Miracle-dz/UniFAR-FTUs huggingface dataset:
Transfer of miR‐4755‐5p through extracellular vesicles and particles induces decitabine resistance in recipient cells by targeting CDKN2B

Decitabine (5‐aza‐2‐deoxycytidine, DAC), a DNA‐hypomethylating agent, has been one of the frontline therapies for clonal hematopoietic stem cell disorders, such as myelodysplastic syndrome and acute myeloid leukemia, but DAC‐resistance often occurs and leads to treatment failure. Therefore, elucidating the mechanisms of DAC resistance is important for improving its therapeutic efficacy. The extracellular vesicles and particles (EVPs) have been reported to be involved in mediating drug resistance by transporting diverse bioactive components. In this study, we established the DAC‐resistant cell line (KG1a‐DAC) from its parental human leukemia‐derived cell line KG1a and observed that EVPs released from KG1a‐DAC can promote DAC‐resistant in KG1a cells. Moreover, treatment with KG1a‐DAC EVPs reduced the expression of cyclin‐dependent kinase inhibitor 2B (CDKN2B) in KG1a cells. miRNA‐Seq analysis revealed that miR‐4755‐5p is overexpressed in EVPs from KG1a‐DAC. Dual‐luciferase reporter assay and flow cytometry analysis confirmed that miR‐4755‐5p rendered KG1a cells resistant to the DAC by targeting CDKN2B gene. Taken together, miR‐4755‐5p in EVPs released from the DAC‐resistant cells plays an essential role in inducing DAC‐resistance, and is a potential therapeutic target for suppression of DAC resistance.
The Drivers of Conversations About Dementia Risk Reduction: A Qualitative Study

Dementia prevention is an area of health where public knowledge remains limited. A growing number of education initiatives are attempting to rectify this, but they tend to reach audiences of limited size and diversity, limiting intervention-associated health equity. However, initiative participants tend to discuss these initiatives and the information they contain with members of their social network, increasing the number and diversity of people receiving dementia risk reduction information. In this qualitative study, we sought to understand the drivers of this information sharing. We interviewed 39 people from Tasmania, Australia who completed the Preventing Dementia Massive Open Online Course in May 2020. We identified themes from responses to semi-structured interview questions using reflexive thematic analysis. We identified three key drivers of information sharing: participants’ personal course experiences; participants finding information sharing opportunities with people they expected to be receptive; and conversation partners’ responses to conversation topics. These drivers aligned with existing communication theories, with dementia-related stigma effecting both actual and perceived conversation partner receptivity. Understanding the drivers of information sharing may allow information about dementia risk reduction, and other preventative health behaviors, to be presented in ways that facilitate information diffusion, increasing equity in preventative health education.
Armadillo Repeat Only protein GS10 negatively regulates brassinosteroid signaling to control rice grain size.

Grain yield and grain quality are major determinants in modern breeding controlled by many quantitative traits loci (QTLs) in rice (Oryza sativa). However, the mechanisms underlying grain shape and quality are poorly understood. Here, we characterize a QTL for grain size and grain quality via map-based cloning from wild rice (W1943), GS10 (Grain Size on Chromosome 10), which encodes a protein with six tandem armadillo (ARM) repeats. The null mutant gs10 shows slender and narrow grains with altered cell size, which has a pleiotropic effect on other agronomical traits. Functional analysis reveals that GS10 interacts with TUD1 (Taihu Dwarf1) and is epistatic to OsGSK2 (glycogen synthase kinase 2) through regulating grain shape and lamina joint inclination, indicating it is negatively involved in brassinosteroid (BR) signaling. Pyramiding gs10 and the grain size gene GW5 into cultivar GLA4 substantially improved grain shape and appearance quality. Natural variation analysis revealed that gs10 from the wild rice Oryza rufipogon W1943 is a rare allele across the rice population. Collectively, these findings advance our understanding of the underlying mechanism of grain shape and provide the beneficial allele of gs10 for future rice breeding and genetic improvement.
Inferring Balancing Selection From Genome-Scale Data

