The implantation of any foreign material into the body leads to the development of an inflammatory and fibrotic process-the foreign body reaction (FBR). Upon implantation into a tissue, cells of the ...immune system become attracted to the foreign material and attempt to degrade it. If this degradation fails, fibroblasts envelop the material and form a physical barrier to isolate it from the rest of the body. Long-term implantation of medical devices faces a great challenge presented by FBR, as the cellular response disrupts the interface between implant and its target tissue. This is particularly true for nerve neuroprosthetic implants-devices implanted into nerves to address conditions such as sensory loss, muscle paralysis, chronic pain, and epilepsy. Nerve neuroprosthetics rely on tight interfacing between nerve tissue and electrodes to detect the tiny electrical signals carried by axons, and/or electrically stimulate small subsets of axons within a nerve. Moreover, as advances in microfabrication drive the field to increasingly miniaturized nerve implants, the need for a stable, intimate implant-tissue interface is likely to quickly become a limiting factor for the development of new neuroprosthetic implant technologies. Here, we provide an overview of the material-cell interactions leading to the development of FBR. We review current nerve neuroprosthetic technologies (cuff, penetrating, and regenerative interfaces) and how long-term function of these is limited by FBR. Finally, we discuss how material properties (such as stiffness and size), pharmacological therapies, or use of biodegradable materials may be exploited to minimize FBR to nerve neuroprosthetic implants and improve their long-term stability.
Long noncoding RNAs (lncRNAs) regulate gene expression by acting with microRNAs (miRNAs). However, the roles of cancer specific lncRNA and its related competitive endogenous RNAs (ceRNA) network in ...hepatocellular cell carcinoma (HCC) are not fully understood. The lncRNA profiles in 372 HCC patients, including 372 tumor and 48 adjacent non-tumor liver tissues, from The Cancer Genome Atlas (TCGA) and NCBI GEO omnibus (GSE65485) were analyzed. Cancer specific lncRNAs (or HCC related lncRNAs) were identified and correlated with clinical features. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in HCC. We found 177 cancer specific lncRNAs in HCC (fold change ≥ 1.5, P < 0.01), 41 of them were also discriminatively expressed with gender, race, tumor grade, AJCC tumor stage, and AJCC TNM staging system. Six lncRNAs (CECR7, LINC00346, MAPKAPK5-AS1, LOC338651, FLJ90757, and LOC283663) were found to be significantly associated with overall survival (OS, log-rank P < 0.05). Collectively, our results showed the lncRNA expression patterns and a complex ceRNA network in HCC, and identified a complex cancer specific ceRNA network, which includes 14 lncRNAs and 17 miRNAs in HCC.
The role of cancer cell FOXP3 in tumorigenesis is conflicting. We aimed to study FOXP3 expression and regulation, function and clinical implication in human non-small cell lung cancer (NSCLC).
One ...hundred and six patients with histologically-confirmed NSCLC who underwent surgery were recruited for the study. Tumor samples and NSCLC cell lines were used to examine FOXP3 and its related molecules. Various cell functions related to tumorigenesis were performed. In vivo mouse tumor xenograft was used to confirm the in vitro results.
NSCLC patients with the high level of FOXP3 had a significant decrease in overall survival and recurrence-free survival. FOXP3 overexpression significantly induced cell proliferation, migration, and invasion, whereas its inhibition impaired its oncogenic function. In vivo studies confirmed that FOXP3 promoted tumor growth and metastasis. The ectopic expression of FOXP3 induced epithelial-mesenchymal transition (EMT) with downregulation of E-cadherin and upregulation of N-cadherin, vimentin, snail, slug, and MMP9. The oncogenic effects by FOXP3 could be attributed to FOX3-mediated activation of Wnt/β-catenin signaling, as FOXP3 increased luciferase activity of Topflash reporter and upregulated Wnt signaling target genes including c-Myc and Cyclin D1 in NSCLC cells. Co-immunoprecipitation results further indicated that FOXP3 could physically interacted with β-catenin and TCF4 to enhance the functions of β-catenin and TCF4, inducing transcription of Wnt target genes to promote cell proliferation, invasion and EMT induction.
