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“Kids and Girls”: Parents convey a male default in child-directed speech
Adults tend to view men (more so than women) as default people , with numerous real-world consequences for gender equity. In the United States, the tendency to center men in concepts of people develops across middle childhood, yet the specific mechanisms that contribute to it remain unknown. Here, we investigate one subtle but potentially powerful social mechanism: the category labels that parents use to describe boys/men and girls/women in conversations with their children. Across two studies ( N = 822 parent–child dyads, predominantly from the United States), parents used gender-neutral labels like “kid” or “person” more often to describe boys/men than girls/women and, conversely, used gender-specific labels (e.g., “girl”) more often to describe girls/women than boys/men. These patterns emerged when parents were shown gender-stereotypical girls/women and boys/men (e.g., a girl painting her nails, a boy digging for worms); when parents viewed counterstereotypical stimuli (e.g., a boy painting his nails, a girl digging for worms), the patterns reversed. Our findings illuminate parents’ category label usage as a critical social mechanism that may undergird the development of a male default in a US cultural context, informing efforts to intervene on this process.
Multilayered hollow transition metal nitride spheres made from single-source precursors for SERS analytics
Comparative analysis of translatomics and transcriptomics in the longissimus dorsi muscle of Luchuan and Duroc pigs
IMF (Intramuscular fat) content is a crucial indicator of meat quality in the livestock industry. However, the molecular mechanisms underlying IMF deposition remain unclear in pigs. In this study, we conducted RNC-seq (ribosome nascent-chain complex-bound RNA sequencing) and RNA-seq (RNA sequencing) analyses on the longissimus dorsi muscle of Duroc pigs (a lean breed) and Luchuan pigs (a fat breed) to uncover the genetic basis for the divergent IMF content. The results show that the overall translation level of Luchuan pigs is significantly higher than Duroc pigs, while there is no significant difference in the transcription level. Enzymes related to fatty acid synthesis and elongation, such as ACACA, FASN, and ELOVL5, are significantly up-regulated at the translation level, while enzymes associated with fatty acid degradation, namely ALDH1B1 and ALDH2, are significantly down-regulated. However, there is no significant difference in their transcription levels. qRT-PCR and Western Blotting experiments for ELOVL5 confirm the reliability of the sequencing results. Additionally, the translation initiation factor eIF4A1, known to positively regulate gene translation, displayed higher expression in Luchuan pigs rather than in Duroc pigs and the 5’UTR structural features of genes involved in translation up-regulation matched the mRNA selectivity of eIF4A1. In conclusion, these findings suggest the up-regulation of the eIF4A1 gene expression in Luchuan pigs may elevate the translation levels of genes related to lipid synthesis through translational regulation, further resulting in an increase in IMF content.
Independent genetic basis of meiotic crossover positioning and interference in domestic pigs
Abstract Meiotic crossover patterning shows huge variation within and between chromosomes, individuals, and species, yet the molecular and evolutionary causes and consequences of this variation remain poorly understood. A key step is to understand the genetic architecture of the crossover rate, positioning, and interference to determine if these factors are governed by common or distinct genetic processes. Here, we investigate individual variation in autosomal crossover count, crossover position (measured as both intra-chromosomal shuffling and distance to telomere), and crossover interference in a large breeding population of domestic pigs (N = 82,474 gametes). We show that all traits are heritable in females at the gamete (h2 = 0.07–0.11) and individual mean levels (h2 = 0.08–0.41). In females, crossover count, and interference are strongly associated with RNF212, but crossover positioning is associated with SYCP2, MEI4, and PRDM9. Our results show that crossover positioning and rate/interference are driven by distinct genetic processes in female pigs and have the capacity to evolve independently.
