Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1+ tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/.

Cardiovascular diseases have become the leading cause of human death. Aging is an independent risk factor for cardiovascular diseases. Cardiac aging is associated with maladaptation of cellular metabolism, dysfunction (or senescence) of cardiomyocytes, a decrease in angiogenesis, and an increase in tissue scarring (fibrosis). These events eventually lead to cardiac remodeling and failure. Senescent cardiomyocytes show the hallmarks of DNA damage, endoplasmic reticulum stress, mitochondria dysfunction, contractile dysfunction, hypertrophic growth, and senescence-associated secreting phenotype (SASP). Metabolism within cardiomyocytes is essential not only to fuel the pump function of the heart but also to maintain the functional homeostasis and participate in the senescence of cardiomyocytes. The senescence of cardiomyocyte is also regulated by the non-myocytes (endothelial cells, fibroblasts, and immune cells) in the local microenvironment. On the other hand, the senescent cardiomyocytes alter their phenotypes and subsequently affect the non-myocytes in the local microenvironment and contribute to cardiac aging and pathological remodeling. In this review, we first summarized the hallmarks of the senescence of cardiomyocytes. Then, we discussed the metabolic switch within senescent cardiomyocytes and provided a discussion of the cellular communications between dysfunctional cardiomyocytes and non-myocytes in the local microenvironment. We also addressed the functions of metabolic regulators within non-myocytes in modulating myocardial microenvironment. Finally, we pointed out some interesting and important questions that are needed to be addressed by further studies.

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The advent of single-cell RNA sequencing (scRNA-seq) has provided insight into the tumour immune microenvironment (TIME). This review focuses on the application of scRNA-seq in investigation of the TIME. Over time, scRNA-seq methods have evolved, and components of the TIME have been deciphered with high resolution. In this review, we first introduced the principle of scRNA-seq and compared different sequencing approaches. Novel cell types in the TIME, a continuous transitional state, and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer. Thus, we concluded novel cell clusters of cancer-associated fibroblasts (CAFs), T cells, tumour-associated macrophages (TAMs) and dendritic cells (DCs) discovered after the application of scRNA-seq in TIME. We also proposed the development of TAMs and exhausted T cells, as well as the possible targets to interrupt the process. In addition, the therapeutic interventions based on cellular interactions in TIME were also summarized. For decades, quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer. Summarizing the current findings, we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy, which can subsequently be implemented in the clinic. Finally, we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

RPF has estrogen-like effect on lipid metabolism in liver and adipose tissue.

Introduction: Low-grade appendiceal mucinous neoplasm (LAMN) is a rare disorder. There is no consensus on the prognosis and management of LAMN. Materials and methods: We reviewed 51 consecutive patients with LAMN from 2013 to 2018. We divided our patients into two groups. The first is patients with an intact appendix. The second group comprises patients with the potential to develop a malignant condition. Comparisons of serum tumor markers between two groups were performed. Survival curves were estimated. Univariate and multivariate Cox proportional hazards were computed for 46 patients with median follow-up of 2.7 years. Results: Comparison of patients in two groups revealed significant differences in the mean level and abnormal ratio of CA125 (p < 0.001, p < 0.001), CA19-9 (p ¼ 0.04, p ¼ 0.04), and CEA (p ¼ 0.001, p ¼ 0.02). Eight patients had relapsed by the last follow-up in the second group. Patients with normal CEA had significantly longer disease-free survival (DFS) time than those with abnormal CEA (p ¼ 0.04). CA19-9 exhibited a significant association with DFS (HR ¼ 5.72, p ¼ 0.02) in the Univariate Cox proportional hazards. Discussion: The prognosis of LAMN is related to serum tumor markers, the surgical procedure and the pathology.

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Aging is a key risk factor for angiogenic dysfunction and cardiovascular diseases, including heart failure, hypertension, atherosclerosis, diabetes, and stroke. Members of the NAD + -dependent class III histone deacetylase family, sirtuins, are conserved regulators of aging and cardiovascular and cerebrovascular diseases. The sirtuin SIRT6 is predominantly located in the nucleus and shows deacetylase activity for acetylated histone 3 lysine 56 and lysine 9 as well as for some non-histone proteins. Over the past decade, experimental analyses in rodents and non-human primates have demonstrated the critical role of SIRT6 in extending lifespan. Recent studies highlighted the pleiotropic protective actions of SIRT6 in angiogenesis and cardiovascular diseases, including atherosclerosis, hypertension, heart failure, and stroke. Mechanistically, SIRT6 participates in vascular diseases via epigenetic regulation of endothelial cells, vascular smooth muscle cells, and immune cells. Importantly, SIRT6 activators (e.g., MDL-800/MDL-811) have provided therapeutic value for treating age-related vascular disorders. Here, we summarized the roles of sirtuins in cardiovascular diseases; reviewed recent advances in the understanding of SIRT6 in vascular biology, cardiovascular aging, and diseases; highlighted its therapeutic potential; and discussed future perspectives.