Miracle-dz/UniFAR-FTUs huggingface dataset:
Global transcriptome analysis reveals partial estrogen-like effects of karanjin in MCF-7 breast cancer cells

Karanjin, an abundantly occurring furanoflavonoid in edible and non-edible legumes, exerts diverse biological effects in vivo, and in vitro. Its potential as an anticancer agent is also gaining traction following recent demonstrations of its anti-proliferative, cell cycle inhibitory, and pro-apoptotic effects. However, the universality of its anticancer potential is yet to be scrutinized, particularly so because flavonoids can act as selective estrogen receptor modulators (SERMs). Even the genomic correlates of its biological activities are yet to be examined in hormone responsive cells. This paper presents the early and direct transcriptomic footprint of 10 μM karanjin in MCF-7 breast cancer cells, using next generation sequencing technology (RNA-seq). We show that karanjin-modulated gene-expression repertoire is enriched in several hallmark gene sets, which include early estrogen-response, and G2/M checkpoint genes. Genes modulated by karanjin overlapped with those modulated by 1 nM 17β-estradiol (E2), or 1 μM tamoxifen. Karanjin altered the expression of selected estrogen-regulated genes in a cell-type, and concentration dependent manner. It downmodulated the expression of ERα protein in MCF-7 cells. Furthermore, ERα knockdown negatively impacted karanjin’s ability to modulate the expression of selected E2 target genes. Our data suggest that karanjin exerts its effects on ERα-positive breast cancer cells, at least in part, via ERα. The apparent SERM-like effects of karanjin pose a caveat to the anticancer potential of karanjin. In-depth studies on cell-type and concentration-dependent effects of karanjin may bring out its true potential in endocrine therapies.
High-Resolution WRF Simulation of Extreme Heat Events in Eastern China: Large Sensitivity to Land Surface Schemes

Regional climate models with high-resolution simulation are particularly useful for providing a detailed representation of land surface processes, and for studying the relationship between land surface processes and heat events. However, large differences and uncertainties exist among different land surface schemes (LSSs). This study comprehensively assesses the sensitivity to different LSSs based on two extreme heat events in eastern China using the Weather Research and Forecasting (WRF) model. Among the five LSSs (i.e., 5TD, CLM4, Noah, Noah-MP and RUC), Noah is closest to observations in reproducing the temperatures and energy fluxes for both two heat events. The modeled warm biases result mainly from the underestimation of evapotranspirative cooling. Our results show that how each LSS partitions the evapotranspiration (ET) and sensible heat largely determines the relationship between the temperature and turbulent fluxes. Although the simulated two extreme heat events manifest similar biases in the temperatures and energy fluxes, the land surface responses (ET and soil moisture) are different.
Effects of the Proprioceptive Neuromuscular Facilitation Contraction Sequence on Motor Skill Learning-Related Increases in the Maximal Rate of Wrist Flexion Torque Development

Background: The proprioceptive neuromuscular facilitation (PNF) reciprocal contraction pattern has the potential to increase the maximum rate of torque development. However, it is a more complex resistive exercise task and may interfere with improvements in the maximum rate of torque development due to motor skill learning, as observed for unidirectional contractions. The purpose of this study was to examine the cost-benefit of using the PNF exercise technique to increase the maximum rate of torque development. Methods: Twenty-six participants completed isometric maximal extension-to-flexion (experimental PNF group) or flexion-only (control group) contractions at the wrist. Ten of the assigned contractions were performed on each of three sessions separated by 48-h for skill acquisition. Retention was assessed with 5 contractions performed 2-weeks after acquisition. Torque and surface electromyographic (sEMG) activity were analyzed for evidence of facilitated contractions between groups, as well as alterations in muscle coordination assessed across test sessions. The criterion measures were: mean maximal isometric wrist flexion toque; the maximal rate of torque development (dτ/dtmax); root-mean-square error (RMSE) variability of the rate of torque versus torque phase-plane; the rate of wrist flexion muscle activation (Q30); a coactivation ratio for wrist flexor and extensor sEMG activity; and wrist flexor electromechanical delay (EMD). Results: There were no significant differences between groups with respect to maximal wrist flexion torque, dτ/dtmax or RMSE variability of torque trajectories. Both groups exhibited a progressive increase in maximal strength (+23.35% p < 0.01, η2 = 0.655) and in dτ/dtmax (+19.84% p = 0.08, η2 = 0.150) from the start of acquisition to retention. RMSE was lowest after a 2-week rest interval (−18.2% p = 0.04, η2 = 0.198). There were no significant differences between groups in the rate of muscle activation or the coactivation ratio. There was a reduction in coactivation that was retained after a 2-week rest interval (−32.60%, p = 0.02, η2 = 0.266). Alternatively, EMD was significantly greater in the experimental group (Δ 77.43%, p < 0.01, η2 = 0.809) across all sessions. However, both groups had a similar pattern of improvement to the third consecutive day of testing (−16.82%, p = 0.049, η2 = 0.189), but returned close to baseline value after the 2-week rest interval. Discussion: The wrist extension-to-flexion contraction pattern did not result in a greater maximal rate of torque development than simple contractions of the wrist flexors. There was no difference between groups with respect to motor skill learning. The main adaptation in neuromotor control was a decrease in coactivation, not the maximal rate of muscle activation.
Mitochondrial Defects in Fibroblasts of Pathogenic MAPT Patients

