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Abstract Background Multiple studies have shown that tumor-associated macrophages (TAMs) promote cancer initiation and progression. However, the reprogramming of macrophages in the tumor microenvironment (TME) and the cross-talk between TAMs and malignant subclones in intrahepatic cholangiocarcinoma (iCCA) has not been fully characterized, especially in a spatially resolved manner. Deciphering the spatial architecture of variable tissue cellular components in iCCA could contribute to the positional context of gene expression containing information pathological changes and cellular variability. Methods Here, we applied spatial transcriptomics (ST) and digital spatial profiler (DSP) technologies with tumor sections from patients with iCCA. Results The results reveal that spatial inter- and intra-tumor heterogeneities feature iCCA malignancy, and tumor subclones are mainly driven by physical proximity. Tumor cells with TME components shaped the intra-sectional heterogenetic spatial architecture. Macrophages are the most infiltrated TME component in iCCA. The protein trefoil factor 3 (TFF3) secreted by the malignant subclone can induce macrophages to reprogram to a tumor-promoting state, which in turn contributes to an immune-suppressive environment and boosts tumor progression. Conclusions In conclusion, our description of the iCCA ecosystem in a spatially resolved manner provides novel insights into the spatial features and the immune suppressive landscapes of TME for iCCA.

Abstract METTL3 is the catalytic subunit of the methyltransferase complex, which mediates m6A modification to regulate gene expression. In addition, METTL3 regulates transcription in an enzymatic activity-independent manner by driving changes in high-order chromatin structure. However, how these functions of the methyltransferase complex are coordinated remains unknown. Here we show that the methyltransferase complex coordinates its enzymatic activity-dependent and independent functions to regulate cellular senescence, a state of stable cell growth arrest. Specifically, METTL3-mediated chromatin loops induce Hexokinase 2 expression through the three-dimensional chromatin organization during senescence. Elevated Hexokinase 2 expression subsequently promotes liquid-liquid phase separation, manifesting as stress granule phase separation, by driving metabolic reprogramming. This correlates with an impairment of translation of cell-cycle related mRNAs harboring polymethylated m6A sites. In summary, our results report a coordination of m6A-dependent and -independent function of the methyltransferase complex in regulating senescence through phase separation driven by metabolic reprogramming.

The digital correlator is one of the most crucial data processing components of a radio telescope array. With the scale of radio interferometeric array growing, many efforts have been devoted to developing a cost-effective and scalable correlator in the field of radio astronomy. In this paper, a 192-input digital correlator with six CASPER ROACH2 boards and seven GPU servers has been deployed as the digital signal processing system for Tianlai cylinder pathfinder located in Hongliuxia observatory. The correlator consists of 192 input signals (96 dual-polarization), 125-MHz bandwidth, and full-Stokes output. The correlator inherits the advantages of the CASPER system, for example, low cost, high performance, modular scalability, and a heterogeneous computing architecture. With a rapidly deployable ROACH2 digital sampling system, a commercially expandable 10 Gigabit switching network system, and a flexible upgradable GPU computing system, the correlator forms a low-cost and easily-upgradable system, poised to support scalable large-scale interferometeric array in the future.

Microinjection molding (μIM) is an important technique to fabricate microparts for applications in the fields of automotive and microelectromechanical systems. However, the prevailing high shear conditions in μIM are unfavorable for constructing intact electrically conductive networks because the added fillers tend to be preferentially aligned along the melt flow direction. In this work, a series of polypropylene/polyamide 6/carbon black (PP/PA6/CB) composites with a selective localization of CB in the PA6 phase were used as the model system to prepare electrically conductive microparts. The prevailing high shearing and extensional flow effects in μIM were utilized to deform CB-rich phase with an aim to in situ construct electrically conductive network, thereby improving the electrical conductivity (σ) of subsequent moldings. The results indicated that a higher σ was achieved for PP/PA6/CB microparts when compared with their PP/CB and PA6/CB counterparts, at a lower filler content (

AbstractObjective As women approach perimenopause, the incidence of Subjective Cognitive Decline (SCD) rises. This study aims to investigate the association between SCD and the severity of perimenopausal symptoms.Setting Conducted at The Affiliated Hospital of Guizhou Medical University Menopause Clinic from November 2022 to June 2023. Participants, aged 40-55 years, were classified as perimenopausal using the STRAW + 10 criteria.Methods SCD was assessed separately using the Chinese version of the SCD-Q9 scale and the SCD International Working Group (SCD-I) conceptual framework, while perimenopausal symptoms were evaluated with the Modified Kupperman Index (MKI). Linear relationships between MKI scores and SCD-Q9 scores were clarified using both univariate and multivariate linear regression analyses. Additionally, a multivariate Logistic regression analysis was conducted to examine the association between MKI scores and SCD classification based on SCD-I criteria.Main Outcome Measures The primary outcomes were the Modified Kupperman Index scores, SCD-Q9 questionnaire scores, and the diagnosis of SCD based on SCD-I criteria.Results Among 101 participants, the average MKI score was 18.90 ± 9.74, and the average SCD-Q9 score was 4.57 ± 2.29. Both univariate and multivariate linear regressions demonstrated a positive correlation between these scores. A multivariate Logistic regression analysis, using MKI as the independent variable and SCD-I criteria classification as the dependent variable, revealed a significant positive association.Conclusions A notable association exists between SCD and perimenopausal symptoms severity. This underscores the potential clinical importance of addressing perimenopausal symptoms to mitigate SCD risks in women. Further studies should focus on clarifying the causality between these factors.

Background: Perimenopausal syndrome (PMS) significantly impacts the quality of life in women during the perimenopausal phase. Despite being the primary treatment, hormone replacement therapy has notable limitations. Consequently, dietary interventions, particularly low-fat diets, have garnered international attention as an alternative. Methods: The prospective Randomized Controlled Trial (RCT), approved by the Ethics Committee of the Affiliated Hospital of Guizhou Medical University, enrolled 62 perimenopausal women. Participants were divided into two groups: a low-fat diet group and a menopausal hormone therapy (MHT) group, with interventions lasting eight weeks. Both groups underwent assessments for perimenopausal symptoms, lipid profile, and oxidative stress markers, including superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS), before and after the interventions. Additionally, DNA methylation levels of the PDE4C and NPAS2 genes were measured in 10 women from the low-fat diet group before and after the intervention. Results: Both the low-fat diet and hormone supplementation improved specific perimenopausal symptoms, reduced specific lipid levels, and had a positive effect on oxidative stress markers. The low-fat diet proved more effective than hormone replacement in improving the serum lipid profile and also resulted in reductions in methylation at specific sites of the PDE4C and NPAS2 genes. Conclusions: A low-fat diet may alleviate perimenopausal symptoms, lower lipid levels, and alter gene methylation sites. Clinical Trial Registration: The study has been registered on https://www.chictr.org.cn/ (registration number: ChiCTR2400084007).