Miracle-dz/UniFAR-FTUs huggingface dataset:
Paclitaxel/sunitinib-loaded micelles promote an antitumor response in vitro through synergistic immunogenic cell death for triple-negative breast cancer

Chemotherapy-induced immunogenic cell death (ICD) may offer a strategy to improve the effect of the therapeutic treatment of triple-negative breast cancer (TNBC) by eliciting broad antitumor immunity. However, chemotherapy shows a limited therapeutic effect because of multi-drug resistance and the immunosuppressive tumor microenvironment (TME) of TNBC. The unique pharmacological actions of sunitinib (SUN) indicate its possible synergies with paclitaxel (PTX) to enhance chemo-immunotherapy for TNBC. Here, we prepared a co-delivery platform composed of poly(styrene-co-maleic anhydride) (SMA) via a self-assembly process for a combination of PTX and SUN, which was able to induce a higher synergistic ICD. The nanomicellar delivery of PTX and SUN loaded at an optimal ratio of 1:5 (PTX:SUN) presented the characteristics of an appropriate particle size, long-term stability, and time sequence release which synergistically promoted the apoptosis of MDA-MB-231 tumor cells. Moreover, we demonstrated that the combination of PTX and SUN could significantly induce a synergistic effect because it promoted an ICD response, improved tumor immunogenicity, and regulated immunosuppressive factors in the TME. Overall, PTX and SUN with synergistic effects entrapped in a self-assembly nano-delivery system could offer the potential for clinical applicationof a combination chemo-immunotherapy strategy to improve the effect of the therapeutic treatment of TNBC.
Development of FRET‐based high‐throughput screening for viral RNase III inhibitors

Abstract The class 1 ribonuclease III (RNase III) encoded by Sweet potato chlorotic stunt virus (CSR3) suppresses RNA silencing in plant cells and thereby counters the host antiviral response by cleaving host small interfering RNAs, which are indispensable components of the plant RNA interference (RNAi) pathway. The synergy between sweet potato chlorotic stunt virus and sweet potato feathery mottle virus can reduce crop yields by 90%. Inhibitors of CSR3 might prove efficacious to counter this viral threat, yet no screen has been carried out to identify such inhibitors. Here, we report a novel high‐throughput screening (HTS) assay based on fluorescence resonance energy transfer (FRET) for identifying inhibitors of CSR3. For monitoring CSR3 activity via HTS, we used a small interfering RNA substrate that was labelled with a FRET‐compatible dye. The optimized HTS assay yielded 109 potential inhibitors of CSR3 out of 6,620 compounds tested from different small‐molecule libraries. The three best inhibitor candidates were validated with a dose–response assay. In addition, a parallel screen of the selected candidates was carried out for a similar class 1 RNase III enzyme from Escherichia coli (EcR3), and this screen yielded a different set of inhibitors. Thus, our results show that the CSR3 and EcR3 enzymes were inhibited by distinct types of molecules, indicating that this HTS assay could be widely applied in drug discovery of class 1 RNase III enzymes.
A method for modelling the oxyhaemoglobin dissociation curve at the level of the cerebral capillary in humans

What is the central question of this study? Can the change in haemoglobin's affinity for oxygen in the human cerebral circulation be modelled in vivo? What is the main finding and its importance? We provide a novel method for modelling the oxyhaemoglobin dissociation curve at the cerebral capillary level in humans, so that the cerebral capillary and mitochondrial oxygen tensions can reliably be estimated. This may be useful in future human‐experimental studies on cerebral oxygen transport.
Morphology and Differentiation of Non‐sensory Cuticular Structures in Mysidacea, Cumacea and Tanaidacea (Crustacea, Peracarida)

The non‐sensory cuticular structures of some peracarideans (Mysidacea, Cumacea, Tanaidacea) were examined by scanning electron microscopy. The various types of structures present in the adult specimens are listed and the relation amongst them is elucidated. Three ways of differentiation of the structures can be distinguished: 1) a differentiation in the complexity of the structures themselves, 2) a differentiation of their arrangement on the body. 3) a differentiation of their distribution on the various parts of the body. A highly differentiated type of arrangement (row) of a number of simple structures (e.g. teeth) may lead to a higher complex structure (comb), which is seen to be developed best on special regions of the body (e.g. the distal segments of thoracic legs). The function of the cuticular structures–by analogy with other taxonomic groups–is discussed.
The impact of position-orientation adaptive smoothing in diffusion weighted imaging—From diffusion metrics to fiber tractography

