Miracle-dz/UniFAR-FTUs huggingface dataset:
3′-Daidzein Sulfonate Sodium Protects Against Chronic Cerebral Hypoperfusion-Mediated Cognitive Impairment and Hippocampal Damage via Activity-Regulated Cytoskeleton-Associated Protein Upregulation

The learning and memory impairment caused by chronic cerebral hypoperfusion (CCH) is permanent and seriously affects the daily life of patients and their families. The compound 3′-daidzein sulfonate sodium (DSS) protects against CCH-mediated memory impairment and hippocampal damage in a rat model. In the present study, we further investigated the underlying mechanisms of this effect in the rat two-vessel occlusion (2VO) and the oxygen and glucose deprivation (OGD) primary hippocampal neuron models. The hippocampal expression of the activity-regulated cytoskeleton associated protein (Arc) following DSS administration was detected in vivo and in vitro and behavioral testing was used to investigate the role of Arc in the DSS-mediated rescue of CCH-induced neurotoxicity. DSS increased hippocampal Arc expression both in vivo and in vitro. Arc overexpression increased and Arc knockdown decreased hippocampal neuronal densities in rat 2VO model, when compared to DSS treatment alone. Arc overexpression decreased and Arc knockdown increased apoptotic hippocampal neurons in rat 2VO and OGD primary hippocampal neuron models, when compared to DSS treatment alone. Arc overexpression enhanced and Arc knockdown inhibited the beneficial effect of DSS on 2VO-induced cognitive impairment. DSS restored the neuronal OGD-mediated phosphorylation decrease in protein kinase alpha (PKA), extracellular signal-regulated protein kinases 1/2 (ERK1/2) and cAMP response element binding protein (CREB), in vitro. PKA and ERK1/2 inhibition blocked the DSS-mediated effects on neuronal apoptosis and OGD-induced Arc downregulation. In conclusion, DSS protects against CCH-mediated cognitive impairment and hippocampal damage via Arc upregulation, which is activated by the PKA/CREB and ERK/CREB signaling pathways. Our study further confirms the potential use of DSS as an effective treatment for CCH-associated diseases.
Metabolome-based prediction of yield heterosis contributes to the breeding of elite rice

Metabolite profiles obtained from parental seedlings can predict yield heterosis of rice hybrids with correctly dissected population structure across different growth conditions. Improvement of the breeding efficiencies of heterotic crops adaptive to different conditions can mitigate the food shortage crisis due to overpopulation and climate change. To date, diverse molecular markers have been used to guide field phenotypic selection, whereas accurate predictions of complex heterotic traits are rarely reported. Here, we present a practical metabolome-based strategy for predicting yield heterosis in rice. The dissection of population structure based on untargeted metabolite profiles as the initial critical step in multivariate modeling performed better than the screening of predictive variables. Then the assessment of each predictive variable’s contribution to predictive models according to all latent factors was more precise than the conventional first one. Metabolites belonging to specific pathways were closely associated with yield heterosis, and the up-regulation of galactose metabolism promoted robust yield heterosis in hybrids under different growth conditions. Our study demonstrates that metabolome-based predictive models with correctly dissected population structure and screened predictive variables can facilitate accurate predictions of yield heterosis and have great potential for establishing molecular marker–based precision breeding programs.
Pes Anserine Tendon Injury Resulting from Cooled Radiofrequency Ablation of the Inferior Medial Genicular Nerve

Early evidence from clinical trials suggests effectiveness of fluoroscopically guided genicular nerve radiofrequency ablation (RFA) for the treatment of chronic knee pain due to osteoarthritis.1 One small sham-controlled study has demonstrated efficacy of this procedure.2 Additionally, there is interest in the use of genicular RFA for the treatment of persistent chronic knee pain post-total knee arthroplasty, though efficacy has yet to be demonstrated.3.
Renal Chemerin Expression is Induced in Models of Hypertensive Nephropathy and Glomerulonephritis and Correlates with Markers of Inflammation and Fibrosis

