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Mec1 plays an essential role in both the DNA damage response and glucose starvation- induced autophagy. We recently reported that Mec1 regulates glucose starvation-induced autophagy through its direct binding to Atg13. However, the role of Mec1's kinase activity in autophagy remains unclear. In this study, we demonstrate that the kinase activity of Mec1 is required for glucose starvation-induced autophagy by regulating the phagophore assembly site (PAS) recruitment of Atg9 vesicles. Mechanistic and functional analyses identified Atg9 as a direct phosphorylation substrate of Mec1, with phosphorylation occurring at the S35, T203, and T243 sites. Mutations at these sites reduce the association of Atg9 with Atg17, Atg23, and Atg27, thereby impairing the PAS recruitment of Atg9 vesicles. Notably, we found that the Mec1-Atg13 binding is a prerequisite for the phosphorylation of Atg9 by Mec1. Furthermore, Mec1-mediated phosphorylation of Atg9 is also crucial for the PAS recruitment of Atg9 vesicles in response to DNA damage. We thus propose that Mec1's kinase activity regulates the PAS recruitment of Atg9 vesicles by phosphorylating Atg9 in response to energy stress and DNA damage. [ABSTRACT FROM AUTHOR]

Introduction Prostate cancer (PCa) progression is regulated by multiple cell types existing within the tumor microenvironment (TME) (1). [CD8.sup.+] T cells, the predominant tumoricidal effector population, are commonly present in [...], The role of tumor-associated macrophages (TAMs), along with the regulatory mechanisms underlying distinct macrophage activation states, remains poorly understood in prostate cancer (PCa). Herein, we report that PCa growth in mice with macrophage-specific Ubc9 deficiency is substantially suppressed compared with that in wild-type littermates, an effect partially ascribed to the augmented [CD8.sup.+] T cell response. Biochemical and molecular analyses revealed that signal transducer and activator of transcription 4 (STAT4) is a crucial UBC9-mediated SUMOylation target, with lysine residue 350 (K350) as the major modification site. Site-directed mutation of STAT4 (K350R) enhanced its nuclear translocation and stability, thereby facilitating the proinflammatory activation of macrophages. Importantly, administration of the UBC9 inhibitor 2-D08 promoted the antitumor effect of TAMs and increased the expression of PD-1 on [CD8.sup.+] T cells, supporting a synergistic antitumor efficacy once it combined with the immune checkpoint blockade therapy. Together, our results demonstrate that ablation of UBC9 could reverse the immunosuppressive phenotype of TAMs by promoting STAT4-mediated macrophage activation and macrophage [CD8.sup.+] T cell crosstalk, which provides valuable insights to halt the pathogenic process of tumorigenesis.

The urban–rural imbalance, a social problem shared globally, is seeing a turnaround as a result of changes in production patterns. Tourism can not only provide employment but also drive the development of related industries, which is an effective measure to solve the urban–rural dichotomy. Against this background, we take the Beijing-Tianjin-Hebei (BTH) urban agglomeration as a sample, uses new urbanization and rural revitalization as a criterion for measuring urban and rural development, and quantifies the degree of urban–rural coordinated (URC) value in the BTH urban agglomeration from 2010 to 2019 by using the coupled coordination degree model. After that, the geographically and temporally weighted regression (GTWR) model is used to analyze the impact of tourism on the URC. The results show that: (1) there are large gaps within the BTH urban agglomeration in terms of urban and rural development, and there may be a threshold effect for the URC; (2) the impact of tourism on the URC shows spatiotemporal heterogeneity and the highest degree of diversity is high-quality intangible cultural heritage resources; (3) the density of highways exerts a negative impact on the URC. Finally, based on the findings, tourism is as an anchoring point to provide policy guidance for sustainable urban–rural development. [ABSTRACT FROM AUTHOR]

A quiet quadruple revolution has been in the making in systems science with convergence of (1) artificial intelligence, machine learning, and other digital technologies; (2) multiomics big data integration; (3) growing interest in the "variability science" of precision/personalized medicine that aims to account for patient-to-patient and between-population differences in disease susceptibilities and responses to health interventions such as drugs, nutrition, vaccines, and radiation; and (4) planetary health scholarship that both scales up and integrates biological, clinical, and ecological contexts of health and disease. Against this overarching background, this article presents and highlights some of the salient challenges and prospects of multiomics research, emphasizing the attendant pivotal role of systems medicine and systems biology. In addition, we emphasize the rapidly growing importance of planetary health research for systems medicine, particularly amid climate emergency, ecological degradation, and loss of planetary biodiversity. Looking ahead, we anticipate that the integration and utilization of multiomics big data and artificial intelligence will drive further progress in systems medicine and systems biology, heralding a promising future for both human and planetary health. [ABSTRACT FROM AUTHOR]

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The genus Impatiens comprises more than 1000 species and displays enormous morphological diversity. As a taxon that is notoriously difficult to classify morphologically, the taxonomic significance of pollen morphology has been discussed in previous studies. However, there was only limited study on the evolution of palynological and macroscopic character in this genus before. In this paper, we observed pollen of 143 species of Impatiens, including all representatives of infrageneric groups and discussed their taxonomic value. Meanwhile, based on the reconstructed phylogenetic framework, we selected five pollen traits, and nine macroscopic traits including both vegetative and reproductive organs for evolutionary analysis. The character reconstruction showed that the morphology and number of aperture, granules in lumina, seed number of per capsule, number of sepals, lateral united petals connate, spur length, and phyllotaxy could be identified as unambiguous, while other characters were ambiguous in the last common ancestor of Impatiens. The results of comprehensively macroscopic characters and palynological evidence suggest that these traits experienced a complicated evolution, exhibit high levels of instability and variability and occur character multiple reversals in the evolutionary processes of Impatiens due to different selection pressures. In addition, we found that there is an evident mosaic evolution in this genus. Pollen and macroscopic character are conserved with a slower evolutionary rate in the I. subgen. Clavicarpa, however, these characters showed higher diversity with a rapid rate of evolution in the I. subgen. Impatiens. Furthermore, the relationship between floral morphology and pollinators was discussed. [ABSTRACT FROM AUTHOR]