Persistent infection with human papillomavirus (HPV) initiates ~5% of all human cancers, and particularly cervical and oropharyngeal cancers. HPV vaccines prevent HPV infection, but do not eliminate ...existing HPV infections. Papillomaviruses induce hyperproliferation of epithelial cells. In this review we discuss how hyperproliferation renders epithelial cells less sensitive to immune attack, and impacts upon the efficiency of the local immune system. These observations have significance for the design of therapeutic HPV cancer immunotherapies.
•The impact of container reshuffling is integrated with space allocation problem.•A simulation model is developed to capture the relations between the reshuffling factors.•The impact of reshuffling ...is approximated by a high-dimensional interpolation method.•Empirical approaches are explored to solve the problem.•Experiment results show that the potential losses from ignoring reshuffling activities can be significant.
Space allocation problem (SAP) in container terminals is one of the yard management challenges in short-term planning, however, the impact of container reshuffling to the SAP is neglected in much of the literature as well as in real terminal planning. This study focuses on the SAP that accounts for container reshuffling, where the macro-level impact of reshuffling is derived from discrete event simulation and integrated into mix integer programming model. Empirical approaches are developed to achieve a trade-off between fast computation and good solutions. The result shows that ignoring reshuffling activities during planning will lead to overestimation on yard capacity.
Root traits are fundamental characteristics of belowground ecosystems that regulate plant growth and drive ecosystem functioning. Nevertheless, the way root traits respond to environmental factors ...and consequently influence productivity remains unexplored on large geographic scales. We examined the root traits of exotic
Spartina alterniflora
and native
Phragmites australis
across China’s coastal salt marshes. Using structural equation models (SEMs), we quantified the direct and indirect effects of mean annual temperature, soil nutrients (e.g., soil dissolved inorganic nitrogen and phosphorus), and root traits on aboveground net primary productivity. Our results showed that root traits of
S. alterniflora
were more sensitive to changing soil nutrient availability than those of
P. australis
. The SEMs indicated that soil nutrient availability increased
S. alterniflora
productivity by increasing root nitrogen concentration and root length density. In
P. australis
, temperature could increase productivity by both increasing root length density and soil nutrient-mediated root nitrogen concentration. The studied root architectural trait (root length density) and nutrient trait (root nitrogen concentration) were effective in predicting productivity, whereas none of the root morphological traits (i.e., specific root length, root tissue density, and root diameter) significantly affected productivity. We provide the first empirical evidence that root trait-based responses modulate the effects of climate and soil nutrients on geographic variation in vegetation productivity, but these effects are species specific.
To improve the efficiency of the container terminals, we propose a simulation optimization iteration approach to integrate the yard allocation problem (YAP) with the vehicle congestion problem. YAP ...is formulated as a mixed integer programming model to reduce the total job travel time. A discrete event simulation model is developed to simulate the terminal operation and traffic movement within the terminal. The approach solves two models iteratively to improve the allocation decisions. Experiment results show that this approach can effectively generate yard allocation decisions, which reduce the overall traffic time comparing with traditional intuitive rules.
Background Tumor-associated macrophages (TAMs), which form a large part of the tumor microenvironment, are normally regulated by metabolic reprogramming. However, the potential mechanisms of the ...immune-metabolism interaction between hepatocellular carcinoma (HCC) cells and TAMs remain unclear. Methods The candidate long non-coding RNAs (lncRNAs) were screened by Smart-seq based scRNA-seq method and then validated by qPCR. Immunostaining analysis was done to examine the levels of markers for TAMs and glycolysis. Exosomes from primary TAMs of human HCC tissues were isolated by centrifugation, and their internalization with lncRNAs was confirmed by immunofluorescence. The underlying mechanism of TAMs-derived exosomal lncRNA to HCC was confirmed by luciferase reporter assay and RNA immunoprecipitation. Metabolism regulation was evaluated through glucose consumption, lactate productions and extracellular acidification rates (ECARs). Mouse xenograft models were used to elucidate the in vivo effect of candidate lncRNAs on tumor growth. Results TAMs augment the aerobic glycolysis in HCC cells and their proliferation by the extracellular exosome transmission of a myeloid-derived lncRNA, M2 macrophage polarization associated lncRNA (lncMMPA). Mechanistically, lncMMPA not only could polarize M2 macrophage, but also could act as an microRNA sponge to interact with miR-548 s and increase the mRNA level of ALDH1A3, then further promote glucose metabolism and cell proliferation in HCC. Moreover, lncMMPA increased HCC cell multiplication through interacting with miR-548 s in vivo. Clinically, lncMMPA expression associates with glycolysis in TAMs and reduced survival of HCC patients. Conclusion LncMMPA plays an important role in regulating HCC malignancy and metabolic reprogramming of miR-548 s/ALDH1A3 pathway. Keywords: LncMMPA, Hepatocellular carcinoma, Tumor associated macrophage, Metabolic reprogramming
Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), but its clinical effects are still limited. In this study we identify Quiescin sulfhydryl oxidase 1 ...(QSOX1) acting as a cellular pro-oxidant, specifically in the context of sorafenib treatment of HCC. QSOX1 disrupts redox homoeostasis and sensitizes HCC cells to oxidative stress by inhibiting activation of the master antioxidant transcription factor NRF2. A negative correlation between QSOX1 and NRF2 expression was validated in tumor tissues from 151 HCC patients. Mechanistically, QSOX1 restrains EGF-induced EGFR activation by promoting ubiquitination-mediated degradation of EGFR and accelerating its intracellular endosomal trafficking, leading to suppression of NRF2 activity. Additionally, QSOX1 potentiates sorafenib-induced ferroptosis by suppressing NRF2 in vitro and in vivo. In conclusion, the data presented identify QSOX1 as a novel candidate target for sorafenib-based combination therapeutic strategies in HCC or other EGFR-dependent tumor types.