Mutations in MAPT gene cause multiple neurological disorders, including frontal temporal lobar degeneration and parkinsonism. Increasing evidence indicates impaired mitochondrial homeostasis and mitophagy in patients and disease models of pathogenic MAPT. Here, using MAPT patients’ fibroblasts as a model, we report that disease-causing MAPT mutations compromise early events of mitophagy. By employing biochemical and mitochondrial assays we discover that upon mitochondrial depolarization, the recruitment of LRRK2 and Parkin to mitochondria and degradation of the outer mitochondrial membrane protein Miro1 are disrupted. Using high resolution electron microscopy, we reveal that the contact of mitochondrial membranes with ER and cytoskeleton tracks is dissociated following mitochondrial damage. This membrane dissociation is blocked by a pathogenic MAPT mutation. Furthermore, we provide evidence showing that tau protein, which is encoded by MAPT gene, interacts with Miro1 protein, and this interaction is abolished by pathogenic MAPT mutations. Lastly, treating fibroblasts of a MAPT patient with a small molecule promotes Miro1 degradation following depolarization. Altogether, our results show molecular defects in a peripheral tissue of patients and suggest that targeting mitochondrial quality control may have a broad application for future therapeutic intervention.
Noninvasive Immuno-PET Imaging of CD8+ T Cell Behavior in Influenza A Virus-Infected Mice

Immuno-positron emission tomography (immuno-PET) is a noninvasive imaging method that enables tracking of immune cells in living animals. We used a nanobody that recognizes mouse CD8α and labeled it with 89Zr to image mouse CD8+ T cells in the course of an infection with influenza A virus (IAV). The CD8+ signal showed a strong increase in the mediastinal lymph node (MLN) and thymus as early as 4 days post-infection (dpi), and as early as 6 dpi in the lungs. Over the course of the infection, CD8+ T cells were at first distributed diffusely throughout the lungs and then accumulated more selectively in specific regions of the lungs. These distributions correlated with morbidity as mice reached the peak of weight loss over this interval. CD8+ T cells obtained from control or IAV-infected mice showed a difference in their distribution and migration when comparing their fate upon labeling ex vivo with 89Zr-labeled anti-CD8α nanobody and transfer into infected versus control animals. CD8+ T cells from infected mice, upon transfer, appear to be trained to persist in the lungs, even of uninfected mice. Immuno-PET imaging thus allows noninvasive, dynamic monitoring of the immune response to infectious agents in living animals.
Extranodal Extension Is an Independent Prognostic Factor in Papillary Thyroid Cancer: A Propensity Score Matching Analysis

