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The RB gene is one of the most frequently mutated genes in human cancers. Canonically, RB exerts its tumor suppressive activity through the regulation of the G1/S transition during cell cycle progression by modulating the activity of E2F transcription factors. However, aberration of the RB gene is most commonly detected in tumors when they gain more aggressive phenotypes, including metastatic activity or drug resistance, rather than accelerated proliferation. This implicates RB controls’ malignant progression to a considerable extent in a cell cycle-independent manner. In this review, we highlight the multifaceted functions of the RB protein in controlling tumor lineage plasticity, metabolism, and the tumor microenvironment (TME), with a focus on the mechanism whereby RB controls the TME. In brief, RB inactivation in several types of cancer cells enhances production of pro-inflammatory cytokines, including CCL2, through upregulation of mitochondrial reactive oxygen species (ROS) production. These factors not only accelerate the growth of cancer cells in a cell-autonomous manner, but also stimulate non-malignant cells in the TME to generate a pro-tumorigenic niche in a non-cell-autonomous manner. Here, we discuss the biological and pathological significance of the non-cell-autonomous functions of RB and attempt to predict their potential clinical relevance to cancer immunotherapy.

Shandong Province (SDP) experienced serious land subsidence from March 2017 to December 2020. Exploring the response relationships between land subsidence and its inducing factors plays an important role in ensuring the development of the economy and residential safety. Firstly, we applied Persistent Scatterers Interferometric Aperture Radar (PS-InSAR) technology to 558 Sentinel-1 images to determine the land subsidence in SDP from March 2017 to December 2020. Secondly, we mosaicked the land subsidence monitoring results of five tracks to obtain a land subsidence map covering the whole SDP and validated the land subsidence monitoring results using Global Positioning System (GPS) monitoring results and leveling benchmark monitoring results observed in the same period. Finally, the response relationships between the land subsidence and its inducing factors in SDP were analyzed. The findings are as follows: (1) the PS-InSAR outcomes showed that the land subsidence was widely distributed in SDP and that the maximum land subsidence rate was −298.9 mm/year during the study period. (2) The PS-InSAR monitoring results coincide well with the GPS monitoring results and leveling benchmark monitoring results; the Pearson correlation coefficient (PCC) values between the PS-InSAR monitoring results and the GPS measurement results and leveling benchmark monitoring results were 0.97 and 0.98, respectively. We found that Spearman’s rank correlation coefficient (SRCC) values between any two adjacent tracks of the mosaic PS-InSAR monitoring results were greater than 0.95, indicating good consistency. (3) The long-term overexploitation of groundwater in middle and deep aquifers and mining of underground mineral resources are the main inducing factors of land subsidence in SDP when considering this problem on a large geographical scale. Moreover, the type of bridge material is an important inducing factor causing the large variation in the land subsidence of the bridge body within a small geographical range. These findings may provide scientific support for land subsidence control measures in SDP.

Cancer stem cells (CSCs) refer to a subpopulation of cancer cells responsible for tumorigenesis, metastasis, and drug resistance. Increasing evidence suggests that CSC-associated tumor neovascularization partially contributes to the failure of cancer treatment. In this review, we discuss the roles of CSCs on tumor-associated angiogenesis via trans-differentiation or forming the capillary-like vasculogenic mimicry, as well as the roles of CSCs on facilitating endothelial cell-involved angiogenesis to support tumor progression and metastasis. Furthermore, we discuss the underlying regulation mechanisms, including the intrinsic signals of CSCs and the extrinsic signals such as cytokines from the tumor microenvironment. Further research is required to identify and verify some novel targets to develop efficient therapeutic approaches for more efficient cancer treatment through interfering CSC-mediated neovascularization.

