Browse Articles

A single cluster of RNA Polymerase II molecules is stably associated with active genes

Abstract In eukaryotic nuclei, transcription is associated with the clustering of RNA Polymerase II (RNAPII) molecules. The mechanisms underlying cluster formation, their interactions with genes, and their impact on transcriptional activity remain heavily debated. Here, we take advantage of the naturally occurring increase in transcriptional activity during Zygotic Genome Activation (ZGA) in Drosophila melanogaster embryos to characterize the functional roles of RNAPII clusters in a developmental context. Using single-molecule tracking and lattice light-sheet microscopy, we find that RNAPII cluster formation depends on transcription initiation and that cluster lifetimes depend on transcriptional activity when not constrained by interphase duration. We show that single clusters are stably associated with active gene loci during transcription and that cluster intensities are strongly correlated with transcriptional output. Collectively, our data and simulations on cluster formation kinetics show that RNAPII clusters reflect local accumulations of transcriptionally engaged polymerases and do not form through higher-order mechanisms such as phase separation.

Community informed recommendations for a campaign to promote awareness of long-acting injectable PrEP among Latino men who have sex with men

Background Across the United Sates, Latino men who have sex with men (LMSM) face disproportionately high HIV risk. Although pre-exposure prophylaxis (PrEP) effectively reduces HIV risk, numerous barriers limit PrEP access among LMSM. Culturally tailored public health campaigns provide one potential strategy for increasing access, awareness, and use of PrEP, including the newest long-acting injectable PrEP (LAI PrEP) formulations. The purpose of the study was to develop community-informed recommendations for a culturally responsive LAI PrEP awareness campaign designed for LMSM. Methods Between June 2023 to March 2024, thirty LMSM participated in four virtual focus groups conducted in Los Angeles, CA. LMSM were recruited through a larger LMSM-centered HIV prevention intervention. In the focus groups, participants shared their perspectives on campaign messaging, imagery, tone, and accessibility. Coding reliability thematic analysis was used to analyze the data. Results Findings suggest that a LAI PrEP campaign for LMSM should: provide basic information about the strategy; highlight its benefits; incorporate humorous and sex-positive messaging or imagery; communicate the seriousness of HIV without stigmatizing, blaming, or scaring LMSM; incorporate important Latine cultural values; and include Latine celebrities, public figures, and everyday individuals as messengers. In addition, there were mixed opinions regarding the use of a syringe in the imagery, with some participants advocating against its use to avoid fear- and pain-based associations with injections. Finally, participants believed that a LAI PrEP campaign should be made accessible to LMSM by providing materials in both English and Spanish and placing physical advertisements in neighborhoods predominately occupied by Latine people. Conclusions Our findings offer several practical recommendations for developing a LAI PrEP awareness campaign for LMSM that can be used by health departments, community-based organizations, and others. Incorporating community insights is crucial to ensure that a campaign resonates with and meets the needs of the LMSM community.

One-step fabrication of superhydrophobic fabrics with stable mechanical performance in harsh conditions

Research on epilepsy detection and recognition based on the combination of time frequency transform and deep learning model

To improve the detection performance of epileptic electroencephalogram (EEG) signals and address their non-stationary characteristics,this paper compares the combined effects of continuous wavelet transform (CWT) and short-time Fourier transform (STFT) with three neural network models—EEGNet,AlexNet,and Shallow ConvNet—and incorporates targeted optimization designs. Specifically,Focal Loss,dynamic data augmentation,and an early stopping mechanism are introduced in the training phase to enhance model robustness. For EEGNet,optimizations are implemented by integrating a Squeeze-and-Excitation (SE) attention module,improving depthwise separable convolution,and dynamically adapting dimensions to reduce classification errors. For Shallow ConvNet,improvements include layered convolution for extracting “time-frequency” features and average pooling to adapt to long-duration data blocks. Experiments are conducted based on subject-independent validation,and the results show that the CWT-based feature extraction method outperforms STFT comprehensively. Among all combinations,the CWT+Shallow ConvNet pair exhibits the optimal overall performance,while the CWT+EEGNet combination follows closely with excellent precision. These findings verify the effectiveness of combining precise time-frequency features (extracted by CWT) with optimized neural network models,providing reliable technical support for clinical epileptic EEG signal detection.

