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Neutrophils are significant compositions of solid tumors and exert distinct functions in different types of tumors. However, the precise role of neutrophils in the progression of breast cancer (BC) is presently unclear. In this study, by investigating the single-cell RNA sequencing data, we identify a new neutrophil subset, C5aR1-positive neutrophils, that correlates with tumor progression and poor survival for BC patients. Furthermore, it is discovered that C5aR1-positive neutrophils enhance BC cell glycolysis via upregulating ENO1 expression. Mechanically, C5aR1-positive neutrophil-secreted IL1β and TNFα cooperatively activate ERK1/2 signaling, which phosphorylates WTAP at serine341 and thereby stabilizes WTAP protein. The stabilization of WTAP further promotes RNA m6A methylation of ENO1, impacting the glycolytic activity of BC cells. Importantly, C5aR1-positive neutrophils also promote breast cancer growth in vivo, and this effect is abolished by WTAP silencing. In clinical BC samples, increased C5aR1-positive neutrophils correlate with elevated IL1β, TNFα, and ENO1 expression. A high co-expression of C5aR1-positive neutrophil gene signature and ENO1 predicts worse prognosis of BC patients compared with a low co-expression. Collectively, our study reveals a novel subset of C5aR1-positive neutrophils that induces breast cancer glycolysis via increasing ERK1/2-WTAP-dependent m6A methylation of ENO1. These findings support the potential for exploration of C5aR1-positive neutrophils as a therapeutic target in breast cancer.

Cellular senescence is characterized by a tumor-suppressive program as well as a pro-inflammatory secretome. Neutrophils constitute significant compositions of malignancies and play key roles in tumor development. However, the role of senescent neutrophils in cancer progression is presently unexplored. Here, we demonstrate that neutrophils display enhanced senescence in breast cancer patients receiving chemotherapy. The senescent neutrophils produce increased number of exosomes, which confer drug resistance to tumor cells in vitro and in vivo. Mechanistically, senescent neutrophils-derived exosomal piRNA-17560 enhances the expression of fat mass and obesity-associated protein (FTO) in breast cancer cells. The upregulation of FTO further strengthens ZEB1 transcripts stability and expression by decreasing N6-methyladenosine (m6A) RNA methylation, leading to chemoresistance and epithelial-mesenchymal transition (EMT) of tumor cells. Clinically, the level of exosomal piR-17560 correlates with poor chemotherapy response in patients with breast cancer. In addition, YTHDF2 is essential for the posttranscriptional regulation of ZEB1 by piRNA-17560/FTO signaling. Senescent neutrophils secret exosomal piR-17560 in a STAT3-dependent manner. Altogether, this study suggests that senescent neutrophils-derived exosomal piR-17560 confers chemoresistance to tumor cells and senescent neutrophils may serve as a potential therapeutic target in breast cancer.

The relationship between the individual and the collective is one of the most important topics in Confucianism. Though this concept has been widely studied, ming 名 (meaning ‘name’), one of its most crucial categories, has not yet been deeply explored within this theoretical domain. This article discusses four aspects of ming and their contributions to the relationship between the self and community. Firstly, Confucius’ proposition of zhengming 正名 (rectifying names or the rectification of names) implies that language, especially that of rulers or gentlemen 君子 (junzi), has a considerable impact on both ethical and political practices. In this sense, ming as language establishes a relationship between rulers and the communities they govern. Secondly, in Confucius’ use of ming, reputation also reflects the attributes of a collectivity. On one hand, reputation functions as a social evaluation system; on the other, it can also be used to shape social values. Both aspects of language and reputation can be found in Confucius’ sayings, and are essentially determined by the sound attributes of ming. Thirdly, ming is interpreted to mean “role” in the later explanations and commentaries of Analects 13.3, which signifies that each individual has their own role in the community to which they belong. The position of a social individual is determined according to their relationship with others. Simultaneously, it is also the idea of “role” that brings a hierarchical order to family, state, clan, and “all under heaven”. Finally, the relationship between ming and yi 義 (appropriateness) implies the correlation between a name and the subject to which it refers. For ethical or political participants, yi means that the name-bearer is bound to a series of demands regarding their behaviors and virtues, which can lead to a “thick” conception of the subject, that is, the role of a complex of virtues, duties, and even rights (albeit implicit). Although the meaning of ming was becoming more complicated and profound during the development of early Confucianism, it has always functioned as the bond between individual and community. In this regard, the Confucian theory of ming can contribute some insights toward the combination of Confucianism and communitarianism, and also toward the modernization of Confucianism.

