Gadd45a promotes DNA demethylation through TDG

Growth arrest and DNA-damage-inducible protein 45 (Gadd45) family members have been implicated in DNA demethylation in vertebrates. However, it remained unclear how they contribute to the demethylation process. Here, we demonstrate that Gadd45a promotes active DNA demethylation through thymine DNA glycosylase (TDG) which has recently been shown to excise 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) generated in Ten-eleven-translocation (Tet)—initiated oxidative demethylation. The connection of Gadd45a with oxidative demethylation is evidenced by the enhanced activation of a methylated reporter gene in HEK293T cells expressing Gadd45a in combination with catalytically active TDG and Tet. Gadd45a interacts with TDG physically and increases the removal of 5fC and 5caC from genomic and transfected plasmid DNA by TDG. Knockout of both Gadd45a and Gadd45b from mouse ES cells leads to hypermethylation of specific genomic loci most of which are also targets of TDG and show 5fC enrichment in TDG-deficient cells. These observations indicate that the demethylation effect of Gadd45a is mediated by TDG activity. This finding thus unites Gadd45a with the recently defined Tet-initiated demethylation pathwa

Cross-domain Transfer of Valence Preferences via a Meta-optimization Approach

Cross-domain recommendation offers a potential avenue for alleviating data sparsity and cold-start problems. Embedding and mapping, as a classic cross-domain research genre, aims to identify a common mapping function to perform representation transformation between two domains. Nevertheless, previous coarse-grained preference representations, non-personalized mapping functions, and excessive reliance on overlapping users limit their performance, especially in scenarios where overlapping users are sparse. To address aforementioned challenges, we propose a novel cross-domain approach, namely CVPM. CVPM formalizes cross-domain interest transfer as a hybrid architecture of parametric meta-learning and self-supervised learning, which not only transfers user preferences at a finer level, but also enables signal enhancement with the knowledge of non-overlapping users. Specifically, with deep insights into user preferences and valence preference theory, we believe that there exists significant difference between users' positive preferences and negative behaviors, and thus employ differentiated encoders to learn their distributions. In particular, we further utilize the pre-trained model and item popularity to sample pseudo-interaction items to ensure the integrity of both distributions. To guarantee the personalization of preference transfer, we treat each user's mapping as two parts, the common transformation and the personalized bias, where the network used to generate the personalized bias is output by a meta-learner. Furthermore, in addition to the supervised loss for overlapping users, we design contrastive tasks for non-overlapping users from both group and individual-levels to avoid model skew and enhance the semantics of representations. Exhaustive data analysis and extensive experimental results demonstrate the effectiveness and advancement of our proposed framework

Neuronally released vasoactive intestinal polypeptide alters atrial electrophysiological properties and may promote atrial fibrillation

BACKGROUND: Vagal hyperactivity promotes atrial fibrillation (AF), which has been almost exclusively attributed to acetylcholine. Vasoactive intestinal polypeptide (VIP) and acetylcholine are neurotransmitters co-released during vagal stimulation. Exogenous VIP has been shown to promote AF by shortening action potential duration (APD), increasing APD spatial heterogeneity, and causing intra-atrial conduction block. OBJECTIVE: The purpose of this study was to investigate the effects of neuronally released VIP on atrial electrophysiologic properties during vagal stimulation. METHODS: We used a specific VIP antagonist (H9935) to uncover the effects of endogenous VIP released during vagal stimulation in canine hearts. RESULTS: H9935 significantly attenuated (1) the vagally induced shortening of atrial effective refractory period and widening of atrial vulnerability window during stimulation of cervical vagosympathetic trunks (VCNS) and (2) vagal effects on APD during stimulation through fat-pad ganglion plexus (VGPS). Atropine completely abolished these vagal effects during VCNS and VGPS. In contrast, VGPS-induced slowing of local conduction velocity was completely abolished by either VIP antagonist or atropine. In pacing-induced AF during VGPS, maximal dominant frequencies and their spatial gradients were reduced significantly by H9935 and, more pronouncedly, by atropine. Furthermore, VIP release in the atria during vagal stimulation was inhibited by atropine, which may account for the concealment of VIP effects with muscarinic blockade. CONCLUSION: Neuronally released VIP contributes to vagal effects on atrial electrophysiologic properties and affects the pathophysiology of vagally induced AF. Neuronal release of VIP in the atria is inhibited by muscarinic blockade, a novel mechanism by which VIP effects are concealed by atropine during vagal stimulation

An inevitably aging world -- Analysis on the evolutionary pattern of age structure in 200 countries