Abstract The identification of genomic regions and genes that have evolved under natural selection is a fundamental objective in the field of evolutionary genetics. While various approaches have been established for the detection of targets of positive selection, methods for identifying targets of balancing selection, a form of natural selection that preserves genetic and phenotypic diversity within populations, have yet to be fully developed. Despite this, balancing selection is increasingly acknowledged as a significant driver of diversity within populations, and the identification of its signatures in genomes is essential for understanding its role in evolution. In recent years, a plethora of sophisticated methods has been developed for the detection of patterns of linked variation produced by balancing selection, such as high levels of polymorphism, altered allele-frequency distributions, and polymorphism sharing across divergent populations. In this review, we provide a comprehensive overview of classical and contemporary methods, offer guidance on the choice of appropriate methods, and discuss the importance of avoiding artifacts and of considering alternative evolutionary processes. The increasing availability of genome-scale datasets holds the potential to assist in the identification of new targets and the quantification of the prevalence of balancing selection, thus enhancing our understanding of its role in natural populations.
Hit discovery of novel 2‐phenyl‐substituted 4‐amino–6,7‐dihydro‐5H‐cyclopenta[d]pyrimidines as potential anti‐glioblastoma therapeutics: Design, synthesis, biological evaluation, and computational screening

Glioblastoma multiforme (GBM) is a highly‐aggressive, dreadful disease with poor prognosis and disappointing clinical success. There is an unmet medical need of molecularly‐targeted therapeutics for GBM treatment. In the present work, a series of novel 2‐phenyl‐substituted 4‐amino–6,7‐dihydro‐5H‐cyclopenta[d]pyrimidines was designed, synthesized, purified, characterized, and evaluated for cytotoxicity against glioblastoma cell line U87‐MG. The design process (virtual library enumeration around the core, physicochemical and molecular property prediction/calculation of the designs, filtering the undesirable ones, and the diversity analyses of the lead‐like designs), was carefully curated so as to obtain a set of structurally‐diverse, novel molecules (total 20), with a particular focus on the relatively unexplored core structure, 6,7‐dihydro‐5H‐cyclopenta[d]pyrimidine. The preliminary screening was done using MTT assay at 10 and 100 μM concentrations of the title compounds F1−F20 and positive control cisplatin, which yielded six hits (% inhibition at 10 μM: ~50%)—F2, F3, F5, F7, F15, and F20, which were taken up for IC50 determination. The top hits F2 and F7 (IC50 < 10 μM) were further used for computational studies such as target prediction, followed by their molecular docking in the binding sites of the top‐3 predicted targets (epidermal growth factor receptor kinase domain, cyclin‐dependent kinase 2 [CDK2]) /cyclin E, and anaplastic lymphoma kinase [ALK]). The docking pose analyses revealed interesting trends. The relatively planar core structure, presence of favorable hinge‐binding substructures, basic groups, all added up, and culminated in appreciable cytotoxicity against GBM cell line.
Association of TLR4 gene 2026A/G (rs1927914), 896A/G (rs4986790), and 1196C/T (rs4986791) polymorphisms and cancer susceptibility: Meta-analysis and trial sequential analysis

Background: This study was performed to assess the association of TLR4 gene 2026A/G (rs1927914), 896A/G (rs4986790), and 1196C/T (rs4986791) polymorphisms and cancer susceptibility based on published case-control studies. Methods: Web of Science, PubMed, Embase, CBM, WanFang Data, CNKI, and VIP database were used for article retrieving. Then, these articles were screened according to the study inclusion and exclusion criteria. The data was extracted, and the study quality was evaluated according to the principle of Newcastle-Ottawa Scale. Meta-analysis was performed by RevMan 5.4 and Stata MP-17 software. Trial sequential analysis was performed by TSA 0.9. 5.10 Beta software. Results: Eighty-seven case-control studies including 25,969 cases and 32,119 controls were included in the meta-analysis. The diseases involved in case groups include prostate cancer, lung cancer, gastric cancer, hepatocellular carcinoma, colorectal cancer, etc. A versus G model of rs1927914, A versus G model of rs4986790 and C versus T model of rs4986791 showed that odds ratio (OR) = 1.08, OR = 0.85, and OR = 0.74 respectively. All the 3 comparisons were statistically significant. Sensitivity analysis showed that the results were stable. Publication bias analysis and trial sequential analysis showed that no significant publication bias was found in the results of the meta-analysis, and the probability of false positives was small. Conclusion: People with A allele of rs1927914, G allele of rs4986790, or T allele of rs4986791 have higher risks of cancer. The results of meta-analysis are stable and have less probability of false positives.
The correlation between nuts and algae-less diet and children’s blood pressure: from a cross-sectional study in Chongqing

