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We further validated its accuracy using three public datasets. Effective drugs for high-risk patients identified using the model were predicted. The novel PCa subtypes and prognostic model developed in this study may improve clinical decision-making.Lymph nodes (LNs) are highly organized secondary lymphoid organs, and reflective of immune responses to infection, injuries, or the presence of cancer. Extensive molecular and morphological analyses of immune and stromal features in tumors and LNs of breast cancer patients have revealed novel patterns indicative of disease progression. Within LNs, there are dynamic structures called germinal centers (GCs), that act as the immunological hubs for B cell development and generation of affinity matured memory B and antibody-producing plasma cells. Acting as a bridge between systemic and local immunity, associations are observed between the frequency of GCs within cancer-free LNs, the levels of stromal tumor infiltrating lymphocytes, and cancer progression. Scattered throughout the tumor microenvironment (TME) or aggregated in clusters forming tertiary lymphoid structures (TLS), the occurrence of tumor infiltrating B cells (TIL-Bs) has been linked mostly to superior disease trajectories in solid cancers. Recent TIL-Bs profiling studies have revealed a plethora of different TIL-B populations, their functional roles, and whether they are derived from GC reactions in the LN, and/or locally from GC-like structures within the TME remains to be investigated. However, parallels between the immunogenic nature of LNs as a pre-metastatic niche, TIL-B populations within the TME, and the presence of TLS will help to decipher local and widespread TIL-Bs responses and their influence on cancer progression to the lymphatics. Therapies that enhance TIL-Bs responses in the LN GC and/or in GC-like structures in the TME are thus emerging management strategies for breast and other cancer patients.Cardiovascular disease is one of the leading causes of death in developed countries. Because the incidence increases exponentially in the aging population, aging is a major risk factor for cardiovascular disease. Cardiac hypertrophy, fibrosis and inflammation are typical hallmarks of the aged heart. The molecular mechanisms, however, are poorly understood. Because glycosylation is one of the most common post-translational protein modifications and can affect biological properties and functions of proteins, we here provide the first analysis of the cardiac glycoproteome of mice at different ages. Western blot as well as MALDI-TOF based glycome analysis suggest that high-mannose N-glycans increase with age. In agreement, we found an age-related regulation of GMPPB, the enzyme, which facilitates the supply of the sugar-donor GDP-mannose. Glycoprotein pull-downs from heart lysates of young, middle-aged and old mice in combination with quantitative mass spectrometry bolster widespread alterations of the cardiac glycoproteome. Major hits are glycoproteins related to the extracellular matrix and Ca2+-binding proteins of the endoplasmic reticulum. We propose that changes in the heart glycoproteome likely contribute to the age-related functional decline of the cardiovascular system.By targeting key genes, the CRISPR system can effectively exert its anti-cancer activity. read more The latest research suggests that the CRISPReader system that regulates gene transcription can effectively target and inhibit bladder cancer cells by sensing transcription factors such as c-Myc and Get-1 in the cell. An interesting question is whether the CRISPReader system can exert its anti-cancer ability against a variety of tumors by sensing the broad-spectrum transcription factor Ets-1. In this work, a CRISPReader system that senses the Ets-1 transcription factor has been constructed. It can effectively identify a variety of cancer cell lines, and specifically induce apoptosis in cancer cells. This study fully confirmed the effectiveness of Ets-1 as a broad-spectrum cancer related signal and provided a new anti-cancer tool based on the CRISPReader system.During aging, the cardiovascular system is especially prone to a decline in function and to life-expectancy limiting diseases. Cardiovascular aging is associated with increased arterial stiffness and vasoconstriction as well as left ventricular hypertrophy and reduced diastolic function. Pathological changes include endothelial dysfunction, atherosclerosis, fibrosis, hypertrophy, inflammation, and changes in micromilieu with increased production of reactive oxygen and nitrogen species. The renin-angiotensin-aldosterone-system is an important mediator of electrolyte and blood pressure homeostasis and a key contributor to pathological remodeling processes of the cardiovascular system. Its effects are partially conveyed by the mineralocorticoid receptor (MR), a ligand-dependent transcription factor, whose activity increases during aging and cardiovascular diseases without correlating changes of its ligand aldosterone. There is growing evidence that the MR can be enzymatically and non-enzymatically modified and that these modifications contribute to ligand-independent modulation of MR activity. Modifications reported so far include phosphorylation, acetylation, ubiquitination, sumoylation and changes induced by nitrosative and oxidative stress. This review focuses on the different posttranslational modifications of the MR, their impact on MR function and degradation and the possible implications for cardiovascular aging and diseases.Traumatic brain injury (TBI) is one of the top three specific neurological disorders, requiring reliable, rapid, and sensitive imaging of brain vessels, tissues, and cells for effective diagnosis and treatment. Although the use of medical imaging such as computed tomography (CT) and magnetic resonance imaging (MRI) for the TBI detection is well established, the exploration of novel TBI imaging techniques is of great interest. In this review, recent advances in fluorescence imaging for the diagnosis and evaluation of TBI are summarized and discussed in three sections imaging of cerebral vessels, imaging of brain tissues and cells, and imaging of TBI-related biomarkers. Design strategies for probes and labels used in TBI fluorescence imaging are also described in detail to inspire broader applications. Moreover, the multimodal TBI imaging platforms combining MRI and fluorescence imaging are also briefly introduced. It is hoped that this review will promote more studies on TBI fluorescence imaging, and enable its use for clinical diagnosis as early as possible, helping TBI patients get better treatment and rehabilitation.

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