Ignoring the differences between countries, human reproductive and dispersal behaviors can be described by some standardized models, so whether there is a universal law of population growth hidden in the abundant and unstructured data from various countries remains unclear. The age-specific population data constitute a three-dimensional tensor containing more comprehensive information. The existing literature often describes the characteristics of global or regional population evolution by subregion aggregation and statistical analysis, which makes it challenging to identify the underlying rules by ignoring national or structural details. Statistical physics can be used to summarize the macro characteristics and evolution laws of complex systems based on the attributes and motions of masses of individuals by decomposing high-dimensional tensors. Specifically, it can be used to assess the evolution of age structure in various countries over the past approximately 70 years, rather than simply focusing on the regions where aging has become apparent. It provides a universal scheme for the growing elderly and working age populations, indicating that the demographics on all continents are inevitably moving towards an aging population, including the current "young" continents of Africa, and Asia, South America with a recent "demographic dividend". It is a force derived from the "life cycle", and most countries have been unable to avoid this universal evolutionary path in the foreseeable future

PromotionLens: Inspecting Promotion Strategies of Online E-commerce via Visual Analytics

Promotions are commonly used by e-commerce merchants to boost sales. The efficacy of different promotion strategies can help sellers adapt their offering to customer demand in order to survive and thrive. Current approaches to designing promotion strategies are either based on econometrics, which may not scale to large amounts of sales data, or are spontaneous and provide little explanation of sales volume. Moreover, accurately measuring the effects of promotion designs and making bootstrappable adjustments accordingly remains a challenge due to the incompleteness and complexity of the information describing promotion strategies and their market environments. We present PromotionLens, a visual analytics system for exploring, comparing, and modeling the impact of various promotion strategies. Our approach combines representative multivariant time-series forecasting models and well-designed visualizations to demonstrate and explain the impact of sales and promotional factors, and to support "what-if" analysis of promotions. Two case studies, expert feedback, and a qualitative user study demonstrate the efficacy of PromotionLens.Comment: IEEE Transactions on Visualization and Computer Graphics (Proc. IEEE VIS 2022

LiveRetro: Visual Analytics for Strategic Retrospect in Livestream E-Commerce

Livestream e-commerce integrates live streaming and online shopping, allowing viewers to make purchases while watching. However, effective marketing strategies remain a challenge due to limited empirical research and subjective biases from the absence of quantitative data. Current tools fail to capture the interdependence between live performances and feedback. This study identified computational features, formulated design requirements, and developed LiveRetro, an interactive visual analytics system. It enables comprehensive retrospective analysis of livestream e-commerce for streamers, viewers, and merchandise. LiveRetro employs enhanced visualization and time-series forecasting models to align performance features and feedback, identifying influences at channel, merchandise, feature, and segment levels. Through case studies and expert interviews, the system provides deep insights into the relationship between live performance and streaming statistics, enabling efficient strategic analysis from multiple perspectives.Comment: Accepted by IEEE VIS 202

High spatial resolution charge sensing of quantum Hall states

Charge distribution offers a unique fingerprint of important properties of electronic systems, including dielectric response, charge ordering, and charge fractionalization. We develop an architecture for charge sensing in two-dimensional electronic systems in a strong magnetic field. We probe local change of the chemical potential in a proximitized detector layer using scanning tunneling microscopy, allowing us to infer the chemical potential and the charge profile in the sample. Our technique has both high energy (<0.3 meV) and spatial (<10 nm) resolution exceeding that of previous studies by an order of magnitude. We apply our technique to study the chemical potential of quantum Hall liquids in monolayer graphene under high magnetic fields and their responses to charge impurities. The chemical potential measurement provides a local probe of the thermodynamic gap of quantum Hall ferromagnets and fractional quantum Hall states. The screening charge profile reveals spatially oscillatory response of the quantum Hall liquids to charge impurities and is consistent with the composite Fermi liquid picture close to the half-filling. Our technique also paves the way to map moiré potentials, probe Wigner crystals, and investigate fractional charges in quantum Hall and Chern insulators

Association between physical activity patterns and the risk of stroke phenotypes:an accelerometer-based prospective cohort study from the UK Biobank

