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Background: Cell death within the tumor microenvironment (TME) plays a crucial role in controlling cancer by influencing the balance of tumor-specific immunity. Cancer-associated fibroblasts (CAFs) significantly contribute to tumor progression through paracrine mechanisms. We found that reprogramming of CAFs by apoptotic cancer cells suppresses tumor volume and lung metastasis. Here, we investigated the mechanisms by which the interaction between apoptotic lung cancer cells and CAFs hinders tumor growth. Methods: Experimental methods including CCK assay, colony formation assay, immunoblotting, co-immunoprecipitation, qRT-PCR analysis, qRT-PCR array, apoptosis assay, ELISA, and immunofluorescent staining were used in this study. Additionally, CAFs were isolated from lung tumors of Kras-mutant (KrasLA1) mice and human lung adenocarcinoma samples using magnetic-activated cell sorting. Murine lung cancer cells (344SQ cells) along with various human cancer cell lines (A549, HCT116, and LoVo) were cultured. In animal study, conditioned medium (CM) derived from CAFs (undiluted or 50% diluted) with or without neutralizing anti-WISP-1 antibody was administered into syngeneic mice to study anti-tumoral effects. To confirm the paracrine role of WISP-1, recombinant WISP-1 (rWISP-1) was administered via intratumoral injection. Results: We demonstrate that treatment with CM from lung CAFs exposed to apoptotic cancer cells suppresses proliferation and promotes apoptosis in lung cancer cells through STAT1 signaling. Pharmacologic inhibition of Notch1 activation or siRNA-mediated Notch1 silencing in CAFs reversed the antiproliferative and proapoptotic effects. Similarly, knockdown of Wnt-induced signaling protein 1 (WISP-1) in CAFs or neutralizing the CM with anti-WISP-1 antibodies reversed the antiproliferative and proapoptotic effects. WISP-1 signaled through integrin ανβ3-STAT1 signaling pathway to inhibit cancer cell growth and promote apoptosis. The in vivo introduction of CM derived from apoptotic 344SQ-exposed CAFs (ApoSQ-CAF CM) potently decelerated tumor growth. This effect was observed alongside the downregulation of proliferative and anti-apoptotic markers, while simultaneously boosting the activation of phosphorylated STAT1 and pro-apoptotic markers in CD326+ tumor cells within syngeneic immunocompetent mice. rWISP-1 effectively replicates the in vivo effects of ApoSQ-CAF CM. Conclusions: These findings suggest that CM from apoptotic cancer cell-exposed CAFs may offer a promising therapeutic approach by lung cancer suppression. [ABSTRACT FROM AUTHOR]

Simple Summary: Siberian musk deer (Moschus moschiefrus) is a vulnerable species on the IUCN Red list, facing threats from illegal poaching and habitat loss. Understanding its dietary habits and ecological needs is essential for supporting conservation efforts. This study is the first to use Next-Generation Sequencing to analyze the diet of M. moschiferus. Our results revealed that the species primarily fed on woody plants in April, with Morus and Quercus being the most consumed genera. Almost half of the identified genera had not previously been reported as part of the M. moschiferus diet using conventional methods, highlighting the need for DNA metabarcoding to more accurately compare the dietary composition of M. moschiferus across different regions. This research provides valuable insights into the types of plants M. moschiferus may consume during the spring season. Understanding the dietary composition of the Siberian musk deer (Moschus moschiferus) is critical for informing conservation efforts, particularly given the species' vulnerable status in the Republic of Korea and its limited ecological data. Previous dietary studies have relied on conventional methods with limitations in taxonomic precision, hindering comprehensive insights into their feeding ecology. To address this gap, we used Next-Generation Sequencing to analyze 16 fecal samples collected in April from Gangwon Province, the habitat of M. moschiferus. Our results revealed 213 unique plant species, with Morus, Quercus, and Prunus accounting for the majority of the diet. Notably, nearly half of the identified genera, including Morus, Actinidia, and Viscum, were reported for the first time as dietary plants of M. moschiferus. This study confirms that M. moschiferus is a concentrate feeder that primarily relies on woody plants (98.8%) and may exhibit tree-climbing behavior to access parasitic shrubs like Viscum. These findings provide a foundation for future dietary analysis research and serve as valuable baseline data for the long-term conservation of M. moschiferus. [ABSTRACT FROM AUTHOR]

Simple Summary: This study examines the relationship between small mammals and the chigger mites (Acari: Trombiculidae) that parasitize them in different habitat types within a region of South Korea. Small mammals are important hosts for chigger mites, which are vectors for diseases such as scrub typhus. We investigated how the distribution of small mammals and their parasitic mites varies across forests, grasslands, agricultural lands, and ecotones. Our findings suggest that grasslands and ecotones near human settlements have the highest abundance of small mammals, particularly Apodemus agrarius, and consequently, higher rates of mite infestation. In particular, the density of A. agrarius increased significantly in the fall, leading to a sharp rise in mite infestation rates and mean intensity. By understanding how habitat characteristics influence the abundance of small mammals and their parasites, this research highlights the importance of habitat management strategies to reduce the spread of mite-borne diseases to humans. While urbanization leads to habitat loss for medium and large mammals, small mammals can survive in fragmented habitats. As they are known to be the primary hosts of chigger mites (Acari: Trombiculidae) that transmit scrub typhus, their habitat can be considered the primary distribution area for chigger mites. This study aims to examine the distribution of small mammals and chigger mites in four habitat types and analyzed species richness, mean intensity (MI), dominance, and infestation rate (IR). A total of six small mammal species were captured, 76.8% of which were identified as Apodemus agrarius. Species richness of small mammals was highest in forests, followed by ecotones, grasslands, and agricultural lands. Apodemus agrarius accounted for 61% of the captures in forests, 80% in ecotones, 84% in grasslands, and 50% in agricultural lands, highlighting its varying dominance across habitat types. The MI of chigger mites was higher in grasslands (215.41 ± 20.70) and ecotones (171.67 ± 30.33) and lower in forests (76.67 ± 32.11). The MI of chigger mites was higher in the fall than that in the spring, and according to the MaxEnt model, they had a narrow, dense distribution in the fall and a wide distribution in the spring. These results suggest that inducing increased species richness of small mammalian hosts by habitat management and vegetation diversification may contribute to a reduction in the MI of chigger mites. [ABSTRACT FROM AUTHOR]