ABSTRACT Background Nuts and algae have been shown to improve BP levels, but their effectiveness is controversial. Aims This study aims to illustrate the effect of dietary pattern with nuts and algae-less on BP levels in children and adolescents from a cross-sectional study. Methods A total of 5645 children from the Chongqing Children’s Health Cohort, aged 9.34 ± 1.74 years with 52.05% males, were analyzed. Stratified analysis was conducted to explore the differences between the two dietary patterns in urban or rural areas, as well as the differences in different gender. Logistic regression was used to analyze the influence factors of increased BP. And a GLM was used to analyze the influence of the two dietary patterns on systolic blood pressure (SBP, mmHg), diastolic blood pressure (DBP, mmHg), and mean arterial pressure (MAP, mmHg). Results Children with nuts and algae-less dietary patterns had higher SBP (104.68 ± 10.31 vs 103.81 ± 9.74, P = .006), DBP (64.27 ± 7.53 vs 63.55 ± 7.52, P = .002), and MAP (77.74 ± 7.75 vs 76.97 ± 7.52, P = .001) compared with those children with a balanced diet. After adjusting for covariates, the nuts and algae-less diet was a risk factor for hypertension in children when compared with the balanced diet(OR(95%CI):1.455(1.097,1.930), P = . 009). The nuts and algae-less diet has a significant influence on SBP (104.68 ± 10.31 mmHg vs.103.81 ± 9.74 mmHg, P = .006). Stratified analysis by sex showed that nuts and algae-less dietary patterns had a more significant impact on females than males. Conclusion Nuts and algae-less dietary pattern correlated with increased BP levels in children, and a greater impact on SBP levels was found in females, suggesting that a balanced diet with appropriate nuts and algae should be proposed for children in China.
Episodic foresight is impaired following acute alcohol intoxication

Background: Alcohol intoxication disrupts many aspects of cognition, including the generation of phenomenological characteristics of future events (a component of episodic foresight), and the execution of directed preparatory behaviours (a component of prospective memory). However, no study has tested whether alcohol intoxication is also associated with deficits engaging episodic foresight to guide future-directed behaviour. Aims: This study was designed to provide the first test of how alcohol intoxication influences the functional application of episodic foresight. The secondary aim was to establish the degree to which any observed episodic foresight difficulties associated with alcohol use might reflect broader problems in retrospective memory and executive control. Sex differences were also examined. Methods: Healthy adult social drinkers randomly received either a moderate dose of 0.6 g/kg alcohol (n = 61) or a matched placebo drink (n = 63) and then completed a validated measure that met strict criteria for assessing the functional application of episodic foresight as well as a broader cognitive test battery. Results: Relative to the placebo condition, episodic foresight was impaired by acute alcohol consumption, with this impairment related to poorer retrospective memory, but not executive control. The negative effects of alcohol intoxication on episodic foresight did not differ as a function of sex. Conclusions: Even a moderate level of intoxication impairs the ability to use episodic foresight in a functionally adaptive way. These findings have implications for understanding many of the maladaptive behaviours that are often associated with acute alcohol use.
Maternal mental-health treatment moderates the association between psychological distress and harsh parenting: A prospective cohort study