Carbene-catalyzed double esterification enables enantioselective conformational self-locking of pillar[5]arenes

Abstract For their chirality, pillar[5]arenes stand out among the most versatile and widely utilized classes of organic host molecules, with numerous applications in materials science and biomedicine. The chirality of these macrocyclic compounds arises from conformational locking induced by sterically demanding substituents. However, preparing enantioenriched pillar[5]arenes often requires laborious chiral or diastereomeric separations. Here, we describe a simple and efficient metal-free protocol for oxidative double esterification of diformylpillar[5]arenes. This method provides a versatile and operationally straightforward route to highly enantioenriched products with broad functional group tolerance, as shown by incorporating biologically active and naturally derived fragments. Moreover, the reaction is readily scalable and enables subsequent derivatization, yielding rotaxane. Therefore, our organocatalytic method for pillar[5]arene self-locking not only streamlines the asymmetric synthesis of enantioenriched macrocyclic hosts but also opens new avenues for the design of chiral functional materials and host-guest systems.

The importance of structure: Using targeted rewiring to explore social networks property interdependencies

Social networks typically have skewed degree distributions and relatively high clustering and assortativity coefficients. Some studies have explored the relationships between these properties, but have given limited attention to social networks and have found conflicting evidence. To expand our understanding of the ways that properties constrain each other in social networks we use separate degree-preserving rewiring algorithms to manipulate assortativity, clustering coefficient and mean geodesic of networks constructed from seven diverse empirical degree sequences. We measured centrality (mean and Gini coefficient of several measures), clustering, assortativity and network distances. Only a small number of property pairs showed a relationship. Further, where interdependencies do exist, they are conditional and occur only for specific value ranges or a subset of the tested networks.

Phanerozoic seawater Mg/Ca variations driven by supercontinent cycles

A protocol for MIndfulness-based Neurofeedback to augment DBT psychotherapy for adults with Borderline Personality Disorder (MIND-BPD)

Borderline personality disorder (BPD) is a severe psychiatric condition associated with high rates of suicide and poor interpersonal functioning. There are no FDA-approved medications, and evidence-based psychotherapies such as dialectical behavior therapy (DBT) are difficult to access and vulnerable to patient dropout. Novel treatment directions are urgently needed. Mindfulness is the core skill in DBT. Our team has developed a mindfulness-based real-time neurofeedback (mbNF) paradigm where individuals learn to reduce default mode network (DMN) versus control network activation in order to increase present-moment awareness. Here, we describe the study protocol for the MIndfulness-based Neurofeedback to Augment DBT Psychotherapy for Borderline Personality Disorder (MIND-BPD) trial. Participants with BPD (N = 52) enrolled in the study will be randomly assigned (1:1 ratio) to receive one session of either real or sham mbNF. Following neurofeedback, all participants will be enrolled in a 6-month DBT psychotherapy group. Supported by a R61/R33 grant from the NIH, the primary outcome of the R61 phase of this trial is change in DMN connectivity between pre- and post-NF resting-state scans, as defined by increased within-network connectivity between the medial prefrontal cortex (mPFC) and posterior cingulate cortex (PCC), and increased connectivity between the mPFC and dorsolateral prefrontal coftex (dlPFC). Change in self-reported mindfulness between pre- and post-NF is a key secondary outcome. This study is registered in the US Clinical Trials Registry (NCT06446765).

