Autophagy and Cell Death: Antitumor Drugs Targeting Autophagy

Autophagy, a degradation mechanism conserved among eukaryotes, plays an important role in cellular homeostasis by maintaining nutrients and energy balance. It is not surprising that autophagy has been associated with various pathological conditions such as neurodegeneration, aging, infection, and cancer. Its roles in cancer are complex and context-dependent. In this chapter, we will give an overview of regulation of autophagy with an emphasis in cancer and summarize the recent efforts in developing cancer therapeutics targeting autophagy

Human Cytomegalovirus Encoded miR-US25-1-5p Attenuates CD147/EMMPRIN-Mediated Early Antiviral Response.

Cellular receptor-mediated signaling pathways play critical roles during the initial immune response to Human Cytomegalovirus (HCMV) infection. However, the involvement of type-I transmembrane glycoprotein CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) in the antiviral response to HCMV infection is still unknown. Here, we demonstrated the specific knockdown of CD147 significantly decreased HCMV-induced activation of NF-κB and Interferon-beta (IFN-β), which contribute to the cellular antiviral responses. Next, we confirmed that HCMV-encoded miR-US25-1-5p could target the 3 UTR (Untranslated Region) of CD147 mRNA, and thus facilitate HCMV lytic propagation at a low multiplicity of infection (MOI). The expression and secretion of Cyclophilin A (sCyPA), as a ligand for CD147 and a proinflammatory cytokine, were up-regulated in response to HCMV stimuli. Finally, we confirmed that CD147 mediated HCMV-triggered antiviral signaling via the sCyPA-CD147-ERK (extracellular regulated protein kinases)/NF-κB axis signaling pathway. These findings reveal an important HCMV mechanism for evading antiviral innate immunity through its encoded microRNA by targeting transmembrane glycoprotein CD147, and a potential cause of HCMV inflammatory disorders due to the secretion of proinflammatory cytokine CyPA

Effect of tiotropium bromide, N-acetylcysteine and respiratory training on pulmonary function, activity tolerance and quality of life of patients with chronic obstructive pulmonary disease

Purpose: To investigate the effect of application of tiotropium bromide and N- acetylcysteine in combination with respiratory training on the treatment of patients with chronic obstructive pulmonary disease (COPD), and the effect of the combined treatment on pulmonary function, tolerance of physical activity, and quality of life.Methods: One hundred COPD patients admitted to The First People’s Hospital of Guiyang (February 2019 - March 2021) were randomly and equally assigned to groups X and Y. Patients in Y were given tiotropium bromide in combination with N-acetylcysteine, while group X was treated with respiratory training, in addition to the treatment regimen in Y. Treatment efficacy, incidence of adverse reactions, pulmonary function indices, activity tolerance, quality of life (QLI) score, activities of daily living (ADL) score, and incidence of COPD at 2 weeks, 1 month and 2 months after treatment were determined, and compared between the two groups.Results: Relative to group Y, group X had significantly higher treatment efficacy, QLI score and ADL score (p < 0.05). Furthermore, group X also had better pulmonary function indices and activity tolerance, lower incidence of adverse reactions, and lower COPD incidence at 2 weeks, 1 month and 2 months after treatment (p < 0.05).Conclusion: Tiotropium bromide and N-acetylcysteine in combination with respiratory training enhanced therapeutic effect, pulmonary function, activity tolerance and quality of life of COPD patients

Biologically Inspired Design of Context-Aware Smart Products

The rapid development of information and communication technologies (ICTs) and cyber–physical sys-tems (CPSs) has paved the way for the increasing popularity of smart products. Context-awareness isan important facet of product smartness. Unlike artifacts, various bio-systems are naturally characterizedby their extraordinary context-awareness. Biologically inspired design (BID) is one of the most commonlyemployed design strategies. However, few studies have examined the BID of context-aware smart prod-ucts to date. This paper presents a structured design framework to support the BID of context-awaresmart products. The meaning of context-awareness is defined from the perspective of product design.The framework is developed based on the theoretical foundations of the situated function–behavior–structure ontology. A structured design process is prescribed to leverage various biological inspirationsin order to support different conceptual design activities, such as problem formulation, structure refor-mulation, behavior reformulation, and function reformulation. Some existing design methods and emerg-ing design tools are incorporated into the framework. A case study is presented to showcase how thisframework can be followed to redesign a robot vacuum cleaner and make it more context-aware.Ó2019 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering andHigher Education Press Limited Company. This is an open access article under the CC BY-NC-ND licens

Investigation Progresses and Applications of Fractional Derivative Model in Geotechnical Engineering

Over the past couple of decades, as a new mathematical tool for addressing a number of tough problems, fractional calculus has been gaining a continually increasing interest in diverse scientific fields, including geotechnical engineering due primarily to geotechnical rheology phenomenon. Unlike the classical constitutive models in which simulation analysis gradually fails to meet the reasonable accuracy of requirement, the fractional derivative models have shown the merits of hereditary phenomena with long memory. Additionally, it is traced that the fractional derivative model is one of the most effective and accurate approaches to describe the rheology phenomenon. In relation to this, an overview aimed first at model structure and parameter determination in combination with application cases based on fractional calculus was provided. Furthermore, this review paper shed light on the practical application aspects of deformation analysis of circular tunnel, rheological settlement of subgrade, and relevant loess researches subjected to the achievements acquired in geotechnical engineering. Finally, concluding remarks and important future investigation directions were pointed out

Screening immune-related blood biomarkers for DKD-related HCC using machine learning

BackgroundDiabetes mellitus is a significant health problem worldwide, often leading to diabetic kidney disease (DKD), which may also influence the occurrence of hepatocellular carcinoma (HCC). However, the relationship and diagnostic biomarkers between DKD and HCC are unclear.MethodsUsing public database data, we screened DKD secretory RNAs and HCC essential genes by limma and WGCNA. Potential mechanisms, drugs, and biomarkers for DKD-associated HCC were identified using PPI, functional enrichment, cMAP, and machine learning algorithms, and a diagnostic nomogram was constructed. Then, ROC, calibration, and decision curves were used to evaluate the diagnostic performance of the nomograms. In addition, immune cell infiltration in HCC was explored using CIBERSORT. Finally, the detectability of critical genes in blood was verified by qPCR.Results104 DEGs associated with HCC using WGCNA were identified. 101 DEGs from DKD were predicated on secreting into the bloodstream with Exorbase datasets. PPI analysis identified three critical modules considered causative genes for DKD-associated HCC, primarily involved in inflammation and immune regulation. Using lasso and RM, four hub genes associated with DKD-associated HCC were identified, and a diagnostic nomogram confirmed by DCA curves was established. The results of immune cell infiltration showed immune dysregulation in HCC, which was associated with the expression of four essential genes. PLVAP was validated by qPCR as a possible blood-based diagnostic marker for DKD-related HCC.ConclusionWe revealed the inflammatory immune pathways of DKD-related HCC and developed a diagnostic nomogram for HCC based on PLVAP, C7, COL15A1, and MS4A6A. We confirmed with qPCR that PLVAP can be used as a blood marker to assess the risk of HCC in DKD patients