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Construction and validation of a nomogram predictive model for assessing the risk of surgical site infections following posterior lumbar fusion surgery
Rapid and quantitative functional interrogation of human enhancer variant activity in live mice
Abstract Functional analysis of non-coding variants associated with congenital disorders remains challenging due to the lack of efficient in vivo models. Here we introduce dual-enSERT, a robust Cas9-based two-color fluorescent reporter system which enables rapid, quantitative comparison of enhancer allele activities in live mice in less than two weeks. We use this technology to examine and measure the gain- and loss-of-function effects of enhancer variants previously linked to limb polydactyly, autism spectrum disorder, and craniofacial malformation. By combining dual-enSERT with single-cell transcriptomics, we characterise gene expression in cells where the enhancer is normally and ectopically active, revealing candidate pathways that may lead to enhancer misregulation. Finally, we demonstrate the widespread utility of dual-enSERT by testing the effects of fifteen previously uncharacterised rare and common non-coding variants linked to neurodevelopmental disorders. In doing so we identify variants that reproducibly alter the in vivo activity of OTX2 and MIR9-2 brain enhancers, implicating them in autism. Dual-enSERT thus allows researchers to go from identifying candidate enhancer variants to analysis of comparative enhancer activity in live embryos in under two weeks.
Knockout or inhibition of DHPS suppresses ovarian tumor growth and metastasis by attenuating the TGFβ pathway
Tracing ancient solar cycles with tree rings and radiocarbon in the first millennium BCE
AbstractThe Sun drives Earth’s energy systems, influencing weather, ocean currents, and agricultural productivity. Understanding solar variability is critical, but direct observations are limited to 400 years of sunspot records. To extend this timeline, cosmic ray-produced radionuclides like 14C in tree-rings provide invaluable insights. However, few records have the resolution or temporal span required to thoroughly investigate important short-term solar phenomena, such as the 11-year solar cycle, or 14C production spikes most likely linked to solar energetic particle (SEP) events. Here we present a continuous, annually resolved atmospheric 14C record from tree-rings spanning the first millennium BCE, confirming no new SEP’s and clearly defining the 11-year solar cycle, with a mean period of 10.5 years, and amplitude of approximately 0.4‰ in 14C concentration. This dataset offers unprecedented detail on solar behavior over long timescales, providing insights for climatic research and solar hazard mitigation, while also offering enhanced radiocarbon calibration and dating accuracy.
Nanotechnology and LSTM machine learning algorithms in advanced fuel spray dynamics in CI engines with different bowl geometries
Factors governing $${\rm H}_{3}^{+}$$ formation from methyl halogens and pseudohalogens
Seepage mode in lamina-developed shale oil reservoirs under strong heterogeneous and strong fluid–solid coupling in Jiyang depression of China
Author Correction: Thermophilic Hadarchaeota grow on long-chain alkanes in syntrophy with methanogens
Associations of time spent on different types of digital media with self-rated general and mental health in Swedish adolescents
AbstractAlthough previous studies have suggested an association between digital media use and health, detailed knowledge about how different types of digital media impact adolescent health is limited. This cross-sectional population-based study explored the relationship between time spent on various digital media and adolescents’ self-rated general and mental health. The study included 3566 Swedish high school students aged 16–17 years. Associations between time spent on digital media (social media, gaming, watching movies/series/video clips etc. and digital schoolwork) and self-rated health outcomes (general health, self-esteem, symptoms of worry/anxiety and low mood/depression, trust in other people, head/neck/shoulder pain and sleep quality) was assessed. Statistical analyses employed logistic regression models adjusted for covariates (sociodemographic variables and health behaviours). In the adjusted models, spending very high amounts of time (≥ 6 h/day) on any digital media, except schoolwork, was associated with poor self-esteem, symptoms of low mood/depression and poor sleep (ORs 1.35–2.93, p < 0.05). Spending six hours or more on digital media was also associated with worry/anxiety (for social media and gaming), head/neck/shoulder pain (for social media, watching movies/series/video clips and schoolwork), poor general health (for gaming and watching movies/series/video clips) and low trust (for gaming) (ORs 1.39–3.18, p < 0.05). High amounts of time (4–5 h/day) of watching movies/series/video clips was associated with daily symptoms of low mood/depression, neck/shoulder pain, and low trust in other people (ORs 1.46, 1.41, and 1.32, p < 0.05). This study indicates a dose-response relationship between digital media use and adverse health outcomes in adolescents, where adverse associations start to appear after 4–5 h, particularly for watching movies/series/video clips. However, further longitudinal studies, randomized controlled trials and public health interventions focused on healthy and balanced use of digital media are warranted.
Hierarchical representations of relative numerical magnitudes in the human frontoparietal cortex
Study on performance of perforated dew point indirect evaporative coolers
Elastic, strong and tough ionically conductive elastomers
Research on the acoustic emission characteristics and instability correlation effect of the dynamic response of waste dump slopes
Spatial tumor immune heterogeneity facilitates subtype co-existence and therapy response in pancreatic cancer
AbstractPancreatic ductal adenocarcinoma (PDAC) displays a high degree of spatial subtype heterogeneity and co-existence, linked to a diverse microenvironment and worse clinical outcome. However, the underlying mechanisms remain unclear. Here, by combining preclinical models, multi-center clinical, transcriptomic, proteomic, and patient bioimaging data, we identify an interplay between neoplastic intrinsic AP1 transcription factor dichotomy and extrinsic macrophages driving subtype co-existence and an immunosuppressive microenvironment. ATAC-, ChIP-, and RNA-seq analyses reveal that JUNB/AP1- and HDAC-mediated epigenetic programs repress pro-inflammatory signatures in tumor cells, antagonizing cJUN/AP1 signaling, favoring a therapy-responsive classical neoplastic state. This dichotomous regulation is amplified via regional TNF-α+ macrophages, which associates with a reactive phenotype and reduced CD8+ T cell infiltration in patients. Consequently, combined preclinical anti-TNF-α immunotherapy and chemotherapy reduces macrophages and promotes CD3+/CD8+ T cell infiltration in basal-like PDAC, improving survival. Hence, tumor cell-intrinsic epigenetic programs, together with extrinsic microenvironmental cues, facilitate intratumoral subtype heterogeneity and disease progression.