Purpose To investigate the prognostic significance of extranodal extension (ENE) in papillary thyroid cancer (PTC). Methods Seven hundred forty-three PTC patients were enrolled in the study from January 2014 to December 2017. The patients were dichotomized according to the presence of ENE. Logistic analysis was used to compare differences between the two groups. Kaplan–Meier (K-M) curve and propensity score matching (PSM) analyses were used for recurrence-free survival (RFS) comparisons. Cox regression was performed to analyze the effects of ENE on RFS in PTC. Results Thirty-four patients (4.58%) had ENE. Univariate analysis showed that age, tumor size, extrathyroidal extension, and nodal stage were associated with ENE. Further logistic regression analysis showed that age, extrathyroidal extension, and nodal stage remained statistically significant. Evaluation of K-M curves showed a statistically significant difference between the two groups before and after PSM. Cox regression showed that tumor size and ENE were independent risk factors for RFS. Conclusions Age ≥55 years, extrathyroidal extension, and lateral cervical lymph node metastasis were identified as independent risk factors for ENE. ENE is an independent prognostic factor in PTC.
Profiling the Interrogee: Applying the Person-Centered Approach in Investigative Interviewing Research

In the past, deception detection research has explored whether there were specific personal characteristics that were related to lying and found that factors such as personality and morality are indeed related to lying. However, past research has usually focused on a variable-centered approach. Yet, a person-centered might be more suitable here as it allows for the study of people in an integrative manner. In this experiment, 673 students completed a questionnaire which included measures of the five factors of personality, the level of moral disengagement, the perceived cognitive load when lying, lying strategies, frequency of lying and the LiES scale, a tool measuring the tendency to tell self-serving, altruistic and vindicative lies. We performed a Latent Profile Analysis to integrate personality, moral disengagement, and perceived cognitive load scores into specific profiles. Then, we related profile membership to lying behavior. We obtained four profiles, and found that extraversion, moral disengagement, and the perceived cognitive load contributed most to profile differences. We also found that lying frequency did not differ across profiles, whereas lying tendency did. In conclusion, our results suggest that several facets of the individual play a joint role in lying behavior, and that adopting a person-centered approach might be a good strategy to explore the role of interpersonal differences in lie detection research.
Characterization of Co-infection With Fowl Adenovirus Serotype 4 and 8a

Fowl adenoviruses (FAdVs), which are distributed worldwide, have caused considerable economic losses to poultry farms. Co-infection with FAdVs and other avian pathogens has been reported previously. However, the pathogenicity of different serotypes of FAdVs causing co-infection remains unclear. Herein, strain HN from FAdV species C serotype 4 (FAdV-4) and strain AH720 from species E serotype 8a (FAdV-8a) were used to assess the pathogenicity of their co-infection in specific-pathogen-free (SPF) chickens. Compared with chickens infected with FAdV-4 alone, those co-infected with FAdV-4 and FAdV-8a showed similar clinical symptoms, mortality rates and degree of tissue lesions, and notably decreased viral loads of HN. Conversely, the viral loads of AH720 increased markedly in the co-infection group compared with that in chickens infected with AH720 strain alone. Increased viral loads of AH720 in the liver were suspected to contribute to the pathogenicity of chickens co-infected with the HN and AH720 strains. This was further investigated by histopathology and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining analyses. Collectively, these data indicated that co-infection with FAdV-4 and FAdV-8a suppresses the replication and proliferation of FAdV-4 but enhances the replication and proliferation of FAdV-8a in chicken liver. This study will provide valuable information for the further investigation of the interactions between FAdV-4 and FAdV-8a during co-infection.
Clinical Effectiveness of Hypofractionated Proton Beam Therapy for Liver Metastasis From Breast Cancer

Background Few studies of proton beam therapy (PBT) for patients with liver metastasis from breast cancer (LMBC) are available to date. The aim of the present study was to evaluate the clinical effectiveness of PBT for patients with LMBC. Material and Methods Seventeen patients with LMBC treated with PBT were included in this study. The median prescribed dose of PBT was 66 GyE (range, 60–80) in 10 fractions, 5 times a week. In patients with LMBC receiving PBT, freedom from local progression (FFLP), progression-free survival (PFS), and overall survival (OS) rates were assessed. Results The median follow-up time was 34.2 months (range, 11.5–56.1). The median FFLP time was not yet reached, and the 3-year FFLP rates were 94.1% (95% confidence interval [CI], 82.9–105.3). The median times of PFS and OS were 7.9 months (95% CI, 5.3–10.5) and 39.3 months (95% CI, 33.2–51.9), respectively, and the 3-year PFS and OS rates were 19.6% (95% CI, -1.8–41.0) and 71.7% (95% CI, 46.8–96.6), respectively. Grade 3 or higher adverse events were not observed. Conclusion PBT for patients with LMBC showed promising FFLP and OS with safe toxicity profiles. These findings suggest that PBT can be considered a local treatment option in patients with LMBC.
A Group Intervention for Individuals With Obesity and Comorbid Binge Eating Disorder: Results From a Feasibility Study