Human stem cells with in vivo high plasticity generated by cell–cell communication
Stem cells possess inherent properties of self-renewal and differentiation, and thus hold significant promise for regenerating damaged tissues or replacing lost cells. Unless their therapeutic effects are solely mediated by paracrine, transplanted stem cells need to be highly plastic to adapt to the host tissue environment and differentiate into constituent tissue-specific cells for tissue repair. Stem cells used in current cell-based therapies either have limited differentiation potential or are pluripotent but must be strictly restricted to avoid tumorigenicity risk in vivo. Here, we describe the derivation of human adult high-plasticity stem cells, which we call guide-integrated adult stem cells (giaSCs), from the interaction of blood-derived guide cells and umbilical cord tissue–derived mesenchymal stromal cells (UC-MSCs). The guide cells are a cell population derived from the peripheral blood of human adults. Unidirectional transfer through nanotube-like structures of granular substances from the guide cells into the recipient UC-MSCs gave rise to giaSCs. Topical application of human giaSCs into full-layer excisional wounds of wild-type mice led to reconstitution of skin tissue. Systemically administered human giaSCs migrated to and reside in mouse small intestinal tissue damaged by lipopolysaccharides and then differentiated into small intestinal epithelial cells for tissue repair. These transplantation experiments demonstrated that giaSCs have in vivo high plasticity. Additional in vivo and in vitro data showed that giaSCs have low immunogenicity and are nontumorigenic. These data indicate that giaSCs offer a highly promising approach to stem cell therapy.
Sphere of arbitrarily polarized exceptional points with a single planar metasurface
Predicting dietary management intention of patients with chronic kidney disease using protection motivation theory
Background Psychological determinants underlying the dietary management intention (DMI) of Chinese patients with chronic kidney disease (CKD) are not well understood. This hinders the development of theory-informed dietary interventions targeting this population. The aim of this study was to identify factors influencing DMI of Chinese patients with CKD through the lens of Protection Motivation Theory (PMT). Methods 500 patients with CKD from a nephrology ward of a large teaching hospital in China completed a survey including measures of PMT constructs (i.e., perceived vulnerability, perceived severity, intrinsic and extrinsic rewards, self-efficacy, response efficacy, and response cost) using validated scales adapted from previous studies. Data were analyzed using confirmatory factor analysis and multiple linear regression. Results Three PMT constructs, namely perceived severity [B = 0.198, P < 0.001], response efficacy [B = 0.331, P < 0.001], and self-efficacy [B = 0.325, P < 0.001], two demographic variables, namely single status [B = -0.180, P = 0.028] and education level [B = 0.080, P = 0.007], and a disease-related variable, namely CKD stage [B = .056, P = 0.001], predicted 39.3% of the variance of the CKD DMI. No significant effect on CKD DMI was observed for other predictor variables (P > 0.05). Conclusions Applying the PMT, significant predictors of DMI in Chinese patients with CKD were identified, which should be targeted in behavior change initiatives aimed at promoting dietary management.
Neutrophil elastase binds at the central domain of extracellular Toll-like receptor 4: AI prediction, docking, and validation in disease model
Pattern separation and pattern completion in early childhood
Pattern separation, or distinguishing similar experiences from one another, and pattern completion, in which components of an experience prompt retrieval or forgetting of an event pattern as a unit, are essential components of episodic memory. However, these two components are sometimes described as opposite ends of a continuum and sometimes described as independent processes. Here, we examined the relations between the two processes for the same events in children between 4 and 7 y. Mnemonic discrimination (the behavioral signature of pattern separation) improved with age; holistic recollection (the behavioral signature of pattern completion) did not change in this age range. Crucially, the two behaviors were unrelated, controlling for the effect of age, and even when examining their relations at the fine-grained level of memory for individual events.