Chemerin and its receptor, chemokine-like receptor 1 (CmklR1), are associated with chemotaxis, inflammation, and endothelial function, especially in metabolic syndrome, coronary heart disease, and hypertension. In humans, circulating chemerin levels and renal function show an inverse relation. So far, little is known about the potential role of chemerin in hypertensive nephropathy and renal inflammation. Therefore, we determined systemic and renal chemerin levels in 2-kidney-1-clip (2k1c) hypertensive and Thy1.1 nephritic rats, respectively, to explore the correlation between chemerin and markers of renal inflammation and fibrosis. Immunohistochemistry revealed a model-specific induction of chemerin expression at the corresponding site of renal damage (tubular vs. glomerular). In both models, renal expression of chemerin (RT-PCR, Western blot) was increased and correlated positively with markers of inflammation and fibrosis. In contrast, circulating chemerin levels remained unchanged. Taken together, these findings demonstrate that renal chemerin expression is associated with processes of inflammation and fibrosis-related to renal damage. However, its use as circulating biomarker of renal inflammation seems to be limited in our rat models.
Individual Differences in Ethanol Drinking and Seeking Behaviors in Rats Exposed to Chronic Intermittent Ethanol Vapor Exposure is Associated with Altered CaMKII Autophosphorylation in the Nucleus Accumbens Shell

Chronic intermittent ethanol vapor exposure (CIE) in rodents produces reliable and high blood ethanol concentration and behavioral symptoms associated with moderate to severe alcohol use disorder (AUD)—for example, escalation of operant ethanol self-administration, a feature suggestive of transition from recreational to addictive use, is a widely replicated behavior in rats that experience CIE. Herein, we present evidence from a subset of rats that do not demonstrate escalation of ethanol self-administration following seven weeks of CIE. These low responders (LR) maintain low ethanol self-administration during CIE, demonstrate lower relapse to drinking during abstinence and reduced reinstatement of ethanol seeking triggered by ethanol cues when compared with high responders (HR). We examined the blood ethanol levels in LR and HR rats during CIE and show higher levels in LR compared with HR. We also examined peak corticosterone levels during CIE and show that LR rats have higher levels compared with HR rats. Lastly, we evaluated the levels of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the nucleus accumbens shell and reveal that the activity of CaMKII, which is autophosphorylated at site Tyr-286, is significantly reduced in HR rats compared with LR rats. These findings demonstrate that dysregulation of the hypothalamic–pituitary–adrenal axis activity and plasticity-related proteins regulating molecular memory in the nucleus accumbens shell are associated with higher ethanol-drinking and -seeking in HR rats. Future mechanistic studies should evaluate CaMKII autophosphorylation-dependent remodeling of glutamatergic synapses in the ventral striatum as a plausible mechanism for the CIE-induced enhanced ethanol drinking and seeking behaviors.
The Effectiveness of a Poster Intervention on Hand Hygiene Practice and Compliance When Using Public Restrooms in a University Setting

Background: Most research on hand hygiene compliance in community settings indicates that compliance is poor. It is not conclusive as to whether poster interventions are effective at improving compliance. Methods: An independent, self-designed poster intervention was installed in one set of male and female public restrooms in a university campus in the UK. The hand hygiene practice and compliance of the university population was measured via indirect observation over a 60 day period. Results: During the pre-intervention observation period, 51.09% of the university population practiced basic hand hygiene compliance (washed hands with water, soap and dried afterwards), and 7.88% practiced adequate hand hygiene compliance (washed hands with water and soap for 20 s or more and dried afterwards for 20 s or more). During the post-intervention observation period, 55.39% of the university population were observed practicing basic hand hygiene compliance, and 7.97% practicing adequate hand hygiene compliance. Gender differences revealed that more females practiced basic hand hygiene in the post-intervention observation period (62.81%) than during the pre-intervention period (49.23%) and this was statistically significant (χ2 = 13.49, p = < 0.01). Discussion: The poster intervention had a limited effect on improving the basic and adequate hand hygiene compliance of the general population when using public restrooms. The use of independent, self-designed posters to improve hand hygiene practice and compliance is largely ineffective in the short term and should be used with caution in future intervention strategies.
Cooperative Interactions between Trichomonas vaginalis and Associated Bacteria Enhance Paracellular Permeability of the Cervicovaginal Epithelium by Dysregulating Tight Junctions

