the Dufour’s gland chemical composition, and hence the compounds found over the egg’s surface. Additionally, we explored whether JH has a gonadotropic effect on workers. Workers treated with the JH-analog acquired a chemical profile that was intermediate between the queen and other treated workers. Interestingly, the same pattern was also seen in the Dufour’s glands and eggs, although more subtle. Furthermore, workers treated with the JH-analog were more fertile when compared to the controls, supporting the fact that JH acts as a gonadotropic hormone. Our results indicate a similar function of JH in societies of related wasp species V. germanica and V. vulgaris.
THE YOUNG BINARY DQ Tau: A HUNT FOR X-RAY EMISSION FROM COLLIDING MAGNETOSPHERES

The young high-eccentricity binary DQ Tau exhibits powerful recurring millimeter-band (mm) flaring attributed to collisions between the two stellar magnetospheres near periastron, when the stars are separated by only ∼8 R⋆. These magnetospheric interactions are expected to have scales and magnetic field strengths comparable to those of large X-ray flares from single pre-main-sequence stars observed in the Chandra Orion Ultradeep Project (COUP). To search for X-rays arising from processes associated with colliding magnetospheres, we performed simultaneous X-ray and mm observations of DQ Tau near periastron phase. We report here several results. (1) As anticipated, DQ Tau was caught in a flare state in both mm and X-rays. A single long X-ray flare spanned the entire 16.5 hr Chandra exposure. (2) The inferred morphology, duration, and plasma temperature of the X-ray flare are typical of those of large flares from COUP stars. (3) However, our study provides three lines of evidence that this X-ray flare likely arises from colliding magnetospheres: the chance of capturing a large COUP-like flare within the span of our observation is small, the relative timing of the X-ray and mm flares indicates the Neupert effect and is consistent with a common coronal structure, the size of the emitting coronal structure (4–5 R⋆) inferred from our analysis (which is admittedly model dependent and should be considered with caution) is comparable to half the binary separation. (4) The peak flare X-ray luminosity is in agreement with an estimate of the power dissipated by magnetic reconnection within the framework of a simple model of interacting magnetospheres.