Giant magneto-cubic in-plane Hall effect in a nonmagnetic material

Effectiveness of a pharmacist diabetes coaching program: A propensity-matched retrospective analysis

Background Limited evidence exists on the clinical and cost impact of diabetes coaching programs integrated into care teams. The Diabetes Care Coach (DCC) program is a pharmacist-driven telehealth coaching program for patients with poorly controlled diabetes. Coaches provide frequent telehealth support to improve glycemic control through medication management, nutrition and lifestyle counseling, leveraging diabetes technologies, initiating mental health referrals, and addressing health-related social needs. The objective of this study was to evaluate the effectiveness of the UMass Memorial Health (UMMH) DCC program. Methods and findings A retrospective matched cohort study was conducted with data collected from the UMMH electronic health record and the UMass Memorial Medicare Accountable Care Organization (ACO) claims database from January 2020 to December 2023. The DCC program was implemented at the UMMH diabetes clinic, a specialty care clinic in Worcester, MA, supported by the UMass Specialty Pharmacy program, which is managed by Shields Health Solutions. Participants included patients with persistent severe hyperglycemia (hemoglobin A1c [A1c] ≥ 9) receiving care at the diabetes clinic. Intervention participants (n = 239) enrolled in the DCC program were matched with comparison participants (n = 815) not enrolled in the program during the study period. Intervention and comparison participants who were also enrolled in ACO were considered for cost analyses. Between-group differences in glycemic control (A1c change), health care utilization (emergency department visits and days hospitalized), and cost (total medical expenditures, TME) were evaluated. Intervention participants experienced a greater mean A1c reduction of –0.4 percentage points (95% CI, –1.1 to 0.3) compared with comparison participants. Within the ACO subgroup, intervention participants also had a greater mean reduction in annual TME of $2,649 per patient (95% CI, –$14,425 to $9,127) and a reduction in hospital days per patient per year of –5.2 (95% CI, –9.8 to –0.6) relative to comparison participants. Conclusions The DCC program was associated with directional improvements in clinical, health care utilization, and cost outcomes and was cost-neutral due to savings and associated revenue. With approximately one-third of participants having Medicaid insurance, the sustainability of such programs increases through leveraging the 340B program to enhance care for economically vulnerable patients.

Structural basis of the cyclin Y/14-3-3 protein-mediated activation of CDK16

The dynamic network characteristics of physical, psychological, and cognitive symptoms of people with HIV based on cross-lagged network analysis in China

Introduction This study aims to construct a dynamic network by collecting longitudinal data, which will assist medical professionals in identifying bridging symptoms associated with disease progression and causal mechanisms. Methods A longitudinal observational study was conducted from March to June 2024, recruiting an initial cohort of people with HIV (PWH) from three designated AIDS medical institutions in Beijing, China. Symptom data were collected at two time points, three months apart, using the Chinese version of the Self-Report Symptom Scale (SRSS) alongside a demographic questionnaire. The data were analyzed using cross-lagged panel network analysis to explore symptom dynamics over time. Results A total of 791 PWH were recruited and 706 participants (89.25%) continued to the 3-month follow-up, with a mean age of 38.37 ± 10.03 years. There were no significant differences in demographic variables between those who missed and those who completed the study, except for clinical indices such as CD4 + cell count, ART duration, and comorbidity. Psychological symptoms, such as feeling helpless, feeling uneasy, and feeling fearful, also appear frequently. The most significant association identified was between becoming confusing and having difficulty in reasoning (COGS5 → COGS4, OR = 1.20). Notable bridging symptoms across two distinct domains included becoming confusing, leading to hardly focusing on anything (COGS5 → PSYS2, OR = 1.12), feeling hopeless, leading to rash (PSYS8 → PHYS8, OR = 1.11), and worry overwhelming leading to sleep disturbance (PSYS3 → PHYS6, OR = 1.11), among others. Conclusions There is an urgent need to enhance the assessment and early monitoring of cognitive status for PWH.