Purpose A common challenge among a subgroup of individuals with obesity is binge eating, that exists on a continuum from mild binge eating episodes to severe binge eating disorder (BED). BED is common among bariatric patients and the prevalence of disordered eating and ED in bariatric surgery populations is well known. Conventional treatments and assessment of obesity seldom address the underlying psychological mechanisms of binge eating and subsequent obesity. This study, titled PnP (People need People) is a psychoeducational group pilot intervention for individuals with BED and obesity including patients with previous bariatric surgery. Design, feasibility, and a broad description of the study population is reported. Material and Methods A total of 42 patients were from an obesity clinic referred to assessment and treatment with PnP in a psychoeducational group setting (3-hour weekly meetings for 10 weeks). Of these, 6 (14.3%) patients had a previous history of bariatric surgery. Feasibility was assessed by tracking attendance, potentially adverse effects and outcome measures including body mass index (BMI), eating disorder pathology, overvaluation of shape and weight, impairment, self-reported childhood difficulties, alexithymia, internalized shame as well as health related quality of life (HRQoL). Results All 42 patients completed the intervention, with no adverse effects and a high attendance rate with a median attendance of 10 sessions, 95% CI (8.9,9.6) and 0% attrition. Extent of psychosocial impairment due to eating disorder pathology, body dissatisfaction and severity of ED symptoms were high among the patients at baseline. Additionally, self-reported childhood difficulties, alexithymia, and internalized shame were high among the patients and indicate a need to address underlying psychological mechanisms in individuals with BED and comorbid obesity. Improvement of HRQoL and reduction of binge eating between baseline and the end of the intervention was observed with a medium effect Conclusion This feasibility study supports PnP as a potential group psychoeducational intervention for patients living with BED and comorbid obesity. Assessments of BED and delivery of this intervention may optimize selection of candidates and bariatric outcomes. These preliminary results warrant further investigation via a randomized control trial (RCT) to examine the efficacy and effectiveness of PnP.
Reproductive Regulation of PrRPs in Teleost: The Link Between Feeding and Reproduction

Prolactin-releasing peptide (PrRP), a sort of vital hypothalamic neuropeptide, has been found to exert an enormous function on the food intake of mammals. However, little is known about the functional role of PrRP in teleost. In the present study, two PrRP isoforms and four PrRP receptors were isolated from grass carp. Ligand-receptor selectivity displayed that PrRP1 preferentially binds with PrRP-R1a and PrRP-R1b, while PrRP-R2a and PrRP-R2b were special receptors for PrRP2. Tissue distribution indicated that both PrRPs and PrRP-Rs were highly expressed in the hypothalamus-pituitary-gonad axis and intestine, suggesting a latent function on food intake and reproduction. Using grass carp as a model, we found that food intake could significantly induce hypothalamus PrRP mRNA expression, which suggested that PrRP should be also an anorexigenic peptide in teleost. Interestingly, intraperitoneal (IP) injection of PrRPs could significantly induce serum luteinizing hormone (LH) secretion and pituitary LHβ and GtHα mRNA expression in grass carp. Moreover, using primary culture grass carp pituitary cells as a model, we further found that PrRPs could directly induce pituitary LH secretion and synthesis mediated by AC/PKA, PLC/IP3/PKC, and Ca2+/CaM/CaMK-II pathways. Finally, estrogen treatment of prepubertal fish elicited increases in PrRPs and PrPR receptors expression in primary cultured grass carp hypothalamus cells, which further confirmed that the PrRP/PrRPR system may participate in the neuroendocrine control of fish reproduction. These results, taken together, suggest that PrRPs might act as a coupling factor in feeding metabolism and reproductive activities in teleost.
Quinazoline Derivatives as Potential Therapeutic Agents in Urinary Bladder Cancer Therapy