FOXP3 can act as a co-activator to facilitate the Wnt-b-catenin signaling pathway, inducing EMT and tumor growth and metastasis in NSCLC.
It is disappointing that only a few patients with hepatocellular carcinoma (HCC) obtain a significant survival benefit from the sorafenib treatment, which is currently regarded as a first-line ...chemotherapeutic therapy in patients with advanced HCC. Most patients are highly refractory to this therapy. Therefore, it is necessary to identify resistant factors and explore potential protocols that can be used to overcome the resistance or substitute sorafenib once the resistance is formed. In fact, a growing body of studies has been focusing on the resistance mechanisms or the method to overcome it. The limitation of sorafenib efficacy has been partially but not fully elucidated. Moreover, some protocols have shown encouraging outcomes but still need to be further verified in clinical trials. In this review, we summarize the recent findings on the potential mechanisms that contribute to sorafenib resistance and discuss strategies that can be used to improve the treatment outcome.
The combined effects of anthropogenic and biological CO
inputs may lead to more rapid acidification in coastal waters compared to the open ocean. It is less clear, however, how redox reactions would ...contribute to acidification. Here we report estuarine acidification dynamics based on oxygen, hydrogen sulfide (H
S), pH, dissolved inorganic carbon and total alkalinity data from the Chesapeake Bay, where anthropogenic nutrient inputs have led to eutrophication, hypoxia and anoxia, and low pH. We show that a pH minimum occurs in mid-depths where acids are generated as a result of H
S oxidation in waters mixed upward from the anoxic depths. Our analyses also suggest a large synergistic effect from river-ocean mixing, global and local atmospheric CO
uptake, and CO
and acid production from respiration and other redox reactions. Together they lead to a poor acid buffering capacity, severe acidification and increased carbonate mineral dissolution in the USA's largest estuary.The potential contribution of redox reactions to acidification in coastal waters is unclear. Here, using measurements from the Chesapeake Bay, the authors show that pH minimum occurs at mid-depths where acids are produced via hydrogen sulfide oxidation in waters mixed upward from anoxic depths.
The reliable operation of battery management systems depends critically on the accurate estimation of the state of charge (SOC) and characterizing parameters of a battery system. SOC estimation ...employs models that must be robust against variations in battery cell electrochemical features, aging, and operating conditions. This paper reveals that commonly used SOC estimation schemes are fundamentally flawed in providing the robustness of SOC estimation against model uncertainties. Parameter estimation methodologies and adaptive SOC estimation design are introduced in this paper to enhance SOC estimation accuracy and robustness. By a scrutiny of the impact of parameter variations on SOC estimation accuracy, the SOC-open-circuit-voltage mapping is identified to be the most critical function that must be accurately established. Identification algorithms are introduced, and their convergence properties are established. The integration of the identification algorithms and SOC estimation schemes lead to an adaptive SOC estimation framework that is superior over the existing methods in providing much improved accuracy and robustness. Experimental studies are conducted to validate the algorithms.
The pathogenesis of hepatocellular carcinoma (HCC) is a multistep process, involving the progressive accumulation of molecular alterations and transcriptomic alterations. The Forkhead-box (FOX) ...transcription factor family is characterized by its unique DNA binding domain (FKH or winged-helix domain). Human FOX family consists of about 17 subfamilies, at least 43 members. Some of them are liver-enriched transcription factors, suggesting that they may play a crucial role in the development or/and functions of the liver. Dysregulation of FOX transcription factors may contribute to the pathogenesis of HCC because they can activate or suppress the expression of various tumor-related molecules, and pinpoint different molecular and cellular events. Here we summarized, analyzed and discussed the status and the functions of the human FOX family of transcription factors in HCC, aiming to help the further development of them as potential therapeutic targets or/and diagnostic/prognostic markers for HCC.
