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Tumor-associated macrophages (TAMs) are pivotal components of tumor microenvironment (TME), and senescent TAMs contribute to the alternation of the profiles of TME. However, the potential biological mechanisms and the prognosis value of senescent macrophages are largely unknown, especially in bladder cancer (BLCA). Based on the single-cell RNA sequencing of a primary BLCA sample, 23 macrophage-related genes were identified. Genomic difference analysis, LASSO, and Cox regression were used to develop the risk model. TCGA-BLCA cohort (n = 406) was utilized as the training cohort, and then, three independent cohorts (n = 90, n = 221, n = 165) from Gene Expression Omnibus, clinical samples from the local hospital (n = 27), and in vitro cell experiments were used for external validation. Aldo-keto reductase family 1 member B (AKR1B1), inhibitor of DNA binding 1 (ID1), and transforming growth factor beta 1 (TGFB1I1) were determined and included in the predictive model. The model serves as a promising tool to evaluate the prognosis in BLCA (pooled hazard ratio = 2.51, 95% confidence interval = [1.43; 4.39]). The model was also effective for the prediction of immunotherapeutic sensitivity and chemotherapy treatment outcomes, which were further confirmed by IMvigor210 cohort (P < 0.01) and GDSC dataset, respectively. Twenty-seven BLCA samples from the local hospital proved that the risk model was associated with the malignant degree (P < 0.05). At last, the human macrophage THP-1 and U937 cells were treated with H2O2 to mimic the senescent process in macrophage, and the expressions of these molecules in the model were detected (all P < 0.05). Overall, a macrophage cell senescence-related gene signature was constructed to predict the prognosis, immunotherapeutic response, and chemotherapy sensitivity in BLCA, which provides novel insights to uncover the underlying mechanisms of macrophage senescence. [ABSTRACT FROM AUTHOR]

Shale gas will become an important substitute of conventional fossil fuels in the future, and the reservoir characteristics of shale are closely related to its pore structures. In order to explore the change characteristics of pore structures and mechanical properties of shale under the cyclic heating and cooling effect, from the perspectives to analyze of physical and mechanical properties and microscopic pore structure, etc. First, the ultrasonic wave velocity test and triaxial compression test were carried out. Afterward, the change law of macroscopic physical and mechanical parameters was microscopically verified based on X-ray diffraction technology, Fourier infrared spectroscopy and low-field nuclear magnetic resonance technology. The research results showed that the specimens drilled perpendicular to stratification direction were more likely to be damaged under the effect of heating–cooling cycles; under the temperature shock brought about by heating–cooling effects, the physical parameters of shale would vary at different degrees; however, chemical properties of shale basically remained unchanged; temperature effect would promote the further propagation of primary fractures and the initiation of secondary fractures and the fractures coalesced to form larger ones. Through the change of T2 spectra obtained based on NMR, it can be inferred that the number of micropores in shale declined while that of macropores increased; with the growth of heating–cooling cycles, the pores in rocks constantly developed under the effect of repeated temperature shocks, which resulted in the increase of the porosity. Additionally, the compressional wave velocity and uniaxial compressive strength generally decreased and the reduction amplitudes of the peak strength of shale treated through 5, 10 and 15 cycles were 4.12, 24.18 and 24.58%, respectively. The research result provides effective reference for efficient mining of shale gas and reconstruction engineering of tight reservoirs. [ABSTRACT FROM AUTHOR]

Heterosis is a common biological phenomenon that can be used to optimize yield and quality of crops. Using heterosis breeding, hybrids with suitable nicotine content have been applied to tobacco leaf production. However, the molecular mechanism of the formation of nicotine heterosis has never been explained from the perspective of protein. The DIA proteomics technique was used to compare the differential proteomics of the hybrid Va116 × Basma, showing strong heterosis in nicotine content from its parent lines Va116 and Basma. Proteomics analysis indicated that 65.2% of DEPs showed over-dominant expression patterns, and these DEPs included QS, BBL, GS, ARAF and RFC1 which related to nicotine synthesis. In addition, some DEPs (including GST, ABCE2 and ABCF1 and SLY1) that may be associated with nicotinic transport exhibited significant heterosis over the parental lines. These findings demonstrated that the efficiency of the synthesis and transport of nicotine in hybrids was significantly higher than that in the parent lines, and the accumulation of over-dominant expression proteins may be the cause of heterosis of nicotinic content in hybrids. [ABSTRACT FROM AUTHOR]