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Metabolites from intestinal microbes modulate the mucosal immune system by regulating the polarization and expansion of T cells. Whether the microbial metabolites influence macrophage polarization, however, is poorly understood. Here, we show that the large bowel microbial fermentation product, butyrate, facilitates M2 macrophage polarization, in vitro and in vivo . The supernatant from butyrate-treated M2 macrophage increased the migration and enhanced the wound closure rate of MLE-12 cells. Butyrate attenuated intestinal inflammation in mice with dextran sulfate sodium (DSS)-induced colitis, with a significant increase in colonic expression of the M2 macrophage-associated protein, Arg1. M2 macrophage treated with butyrate, had increased activation of the H3K9/STAT6 signaling pathway, suggesting a mechanism for butyrate facilitated M2 macrophage polarization. Collectively, our study indicated that commensal microbe-derived butyrate is a novel activator of STAT6-mediated transcription through H3K9 acetylation driving M2 macrophage polarization and delineated new insights into the immune interplay underlying inflammatory bowel disease.

Numerous studies indicated that tumor-infiltrated immune cells (TIC) in the microenvironment are substantially linked to immunotherapy response and cancer prognosis. However, systematic studies of infiltrated immune cell characterization in uveal melanoma (UM) for prognosis and immune checkpoint blockade therapy are lacking. UM datasets were extracted from open access resources (TCGA and GEO databases). The tumor-infiltrated immune cells in the microenvironment were decoded by using the CIBERSORT algorithm, which was further applied to classify UM patients into subgroups using an unsupervised clustering method. The Boruta algorithm and principal component analysis were used to calculate the TIC scores for UM patients. Kaplan-Meier curves were plotted to prove the prognostic value of TIC scores. Besides, the correlations of the TIC score with clinical features, mutated characteristics, and the immune therapeutic response were subsequently investigated. As a result, we defined three subtypes among 171 UM patients according to the TIC profiles and then calculated the TIC score to characterize the immune patterns for all patients. We discovered that high-TIC score patients with low BAP1 and high EIF1AX mutations have a better prognosis than low-TIC score patients. Activation of immune inflammatory response and increase in immune checkpoint-related genes in high-TIC score patients may account for good prognosis and immunotherapy response. Three melanoma cohorts received immunotherapy, proving that high-TIC score patients have substantial clinical and immune therapeutic improvements. Besides, several potential therapeutic agents were identified in the low-TIC score group. Our study afforded a comprehensive view of infiltrated immune cell characterization to elucidate different immune patterns of UM. We also established a robust TIC-score signature, which may work as a prognostic biomarker and immune therapeutic predictor.

As one of the important carriers of Tibetan ethnic minority culture inheritance on the Qinghai–Tibet Plateau, the basic properties and fiber morphology of grass paper from Stellera chamaejasme have a significant impact on its paper quality. The basic properties of grass paper from Stellera chamaejasme from six different production areas on the Qinghai–Tibet Plateau were systematically tested and analyzed according to relevant national standards, and the fiber morphology characteristics were experimentally observed. The results showed that the grammage, thickness, density, bulk, brightness, gloss, folding resistance, and tensile strength performance indicators of grass paper from Stellera chamaejasme on the Qinghai–Tibet Plateau were generally good; the basic properties of grass paper from Stellera chamaejasme in different origins vary to some extent; and the fibers of grass paper from Stellera chamaejasme are mostly yellow in color, with slender fibers and small, uneven widths. The ends of the fibers are sharp, and the fibers are arranged in a staggered manner. There is a phenomenon of fiber aggregation, showing a clear flat band structure with a clear mesh structure. The surface has many rough horizontal knots, visible cell cavities, mixed cells, and obvious longitudinal wavy folds. Therefore, the basic performance of grass paper from Stellera chamaejasme is excellent, which is consistent with the historical description of the excellent quality of Tibetan paper, and is closely related to its fiber morphology characteristics.

