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Abstract Chronic hepatitis C virus (HCV) infection is an important public health issue. However, knowledge on how the virus remodels the metabolic and immune response toward hepatic pathologic environment is limited. The transcriptomic and multiple evidences reveal that the HCV core protein–intestine‐specific homeobox (ISX) axis promotes a spectrum of metabolic, fibrogenic, and immune modulators (e.g., kynurenine, PD‐L1, and B7‐2), regulating HCV‐infection relevant pathogenic phenotype in vitro and in vivo. In a transgenic mice model, the HCV core protein–ISX axis enhance metabolic disturbance (particularly lipid and glucose metabolism) and immune suppression, and finally, chronic liver fibrosis in a high‐fat diet (HFD)‐induced disease model. Mechanistically, cells with HCV JFH‐1 replicons upregulate ISX and, consequently, the expressions of metabolic, fibrosis progenitor, and immune modulators via core protein‐induced nuclear factor‐κB signaling. Conversely, cells with specific ISX shRNAi inhibit HCV core protein‐induced metabolic disturbance and immune suppression. Clinically, the HCV core level is significantly correlated with ISX, IDOs, PD‐L1, and B7‐2 levels in HCC patients with HCV infection. Therefore, it highlights the significance of HCV core protein–ISX axis as an important mechanism in the development of HCV‐induced chronic liver disease and can be a specific therapeutic target clinically.

BackgroundFew studies assess cord blood biomarkers to predict prenatal exposure to di(2-ethylhexyl) phthalate (DEHP) on the development of allergic diseases later in childhood. IL-33 has been indicated to play an important role in allergic diseases. We evaluated the association of prenatal DEHP exposure and IL-33 in cord blood on the development of allergic diseases. We also investigated the mechanism of DEHP in human lung epithelial cells and asthma animal models.Methods66 pregnant women were recruited, and their children followed when they were aged 3 years. Maternal urinary DEHP metabolites were determined using liquid chromatography-electrospray-ionization-tandem mass spectrometry. The effect of DEHP on IL-33 production was investigated in human lung epithelial cells and club cell-specific aryl hydrocarbon receptor (AhR) deficiency mice. ELISA and RT-PCR, respectively, measured the IL-33 cytokine concentration and mRNA expression.ResultsThe concentrations of maternal urinary DEHP metabolites and serum IL-33 in cord blood with childhood allergy were significantly higher than those in the non-childhood allergy group. DEHP and MEHP could induce IL-33 production and reverse by AhR antagonist and flavonoids in vitro. Enhanced ovalbumin-induced IL-4 and IL-33 production in bronchoalveolar lavage fluid (BALF) by DEHP exposure and suppressed in club cell-specific AhR null mice. Kaempferol has significantly reversed the DEHP effect in the asthma animal model.ConclusionsCord blood IL-33 level was correlated to childhood allergy and associated with maternal DEHP exposure. IL-33 might be a potential target to assess the development of DEHP-related childhood allergic disease. Flavonoids might be the natural antidotes for DEHP.

Acute lymphoblastic leukaemia (ALL) is the most prevalent cancer in children, and excessive iron buildup resulting from blood transfusions and chemotherapy potentially has a negative impact on treatment outcomes and prognosis in patients with ALL. Therefore, initiating early iron chelation therapy during ALL treatment is a logical approach. Ideally, the selected iron chelator should also possess anti-leukaemia properties. The aim of the present study was to explore the potential impact and underlying mechanism of deferasirox (DFX) in ALL therapy. This study proved that DFX, an iron chelator, is capable of inducing leukaemia cell death through ferroptosis, which is achievable by increasing the expression of acetylated nuclear factor erythroid 2-related factor 2 (NRF2). More specifically, NRF2 acetylation on Lys599 was facilitated by acetyltransferase-p300/CBP. These findings indicate that DFX could serve as a potent adjunctive medication for patients with ALL. Moreover, DFX may offer dual benefits in ALL treatment, functioning as both an iron chelator and NRF2-modulating agent. Further research and clinical trials are necessary to fully elucidate the therapeutic potential of DFX in patients with ALL and incorporate it into treatment protocols.

There is growing concern regarding air pollutants (NOx, SOx, and PM) and carbon emissions from ocean-going vessels in harbor areas and the role of high-voltage shore connection (HVSC) systems in mitigating these emissions during vessel berthing. The HVSC operates as a TN grounding system in humid environments, and it needs a proper grounding design to ensure safety when faults occur. This article intends to examine the overvoltage resulting from fault currents and its implications for the safety of operators when a single line-to-ground fault takes place within the design of HVSC grounding systems. The assessment is carried out by employing actual scenarios and parameters from a container berth at Kaohsiung Harbor in Taiwan. Considering site conditions, such as the wet ground surface, human body resistance, and electric shock duration, the tolerable safe voltage level is derived using IEEE Std. 80 and IEC 60479-1. Based on the shore power system grounding architecture specified in IEEE/IEC 80005-1, an equivalent circuit model is constructed to calculate the fault currents using symmetrical component analysis. The actual touch voltages generated in various locations are analyzed under scenarios of connecting or disconnecting the equipotential bonding between the ship and the shore using neutral grounding resistor (NGR) designs. This article delves into the scenarios of electric shock that may occur during the operation of an actual container ship’s shore power system. It evaluates whether various contact voltage values exceed current international standards and verifies the grounding design and safety voltage specifications of IEEE/IEC 80005-1. According to the results of this study, the use of NGR and protective earthed neutral (PEN) conductors in HVSC is crucial. This can limit fault currents, reduce touch voltage, and ensure the safety of personnel and equipment. Therefore, ensuring and monitoring equipment conductors and adopting NGRs of appropriate sizes are crucial elements in maintaining electrical safety in HVSC systems.