Automating retrosynthesis with artificial intelligence expedites organic chemistry research in digital laboratories. However, most existing deep-learning approaches are hard to explain, like a “black box” with few insights. Here, we propose RetroExplainer, formulizing the retrosynthesis task into a molecular assembly process, containing several retrosynthetic actions guided by deep learning. To guarantee a robust performance of our model, we propose three units: a multi-sense and multi-scale Graph Transformer, structure-aware contrastive learning, and dynamic adaptive multi-task learning. The results on 12 large-scale benchmark datasets demonstrate the effectiveness of RetroExplainer, which outperforms the state-of-the-art single-step retrosynthesis approaches. In addition, the molecular assembly process renders our model with good interpretability, allowing for transparent decision-making and quantitative attribution. When extended to multi-step retrosynthesis planning, RetroExplainer has identified 101 pathways, in which 86.9% of the single reactions correspond to those already reported in the literature. As a result, RetroExplainer is expected to offer valuable insights for reliable, high-throughput, and high-quality organic synthesis in drug development. Automating retrosynthesis prediction in organic chemistry is a major application of ML. Here the authors present RetroExplainer, which offers a high-performance, transparent and interpretable deep-learning framework providing valuable insights for drug development.

Amid the intensifying challenges of climate change and human activities such as shifts in agricultural practices, the pressure on water resources, particularly regarding water quality, has intensified. As a result, improving water quality monitoring and prediction has emerged as an essential strategy to tackle these challenges and ensure the sustainable management of water resources. Traditional water quality monitoring technologies have inherent limitations; however, integrating remote sensing (RS) technologies with modeling approaches has shown significant promise in enhancing water quality monitoring and prediction. This integrated approach significantly improves the accuracy and intelligence of monitoring and prediction, while extending spatiotemporal coverage, lowering monitoring costs, and enabling more comprehensive analysis through optimized monitoring design, multi-source data fusion, and the synergistic coupling of data-driven and process-based models (PBMs). Advanced models, particularly those combining PBMs with AI techniques, further enhance predictive capabilities for water quality. Despite these advances, the application of these integrated methods faces challenges in areas such as data management, monitoring elusive pollutants, model accuracy and efficiency, system integration, and real-world implementation. In response to these challenges, this paper reviews the current status of the integration of RS technology with multi-source data, machine learning (ML), and PBMs for water quality monitoring, modeling, and management, along with practical applications. It offers a thorough analysis of their advantages and challenges, identifies the current research gaps, and outlines future research directions. The goal is to enhance the role of integrated methods in improving water quality in aquatic ecosystems, support sustainable water resource management, and strengthen scientific decision-making in the face of climate change and growing anthropogenic pressures.

Upland buzzard (Buteo hemilasius), Saker falcon (Falco cherrug), and Himalayan vulture (Gyps himalayensis) are three common large raptors in the Sanjiangyuan National Park (SNP), China's first national park. Among them, Upland buzzard and Saker falcon play a significant role in controlling plateau rodent populations and reducing the transmission of pathogens carried by rodents. The Himalayan vulture can provide services for the redistribution and recycling of nutrients in the ecosystem, and play an irreplaceable role in the celestial burial culture of Tibetans in China. Exploring their habitat suitability is important for the protection of the three raptors. Our research was based on the current distribution of Upland buzzard, Saker falcon, and Himalayan vulture that we had extensively surveyed in the Sanjiangyuan National Park from 2016 to 2017. Combined with the correlation analysis of environmental variables, we utilized maximum entropy model (MaxEnt) to evaluate and compare the habitat suitability of the three species in the Sanjiangyuan National Park. Elevation, climate, and human disturbance factors, which had direct or indirect effects on species survival and reproduction, were all included in the model. Among them, elevation was the most important environmental variables affecting the suitability of habitats of three species. Temperature‐related factor was another important predictor. The high (>60%) suitable habitat areas for Upland buzzard, Saker falcon, and Himalayan vulture were 73,017.63, 40,732.78, and 61,654.33 km2, respectively, accounted for 59.32%, 33.09%, and 50.08% of the Sanjiangyuan National Park and their total suitable area (i.e., the sum area of high and moderate habitats) reached 96.07%, 60.59%, and 93.70%, respectively. Besides, the three species have overlapping areas for the suitable habitats, which means that overlapping areas should be highly valued and protected. Therefore, understanding the distribution of suitable habitats of the three raptors can provide useful information and reasonable reference for us to put forward suggestions for their protection and regional management. This study used the maxent model to assess the habitat suitability of Upland buzzard, Saker falcon, and Himalayan vulture in Sanjiangyuan National Park, China (China's first national park). This research might provide a scientific basis for the conservation and management of species in Sanjiangyuan National Park, while raptors as umbrella species can benefit other species when they are protected and concerned.