In contrast to commonly used approaches to improve data quality in diffusion weighted imaging, position-orientation adaptive smoothing (POAS) provides an edge-preserving post-processing approach. This study aims to investigate its potential and effects on image quality, diffusion metrics, and fiber tractography of the corticospinal tract in relation to non-post-processed and averaged data. 22 healthy volunteers were included in this study. For each volunteer five clinically applicable diffusion weighted imaging data sets were acquired and post-processed by standard averaging and POAS. POAS post-processing led to significantly higher signal-to-noise-ratios (p < 0.001), lower fractional anisotropy across the whole brain (p < 0.05) and reduced intra-subject variability of diffusion weighted imaging signal intensity and fractional anisotropy (p < 0.001, p = 0.006). Fiber tractography of the corticospinal tract resulted in significantly (p = 0.027, p = 0.014) larger tract volumes while fiber density was the lowest. Similarity across tractography results was highest for POAS post-processed data (p < 0.001). POAS post-processing enhances image quality, decreases the intra-subject variability of signal intensity and fractional anisotropy, increases fiber tract volume of the corticospinal tract, and leads to higher reproducibility of tractography results. Thus, POAS post-processing supports a reliable and more accurate fiber tractography of the corticospinal tract, being mandatory for the clinical use.
The Genetic Diversity of TLR4 MHC-DRB Genes in Dairy Goats Using PCR-RFLP Technique

This research was aimed at evaluating the genetic polymorphism of TLR4 and MHC-DRB genes in dairy goats [(Saanen, Etawah Grade-Saanen Crossbred (PESA), and Etawah Grade (PE)] using PCR -RFLP. The two genes are involved in immunity where they play a crucial role in pathogens recognition and presentation to T-cells and CD4 cells. PCR was used to amplify genomic DNA for TLR4 (382 bp) and CaLA-DRB (285 bp) genes fragments. Genetic polymorphism was detected by digesting TLR4 amplimer with AluI while DRB amplimers were digested with PstI and TaqI in two separate reactions. The results showed that TLR4|AluI was monomorphic and fixed with allele T in all three breeds while DRB|TaqI and DRB|PstI loci were found polymorphic for all breeds. Heterozygosity expected (He) and PIC were found low at both DRB|TaqI and DRB|PstI loci in PE and Saanen. Χ2 results showed that DRB|PstI in PE and DRB|TaqI in PESA were not in H-W equilibrium and did not display homozygous recessive genotype. The results declared that TLR4|AluI was not a good for marker for diseases resistance whereas DRB|TaqI and DRB|PstI gave hope for resistance based on their PIC.
Mindfulness-based strengths practice improves well-being and retention in undergraduates: a preliminary randomized controlled trial

Abstract Objective With high rates of mental health concerns on college campuses, effective positive psychology interventions could greatly improve student well-being and academic outcomes. Participants: Working undergraduates (N = 52). Methods: This preliminary, randomized controlled trial investigated the effects of the 8-week Mindfulness-based strengths practice (MBSP) on Seligman’s five domains of well-being, as measured by the PERMA-Profiler, Workplace PERMA-Profiler, and student retention in working undergraduates. Results: Students in the MBSP intervention had significantly higher well-being, engagement, meaning, and health following the MBSP program (P < 0.0042). No such changes were observed in the control group. Students in the intervention group also had modestly higher retention rates in the following academic year than those in the control group. Conclusions: This study provides the first evidence to date that an MBSP program can improve college student well-being and retention.
Maintenance of Germinal Center B Cells by Caspase-9 through Promotion of Apoptosis and Inhibition of Necroptosis

