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Colorectal cancer (CRC) is a major cause of cancer mortality and a serious health problem worldwide. Mononuclear phagocytes are the main immune cells in the tumor microenvironment of CRC with remarkable plasticity, and current studies show that macrophages are closely related to tumor progression, invasion and dissemination. To understand the immunological function of mononuclear phagocytes comprehensively and deeply, we use single-cell RNA sequencing and classify mononuclear phagocytes in CRC into 6 different subsets, and characterize the heterogeneity of each subset. We find that tissue inhibitor of metalloproteinases (TIMPs) involved in the differentiation of proinflammatory and anti-inflammatory mononuclear phagocytes. Trajectory of circulating monocytes differentiation into tumor-associated macrophages (TAMs) and the dynamic changes at levels of transcription factor (TF) regulons during differentiation were revealed. We also find that C5 subset, characterized by activation of lipid metabolism, is in the terminal state of differentiation, and that the abundance of C5 subset is negatively correlated with CRC patients' prognosis. Our findings advance the understanding of circulating monocytes' differentiation into macrophages, identify a new subset associated with CRC prognosis, and reveal a set of TF regulons regulating mononuclear phagocytes differentiation, which are expected to be potential therapeutic targets for reversing immunosuppressive tumor microenvironment. Author summary: Colorectal cancer (CRC) is a serious health problem worldwide. Mononuclear phagocytes are the main immune cells in the tumor microenvironment of CRC with remarkable plasticity. In this study, single-cell RNA sequencing technology was used to study the subsets and characteristics of mononuclear phagocytes in CRC. We classify mononuclear phagocytes in CRC into 6 different subsets and demonstrate the heterogeneity in infiltrating mononuclear phagocytes of CRC. We find that tissue inhibitor of metalloproteinases (TIMPs) involved in the differentiation of proinflammatory and anti-inflammatory mononuclear phagocytes and reveal the trajectory and characteristics of circulating monocytes differentiation into tumor-associated macrophages (TAMs). We also find a new immunosuppressive subset of mononuclear phagocytes, which is associated with the prognosis of CRC patients. Our findings identify the heterogeneity in infiltrating mononuclear phagocytes of CRC, find a new subset associated with CRC prognosis. Also, we reveal the differentiation of mononuclear phagocytes would lead to an immunosuppressive tumor microenvironment and provide potential targets for reversing the process. [ABSTRACT FROM AUTHOR]

In this article, a novel globally exponentially convergent velocity observer for a class of mechanical systems with l nonholonomic constraints is presented. Through using a special coordinate transformation, the constrained system is converted into the integral cascade Euler–Lagrange form, which could avoid solving partial differential equations and eliminate the influence of the constraint force when reconstructing the speed information. The proposed observer has a simple structure and lower dimensions compared with other globally exponentially stable observers by using dynamic scaling and gain filtering. The simulation results demonstrate the stability and effectiveness of proposed reduced‐dimensional observer. [ABSTRACT FROM AUTHOR]

The HO 2 + SO 2 → HOSO + 3 O 2 reaction, both without a catalyst and with (H 2 O) n ( n = 1-3) as a catalyst, has been investigated using CCSD(T)/CBS//M06-2X/aug-cc-pVTZ methods, and canonical variational transition state theory with small curvature tunneling (CVT/SCT). The calculated results show that H 2 O exerts the strongest catalytic role in the hydrogen atom transfer processes of HO 2 + SO 2 → HOSO + 3 O 2 as compared with (H 2 O) 2 and (H 2 O) 3 . In the atmosphere at 0 km altitude within the temperature range of 280.0-320.0 K, the reaction with H 2 O is dominant, compared with the reaction without a catalyst, with an effective rate constant 2-3 orders of magnitude larger. In addition, at 0 km, it is worth mentioning that the relevance of the HO 2 + SO 2 → HOSO + 3 O 2 reaction with H 2 O depends heavily on its ability to compete with the primary loss mechanism of HO 2 radicals (such as the HO 2 + HO 2 and HO 2 + NO 3 reactions) and SO 2 (such as the SO 2 + HO reaction). The calculated results show that the HO 2 + SO 2 → HOSO + 3 O 2 reaction with H 2 O cannot be neglected in the primary loss mechanism of the HO 2 radical and SO 2 . The calculated results also show that for the formation of HOSO and 3 O 2 , the contribution of H 2 O decreases from 99.98% to 27.27% with an increase in altitude from 0 km to 15 km, due to the lower relative concentration of water. With the altitude increase, the HO 2 + SO 2 → HOSO + 3 O 2 reaction with H 2 O cannot compete with the primary loss mechanism of HO 2 radicals. The present results provide new insight into (H 2 O) n ( n = 1-3) catalysts, showing that they not only affect energy barriers, but also have an influence on loss mechanisms. The present findings should have broad implications in computational chemistry and atmospheric chemistry., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)