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  1. Abstract

    IRF family genes have been shown to be crucial in tumorigenesis and tumour immunity. However, information about the role of IRF in the systematic assessment of pan‐cancer and in predicting the efficacy of tumour therapy is still unknown. In this work, we performed a systematic analysis of IRF family genes in 33 tumour samples, including expression profiles, genomics and clinical characteristics. We then applied Single‐Sample Gene‐Set Enrichment Analysis (ssGSEA) to calculate IRF‐scores and analysed the impact of IRF‐scores on tumour progression, immune infiltration and treatment efficacy. Our results showed that genomic alterations, including SNPs, CNVs and DNA methylation, can lead to dysregulation of IRFs expression in tumours and participate in regulating multiple tumorigenesis. IRF‐score expression differed significantly between 12 normal and tumour samples and the impact on tumour prognosis and immune infiltration depended on tumour type. IRF expression was correlated to drug sensitivity and to the expression of immune checkpoints and immune cell infiltration, suggesting that dysregulation of IRF family expression may be a critical factor affecting tumour drug response. Our study comprehensively characterizes the genomic and clinical profile of IRFs in pan‐cancer and highlights their reliability and potential value as predictive markers of oncology drug efficacy. This may provide new ideas for future personalized oncology treatment.

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  2. Abstract

    While most models agree that the Atlantic meridional overturning circulation (AMOC) becomes weaker under greenhouse gas emission and is likely to weaken over the twenty-first century, they disagree on the projected magnitudes of AMOC weakening. In this work, CMIP6 models with stronger climatological AMOC are shown to project stronger AMOC weakening in both 1% ramping CO2and abrupt CO2quadrupling simulations. A physical interpretation of this result is developed. For models with stronger mean state AMOC, stratification in the upper Labrador Sea is weaker, allowing for stronger mixing of the surface buoyancy flux. In response to CO2increase, surface warming is mixed to the deeper Labrador Sea in models with stronger upper-ocean mixing. This subsurface warming and corresponding density decrease drives AMOC weakening through advection from the Labrador Sea to the subtropics via the deep western boundary current. Time series analysis shows that most CMIP6 models agree that the decrease in subsurface Labrador Sea density leads AMOC weakening in the subtropics by several years. Also, idealized experiments conducted in an ocean-only model show that the subsurface warming over 500–1500 m in the Labrador Sea leads to stronger AMOC weakening several years later, while the warming that is too shallow (<500 m) or too deep (>1500 m) in the Labrador Sea causes little AMOC weakening. These results suggest that a better representation of mean state AMOC is necessary for narrowing the intermodel uncertainty of AMOC weakening to greenhouse gas emission and its corresponding impacts on future warming projections.

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  3. Abstract

    The concentration of dopamine (DA) and tyrosine (Tyr) reflects the condition of patients with Parkinson's disease, whereas moderate paracetamol (PA) can help relieve their pain. Therefore, real‐time measurements of these bioanalytes have important clinical implications for patients with Parkinson's disease. However, previous sensors suffer from either limited sensitivity or complex fabrication and integration processes. This work introduces a simple and cost‐effective method to prepare high‐quality, flexible titanium dioxide (TiO2) thin films with highly reactive (001)‐facets. The as‐fabricated TiO2film supported by a carbon cloth electrode (i.e., TiO2–CC) allows excellent electrochemical specificity and sensitivity to DA (1.390 µA µM−1 cm−2), Tyr (0.126 µA µM−1 cm−2), and PA (0.0841 µA µM−1 cm−2). More importantly, accurate DA concentration in varied pH conditions can be obtained by decoupling them within a single differential pulse voltammetry measurement without additional sensing units. The TiO2–CC electrochemical sensor can be integrated into a smart diaper to detect the trace amount of DA or an integrated skin‐interfaced patch with microfluidic sampling and wireless transmission units for real‐time detection of the sweat Try and PA concentration. The wearable sensor based on TiO2–CC prepared by facile manufacturing methods holds great potential in the daily health monitoring and care of patients with neurological disorders.

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  4. Huber, Julie A. (Ed.)
    ABSTRACT Wind-driven upwelling followed by relaxation results in cycles of cold nutrient-rich water fueling intense phytoplankton blooms followed by nutrient depletion, bloom decline, and sinking of cells. Surviving cells at depth can then be vertically transported back to the surface with upwelled waters to seed another bloom. As a result of these cycles, phytoplankton communities in upwelling regions are transported through a wide range of light and nutrient conditions. Diatoms appear to be well suited for these cycles, but their responses to them remain understudied. To investigate the bases for diatoms’ ecological success in upwelling environments, we employed laboratory simulations of a complete upwelling cycle with a common diatom, Chaetoceros decipiens , and coccolithophore, Emiliania huxleyi . We show that while both organisms exhibited physiological and transcriptomic plasticity, the diatom displayed a distinct response enabling it to rapidly shift-up growth rates and nitrate assimilation when returned to light and available nutrients following dark nutrient-deplete conditions. As observed in natural diatom communities, C. decipiens highly expresses before upwelling, or frontloads, key transcriptional and nitrate assimilation genes, coordinating its rapid response to upwelling conditions. Low-iron simulations showed that C. decipiens is capable of maintaining this response when iron is limiting to growth, whereas E. huxleyi is not. Differential expression between iron treatments further revealed specific genes used by each organism under low iron availability. Overall, these results highlight the responses of two dominant phytoplankton groups to upwelling cycles, providing insight into the mechanisms fueling diatom blooms during upwelling events. IMPORTANCE Coastal upwelling regions are among the most biologically productive ecosystems. During upwelling events, nutrient-rich water is delivered from depth resulting in intense phytoplankton blooms typically dominated by diatoms. Along with nutrients, phytoplankton may also be transported from depth to seed these blooms then return to depth as upwelling subsides creating a cycle with varied conditions. To investigate diatoms’ success in upwelling regions, we compare the responses of a common diatom and coccolithophore throughout simulated upwelling cycles under iron-replete and iron-limiting conditions. The diatom exhibited a distinct rapid response to upwelling irrespective of iron status, whereas the coccolithophore’s response was either delayed or suppressed depending on iron availability. Concurrently, the diatom highly expresses, or frontloads, nitrate assimilation genes prior to upwelling, potentially enabling this rapid response. These results provide insight into the molecular mechanisms underlying diatom blooms and ecological success in upwelling regions. 
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  5. null (Ed.)