Printable Newtonian fluid photocatalysts for scale-up solar CO2 conversion

WaveMamba-YOLO: Combining frequency awareness and state-space modeling for defect localization

Steel surface defect detection is critical for ensuring the reliability and safety of automotive manufacturing. However, existing methods often suffer from high computational cost, weak sensitivity to fine textures, and limited adaptability to diverse defect scales. To address these challenges, we propose WaveMamba-YOLO, a real-time detection framework that integrates frequency-domain enhancement with efficient state-space modeling. The architecture introduces three key modules: (1) CHDWT, which combines Haar wavelet decomposition and residual learning to preserve structural details during downsampling; (2) GLaM, a global-local-aware Mamba module that couples large-kernel convolution with state-space modeling to capture long-range dependencies at linear complexity; and (3) LWGA, a lightweight group attention mechanism that adaptively attends to micro-, regular-, medium-, and large-scale defects. Experiments on the Severstal Steel Defect and NEU-DET datasets demonstrate that WaveMamba-YOLO achieves superior performance, reaching 51.70% mAP@0.5 and 58.60% precision on Severstal and 77.70% mAP@0.5 on NEU-DET, consistently surpassing mainstream lightweight detectors. These results confirm the effectiveness of WaveMamba-YOLO in balancing detection accuracy and efficiency, highlighting its potential for real-time industrial inspection.

Aligned representation of visual and tactile motion directions in hMT+/V5 and fronto-parietal regions

Has the establishment of national parks improved nature-based tourism experiences? Evidence from social media data

National parks are vital institutions for conserving biodiversity and preserving biocultural heritage that safeguard exceptional natural resources and sustain key cultural ecosystem services (CESs), such as aesthetic appreciation, nature-based recreation, and environmental education. However, the essentially subjective and intangible characteristics of CESs are obstacles to effectively collecting data and measuring their diverse values. This study developed a supply–support–demand framework for analyzing nature-based tourism in national parks, using Giant Panda National Park, one of China’s earliest national parks, as the case study site for the years 2009–2023. To investigate the impact of national park establishment, we employed a difference-in-differences (DID) approach to assess its effects on counties within national parks. We found that tactile and visual impressions play a key role in shaping visitors’ experiences, whereas olfactory, gustatory, and auditory perceptions exhibit cooccurring, supportive influences on visual and tactile impressions, as revealed through the rich expressions captured in social interactions. The establishment of national parks has the potential to enhance nature-based tourism experiences by increasing local fiscal expenditure and expanding the tourism industry. The effects exhibit clear regional heterogeneity and differences in policy intensity. At the regional level, Sichuan and Shaanxi, regions with relatively stronger infrastructure and resource endowments, show better improvement in nature-based tourism experiences, whereas Gansu shows an insignificant effect. In terms of policy intensity, stronger interventions are accompanied by stricter ecological protection constraints. As a result, the improvement in nature-based tourism experiences is significantly greater in the low-intensity policy group than in the high-intensity policy group.

Patterns of opioid dose escalation in patients with chronic kidney disease initiated on opioids for the treatment of non-cancer pain

Background Pain management in chronic kidney disease (CKD) is challenging due to altered drug metabolism, impaired excretion, and higher opioid toxicity risk. Despite this, opioids are commonly prescribed, yet real-world data on dose escalation in CKD remain limited. Objective To investigate patterns and timing of opioid dose escalation to ≥50 and ≥90 MME/day among new opioid users across kidney function levels. Methods This population-based cohort study used data from the Stockholm Creatinine Measurements (SCREAM) project linking diagnoses, prescriptions, and laboratory records. Adult new opioid users (no prior opioid in 12 months) from 2012–2021 were categorized by baseline eGFR (≥60, 30–59, < 30 mL/min/1.73m²). Opioids were identified using ATC codes, and daily doses (MME/day) were calculated based on strength, quantity, and equianalgesic ratios. Fine–Gray competing-risks regression assessed time to dose escalation (≥50 and ≥90 MME/day), accounting for death as a competing event. Results Of 81,987 adult new opioid users, 5,987 (7.3%) escalated to ≥50 MME/day comprising 7.4%, 6.8%, and 8.1% of patients with eGFR ≥ 60, 30–59, and <30 mL/min/1.73m², respectively. For ≥90 MME/day, 2,067 (2.5%) escalated, 2.5%, 2.3%, and 2.9% across the same eGFR categories. Competing risks regression showed significantly lower risks of escalation among patients with reduced eGFR levels. For ≥50 MME/day, the sub distribution hazard ratios (SHRs) were 0.67 (95% CI: 0.56–0.81, p  < 0.001) for eGFR 30–59 and 0.64 (95% CI: 0.42–0.99, p   = 0.043) for those with eGFR < 30.For ≥90 MME/day, SHRs were 0.57 (95% CI: 0.43–0.75 , p < 0.001 )and 0.31(95% CI: 0.15–0.65, p = 0.002 ), respectively. Most escalation occurred within six months, with minimal increase thereafter. Conclusion Opioid dose escalation occurred across all eGFR levels, underscoring the need for cautious, individualized prescribing and close monitoring, especially in patients with reduced kidney function.