In the practice of cloud manufacturing, there still exist some major challenges, including: 1) cloud based big data analytics and decision-making cannot meet the requirements of many ...latency-sensitive applications on shop floors; 2) existing manufacturing systems lack enough reconfigurability, openness and evolvability to deal with shop-floor disturbances and market changes; and 3) big data from shop-floors and the Internet has not been effectively utilized to guide the optimization and upgrade of manufacturing systems. This paper proposes an open evolutionary architecture of the intelligent cloud manufacturing system with collaborative edge and cloud processing. Hierarchical gateways connecting and managing shop-floor things at the "edge" side are introduced to support latency-sensitive applications for real-time responses. Big data processed both at the gateways and in the cloud will be used to guide continuous improvement and evolution of edge-cloud systems for better performance. As software tools are becoming dominant as the "brain" of manufacturing control and decision-making, this paper also proposes a new mode - "AI-Mfg-Ops" (AI enabled Manufacturing Operations) with a supporting software defined framework, which can promote fast operation and upgrading of cloud manufacturing systems with smart monitoring-analysis-planning-execution in a closed loop. This research can contribute to the rapid response and efficient operation of cloud manufacturing systems.
Hepatocellular carcinoma (HCC) is the fifth common cancer. The differential expression of microRNAs (miRNAs) has been associated with the prognosis of various cancers. However, limited information is ...available regarding genome-wide miRNA expression profiles in HCC to generate a tumor-specific miRNA signature of prognostic values. In this study, the miRNA profiles in 327 HCC patients, including 327 tumor and 43 adjacent non-tumor tissues, from The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) were analyzed. The associations of the differentially expressed miRNAs with patient survival and other clinical characteristics were examined with t-test and Cox proportional regression model. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate\multivariate Cox regression analyses and KEGG pathway analysis. Results showed that a total of 207 miRNAs were found differentially expressed between tumor and adjacent non-tumor HCC tissues. 78 of them were also discriminatively expressed with gender, race, tumor grade and AJCC tumor stage. Seven miRNAs were significantly associated with survival (P value <0.001). Among the seven significant miRNAs, six (hsa-mir-326, hsa-mir-3677, hsa-mir-511-1, hsa-mir-511-2, hsa-mir-9-1, and hsa-mir-9-2) were negatively associated with overall survival (OS), while the remaining one (hsa-mir-30d) was positively correlated. A tumor-specific 7-miRNAs signature was generated and validated as an independent prognostic predictor. Collectively, we have identified and validated an independent prognostic model based on the expression of seven miRNAs, which can be used to assess patients' survival. Additional work is needed to translate our model into clinical practice.
•Two new test benches were built to test the ash’s effect on both deposition and regeneration processes.•Ash is able to lower the pressure drop. 1g/L reaches the lowest pressure drop.•Small diameter ...ash has negative effect on deposition process, but positive effect on regeneration process.•Mixed ash has positive effect on both deposition and regeneration processes.
Particulate matter (PM) emissions from diesel engines are a major problem for the environment and human health. Diesel Particulate Filters (DPF) are widely used to remove PM to achieve strict regulatory emission standards for diesel engines. As the amount of PM deposition inside of the DPF increases, the back pressure of the engine rises, which reduces the engine output performance. A periodical heating to regenerate the DPF can effectively solve the above problem but a study of the effect of residual ash is needed. This paper discusses the influence of ash loading, ash particle size, and ash composition on filter performance due to deposition and regeneration processes on two different testing benches. The lowest pressure drop was obtained when the ash loading was 1g/L in the soot deposition process. Larger ash loading was beneficial for reaching higher temperature and regeneration efficiency. The regeneration efficiency increased 47% when ash loading increased from 0g/L to 10g/L, but the regeneration efficiency only increased 4% when the ash loading increased from 10g/L to 40g/L. Smaller diameter ash particles resulted in lower pressure drop, and higher regeneration efficiency. Compared with pure Al2O3 ash, ash mixtures of Al2O3+SiO2 had lower pressure drop and higher regeneration efficiency.
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