Cancer diseases remain major health problems in the world despite significant developments in diagnostic methods and medications. Many of the conventional therapies, however, have limitations due to multidrug resistance or severe side effects. Bladder cancer is a complex disorder, and can be classified according to its diverse genetic backgrounds and clinical features. A very promising direction in bladder cancer treatment is targeted therapy directed at specific molecular pathways. Derivatives of quinazolines constitute a large group of chemicals with a wide range of biological properties, and many quinazoline derivatives are approved for antitumor clinical use, e.g.,: erlotinib, gefitinib, afatinib, lapatinib, and vandetanib. The character of these depends mostly on the properties of the substituents and their presence and position on one of the cyclic compounds. Today, new quinazoline-based compounds are being designed and synthesized as potential drugs of anticancer potency against bladder cancers.
Immobilization of the Tannase From Aspergillus fumigatus CAS21: Screening the Best Derivative for the Treatment of Tannery Effluent Using a Packed Bed Reactor

Enzyme immobilization is an important alternative to stabilize enzyme properties favoring the efficiency of derivatives (enzyme + support/matrix) for different purposes. According to this, the current study aimed to immobilize the Aspergillus fumigatus CAS21 tannase and the use of the derivatives in the treatment of the effluent produced by the tannery industry. The tannase was immobilized on sodium alginate, DEAE-Sephadex, amberlite, and glass pearls as supports. Calcium alginate was the most adequate support for tannase immobilization with 100% yield and 94.3% for both efficiency and activity. The best tannase activity for the calcium alginate derivative was obtained at 50°C–60°C and pH 5.0. Thermal and pH stabilities evaluated for 24 h at 30°C–60°C and pH 4–7, respectively, were improved if compared to the stability of the free enzyme. Considering the reuse of the calcium alginate derivative, 78% of the initial activity was preserved after 10 catalytic cycles, and after the 9-month storage at 4°C, the activity was maintained in 70%. This derivative was applied in a packed bed reactor (PBR) for the treatment of tannin-rich effluents from the tannery industry. The reduction of the tannin content was effective reaching degradation of 74–78% after 48 h of PBR operation. The concentration of total phenolic compounds was also reduced, and the color and clarity of the effluent improved. In conclusion, the calcium alginate derivative is an attractive alternative as biocatalyst for large-scale treatment of the effluents from the tannery industry.
Jinmaitong Alleviates Diabetic Neuropathic Pain Through Modulation of NLRP3 Inflammasome and Gasdermin D in Dorsal Root Ganglia of Diabetic Rats

Jinmaitong (JMT) is a compound prescription of traditional Chinese medicine that has been used to treat diabetic neuropathic pain (DNP) for many years. Here, we investigated the effects of JMT on the activation of NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome and pyroptosis in Dorsal root ganglia (DRG) of diabetic rats. Streptozotocin (STZ)-induced diabetic rats were gavaged with JMT (0.88 g/kg/d) or alpha-lipoic acid (ALA, positive control, 0.48 mmol/kg/d) for 12 weeks. Distilled water was administered as a vehicle control to both diabetic and non-affected control rats. Blood glucose levels and body weights were measured. Behavioral changes were tested with mechanical withdrawal threshold (MWT) and tail-flick latency (TFL) tests. Morphological injury associated with DRG was observed with hematoxylin and eosin (H&E) and Nissl’s staining. mRNA and protein levels of NLRP3 inflammasome components (NLRP3, ASC, caspase-1), downstream IL-1β and gasdermin D (GSDMD) were evaluated by immunohistochemistry, quantitative real time-PCR and western blot. The results showed that JMT had no effect on blood glucose levels and body weights, but significantly improved MWT and TFL behavior in diabetic rats, and attenuated morphological damage in the DRG tissues. Importantly, JMT decreased the mRNA and protein levels of components of NLRP3 inflammasome, including NLRP3, ASC and caspase-1. JMT also down-regulated the expression of IL-1β and GSDMD in the DRG of DNP rats. In addition, ALA treatment did not perform better than JMT. In conclusion, JMT effectively relieved DNP by decreasing NLRP3 inflammasome activation and pyroptosis, providing new evidence supporting JMT as an alternative treatment for DNP.