Isotropic fluid structures and role of non-metricity on their dynamics governed by an electric charge: A theoretical study

This research explores the dynamics of compact stellar objects characterized by the Kohler-Chao-Tikekar and Tolman IV spacetimes under the effects of an electric charge within the framework of f ( Q ) gravity, where Q indicates the non-metricity. We start our analysis with the assumption of a static spherical line element and formulate the field equations corresponding to an isotropic interior fluid setup. We then construct two novel solutions under the two above-mentioned metrics which involve multiple unknown constants. These constants are calculated using junction conditions at the boundary, where we match our interior solutions with the exterior Reissner-Nordström line element. Afterwards, we analyze specific conditions that must be met to ensure the feasibility of compact models in real-world applications. The graphical analysis is performed under a particular star candidate, namely LMC X-4 with several choices of the considered model parameters. Under certain chosen values, our results show that both stellar solutions are in good agreement with the physically existence criterion. In light of the current findings, we deduce that our work significantly advances the understanding of how the interior fluid dynamics of compact stars are influenced by the symmetric teleparallel gravity, offering vital information for further research in astrophysics.

The effect of client-auditor mismatches on earnings management using classification shifting: Evidence from China

Using a sample of Shanghai and Shenzhen A-share listed companies from 2008 to 2022, this study examines the impact of client-auditor mismatch on earnings management using classification shifting. The results indicate that upward mismatches—where clients engage higher-tier auditors than expected—mitigate classification shifting, while downward mismatches amplify it. Further analysis reveals that strong internal control moderates this relationship, constraining earnings management behavior. Additionally, we find that auditor industry expertise partially mediates the relationship between client-auditor mismatch and classification shifting.

Effect of noise and green space exposure on depression, anxiety and stress among the Lebanese population

Background Environmental exposure significantly influences mental well-being. Green spaces offer psychological benefits, while noise exposure is a recognized environmental stressor. However, their effects on mental health outcomes such as depression, anxiety, and stress remain underexplored in Lebanon. This study investigates the influence of green space and noise exposure on mental health in the Lebanese population. Methods A cross-sectional study was conducted using an online survey distributed across the Lebanese population. A total of 653 participants aged 18–65 years completed the questionnaire, which assessed socio-demographics, green space exposure, noise exposure, and mental health using the Arabic versions of the validated scales for depression (PHQ-9), anxiety (GAD-7), and stress (PSS-10). Data was analyzed using SPSS version 25. Results Higher green space exposure—such as proximity to greenery, views of natural environments, and more frequent visits—was significantly associated with lower levels of depression, anxiety, and stress (p < 0.05). Conversely, greater noise exposure at home or work, and symptoms such as sleep disturbance, irritability, or difficulty concentrating due to noise, were significantly associated with higher scores across all three mental health domains (p < 0.001). Multiple linear regression showed that some noise-related symptoms were consistently associated with higher depression, anxiety, and stress. Conclusions Environmental exposures play a critical role in shaping the mental health. Increasing access to green spaces and reducing noise pollution may serve as effective public health interventions to decrease levels of depression, anxiety, and stress among Lebanese residents. Urban planning and public policy should integrate these findings into mental health promotion strategies.