Key Points Caspase-9 promotes apoptosis in GC B cells. Caspase-9 inhibits necroptosis in GC B cells. In response to T cell–dependent Ag encounter, naive B cells develop into germinal center (GC) B cells, which can further differentiate into Ab-secreting plasma cells or memory B cells. GC B cells are short lived and are prone to caspase-mediated apoptosis. However, how apoptotic caspases regulate GC B cell fate has not been fully characterized. In this study, we show that mice with B cell–specific knockout of caspase-9 had decreases in GC B cells and Ab production after immunization. Caspase-9–deficient B cells displayed defects in caspase-dependent apoptosis but increases in necroptosis signaling. Additional deletion of Ripk3 restored GC B cells and Ab production in mice with B cell–specific knockout of caspase-9. Our results indicate that caspase-9 plays an important role in the maintenance of Ab responses by promoting apoptosis and inhibiting necroptosis in B cells.
Fiberoptic Endoscopic Evaluation of Swallowing in Patients with Type 2 Diabetes Who Have Self-Reported Swallowing Difficulties

Introduction: People with diabetes frequently have gastrointestinal problems and related deglutition disorders. Objective: The aims of the present study are to determine the symptomatic swallowing complaints and to evaluate the functionality of oropharyngeal swallowing in patients with type 2 diabetes mellitus (T2DM) by using the Turkish Eating Assessment Tool-10 (T-EAT-10) and fiberoptic endoscopic evaluation of swallowing (FEES). Methods: In this descriptive cross-sectional study, the T-EAT-10 questionnaire was completed by 121 patients with diabetes, and FEES was planned for each individual whose baseline score of the T-EAT-10 was ≥3. Before swallowing trials via samples of nectar-thick consistency, laryngeal sensation and severity of secretion in the hypopharynx were observed. While the swallowing safety was determined using the Penetration-Aspiration Scale (PAS), the Yale Pharyngeal Residue Severity Rating Scale was used to assess the swallowing efficiency. Results: Of the total participants, 22.3% (n = 27) were found to have abnormal swallowing function (T-EAT-10 ≥3), 27.3% (n = 33) had concomitant neuropathy and 28.1% (n = 34) mentioned a reflux complaint. The results of the multivariate linear regression analysis exposed that the T-EAT-10 score was significantly associated with neuropathy (r = 3.763, p < 0.001) and reflux complaint (r = 2.254, p = 0.031). Of the total FEES-tested subjects (n = 20), 95% (n = 19) had a safe swallowing function (PAS = 1). However, diminished laryngeal sensation, increased secretion and presence of residue revealed that patients with T2DM who have self-reported swallowing difficulties have reduced swallowing efficiency. Conclusions: This study has demonstrated that almost 1 out of 4 T2DM patients reported to have swallowing-related problems, and the score of the T-EAT-10 was found to be independently associated with both neuropathy and reflux complaint. FEES results pointed out that swallowing efficiency was relatively reduced in the target population. However, further research is still necessary before obtaining a definitive answer to oropharyngeal swallowing problems in patients with T2DM.
V-ATPase subunit B plays essential roles in the molting process of the Chinese mitten crab, Eriocheir sinensis

ABSTRACT Vacuolar ATPase (V-ATPase) is a proton pump driven by ATP hydrolysis, and it plays an important role in numerous biological processes, such as protein degradation and synthesis, cell growth, and cell autophagy. The V-ATPase subunit B (VATB) is a conservative and regulatory subunit required for ATP hydrolysis during proton pumping. The VATB of Eriocheir sinensis (EsVATB), which includes an open reading frame (ORF) length of 1467 bp encoding 489 amino acids, was cloned to unveil the biological function of VATB during the molting process of crustaceans. Spatial and temporal expression profiles showed that EsVATB was highly expressed in the posterior gill accompanied with the highest osmotic pressure in the premolt (PrM) stage. Meanwhile, the highest expression level of EsVATB was identified in the hepatopancreas and heart during the postmolt stage and epidermis in the intermolt stage, indicating that EsVATB may perform diverse biological functions in different tissues during the molting process. The individual crabs in the interference group showed a high mortality rate (74%) and a low molting rate (26%) and failed to form a new epicuticle in the PrM stage. Meanwhile, a significant difference in osmotic pressure was identified between the interference and control groups. Our results indicate that EsVATB is an indispensable functional gene that may participate in osmoregulation and help with the new epicuticle formation during the molting process of E. sinensis. Summary: V-ATPase subunit B may participate in osmoregulation and help with the new epicuticle formation during the molting process of Chinese mitten crab Eriocheir sinensis.
Sugary drink warnings: A meta-analysis of experimental studies