Ultrasound is gaining traction as a neuromodulation method due to its ability to remotely and non-invasively modulate neuronal activity with millimeter precision. However, there is little consensus about optimal ultrasound parameters required to elicit neuromodulation and how specific parameters drive mechanisms that underlie ultrasound neuromodulation. We address these questions in this work by performing a study to determine effective ultrasound parameters in a transgenic mouse brain slice model that enables calcium imaging as a quantitative readout of neuronal activity for ultrasound neuromodulation. We report that (1) calcium signaling increases with the application of ultrasound; (2) the neuronal response rate to ultrasound is dependent on pulse repetition frequency (PRF); and (3) ultrasound can reversibly alter the inhibitory effects of tetrodotoxin (TTX) in pharmacological studies. This study offers mechanistic insight into the PRF dependence of ultrasound neuromodulation and the nature of ultrasound/ion channel interaction.

(1) Background: The provision of monofunctional or inadequately distributed services in urban park green spaces often constrains residents’ opportunities and diversity for outdoor activities, particularly limiting access and participation for specific age groups or activity preferences. However, functional nodes with temporal and spatial flexibility demonstrate high-quality characteristics of resilient and shared services through integrated development. Accurately identifying user demand provides a solid basis for optimizing the functional configuration of urban parks. (2) Methods: This study took the old city area of Zhengzhou, Henan Province, China, as a case study. By collecting and integrating various types of data, such as geographic spatial data, field investigation data, and behavioral observations, we developed a population demand quantification method and a modular analysis approach for park service functions. This framework enabled correlation analysis between diverse user needs and park services. The study further classified and combined park functions into modular units, quantifying their elastic and shared service capabilities—namely, the adaptive flexibility and shared utilization capacity of park services. Additionally, we established a demand-responsive evaluation system for identifying and diagnosing problem areas in park services based on multi-source data. (3) Results: The demand response index and diagnostic results indicate that the supply of fitness facilities—particularly equipment-based installations—is insufficient within the old urban district of Zhengzhou. Among the three user groups—children, young and middle-aged adults, and the elderly—the elderly population exhibited the lowest demand response index, revealing a significant gap in meeting their specific needs. (4) Conclusions: Based on the research findings, a three-tier optimization strategy is proposed: A. improve green space connectivity to expand the service coverage of parks; B. implement multifunctional overlay and coordinated integration in spatial design based on site characteristics and demand diagnostics; and C. increase the total supply of facilities to enhance spatial efficiency in parks. By integrating the demand assessment data and diagnostic results, this approach enabled a data-driven reorganization of service types and targeted allocation of resources within existing park infrastructure, offering a practical tool and reference for the planning of urban outdoor activity spaces.

The neocortex consists of a vast number of diverse neurons that form distinct layers and intricate circuits at the single-cell resolution to support complex brain functions 1 . Diverse cell-surface molecules are thought to be key for defining neuronal identity, and they mediate interneuronal interactions for structural and functional organization 2 – 6 . However, the precise mechanisms that control the fine neuronal organization of the neocortex remain largely unclear. Here, by integrating in-depth single-cell RNA-sequencing analysis, progenitor lineage labelling and mosaic functional analysis, we report that the diverse yet patterned expression of clustered protocadherins (cPCDHs)—the largest subgroup of the cadherin superfamily of cell-adhesion molecules 7 —regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex. The expression of  cPcdh genes in individual neocortical excitatory neurons is diverse yet exhibits distinct composition patterns linked to their developmental origin and spatial positioning. A reduction in functional cPCDH expression causes a lateral clustering of clonally related excitatory neurons originating from the same neural progenitor and a significant increase in synaptic connectivity. By contrast, overexpression of a single cPCDH isoform leads to a lateral dispersion of clonally related excitatory neurons and a considerable decrease in synaptic connectivity. These results suggest that patterned cPCDH expression biases fine spatial and functional organization of individual neocortical excitatory neurons in the mammalian brain. The diverse yet patterned expression of clustered protocadherins regulates the precise spatial arrangement and synaptic connectivity of excitatory neurons in the mouse neocortex.

Cerebral cortex expansion is a hallmark of mammalian brain evolution; yet, how increased neurogenesis is coordinated with structural and functional development remains largely unclear. The T-box protein TBR2/EOMES is preferentially enriched in intermediate progenitors and supports cortical neurogenesis expansion. Here we show that TBR2 regulates fine-scale spatial and circuit organization of excitatory neurons in addition to enhancing neurogenesis in the mouse cortex. TBR2 removal leads to a significant reduction in neuronal, but not glial, output of individual radial glial progenitors as revealed by mosaic analysis with double markers. Moreover, in the absence of TBR2, clonally related excitatory neurons become more laterally dispersed and their preferential synapse development is impaired. Interestingly, TBR2 directly regulates the expression of Protocadherin 19 (PCDH19), and simultaneous PCDH19 expression rescues neurogenesis and neuronal organization defects caused by TBR2 removal. Together, these results suggest that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly via PCDH19 in the mammalian cortex. The T-box protein TBR2 is involved in cortical neurogenesis expansion during neurodevelopment and is preferentially enriched in intermediate progenitors. The authors show that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly in the mouse cortex via PCDH19.