This paper addresses the growing concern over air pollutant emissions (NOx, SOx, PM, CO2) from ocean-going vessels in harbor areas and the role of Onshore Power Supply (OPS) systems in mitigating these emissions during vessel berthing. However, the slow progress in global shore power facilities is attributed to safety- and specification-related concerns. Our study conducts a comprehensive analysis, comparing international shore power regulations, with a specific focus on the IEC/IEEE 80005-1 standard and guidelines from various ship classification societies. We introduce checklists, scoring tables, and spider diagrams to evaluate the regulatory content, highlighting the strengths and weaknesses of each approach. Furthermore, this paper emphasizes the significance of a well-defined operational process for high-voltage shore connection (HVSC) to ensure the safety of OPS operations. We present process diagrams for key operational stages, based on IEC/IEEE 80005-1 specifications and evaluation criteria. The ultimate goal of this research is to drive the global adoption of shore power and foster the establishment of shore power facilities worldwide. This aligns with the broader environmental protection objectives of achieving cleaner ports and reducing emissions for a sustainable future.

This paper describes the non-contact optical detection of debris material that adheres to the substrates of color filters (CFs) and thin-film transistors (TFTs) by area charge-coupled devices (CCDs) and laser sensors. One of the optical detections is a side-view illumination by an area CCD that emits a coherency light to detect debris on the CF. In contrast to the height of the debris material, the image is acquired by transforming the geometric shape from a square to a circle. As a result, the side-view illumination from the area CCD identified the height of the debris adhered to the black matrix (BM) as well as the red, green, and blue of a CF with 95, 97, 98, and 99% accuracy compared to the golden sample. The uncertainty analysis was at 5% for the BM, 3% for the red, 2% for the green, and 1% for the blue. The other optical detection, a laser optical interception with a horizontal alignment, inspected the material foreign to the TFT. At the same time, laser sensors intercepted the debris on the TFT at a voltage of 3.5 V, which the five sets of laser optics make scanning the sample. Consequently, the scanning rate reached over 98% accuracy, and the uncertainty analysis was within 5%. Thus, both non-contact optical methods can detect debris at a 50 μm height or lower. The experiment presents a successful design for the efficient prevention of a valuable component malfunction.

BACKGROUND: Ambient particulate matter with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) is suggested to act as an adjuvant for allergen-mediated sensitization and recent evidence suggests the importance of T follicular helper (Tfh) cells in allergic diseases. However, the impact of PM2.5 exposure and its absorbed polycyclic aromatic hydrocarbon (PAHs) on Tfh cells and humoral immunity remains unknown. OBJECTIVES: We aimed to explore the impact of environmental PM2.5 and indeno[1,2,3-cd]pyrene (IP), a prominent PAH, as a model, on Tfh cells and the subsequent pulmonary allergic responses. METHODS: PM2.5- or IP-mediated remodeling of cellular composition in lung lymph nodes (LNs) was determined by mass cytometry in a house dust mite (HDM)-induced mouse allergic lung inflammation model. The differentiation and function of Tfh cells in vitro were analyzed by flow cytometry, quantitative reverse transcription polymerase chain reaction, enzyme-linked immunosorbent assay, chromatin immunoprecipitation, immunoprecipitation, and western blot analyses. RESULTS: Mice exposed to PM2.5 during the HDM sensitization period demonstrated immune cell population shifts in lung LNs as compared with those sensitized with HDM alone, with a greater number of differentiated Tfh2 cells, enhanced allergen-induced immunoglobulin E (IgE) response and pulmonary inflammation. Similarly enhanced phenotypes were also found in mice exposed to IP and sensitized with HDM. Further, IP administration was found to induce interleukin-21 (Il21) and Il4 expression and enhance Tfh2 cell differentiation in vitro, a finding which was abrogated in aryl hydrocarbon receptor (AhR)-deficient CD4+ T cells. Moreover, we showed that IP exposure increased the interaction of AhR and cellular musculoaponeurotic fibrosarcoma (c-Maf) and its occupancy on the Il21 and Il4 promoters in differentiated Tfh2 cells. DISCUSSION: These findings suggest that the PM2.5 (IP)–AhR–c-Maf axis in Tfh2 cells was important in allergen sensitization and lung inflammation, thus adding a new dimension in the understanding of Tfh2 cell differentiation and function and providing a basis for establishing the environment–disease causal relationship. [ABSTRACT FROM AUTHOR]