Objective Parental psychological distress (depression, anxiety) is detrimental to child mental health. A key reason for this is that depressed and anxious parents are at risk of engaging in more negative, reactive and harsh parenting. While treatment for psychological distress has a long history of success in adults, less is known about how treatment for parental psychological distress may positively influence parenting behaviours, particularly in the general population. We examined the moderating role of mothers receiving treatment for depression or anxiety on the longitudinal relationship between maternal psychological distress and the development of harsh parenting (smacking and shouting) across early childhood (ages 3 to 7). Method Using prospective data from 16,131 families participating in the UK’s Millennium Cohort Study, we conducted moderator analysis within a multilevel repeated measures model to test whether receiving treatment for mental health problems could protect mothers with high psychological distress from engaging in harsh parenting. Results In each wave, about 7% of mothers reported undergoing treatment for depression or anxiety at that time. Maternal psychological distress was associated with increased use of harsh parenting and that, adjusting for psychological distress, receiving psychological treatment was related to decreased use of harsh parenting. Importantly, receiving psychological treatment buffered the negative effect of psychological distress on harsh parenting. Conclusion In early-to-middle childhood, mental health treatment may help mothers with depression or anxiety to be less harsh toward their children, thereby benefiting their child’s psychological adjustment.
Breaking self‐regulation of Regnase‐1 promotes its own protein expression

The RNA‐binding protein (RBP) Regnase‐1 is an endonuclease that regulates immune responses by modulating target mRNA stability. Regnase‐1 degrades a group of inflammation‐associated mRNAs, which contributes to a balanced immune response and helps prevent autoimmune diseases. Regnase‐1 also cleaves its own mRNA by binding stem‐loop (SL) RNA structures in its 3′UTR. To understand how this autoregulation is important for immune responses, we generated mice with a 2‐bp genome deletion in the target SL of the Regnase‐1 3′‐untranslated region (3′UTR). Deletion of these nucleotides inhibited SL formation and limited Regnase‐1‐mediated mRNA degradation. Mutant mice had normal hematopoietic cell differentiation. Biochemically, mutation of the 3′UTR SL increased Regnase‐1 mRNA stability and enhanced both Regnase‐1 mRNA and protein levels in mouse embryonic fibroblasts (MEFs). The expression of Il6, a Regnase‐1 target gene, was constitutively suppressed at steady‐state in mutant MEFs. Additionally, Regnase‐1 protein expression in mutant MEFs was significantly elevated compared to that in wild‐type MEFs at steady state and upon proinflammatory cytokine stimulation. These data suggest a negative feedback mechanism for Regnase‐1 expression and represent a unique mouse model to probe Regnase‐1 overexpression in vivo.
Towards preferential selection in the prisoner’s dilemma game

In previous works, the choice of learning neighbor for an individual has generally obeyed pure random selection or preferential selection rules. In this paper, we introduce a tunable parameter ε to characterize the strength of preferential selection and focus on the transition towards preferential selection in the spatial evolutionary game by controlling ε to guide the system from pure random selection to preferential selection. Our simulation results reveal that the introduction of preferential selection can hugely alleviate social dilemmas and enhance network reciprocity. A larger ε leads to a higher critical threshold of the temptation b for the extinction of cooperators. Moreover, we provide some intuitive explanations for the above results from the perspective of strategy transition and cooperative clusters. Finally, we examine the robustness of the results for noise K and different topologies, find that qualitative features of the results are unchanged.
Relating turbulent pressure and macroturbulence across the HR diagram with a possible link to γ Doradus stars

Accepted 14 October 2015 ABSTRACT A signiﬁcant fraction of the envelope of low- and intermediate-mass stars is unstable to convection, leading to sub-surface turbulent motion. Here, we consider and include the e ﬀ ects of turbulence pressure in our stellar evolution calculations. In search of an observational signature, we compare the fractional contribution of turbulent pressure to the observed macroturbulent velocities in stars at di ﬀ erent evolutionary stages. We ﬁnd a strong correlation between the two quantities, similar to what was previously found for massive OB stars. We therefore argue that turbulent pressure ﬂuctuations of ﬁnite amplitude may excite high-order, high-angular degree stellar oscillations, which manifest themselves at the surface an additional broadening of the spectral lines, i.e., macroturbulence, across most of the HR diagram. When considering the locations in the HR diagram where we expect high-order oscillations to be excited by stochastic turbulent pressure ﬂuctuations, we ﬁnd a close match with the observational γ Doradus instability strip, which indeed contains high-order, non-radial pulsators. We suggest that turbulent pressure ﬂuctuations on a percentual level may contribute to the γ Dor phenomenon, calling for more detailed theoretical
The ameliorative effect of CangFu Daotan Decoction on polycystic ovary syndrome of rodent model is associated with m6A methylation and Wnt/β-catenin pathway