Author Correction: VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification
A Swedish genome-wide haplotype association analysis identifies novel candidate loci associated with endometrial cancer risk
Genome-wide association studies [GWAS] have identified a limited number of endometrial cancer risk loci by analyzing single nucleotide polymorphisms [SNPs]. We hypothesized that analyzing haplotypes rather than SNPs could provide novel and more detailed information on genetic cancer susceptibility loci. To examine the association of a SNP or haplotype with endometrial cancer risk we performed a two-stage haplotype GWAS. The discovery GWAS included a sub-cohort of 1,116 Swedish endometrial cancer cases and 5,021 controls from previously published GWAS data. A sliding window analysis was employed with window sizes of 1-25 SNPs using a logistic regression model. The Swedish haplotype analysis identified 15 novel candidate risk loci (2q31.1, 4p16.1, 4p15.31, 6q13, 7p21.1, 9p13.3, 10q26.3, 11q21, 12q13.11, 13q12.11, 15q13.3, 16q24.3, 19q13.32, 20p12.3 and 22q13.2) with OR ranging from 1.6 to 3.3 and p-values from 4.25 × 10−8 to 9.86 × 10−15. A second replication haplotype analysis of the Swedish novel loci was performed using two cohorts from Belgium and Germany. In spite of small sample sizes in the replication cohorts, there was still support for most loci with positive ORs. In addition, the findings in the two European cohorts motivates further studies to search for founder haplotypes. These novel findings suggested that endometrial cancer loci, identified through haplotype analysis, conferred a higher risk compared to previous single-variant GWAS.
Two stage multiobjective topology optimization method via SwinUnet with enhanced generalization
Enhancement of mitochondrial calcium uptake is cardioprotective against maladaptive hypertrophy by retrograde signaling uptuning Akt
Regulation of mitochondrial Ca 2+ uptake is critical in cardiac adaptation to chronic stressors. Abnormalities in Ca 2+ handling, including mitochondrial uptake mechanisms, have been implicated in pathological heart hypertrophy. Enhancing mitochondrial Ca 2+ uniporter (MCU) expression has been suggested to interfere with maladaptive development of heart failure. Here, we addressed whether MCU modulation affects the cardiac response to pressure overload. MCU content was quantified in human and murine hearts at different phases of myocardial hypertrophy. Cardiac function/structure were analyzed after Transverse Aortic Constriction (TAC) in mice undergone viral-assisted overexpression or downregulation of MCU. In vitro and ex vivo assays determined the effect of MCU modulation on mitochondrial Ca 2+ uptake, cellular phenotype and hypertrophic signaling. In human and murine hearts MCU levels increased in the adaptive phase of myocardial hypertrophy and declined in the failing stage. Consistently, modulation of MCU had a cell-autonomous effect in cardiomyocyte/heart adaptation to chronic overload. Indeed, upon TAC MCU-downregulation accelerated development of contractile dysfunction, interstitial fibrosis and heart failure. Conversely, MCU-overexpression prolonged the adaptive phase of hypertrophic response, as, in advanced stages upon TAC, hearts showed preserved contractility, absence of fibrosis and intact vascularization. In vitro and ex vivo analyses indicated that enhancement in mitochondrial Ca 2+ uptake in cardiomyocytes entails “mitochondrion-to-cytoplasm” signals leading to ROS-mediated activation of Akt, which may explain the protective effects towards heart response to TAC. Enhanced mitochondrial Ca 2+ uptake affects the compensatory response to pressure overload via retrograde mitochondrial-Ca 2+ /ROS/Akt signaling, thus uncovering a potentially targetable mechanism against maladaptive myocardial hypertrophy.