Background Efforts to predict the outcomes of patients with gastric cancer (GC) following immune checkpoint inhibitor (ICI) treatments remain limited, owing to a lack of reliable biomarkers. Studies have found that extracellular vesicle (EV)-derived lncRNA-GC1 may serve as a GC-specific biomarker. This study was designed to expand on these previous results by estimating the usefulness of EV-derived lncRNA-GC1 as a predictive indicator for patients with GC who undergo ICI treatments. Methods EV-derived lncRNA-GC1 levels were measured using real-time polymerase chain reaction (RT-PCR) in patients with unresectable or metastatic GC who were receiving ICI treatments. Correlations between this biomarker and ICI treatment outcomes were analyzed in a training cohort ( n  = 136), two external validation cohorts ( n  = 188 and n  = 214), one expanding cohort ( n  = 30), and one prospective cohort ( n  = 192). Results Circulating EVs exhibited a lncRNA-GC1 expression profile that was distinct from that of tissues or circulating cells. EV-derived lncRNA-GC1 levels were found to be independent of PD-L1 expression status or the density of CD8 + T cell infiltration. EV-derived lncRNA-GC1 could be used to effectively predict ICI-related patient outcomes, and could be used for dynamic monitoring throughout treatments. Lower levels of EV-derived lncRNA-GC1 were associated with tumor microenvironmental characteristics such as more robust antitumor immunity—including higher levels of activated CD8 + T/NK cells and an increased TH1/TH2 ratio. Such biomarkers can be stably detected in clinical practice. These results were consistent in both the two external validation cohorts and the one prospective cohort. Conclusions EV-derived lncRNA-GC1 can be used to reliably predict immunotherapeutic outcomes in patients with GC who undergo ICI treatments, suggesting that targeted analyses of this lncRNA may be useful for guiding treatment planning, monitoring, and associated decision-making processes.

This study addresses the challenge of variable selection in partially linear additive spatial autoregressive models through a novel approach that leverages orthogonal projection based on the QR decomposition technique. This method ensures the validity and compatibility of examining the influence of e-commerce on rural high-quality development while minimizing bias in spatial spillover benefits analysis. By constructing a comprehensive evaluation index system, the research applies a partially linear weighted spatial autoregressive model with orthogonal projection to assess e-commerce’s impact on rural development. Analysis of baseline regression for selected villages, supplemented by heterogeneity tests, threshold effects, and spatial analyses, reveals a significant relationship: a one-unit increase in e-commerce activity corresponds to a 0.0038 unit increase in high-quality rural development. This growth comprises both a direct effect of 0.0011 units and a spillover effect of 0.0027 units, highlighting e-commerce’s pivotal role in promoting rural prosperity and its beneficial spillover to adjacent areas.

The rural revitalization strategy is underway and can provide the promotion of high-quality growing rural e-commerce as well as supply the facilities and industrial support required for its growth. The complete score of the rural e-commerce development level was assessed using the entropy value technique by analyzing data from 31 Chinese provinces, municipalities, and autonomous regions. The efficiency of rural e-commerce growth was evaluated using the BCC model and the super-efficient DEA model within the DEA model. The study examined the effects of rural revival on the effectiveness of electronic commerce in rural development. Both input and output views were considered when selecting the related factors. After that, the productivity value was examined by merging information on the growth of rural e-commerce between 2016 and 2020. The research indicates that between 2015 and 2022, the comprehensive score of rural e-commerce growth experienced a high-quality increase of 173.50%. Furthermore, 8 out of 31 provinces, municipalities, and autonomous areas had DEA-achieved e-commerce development efficiency, with a mean complete efficiency score of 0.700. However, the mean value of total efficiency decreased by 35.29% when the progress level of rural rejuvenation was eliminated. Apart from providing support for infrastructure construction, rural revitalization can also provide policy assurances and an industrial base for the expansion of rural electronic commerce.