The human protozoan Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection, which is accompanied by a species-diversified vaginal microbiota named community state type IV (CST-IV). Coincidently, CST-IV includes species associated with bacterial vaginosis (e.g. ABSTRACT The human protozoan Trichomonas vaginalis is the causative agent of trichomoniasis, a prevalent sexually transmitted infection, which is accompanied by a species-diversified vaginal microbiota named community state type IV (CST-IV). Coincidently, CST-IV includes species associated with bacterial vaginosis (e.g. Gardnerella vaginalis, Atopobium vaginae, and Prevotella bivia). Both diseases are linked to the transmission of human immunodeficiency virus (HIV) and preterm birth, which complications are likely to result from the disruption of the cervicovaginal epithelial barrier. Here, we show that paracellular permeability of fluorescein isothiocyanate (FITC)-dextran through a monolayer of human ectocervical cells (hECs) is increased as a consequence of the activity of T. vaginalis and the aforementioned species of CST-IV bacteria cooperatively. T. vaginalis enhances paracellular permeability of hECs two times more than the individual bacterial species, by up to ∼10% versus ∼5%, respectively. However, any two or all three bacterial species are capable of synergizing this effect. T. vaginalis and the bacteria together increase the paracellular permeability of hECs by ∼50%, which is 5 to 10 times more than the results seen with the protozoan or bacteria alone. This effect is accompanied by enhancement of phosphatase activity, while phosphatase inhibition results in preservation of the integrity of the ectocervical cell monolayer. In addition, these microorganisms induce changes in the expression of tight junction proteins, particularly occludin, and of proinflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α). Together, our findings establish that cooperative interactions between CST-IV bacteria and T. vaginalis enhance the paracellular permeability of the cervicovaginal epithelium by disturbing the integrity of the tight junction complex. Our study results highlight the importance of understanding the contribution of the vaginal microbiota to trichomoniasis.
Accounting for phenology in the analysis of animal movement

The analysis of animal tracking data provides important scientific understanding and discovery in ecology. Observations of animal trajectories using telemetry devices provide researchers with information about the way animals interact with their environment and each other. For many species, specific geographical features in the landscape can have a strong effect on behavior. Such features may correspond to a single point (eg, dens or kill sites), or to higher dimensional subspaces (eg, rivers or lakes). Features may be relatively static in time (eg, coastlines or home‐range centers), or may be dynamic (eg, sea ice extent or areas of high‐quality forage for herbivores). We introduce a novel model for animal movement that incorporates active selection for dynamic features in a landscape. Our approach is motivated by the study of polar bear (Ursus maritimus) movement. During the sea ice melt season, polar bears spend much of their time on sea ice above shallow, biologically productive water where they hunt seals. The changing distribution and characteristics of sea ice throughout the year mean that the location of valuable habitat is constantly shifting. We develop a model for the movement of polar bears that accounts for the effect of this important landscape feature. We introduce a two‐stage procedure for approximate Bayesian inference that allows us to analyze over 300 000 observed locations of 186 polar bears from 2012 to 2016. We use our model to estimate a spatial boundary of interest to wildlife managers that separates two subpopulations of polar bears from the Beaufort and Chukchi seas.
Families and Social Media Use: The Role of Parents’ Perceptions about Social Media Impact on Family Systems in the Relationship between Family Collective Efficacy and Open Communication

Communication through social media characterizes modern lifestyles and relationships, including family interactions. The present study aims at deepening the role that parents’ perceptions about social media effects on family systems can exert within their family functioning, specifically referring to the relationship between collective family efficacy and open communications within family systems with adolescents. A questionnaire to detect the openness of family communications, the collective family efficacy and the perceptions about the impacts of social media on family systems was administered to 227 Italian parents who had one or more teenage children, and who use Facebook and WhatsApp to communicate with them. From the results, these perceptions emerge as a mediator in the relationship between the collective family efficacy and the openness of communications, suggesting that it is not only the actual impact of social media on family systems that matters but also parents’ perceptions about it and how much they feel able to manage their and their children’s social media use without damaging their family relationships. Thus, the need to foster parents’ positive perceptions about social media’s potential impact on their family relationships emerges. A strategy could be the promotion of knowledge on how to functionally use social media.
Wave patterns organize cellular protrusions and control cortical dynamics