As a common geological hazard, land subsidence is widely distributed in the Eastern Beijing Plain. The pattern of evolution of this geological phenomenon is controlled by many factors, including groundwater level change in different aquifers, compressible layers of different thicknesses, and static and dynamic loads. First, based on the small baseline subset Interferometric Synthetic Aperture Radar (SBAS-InSAR) technique, we employed 47 ENVISAT ASAR images and 48 RADARSAT-2 images to acquire the ground deformation of the Beijing Plain from June 2003 to November 2015 and then validated the results using leveling benchmark monitoring. Second, we innovatively calculated additional stress to obtain static and dynamic load information. Finally, we evaluated the contribution rate of the influencing factors to land subsidence by using the Spearman’s rank correlation coefficient (SRCC) and extremely randomized trees (ERT) machine learning methods. The SBAS-InSAR outcomes revealed that the maximum deformation rate was 110.7 mm/year from 2003 to 2010 and 144.4 mm/year from 2010 to 2015. The SBAS-InSAR results agreed well with the leveling benchmark monitoring results; the correlation coefficients were 0.97 and 0.96 during the 2003–2010 and 2013–2015 periods, respectively. The contribution rate of the second confined aquifer to the cumulative land subsidence was 49.3% from 2003 to 2010, accounting for the largest proportion; however, its contribution rate decreased to 23.4% from 2010 to 2015. The contribution rate of the third confined aquifer to the cumulative land subsidence increased from 2003 to 2015. Although the contribution of additional stress engendered from static and dynamic loads to the cumulative land subsidence was slight, it had a significant effect on the uneven land subsidence, with a contribution rate of 33.8% from 2003 to 2010 and 23.1% from 2010 to 2015. These findings provide scientific support for mitigating hazards associated with land subsidence.

Our previous studies have showed that C-C motif chemokine ligand 20 (CCL20) advanced tumor progression and enhanced the chemoresistance of cancer cells by positively regulating breast cancer stem cell (BCSC) self-renewal. However, it is unclear whether CCL20 affects breast cancer progression by remodeling the tumor microenvironment (TME). Here, we observed that polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were remarkably enriched in TME of CCL20-overexpressing cancer cell orthotopic allograft tumors. Mechanistically, CCL20 activated the differentiation of granulocyte-monocyte progenitors (GMPs) via its receptor C-C motif chemokine receptor 6 (CCR6) leading to the PMN-MDSC expansion. PMN-MDSCs from CCL20-overexpressing cell orthotopic allograft tumors (CCL20-modulated PMN-MDSCs) secreted amounts of C-X-C motif chemokine ligand 2 (CXCL2) and increased ALDH + BCSCs via activating CXCR2/NOTCH1/HEY1 signaling pathway. Furthermore, C-X-C motif chemokine receptor 2 (CXCR2) antagonist SB225002 enhanced the docetaxel (DTX) effects on tumor growth by decreasing BCSCs in CCL20 high -expressing tumors. These findings elucidated how CCL20 modulated the TME to promote cancer development, indicating a new therapeutic strategy by interfering with the interaction between PMN-MDSCs and BCSCs in breast cancer, especially in CCL20 high -expressing breast cancer.

Breast cancer brain metastasis (BCBrM) remains a major clinical challenge with limited therapeutic options and poor prognosis. Despite advances in systemic therapy, the incidence of BCBrM is rising due to prolonged survival of patients with advanced breast cancer, yet effective brain‐targeted strategies remain scarce, underscoring a critical research gap. This review integrates recent mechanistic insights that illuminate the complex biology underpinning BCBrM and explores how these discoveries are driving therapeutic innovation. We detail the metastatic cascade from local invasion to brain colonization, and examine key signaling pathways orchestrating brain‐specific metastasis. Emphasis is placed on the dynamic crosstalk between tumor cells and the brain microenvironment, including astrocytes, microglia, and neurons, as well as metabolic reprogramming and immune evasion. We critically evaluate current preclinical models and their translational relevance, highlighting recent advances in humanized and imaging‐based systems. Emerging therapies, such as central nervous system‐penetrant kinase inhibitors, antibody–drug conjugates, and immunotherapies, are discussed alongside persistent challenges in drug delivery and resistance. Finally, we outline future directions, calling for cross‐disciplinary collaboration and innovative clinical trial designs to personalize care and improve patient outcomes. Together, this review underscores the urgent need to bridge biology and therapy to transform the management of BCBrM. Breast cancer brain metastasis (BCBrM) is driven by a multistep metastatic cascade and shaped by dynamic tumor–brain interactions. This review integrates current mechanistic insights, from molecular signaling pathways to immune evasion, and evaluates preclinical models and emerging therapies. We highlight therapeutic challenges and outline future strategies to personalize treatment, bridge cancer with neuroscience, and improve clinical outcomes in BCBrM.