Perturbing human V1 degrades the fidelity of visual working memory
Retraction: Design and development of human resource management computer system for enterprise employees
Identifying novel risk factors for aneurysmal subarachnoid haemorrhage using machine learning
Abstract Aneurysmal subarachnoid haemorrhage (aSAH) is a type of stroke with high mortality and morbidity. This study aimed to identify novel aSAH risk factors by combining machine learning (ML) and traditional statistical methods. Using the UK Biobank, we identified aSAH cases via hospital-based ICD codes and analysed 618 baseline variables covering demographics, lifestyle, medical history, and physical measurements. The CatBoost ML algorithm and Shapley Additive Explanations (SHAP) identified the top 25 variables most influential in predicting aSAH. Logistic regression further described these variables while adjusting for established aSAH risk factors. Among 501,847 participants, 893 aSAH cases were identified. ML identified 214 variables with non-zero SHAP values. Logistic regression of the top 25 variables revealed four potential novel aSAH risk factors. Increased aSAH risk was associated with mean sphered cell volume (OR 1.02, 95% CI 1.00-1.03) and tea intake (OR 1.03, 95% CI 1.01–1.05). Decreased aSAH risk was associated with peak expiratory flow (OR 0.80, 95% CI 0.66–0.96), and haematocrit percentage (OR 0.97, 95% CI 0.95-1.00). Future research should validate these findings and explore the potential non-linear relationships and interactions indicated by the ML models.
Dual mRNA nanoparticles strategy for enhanced pancreatic cancer treatment and β-elemene combination therapy
Pancreatic ductal adenocarcinoma (PDAC) is notoriously immune-resistant, limiting the clinical efficacy of single-agent immune modulators and thereby necessitating the exploration of multimodal immunotherapy combinations. Traditional approaches combining conventional immune checkpoint inhibitors with neoantigen vaccines have shown some promise in treating PDAC but are often compromised by intratumoral T lymphocyte exhaustion and systemic toxicity. Hence, novel approaches are needed to address these challenges. Herein, we demonstrate that mRNA polymeric nanoparticles encoding anti-PD-1 antibodies in situ at the tumor site enhance the therapeutic efficacy of neoantigen-based mRNA vaccine for PDAC. This mRNA-based, in situ anti-PD-1 antibody production strategy also protects tumor-infiltrating T cells from PD-1 inhibition, potentially reducing the toxicities induced by systemic checkpoint inhibition. Our study may provide an innovative dual mRNA nanoparticle strategy for effective tumor neoantigen immunotherapy, as well as an mRNA cancer combination therapy strategy with other clinically approved drugs (e.g., β-elemene).
The primate-specific Nedd4-1(NE) localizes to late endosomes in response to amino acids to suppress autophagy
The association between oral health and risk behaviours of university students
Background Young adults are exposed to a variety of risk-related behaviours such as alcohol, smoking, and changes in dietary habits, which may result in unknown outcomes in their oral health. There is limited evidence on whether different risk behaviours are associated with oral health behaviours in the university student population. This study gathers data on the behaviours of students in their first year of university, which will inform the future development of oral health behaviour change interventions for this population. Method This longitudinal quantitative survey involved 205 first-year students aged 18-24 at the University of Manchester. Students completed online questionnaires at baseline and again at a 6-month follow-up interval, providing information regarding self-reported oral health status, hygiene routines, and risk behaviours (e.g., diet, smoking, alcohol). Results The findings showed associations between oral health behaviours with risk behaviours, including links with oral care routines, bleeding gums, brushing frequency, with exercise, vaping, and unhealthy food and drink intake. Significant changes over the two-time points were also observed, including the worsening of the self-reported condition of the teeth (p < 0.001), a reduction in the self-reported condition of the gums (p = 0.004), a decrease in brushing frequency (p = 0.003), fewer regular dental visits (p = 0.013), more students intending to visit their previous dentist rather than finding a new dentist at university (p = 0.026), and greater consumption of unhealthy non-alcoholic drinks (p = 0.003). Positive changes over time included reduced frequency and units of alcohol consumption (p = 0.030 and p = 0.001), fewer instances of binge drinking (p = 0.014), and less frequent consumption of unhealthy foods (p = 0.034). Conclusion The findings highlighted the complex relationship between oral health and risk behaviours in this demographic. Poorer oral health behaviours were linked to engagement in risk behaviours. Thus, oral health behaviours should be targeted alongside other risk behaviours, and tailored interventions should be developed to improve behaviours among university students.