Cellular protrusions are typically considered as distinct structures associated with specific regulators. However, we found that these regulators coordinately localize as propagating cortical waves, suggesting a common underlying mechanism. These molecular events fell into two excitable networks, the signal transduction network STEN and the cytoskeletal network CEN with different wave substructures. Computational studies using a coupled‐network model reproduced these features and showed that the morphology and kinetics of the waves depended on strengths of feedback loops. Chemically induced dimerization at multiple nodes produced distinct, coordinated alterations in patterns of other network components. Taken together, these studies indicate: STEN positive feedback is mediated by mutual inhibition between Ras/Rap and PIP2, while negative feedback depends on delayed PKB activation; PKBs link STEN to CEN; CEN includes positive feedback between Rac and F‐actin, and exerts fast positive and slow negative feedbacks to STEN. The alterations produced protrusions resembling filopodia, ruffles, pseudopodia, or lamellipodia, suggesting that these structures arise from a common regulatory mechanism and that the overall state of the STEN‐CEN system determines cellular morphology.
Synthesis of RNA Crosslinking Oligonucleotides Modified with 2‐Amino‐7‐Deaza‐7‐Propynyl‐6‐Vinylpurine

This article describes procedures to synthesize 2′‐OMe‐RNA modified with cross‐linkable 2‐amino‐7‐deaza‐7‐propynyl‐6‐vinylpurine (ADpVP) and preparation of the RNA‐crosslinking experiment in vitro. All synthesis steps yield the desired compound in moderate or high yield without expensive chemical reagents or specific devices. The crosslink‐active form of modified RNA can also be purified by commonly used reversed‐phase HPLC, can be stored at −80°C after lyophilization for a few days, and is ready to use for crosslinking experiments. This crosslink‐active RNA can efficiently form covalent bonds with complementary RNA in a sequence‐specific manner. © 2019 by John Wiley & Sons, Inc.
Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma

Head and neck squamous cell carcinoma (HNSCC) is a common and debilitating form of cancer characterized by poor patient outcomes and low survival rates. In HNSCC, genetic aberrations in phosphatidylinositol 3-kinase (PI3K) and epidermal growth factor receptor (EGFR) pathway genes are common, and small molecules targeting these pathways have shown modest effects as monotherapies in patients. Whereas emerging preclinical data support the combined use of PI3K and EGFR inhibitors in HNSCC, in-human studies have displayed limited clinical success so far. Here, we examined the responses of a large panel of patient-derived HNSCC cell lines to various combinations of PI3K and EGFR inhibitors, including EGFR agents with varying specificity and mechanistic characteristics. We confirmed the efficacy of PI3K and EGFR combination therapies, observing synergy with α isoform-selective PI3K inhibitor HS-173 and irreversible EGFR/ERBB2 dual inhibitor afatinib in most models tested. Surprisingly, however, our results demonstrated only modest improvement in response to HS-173 with reversible EGFR inhibitor gefitinib. This difference in efficacy was not explained by differences in ERBB target selectivity between afatinib and gefitinib; despite effectively disrupting ERBB2 phosphorylation, the addition of ERBB2 inhibitor CP-724714 failed to enhance the effect of HS-173 gefitinib dual therapy. Accordingly, although irreversible ERBB inhibitors showed strong synergistic activity with HS-173 in our models, none of the reversible ERBB inhibitors were synergistic in our study. Therefore, our results suggest that the ERBB inhibitor mechanism of action may be critical for enhanced synergy with PI3K inhibitors in HNSCC patients and motivate further preclinical studies for ERBB and PI3K combination therapies.
Labeling of Monilinia fructicola with GFP and Its Validation for Studies on Host-Pathogen Interactions in Stone and Pome Fruit