BackgroundAlthough the antitumor efficacy of docetaxel (DTX) has long been attributed to the antimitotic activities, its impact on the tumor microenvironment (TME) has recently gained more attention. Macrophages are a major component of the TME and play a critical role in DTX efficacy; however, the underlying action mechanisms remain unclear.MethodsDTX chemotherapeutic efficacy was demonstrated via both macrophage depletion and C–C motif chemokine ligand 3 (Ccl3)-knockout transgenic allograft mouse model. Ccl3-knockdown and Ccl3-overexpressing breast cancer cell allografts were used for the in vivo study. Combination therapy was used to evaluate the effect of Ccl3 induction on DTX chemosensitivity. Vital regulatory molecules and pathways were identified using RNA sequencing. Macrophage phagocytosis of cancer cells and its influence on cancer cell proliferation under DTX treatment were assessed using an in vitro coculture assay. Serum and tumor samples from patients with breast cancer were used to demonstrate the clinical relevance of our study.ResultsOur study revealed that Ccl3 induced by DTX in macrophages and cancer cells was indispensable for the chemotherapeutic efficacy of DTX. DTX-induced Ccl3 promoted proinflammatory macrophage polarization and subsequently facilitated phagocytosis of breast cancer cells and cancer stem cells. Ccl3 overexpression in cancer cells promoted proinflammatory macrophage polarization to suppress tumor progression and increase DTX chemosensitivity. Mechanistically, DTX induced Ccl3 by relieving the inhibition of cAMP-response element binding protein on Ccl3 via reactive oxygen species accumulation, and Ccl3 then promoted proinflammatory macrophage polarization via activation of the Ccl3–C-C motif chemokine receptor 5–p38/interferon regulatory factor 5 pathway. High CCL3 expression predicted better prognosis, and high CCL3 induction revealed better DTX chemosensitivity in patients with breast cancer. Furthermore, both the Creb inhibitor and recombinant mouse Ccl3 significantly enhanced DTX chemosensitivity.ConclusionsOur results indicate that Ccl3 induced by DTX triggers proinflammatory macrophage polarization and subsequently facilitates phagocytosis of cancer cells. Ccl3 induction in combination with DTX may provide a promising therapeutic rationale for increasing DTX chemosensitivity in breast cancer.

In metropolitan areas, the static load of high-rise buildings may result in uneven settlement, which seriously threatens residents’ living safety. Studying the response relationship between the additional stress of high-rise buildings and foundation settlement plays an important role in ensuring the safe development of metropolitan cities. Firstly, based on Persistent Scatterers Interferometric Aperture Radar (PS-InSAR) technology, we used 68 descending TerraSAR-X images to obtain the surface settlement in the study area from April 2010 to October 2018, which were validated with leveling benchmark monitoring results. Secondly, we calculated the additional stress of the building loads to quantify its effect on the uneven settlement in the Central Business District (CBD) of Beijing. Finally, two sets of characteristic points were selected to analyze the response relationships between foundation settlement and additional stress generated by building loads. The findings show: (1) The surface settlement rate varied from −145.2 to 24 mm/year in the Beijing Plain. The InSAR results agree well with the monitoring results derived from the leveling benchmark; the Pearson correlation coefficients were 0.98 and 0.95 in 2011–2013 and 2015–2016, respectively. (2) The stress results show that the depth of the influence of the static load of high-rise buildings was 74.9 m underground in the CBD. (3) The spatial distribution pattern of the additional stress is consistent with the foundation settlement. A characteristic point with greater additional stress in the same group has a higher foundation settlement rate. This relationship has also been found between the uneven foundation settlement and additional stress gradients. These findings provide scientific support for mitigating economic losses due to foundation settlement caused by additional stresses derived from building loads.

As a direct and effective biometric technology that follows human life habits, facial recognition has gradually become a mainstream, stable and reliable recognition method in the process of further development of science and technology. Facial recognition is a kind of biometric authentication based on recognition technology that is an original biological characteristic. After collecting the biometric functions, use a computer for digital image processing and template matching to complete the process of facial recognition. In the face of MOOC, establish a high-quality resource sharing mechanism, use this opportunity to explore innovative education models, and truly feel the strong momentum of traditional Chinese higher education, which has greatly improved the quality of education in Chinese universities. In addition, in order to vigorously promote the internationalization of education in China, education scholars need to conduct a lot of in-depth research on MOOC. In this article, a demand-based testing method is used to establish a skin color distribution model for color image preprocessing, and then develop and construct according to the comprehensive analysis of the university English class in the MOOC platform implementation mechanism (including the establishment of basic principles of operation mechanism), thereby become a guarantee and support for curriculum and education quality evaluation system. This article combines the characteristics of educational practice and MOOC education, takes college English courses as an example, studies its application mechanism, builds a MOOC platform, and continuously enhances students' interest in learning English, aiming to provide a practical reference for the reform of Chinese college English education.