Diamond-like carbon (DLC)-coated tools are suitable for the machining of various aluminum alloys, graphite, and other non-ferrous metals. The shortcomings of DLC-coated tools such as high internal residual stress, low toughness, and poor adhesion strength limit their application. In order to reveal the mechanical and cutting performance of DLC-coated tools, a DLC monolayer coating, Cr/CrN/DLC composite coating, and Cr/W-DLC/DLC composite coating had been prepared on the cemented carbide cutting tools. The influences of transition interlayer on the microstructure and mechanical properties of DLC coatings were analyzed. Tool lives, wear mechanism, and machined surface roughness obtained with uncoated cemented carbide tool, DLC monolayer–coated tool, and Cr/ x /DLC - coated tool during the machining of Al-Si alloys were investigated. Compared with DLC monolayer coating, the strength ratio (ID/IG) of the DLC composite coatings with Cr/ x transition structure was improved, while the sp 3 covalent bond contents was decreased. The results show that the adhesion strength and toughness of the Cr/ x /DLC composite coating were enhanced, and the residual stress was greatly reduced. The cutting tests further indicate that the DLC coating significantly improved the tool life. Based on comprehensive evaluation, the Cr/W-DLC/DLC composite coating has the highest adhesion, highest toughness, the lowest residual stress, and the longest tool life, and it is suitable for the machining of non-ferrous metal.

Background Triple-negative breast cancer (TNBC) remains a great challenge in clinical treatment due to a shortage of effective therapeutic targets and acquired chemoresistance. Here, we identified the role of an RNA-binding protein, CUG-BP Elav-like family member 6 (CELF6), in the TNBC development and paclitaxel (PTX) chemoresistance. Methods Stable CELF6-overexpressing cell lines were established in BT549 and MDA-MB-231 cells. Cell proliferation was determined using cell counting, two-dimensional colony formation, and MTT assay. Meanwhile, cell migration and cell invasion were detected by Transwell assay. Furthermore, the downstream target gene of CELF6 was identified and the direct interaction was further determined by luciferase reporter assay, immunoprecipitation, and RNA pull-down. Additionally, the PTX resistant cell line was established to determine the role of CELF6 in PTX resistance. Results CELF6 overexpression suppressed cell proliferation, cell migration, and cell invasion. Mechanistically, Fructose-Bisphosphatase 1 (FBP1) was identified as the target gene of CELF6 and stabilized by CELF6 via binding 3′UTR. CELF6 overexpression mediated inhibition in TNBC development was dependent on FBP1. Moreover, CELF6 overexpression increased the sensitivity to PTX treatment. Conclusion CELF6 functions as a tumor suppressor by upregulating FBP 1 expression via stabilizing its mRNA, and thereby inhibits TNBC progression.

Gaussian processes (GPs) are popular models for functions, time series, and spatial fields, but direct application of GPs is computationally infeasible for large datasets. We propose a multi-scale Vecchia (MSV) approximation of GPs for modeling and analysis of multi-scale phenomena, which are ubiquitous in geophysical and other applications. In the MSV approach, increasingly large sets of variables capture increasingly small scales of spatial variation, to obtain an accurate approximation of the spatial dependence from very large to very fine scales. For a given set of observations, the MSV approach decomposes the data into different scales, which can be visualized to obtain insights into the underlying processes. We explore properties of the MSV approximation and propose an algorithm for automatic choice of the tuning parameters. We provide comparisons to existing approaches based on simulated data and using satellite measurements of land-surface temperature.

RGF1, a secreted peptide hormone, plays key roles in root meristem development in Arabidopsis . Previous studies indicated that a functional RGF1 needs to be sulfated at a tyrosine residue by a tyrosylprotein sulfotransferase and that RGF1 regulates the root meristem activity mainly via two downstream transcription factors, PLETHORA 1 (PLT1) and PLT2. How extracellular RGF1 is perceived by a plant cell, however, is unclear. Using genetic approaches, we discovered a clade of leucine-rich repeat receptor-like kinases, designated as RGF1 INSENSITIVE 1 (RGI1) to RGI5, serving as receptors of RGF1. Two independent rgi1 rgi2 rgi3 rgi4 rgi5 quintuple mutants display a consistent short primary root phenotype with a small size of meristem. An rgi1 rgi2 rgi3 rgi4 quadruple mutant shows a significantly reduced sensitivity to RGF1, and the quintuple mutant is completely insensitive to RGF1. The expression of PLT1 and PLT2 is almost undetectable in the quintuple mutant. Ectopic expression of PLT2 driven by an RGI2 promoter in the quintuple mutant greatly rescued its root meristem defects. One of the RGIs, RGI1, was subsequently analyzed biochemically in detail. In vitro dot blotting and pull-down analyses indicated that RGI1 can physically interact with RGF1. Exogenous application of RGF1 can quickly and simultaneously induce the phosphorylation and ubiquitination of RGI1, indicating that RGI1 can perceive and transduce the RGF1 peptide signal. Yet, the activated RGI1 is likely turned over rapidly. These results demonstrate that RGIs, acting as the receptors of RGF1, play essential roles in RGF1-PLT-mediated root meristem development in Arabidopsis thaliana .