To compare in vivo the infection process of Monilinia fructicola on nectarines and apples using confocal microscopy it is necessary to transform a pathogenic strain with a construct expressing a fluorescent chromophore such as GFP. Thus, germinated conidia of the pathogen were transformed with Agrobacterium tumefaciens carrying the plasmid pPK2-hphgfp that allowed the expression of a fluorescent Hph-GFP chimera. The transformants were selected according to their resistance to hygromycin B, provided by the constitutive expression of the hph-gfp gene driven by the glyceraldehyde 3P dehydrogenase promoter of Aspergillus nidulans. The presence of T-DNA construct in the genomic DNA was confirmed by PCR using a range of specific primers. Subsequent PCR-mediated analyses proved integration of the transgene at a different genomic location in each transformant and the existence of structural reorganizations at these insertion points. The expression of Hph-GFP in three independent M. fructicola transformants was monitored by immunodetection and epifluorescence and confocal microscopy. The Atd9-M. fructicola transformant displayed no morphological defects and showed growth and pathogenic characteristics similar to the wild type. Microscopy analysis of the Atd9 transformant evidenced that nectarine infection by M. fructicola was at least three times faster than on apples.
The effect of emotional information from eyes on empathy for pain: A subliminal ERP study

Facial expressions are deeply tied to empathy, which plays an important role during social communication. The eye region is effective at conveying facial expressions, especially fear and sadness emotions. Further, it was proved that subliminal stimuli could impact human behavior. This research aimed to explore the effect of subliminal sad, fearful and neutral emotions conveyed by the eye region on a viewer’s empathy for pain using event-related potentials (ERP). The experiment used an emotional priming paradigm of 3 (prime: subliminal neutral, sad, fear eye region information) × 2 (target: painful, nonpainful pictures) within-subject design. Participants were told to judge whether the targets were in pain or not. Results showed that the subliminal sad eye stimulus elicited a larger P2 amplitude than the subliminal fearful eye stimulus when assessing pain. For P3 and late positive component (LPC), the amplitude elicited by the painful pictures was larger than the amplitude elicited by the nonpainful pictures. The behavioral results demonstrated that people reacted to targets depicting pain more slowly after the sad emotion priming. Moreover, the subjective ratings of Personal Distress (PD) (one of the dimensions in Chinese version of Interpersonal Reactivity Index scale) predicted the pain effect in empathic neural responses in the N1 and N2 time window. The current study showed that subliminal eye emotion affected the viewer’s empathy for pain. Compared with the subliminal fearful eye stimulus, the subliminal sad eye stimulus had a greater impact on empathy for pain. The perceptual level of pain was deeper in the late controlled processing stage.
Efficacy of a newly developed cartoon video on dry powder inhaler technique: a multicenter study.

BACKGROUND One of the factors associated with uncontrolled pediatric asthma is inadequate delivery of inhaled medication to the lungs. Incorrect inhaler technique has been reported. We developed a 2-minute cartoon video instruction aiming to improve dry powder inhaler (DPI) technique. OBJECTIVE To assess the efficacy of video instruction in improvement of DPI technique in Thai children with asthma. METHODS The prospective multicenter cohort study was conducted during March 2018 - February 2019. Children with asthma aged 6-15 years were recruited from the outpatient departments. Five videotapes demonstrated how the patients use DPI devices were recorded as the followings: before and after watching video (V₁pre and V₁post), at one-month (V₂post), at three-month (V₃post) after watching the video and at 5-month follow-up without watching the video (V₄pre). Scoring of correct DPI steps were evaluated by two independent respiratory specialists. RESULT Of 57 patients recruited, 30 used Accuhaler™ while 27 used Easyhaler™. In Accuhaler™ group, the median age (range) of 10 (8, 11) year. The mean score of V₁pre, V₁post, V₂post and V₃post were 10.7, 12.3, 12.4, and 12.2 out of 14 respectively. In Easyhaler™ group, the median age (range) of 11 (9-12) year. The mean score of V₁pre, V₁post, V₂post and V₃post were 8.6, 10.4, 11.2 and 11.4 out of 12 respectively. At the five-month follow-up, without watching video, the V₄pre score was still as high as 12.9 ± 1.3 in Accuhaler™ and 11.8 ± 0.4 in Easyhaler™. CONCLUSION Our video instruction could improve Accuhaler± and Easyhaler± technique among Thai children with asthma.