Objective: There is growing evidence of an association between exercise duration and stroke risk. However, there is no high-quality prospective evidence to confirm the equal distribution of the two exercise patterns, weekend warriors and exercise duration, and whether there are differences between different stroke subtypes. Therefore, the aim of this study was to explore the association between different exercise patterns and stroke and its subtypes using exercise data from the UK Biobank. Method: This study analyzed data from 90,926 UK Biobank participants with long‐term follow-up (mean ranging from 7.56 to 7.83 years). Accelerometer-derived MVPA data were used to classify individuals into three groups based on current guidelines: inactive (MVPA &lt; 150 min per week), active conventional (MVPA ≥ 150 min per week with &lt; 50% accumulated in 1–2 days), and active weekend warrior (WW; MVPA ≥ 150 min per week with ≥ 50% accrued in 1–2 days). Multivariable Cox proportional hazards models were applied to estimate the hazard ratios (HRs) for overall stroke, ischemic stroke (IS), intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH), while adjusting for covariates including age, sex, body mass index, ethnicity, healthy diet score, Townsend Deprivation Index, annual income, smoking status, alcohol consumption, diabetes status, family history of stroke, and education level. Stratified analyses based on MVPA distribution percentiles (25th, 50th, and 75th) were also performed to assess model stability. Results: Relative to inactive individuals, both the active WW group (HR = 0.70; 95% CI = 0.62–0.80; P &lt; 0.001) and the active conventional group (HR = 0.78; 95% CI = 0.66–0.91; P &lt; 0.001) demonstrated significantly lower overall stroke risk, with no significant difference between the two active patterns (HR = 0.90; 95% CI = 0.77–1.06; P = 0.099). For ischemic stroke, the active WW group exhibited a modest, non-significant risk reduction (HR = 0.88; 95% CI = 0.74–1.05; P = 0.153), whereas the active conventional group showed a significantly elevated risk (HR = 1.31; 95% CI = 1.10–1.55; P = 0.002); direct comparisons indicated that the WW pattern conferred a significantly lower risk than the conventional pattern (HR = 0.67; 95% CI = 0.58–0.77; P &lt; 0.001). For subarachnoid hemorrhage, the active conventional pattern was associated with an increased risk (HR = 2.03; 95% CI = 1.15–3.59; P = 0.015) relative to inactivity, while the risk in the active WW group was not significantly different (HR = 1.40; 95% CI = 0.79–2.49; P = 0.247). No significant differences were observed in the risk for intracerebral hemorrhage across groups. Conclusions: Meeting the recommended 150 min of weekly MVPA is associated with a reduced overall risk of stroke. Both active exercise patterns provide protection against ischemic stroke; however, a conventional distribution of physical activity may be linked to a higher risk of subarachnoid hemorrhage. These findings suggest that, in addition to total MVPA volume, the temporal pattern of activity accumulation plays a critical role in modulating stroke risk.</p

Effect of Kang Fu Yan capsule on phenol mucilage-induced intrauterine adhesion injury in female rats

Purpose: To investigate the effect of Kang fu yan capsule (KFYC) on phenol mucilage-induced intrauterine adhesion (IUA) in a rat model, and the underlying mechanisms. Methods: An IUA model was established by injecting 0.06 mL of 25 % phenol mucilage into the uterus of female Sprague-Dawley rats. The IUA model rats (n=59) were randomly divided into 5 groups: IUA group, fuke qianjin tablet group (FKQJT, 0.22 mg/kg), and 3 KFYC groups given different doses of the drug i.e. 0.13, 0.39and 1.17 mg/kg. A group of 10 healthy female rats served as control. After 19 days treatment, blood samples were collected for determination of IL-2 and IL-10 by ELISA, while uterine tissues were subjected to histological examination using hematoxylin and eosin staining (H&amp;E) and Masson staining. Expressions of Notch1, recombination signal binding protein-JK (RBP-JK), a disintegrin and metalloprotease (ADAM)-12, ADAM-15, matrix metalloprotein-9 (MMP-9), and inhibitor of NF-κB (IĸB) in uterine tissues were determined using RT-qPCR and western blot analysis. Results: Compared to IUA group, histological results showed reduced inflammatory cell infiltration in rat uterine tissue of KFYC group. Moreover, KFYC significantly reversed uterine fibrosis (p &lt; 0.05). Serum concentrations of IL-2 significantly decreased in KFYC groups (p &lt; 0.05 or p &lt; 0.01), and there was significant increases the serum concentrations of IL-10 in KFYC groups (p &lt; 0.05 or &lt; 0.01), when compared to IUA group. The mRNA and protein expressions of Notch1, RBP-JK, ADAM-12, ADAM-15, MMP-9 were also significantly down-regulated (p &lt; 0.05), while protein expression of IĸB was upregulated in KFYC group, when compared to IUA group. Conclusion: KFYC exerts an anti-IUA effect via amelioration of uterine inflammation and fibrosis, probably via a mechanism involving regulation of Notch1/ADAM pathway