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Tumor-infiltrating myeloid cells contribute to the development of the immunosuppressive tumor microenvironment. Myeloid cell expression of arginase 1 (ARG1) promotes a protumor phenotype by inhibiting T cell function and depleting extracellular L-arginine, but the mechanism underlying this expression, especially in breast cancer, is poorly understood. In breast cancer clinical samples and in our mouse models, we identified tumor-derived GM-CSF as the primary regulator of myeloid cell ARG1 expression and local immune suppression through a gene-KO screen of breast tumor cell-produced factors. The induction of myeloid cell ARG1 required GM-CSF and a low pH environment. GM-CSF signaling through STAT3 and p38 MAPK and acid signaling through cAMP were required to activate myeloid cell ARG1 expression in a STAT6-independent manner. Importantly, breast tumor cell-derived GM-CSF promoted tumor progression by inhibiting host antitumor immunity, driving a significant accumulation of ARG1-expressing myeloid cells compared with lung and melanoma tumors with minimal GMCSF expression. Blockade of tumoral GM-CSF enhanced the efficacy of tumor-specific adoptive T cell therapy and immune checkpoint blockade. Taken together, we show that breast tumor cell-derived GM- CSF contributes to the development of the immunosuppressive breast cancer microenvironment by regulating myeloid cell ARG1 expression and can be targeted to enhance breast cancer immunotherapy., Introduction Immunotherapy is heralded for its promise in the treatment of cancer (1). Emerging clinical evidence suggests that the immunosuppressive tumor microenvironment (TME) represents a major obstacle for treatment success [...]

The radiation range of the corridor effect holds great significance for the ecological restoration, planning, and sustainable development of river corridors. This study focuses on the Beijing plain section of the Yongding River, which has been cut off for half a century, and improves the research methodology. Utilizing land use data from 1967 and 1980, ArcGIS and Fragstats were employed to establish 5 km buffer zones on both sides of the Yongding River corridor. The buffer zone analysis method was then applied to investigate landscape pattern changes. Through SPSS correlation analysis and curve fitting, sensitive landscape indices were identified, and their change characteristics were analyzed to unveil the historical spatial radiation range and characteristics of the Yongding River corridor. The findings of this research are as follows: First, as the buffer width increases, the landscape pattern changes, showing a decrease in heterogeneity, an increase in aggregation and spread, and a good connection between dominant patches. Forest land exhibited higher levels of fragmentation and dispersion, cultivated land demonstrated improved dominance, and construction land became more regular and dispersed. Second, the spatial radiation range of the landscape level within the river corridor was approximately 4 km. The inflection point for the radiation range on forest land was found at 3.5–4 km, while for construction land, it occurred at 4.5 km. The outcomes of this study can be utilized to evaluate the impact of river corridors on landscape patterns in the period of good historical ecology. They also provide more targeted measures and scientific basis for landscape pattern protection and river ecological restoration planning after the restoration of water flow in the Yongding River plain. [ABSTRACT FROM AUTHOR]

The watershed habitat, especially floodplains, is often impacted by the interaction between the natural environment and human activities, and the fragile ecological balance is easily disturbed. Therefore, the study of the changes in habitat quality in floodplains is significant for the reconstruction of damaged habitats. In this study, the landscape patterns and habitat quality in the Yongding River floodplain from 1967 to 2018 were evaluated. We employed spatial analysis to explore the characteristics and correlation of its spatio-temporal pattern change. Our results show that, first, the overall landscape pattern of the Yongding River floodplain was dominated by arable land and forestland while the construction land expanded. Second, the landscape pattern tended toward fragmentation, and the degree of landscape complexity increased. Third, the habitat quality was generally above the medium level. However, the low-quality area continued to increase. Furthermore, there was a strong correlation between habitat quality and the Aggregation Index, Diversity Index, and the area of water and forestland. In this context, the protection of the integrity and diversity of the landscape, reducing or even prohibiting the loss of water and forestland habitats, and restoring the ecological river, should be strengthened. The contribution of this paper provides a scientific reference to the comprehensive management and ecological restoration of river ecosystems. [ABSTRACT FROM AUTHOR]

A base‐promoted three‐component oxidative sulfuration/cyclization reaction of 2‐amino‐1,4‐naphthoquinone, aldehyde and elemental sulfur was developed. The naphtho[2,3‐d]thiazole ring was determined by forming two C−S bonds and one C=N bond, which demonstrates the advantages of cheap raw materials, no transition metal, and economic efficiency. The substrate scope was broad with aromatic and aliphatic aldehydes. The mechanistic study might promote the reaction design for a oxidative sulfuration/cyclization reaction. [ABSTRACT FROM AUTHOR]

Iodine‐promoted direct diamination of α,β‐unsaturated ketone to form two C−N bonds has been developed starting from chalcone and secondary amine. This reaction was performed in THF at 50 °C in the presence of I2 and K2CO3. The protocol is metal‐free, operationally simple and carried out under mild conditions, providing an effective new way for directing diamination reactions. [ABSTRACT FROM AUTHOR]

Long terminal repeat ( LTR) retrotransposons are closely related to retroviruses, and their activities shape eukaryotic genomes. Here, we present a complete Lotus japonicus insertion mutant collection generated by identification of 640 653 new insertion events following de novo activation of the LTR element Lotus retrotransposon 1 ( LORE1) (). Insertion preferences are critical for effective gene targeting, and we exploit our large dataset to analyse LTR element characteristics in this context. We infer the mechanism that generates the consensus palindromes typical of retroviral and LTR retrotransposon insertion sites, identify a short relaxed insertion site motif, and demonstrate selective integration into CHG-hypomethylated genes. These characteristics result in a steep increase in deleterious mutation rate following activation, and allow LORE1 active gene targeting to approach saturation within a population of 134 682 L. japonicus lines. We suggest that saturation mutagenesis using endogenous LTR retrotransposons with germinal activity can be used as a general and cost-efficient strategy for generation of non-transgenic mutant collections for unrestricted use in plant research. [ABSTRACT FROM AUTHOR]

Describes the method of numerical simulation on solidification process of horizontally continuously cast round iron bars in China. Factors influencing the calculation of heat transfer; Distribution of heat flux; Determination of thermal conductivity of air gap.

Circular RNAs (circRNAs) constitute a group of RNAs defined by a covalent bond between the 5' and 3' end formed by a unique back-splicing event. Most circRNAs are composed of more than one exon, which are spliced together in a linear fashion. This protocol describes methods to sequence full-length circRNA across the back-splicing junction, allowing unambiguous characterization of circRNA-specific exon-intron structures by long-read sequencing (LRS). Two different sequencing approaches are provided: (1) Global circRNA sequencing (the circNick-LRS strategy) relying on circRNA enrichment from total RNA followed by total circRNA long-read sequencing, and (2) targeted circRNA sequencing (the circPanel-LRS strategy) where a preselected panel of circRNA are sequenced without prior circRNA enrichment. Both methods were originally described in Karim et al. (Rahimi et al., Nat Commun 12: 4825, 2021) where they were applied to characterize the exon-intron structure of >10.000 circRNAs in mouse and human brains., (© 2024. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)