Background Policymakers worldwide are considering requiring warnings for sugary drinks. A growing number of experimental studies have examined sugary drink warnings’ impacts, but no research to our knowledge has synthesized this literature. To inform ongoing policy debates, this study aimed to identify the effects of sugary drink warnings compared with control conditions. Methods and findings We systematically searched 7 databases on June 21, 2019, and October 25, 2019. We also searched reference lists of relevant articles. Two investigators independently screened titles, abstracts, and full texts to identify peer-reviewed articles that used an experimental protocol to examine the effects of sugary drink warnings compared to a control condition. Two investigators independently extracted study characteristics and effect sizes from all relevant full-text articles. We meta-analyzed any outcome assessed in at least 2 studies, combining effect sizes using random effects meta-analytic procedures. Twenty-three experiments with data on 16,241 individuals (mean proportion female, 58%) were included in the meta-analysis. Most studies took place in Latin America (35%) or the US or Canada (46%); 32% included children. Relative to control conditions, sugary drink warnings caused stronger negative emotional reactions (d = 0.69; 95% CI: 0.25, 1.13; p = 0.002) and elicited more thinking about the health effects of sugary drinks (d = 0.65; 95% CI: 0.29, 1.01; p < 0.001). Sugary drink warnings also led to lower healthfulness perceptions (d = −0.22; 95% CI: −0.27, −0.17; p < 0.001) and stronger disease likelihood perceptions (d = 0.15; 95% CI: 0.06, 0.24; p = 0.001). Moreover, sugary drink warnings reduced both hypothetical (d = −0.32; 95% CI: −0.44, −0.21; p < 0.001) and actual consumption and purchasing behavior (d = −0.17; 95% CI: −0.30, −0.04; p = 0.012). Statistically significant effects were not observed for perceptions of added sugar or positive sugary drink attitudes (p’s > 0.10). Moderation analyses revealed that health warnings (e.g., “Beverages with added sugar contribute to obesity”) led to greater reductions in hypothetical sugary drink purchases than did nutrient warnings (e.g., “High in sugar”; d = −0.35 versus −0.18; Qb = 4.04; p = 0.04). Limitations of this study include that we did not review grey literature and that we were unable to conduct moderation analyses for several prespecified moderators due to an insufficient number of studies. Conclusions This international body of experimental literature supports sugary drink warnings as a population-level strategy for changing behavior, as well as emotions, perceptions, and intentions. Protocol Registry PROSPERO ID 146405.
Imitation recognition and its prosocial effects in 6-month old infants

The experience of being imitated is theorised to be a driving force of infant social cognition, yet evidence on the emergence of imitation recognition and the effects of imitation in early infancy is disproportionately scarce. To address this lack of empirical evidence, in a within-subjects study we compared the responses of 6-month old infants when exposed to ipsilateral imitation as opposed to non-imitative contingent responding. To examine mediating mechanisms of imitation recognition, infants were also exposed to contralateral imitation and bodily imitation with suppressed emotional mimicry. We found that testing behaviours—the hallmark of high-level imitation recognition—occurred at significantly higher rates in each of the imitation conditions compared to the contingent responding condition. Moreover, when being imitated, infants showed higher levels of attention, smiling and approach behaviours compared to the contingent responding condition. The suppression of emotional mimicry moderated these results, leading to a decrease in all social responsiveness measures. The results show that imitation engenders prosocial effects in 6-month old infants and that infants at this age reliably show evidence of implicit and high-level imitation recognition. In turn, the latter can be indicative of infants’ sensitivity to others’ intentions directed toward them.
TICT-Based Near-Infrared Ratiometric Organic Fluorescent Thermometer for Intracellular Temperature Sensing.

