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In CRA patients, relative abundance of the selected 28 species more closely resembled those in CRC patients than HC. By comparing with fecal metagenomics studies, we found there was moderate positive correlation between fold changes of the overlapped fecal and circulating bacterial DNA. Finally, species correlation analysis revealed that CRC and HC displayed distinct patterns of species association. In conclusion, this study demonstrated alterations of circulating bacterial DNA in colorectal neoplasia patients, which had the potential to become non-invasive biomarkers for colorectal neoplasia screening and early diagnosis.Aberrant activation of the Hedgehog (Hh) pathway leads to the development of several tumors, including medulloblastoma (MB), the most common pediatric brain malignancy. Hh inhibitors acting on GLI1, the final effector of Hh signaling, offer a valuable opportunity to overcome the pitfalls of the existing therapies to treat Hh-driven cancers. In this study, the toxicity, delivery, biodistribution, and anticancer efficacy of Glabrescione B (GlaB), a selective GLI1 inhibitor, were investigated in preclinical models of Hh-dependent MB. To overcome its poor water solubility, GlaB was formulated with a self-assembling amphiphilic polymer forming micelles, called mPEG5kDa-cholane. mPEG5kDa-cholane/GlaB showed high drug loading and stability, low cytotoxicity, and long permanence in the bloodstream. We found that mPEG5kDa-cholane efficiently enhanced the solubility of GlaB, thus avoiding the use of organic solvents. mPEG5kDa-cholane/GlaB possesses favorable pharmacokinetics and negligible toxicity. Remarkably, GlaB encapsulated in mPEG5kDa-cholane micelles was delivered through the blood-brain barrier and drastically inhibited tumor growth in both allograft and orthotopic models of Hh-dependent MB. Our findings reveal that mPEG5kDa-cholane/GlaB is a good candidate for the treatment of Hh-driven tumors and provide relevant implications for the translation of GlaB into clinical practice.Chronic hepatitis B virus (HBV) infection is one of the major global health problems. Although the small protein of hepatitis B virus surface antigen (HBsAg), SHBs, is the most abundant HBV viral protein, its pathogenic role and molecular mechanism in malignant progression of HBV-related hepatocellular carcinoma (HCC) remain largely unknown. Here we reported that SHBs expression induced epithelial-mesenchymal transition (EMT) process in HCC cells and significantly increased their migratory and invasive ability as well as metastatic potential. Mechanistically, SHBs expression in HCC cells induced endoplasmic reticulum (ER) stress that activated the activating transcription factor 4 (ATF4) to increase the expression and secretion of fibroblast growth factor 19 (FGF19). The autocrine released FGF19 in turn activated JAK2/STAT3 signaling for induction of EMT process in HCC. Notably, SHBs was positively correlated with the expression of mesenchymal markers, the phosphorylation status of JAK2 and STAT3 as well as FGF19 levels in human HCC samples. HCC patients with SHBs positive had a more advanced clinical stage and worse prognosis. These results suggest an important role of SHBs in the metastasis and progression of HCC and may highlight a potential target for preventive and therapeutic intervention of HBV-related HCC and its malignant progression.Exhausted T cells in the tumor microenvironment are major targets of immunotherapies. However, the exhaustion status of CD8+ tumor-infiltrating lymphocytes (TILs) in bladder cancer has not been comprehensively evaluated. Herein, we examined distinct exhaustion status of CD8+ TILs based on the level of programmed cell death-1 (PD-1) and thymocyte selection-associated high mobility group box protein (TOX) expression in urothelial bladder cancer. We also evaluated the reinvigoration of exhausted CD8+ TILs upon ex vivo treatment with inhibitory checkpoint blockers. TOX-expressing PD-1highCD8+ TILs had the highest expression of immune checkpoint receptors (ICRs), the most terminally exhausted features, and the highest tumor antigen reactivity among PD-1+CD8+ TILs. Bladder cancer patients with a high percentage of PD-1highTOX+CD8+ TILs had more progressed T-cell exhaustion features and higher programmed death-ligand 1 expression in tumor tissues. TIGIT was the most frequent co-expressed ICR on PD-1+CD8+ TILs, and TIGIT blockade enhanced the PD-1 blockade-mediated cytokine production by CD8+ TILs from bladder cancer patients. Our findings provide an improved understanding of the heterogeneous exhaustion status of CD8+ TILs and additional immunotherapy strategies to improve outcomes of bladder cancer patients.The purpose of this study was to determine whether sarcopenic obesity accelerates impairments in muscle maintenance through the investigation of cell cycle progression and myogenic, inflammatory, catabolic and protein synthetic signaling in mouse gastrocnemius muscles. At 4 weeks old, 24 male C57BL/6 mice were fed either a high fat diet (HFD, 60 % fat) or normal chow (NC, 17 % fat) for either 8-12 weeks or 21-23 months. At 3-4 months or 22-24 months the gastrocnemius muscles were excised. In addition, plasma was taken for C2C12 differentiation experiments. Mean cross-sectional area (CSA) was reduced by 29 % in aged HFD fed mice compared to the aged NC mice. Ro 20-1724 mw MyoD was roughly 50 % greater in the aged mice compared to young mice, whereas TNF-α and IGF-1 gene expression in aged HFD fed mice were reduced by 52 % and 65 % in comparison to aged NC fed mice, respectively. Myotubes pretreated with plasma from aged NC fed mice had 14 % smaller myotube diameter than their aged HFD counterparts. Aged obese mice had greater impairments to mediators of muscle maintenance as evident by reductions in muscle mass, CSA, along with alterations in cell cycle regulation and inflammatory and insulin signaling.A wide range of insults can trigger acute injury in the lungs, which eventually may lead to respiratory failure and death of patients. Current treatment relies mainly on supportive measures and mechanical ventilation. Even so, survivors frequently develop important sequels that compromise quality of life. In the search for new approaches to prevent and treat acute lung injury, many investigations have focused on molecular and cellular pathways which could exert a pathogenic role in this disease. Herein, we review recent findings in the literature suggesting that cellular senescence could be involved in lung injury and discuss the potential use of senotherapies to prevent disease progression.