Abstract Objective: This study investigates the effects of CangFu Daotan Decoction (CDD) on m6A methylation and Wnt/β-catenin pathway in rats with polycystic ovary syndrome (PCOS). Methods: The PCOS rat model was established by letrozole gavage. The rats were fed high-fat chow, and their body weight and blood glucose were recorded. The expressions of follicle-stimulating hormone(FSH), luteinizing hormone(LH), and testosterone(T) were quantified by ELISA. Chemical components in CDD were analyzed using UPLC-Q/TOF-MS. Based on network pharmacology methods, related targets of CDD on PCOS were screened. An enrichment analysis according to Tokyo Encyclopedia of Genes and Genomes (KEGG) was conducted to predict the potential signaling pathway of CDD in PCOS. The expressions of Wnt-1, β-Catenin, GSK-3β, C-MYC, Beclin1, LC3II, Bax, and PCNA were detected by western blotting. The expressions of Mettl3, Mettl14, Fto, Alkbh5, Ythdf1, and Ythdf2 were monitored by RT-PCR. The expressions of Mettl3, Fto, and Ythdf1 were detected by western blotting.Results: Letrozole and a high-fat diet induced ovarian dysfunction in rats, which was attenuated by CDD. CDD decreased blood glucose, LH, and T concentrations and increased FSH expression in PCOS. After removing duplicates, a total of 71 compounds were identified by UHPLC-Q/TOF-MS, among which terpenoids and flavonoids account for the main proportion. The clustering analysis showed that the active site of CDD might be in the Wnt/β-catenin pathway. CDD decreased the expressions of Wnt-1, β-Catenin, GSK-3β, C-MYC, Beclin1, LC3II, and Bax and increased PCNA expression in the ovarian tissue of PCOS rats. CDD decreased the m6A gene expressions of Mettl3, Mettl14, Fto, Alkbh5, Ythdf1, and Ythdf2 in peripheral blood and ovarian tissue of PCOS rats. CDD reduced the m6A proteins expressions of Mettl3, Fto, and Ythdf1 in the ovarian tissue of PCOS rats.Conclusion: CDD can regulate m6A modification and inhibit the Wnt/β-catenin signaling pathway in PCOS rats, thereby reducing body weight, lowering blood glucose levels, improving sex hormone disorders, and decreasing autophagy and apoptosis in ovarian tissue to promote the recovery of ovarian morphology.
scGCL: an imputation method for scRNA-seq data based on graph contrastive learning

Abstract Motivation Single-cell RNA-sequencing (scRNA-seq) is widely used to reveal cellular heterogeneity, complex disease mechanisms and cell differentiation processes. Due to high sparsity and complex gene expression patterns, scRNA-seq data present a large number of dropout events, affecting downstream tasks such as cell clustering and pseudo-time analysis. Restoring the expression levels of genes is essential for reducing technical noise and facilitating downstream analysis. However, existing scRNA-seq data imputation methods ignore the topological structure information of scRNA-seq data and cannot comprehensively utilize the relationships between cells. Results Here, we propose a single-cell Graph Contrastive Learning method for scRNA-seq data imputation, named scGCL, which integrates graph contrastive learning and Zero-inflated Negative Binomial (ZINB) distribution to estimate dropout values. scGCL summarizes global and local semantic information through contrastive learning and selects positive samples to enhance the representation of target nodes. To capture the global probability distribution, scGCL introduces an autoencoder based on the ZINB distribution, which reconstructs the scRNA-seq data based on the prior distribution. Through extensive experiments, we verify that scGCL outperforms existing state-of-the-art imputation methods in clustering performance and gene imputation on 14 scRNA-seq datasets. Further, we find that scGCL can enhance the expression patterns of specific genes in Alzheimer’s disease datasets. Availability and implementation The code and data of scGCL are available on Github: https://github.com/zehaoxiong123/scGCL. Supplementary information Supplementary data are available at Bioinformatics online.