Fluorescent thermometers with near infrared (NIR) emission play an important role in visualizing the intracellular temperature with high resolution and investigating the cellular functions and biochemical activities. Herein, we designed and synthesized a donor-Π-accepter luminogen, 2-([1,1'-biphenyl]-4-yl)-3-(4-((E)-4-(diphenylamino)styryl) phenyl) fumaronitrile (TBB) by Suzuki coupling reaction. TBB exhibited twisted intramolecular charge transfer based NIR emission, aggregation-induced emission and temperature-sensitive emission features. Ratiometric fluorescent thermometer was constructed by encapsulating thermo-sensitive NIR fluorophore TBB and Rhodamine 110 dye into an amphiphilic polymer matrix F127 to form TBB&R110@F127 nanoparticles (TRF NPs). TRF NPs showed good temperature sensitivity of 2.37 %·°C-1, wide temperature response ranges from 25 to 65 °C and excellent temperature-sensitive emission reversibility. Intracellular thermometry experiments indicated that TRF NPs could monitor the cellular temperature change from 25 to 53°C for Hep-G2 cells under photothermal therapy agent heating process, indicating the considerable potential applications of TRF NPs in biological thermometry field.
The transcriptional corepressor CBFA2T3 inhibits all-trans-retinoic acid–induced myeloid gene expression and differentiation in acute myeloid leukemia

CBFA2/RUNX1 partner transcriptional co-repressor 3 (CBFA2T3, also known as MTG16 or ETO2) is a myeloid translocation gene family protein that functions as a master transcriptional corepressor in hematopoiesis. Recently, it has been shown that CBFA2T3 maintains leukemia stem cell gene expression and promotes relapse in acute myeloid leukemia (AML). However, a role for CBFA2T3 in myeloid differentiation of AML has not been reported. Here, we show that CBFA2T3 represses retinoic acid receptor (RAR) target gene expression and inhibits all-trans-retinoic acid (ATRA)-induced myeloid differentiation of AML cells. ChIP-Seq revealed that CBFA2T3 targets the RARα/RXRα cistrome in U937 AML cells, predominantly at myeloid-specific enhancers associated with terminal differentiation. CRISPR/Cas9-mediated abrogation of CBFA2T3 resulted in spontaneous and ATRA-induced activation of myeloid-specific genes in a manner correlated with myeloid differentiation. Importantly, these effects were reversed by CBFA2T3 re-expression. Mechanistic studies showed that CBFA2T3 inhibits RAR target gene transcription by acting at an early step to regulate histone acetyltransferase recruitment, histone acetylation, and chromatin accessibility at RARα target sites, independently of the downstream, RAR-mediated steps of transcription. Finally, we validated the inhibitory effect of CBFA2T3 on RAR in multiple AML subtypes and patient samples. To our knowledge, this is the first study to show that CBFA2T3 down-regulation is both necessary and sufficient for enhancing ATRA-induced myeloid gene expression and differentiation of AML cells. Our findings suggest that CBFA2T3 can serve as a potential target for enhancing AML responsiveness to ATRA differentiation therapies.
Variation in the diet of the viperine snake Natrix maura in relation to prey availability

The diet of the viperine snake was compared with food availability in the Ebro Delta, a wetland largely occupied by rice fields, in 1990 and 1991. Snake selection of prey type and size was studied seasonally and by snake group: males, females and immature snakes. Overall, feeding activity (percentage of individuals with prey and number of prey per stomach) increased with food availability. Diet analysis showed that viperine snakes mainly foraged on the green frog Rana perezi (adults and tadpoles) and the carp Cyprinus carpio. Conversely, viperine snakes rejected the mosquito fish Gambusia holbroki which is the most abundant species in autumn, when Natrix maura has a low feeding activity. Statistical comparisons between viperine snake diet and prey availability showed that males selected small carp, immature snakes selected tadpoles and, in spring, females selected frogs. The selection of small carp by males may reflect a sexual divergence of trophic niche related to sexual size dimorphism, as females are larger than males. As tadpoles are presumably easier to catch than fish, tadpole selection by immature individuals may reflect variance in capture abilities. In spring, the selection of frogs by females overlapped with vitellogenesis, suggesting that females compensate for the cost of reproduction by selecting green frogs, which have a greater biomass and higher energy content than fish. Carps eaten in spring were smaller than in summer. Moreover, in summer viperine snakes selected smaller carp than the available mean size. This divergent tendency between carp size selection and carp size availability reveals how seasonal diet shifts in prey size selection may be a response to an increase in prey size.