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•QSOX1 impairs the antioxidant capacity of HCC cells by inhibiting NRF2 activation.•QSOX1 inhibits NRF2 activation by accelerating EGFR signaling termination.•QSOX1 promotes sorafenib-induced ferroptosis in HCC.•QSOX1 is a potential biomarker for adjuvant sorafenib treatment in HCC patients.
While breast cancer has not been considered a cancer amenable to immunotherapeutic approaches, recent studies have demonstrated evidence of significant immune cell infiltration via tumor-infiltrating ...lymphocytes in a subset of patient tumors. In this review we present the current evidence highlighting the clinical relevance and utility of tumor-infiltrating lymphocytes in breast cancer. Retrospective and prospective studies have shown that the presence of tumor-infiltrating lymphocytes is a prognostic marker for higher responses to neoadjuvant chemotherapy and better survival, particularly in triple negative and HER2-positive early breast cancer. Further work is required to determine the immune subsets important in this response and to discover ways of encouraging immune infiltrate in tumor-infiltrating lymphocytes-negative patients.
The growing role of precision medicine in hepatocellular carcinoma (HCC) is expected to ameliorate the poor prognosis and high mortality of this highly malignant disease; however, it is faced with ...challenges such as the low frequency of tissue biopsy. Hence, attention is turning to the circulating tumor DNA (ctDNA), an important component of liquid biopsy. Obtaining molecular information about cancer from blood provides a good prospect in precision oncology including molecular diagnosis, molecular classification, targeted therapy, personalized decision making, and detection of drug-resistance mutations. However, inherent constraints of HCC and ctDNA (like background chronic liver diseases (CLD) and low concentration of ctDNA) along with some technical issues should be well handled and solved before the potential of ctDNA in precision medicine of HCC can be truly realized. In this review, we will focus on the prospects and challenges of ctDNA in HCC precision medicine.
Tumor-secreted factors contribute to the development of a microenvironment that facilitates the escape of cancer cells from immunotherapy. In this study, we conduct a retrospective comparison of the ...proteins secreted by hepatocellular carcinoma (HCC) cells in responders and non-responders among a cohort of ten patients who received Nivolumab (anti-PD-1 antibody). Our findings indicate that non-responders have a high abundance of secreted RNase1, which is associated with a poor prognosis in various cancer types. Furthermore, mice implanted with HCC cells that overexpress RNase1 exhibit immunosuppressive tumor microenvironments and diminished response to anti-PD-1 therapy. RNase1 induces the polarization of macrophages towards a tumor growth-promoting phenotype through activation of the anaplastic lymphoma kinase (ALK) signaling pathway. Targeting the RNase1/ALK axis reprograms the macrophage polarization, with increased CD8
T- and Th1- cell recruitment. Moreover, simultaneous targeting of the checkpoint protein PD-1 unleashes cytotoxic CD8
T-cell responses. Treatment utilizing both an ALK inhibitor and an anti-PD-1 antibody exhibits enhanced tumor regression and facilitates long-term immunity. Our study elucidates the role of RNase1 in mediating tumor resistance to immunotherapy and reveals an RNase1-mediated immunosuppressive tumor microenvironment, highlighting the potential of targeting RNase1 as a promising strategy for cancer immunotherapy in HCC.
More than 15% of Chinese respondents reported somatic symptoms in the last week of January 2020. Promoting resilience is a possible target in crisis intervention that can alleviate somatization.
This ...study aims to investigate the relationship between resilience and somatization, as well as the underlying possible mediating and moderating mechanism, in a large sample of Chinese participants receiving a crisis intervention during the coronavirus disease 2019 epidemic.
Participants were invited online to complete demographic information and questionnaires. The Symptom Checklist-90 somatization subscale, 10-item Connor-Davidson resilience scale, and 10-item Perceived Stress Scale were measured.
A total of 2,557 participants were included. Spearman correlation analysis revealed that lower resilience was associated with more somatic symptoms (
< 0.001). The conditional process model was proved (indirect effect = -0.01, 95% confidence interval = -0.015, -0.002). The interaction effects between perceived stress and sex predicted somatization (
= 0.05,
= 0.006).
Resilience is a key predictor of somatization. The mediating effects of perceived stress between resilience and somatization work in the context of sex difference. Sex-specific intervention by enhancing resilience is of implication for alleviating somatization during the coronavirus disease 2019 epidemic.
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