Metastatic disease is the leading cause of cancer mortality. Identifying biomarkers and regulatory mechanisms is important toward developing diagnostic and therapeutic tools against metastatic ...cancer. In this study, we demonstrated that podocalyxin-like 1 (PODXL) is overexpressed in breast tumor cells and increased in lymph node metastatic cancer. Mechanistically, we found that the expression of PODXL was associated with cell motility and invasiveness. Suppression of PODXL in MDA-MB-231 cells reduced lamellipodia formation and focal adhesion kinase (FAK) and paxillin phosphorylation. PODXL knockdown reduced the formation of invadopodia, such as inhibiting the colocalization of F-actin with cortactin and suppressing phosphorylation of cortactin and neural Wiskott-Aldrich syndrome protein. Conversely, overexpression of PODXL in MCF7 cells induced F-actin/cortactin colocalization and enhanced invadopodia formation and activation. Invadopodia activity and tumor invasion in PODXL-knockdown cells are similar to that in cortactin-knockdown cells. We further found that the DTHL motif in PODXL is crucial for regulating cortactin phosphorylation and Rac1/Cdc42 activation. Inhibition of Rac1/Cdc42 impeded PODXL-mediated cortactin activation and FAK and paxillin phosphorylation. Moreover, inhibition of PODXL in MDA-MB-231 cells significantly suppressed tumor colonization in the lungs and distant metastases, similar to those in cortactin-knockdown cells. These findings show that overexpression of PODXL enhanced invadopodia formation and tumor metastasis by inducing Rac1/Cdc42/cortactin signaling network.
Peracetic acid (PAA) is a widely used green antimicrobial agent of the environmental protection chemicals, whose registered applications have expanded to include in sanitation at food processing and ...pasteurizers in beverage plants, agricultural premises, wineries and breweries, as well as the disinfection of medical supplies, to prevent biofilm formation in pulp industries, and as a water purifier and disinfectant. The thermal reactivity and hazard characteristics were evaluated for PAA solutions by calorimetry analysis methodology, where the thermal reaction and kinetic data were programmed by differential scanning calorimetry. The thermal stability screening test was able to determine the self-decomposition of PAA solutions, and to observe the initial exothermic temperature (
T
i
) and heat of decomposition (Δ
H
d
). The thermokinetic parameters of PAA were also calculated according to the experimental data by temperature programming and thermal analysis model with Arrhenius equation. The purpose of this study was to elucidate the self-heating exothermic excursions associated with the various PAA solutions via C++ programming language. Understanding the thermal decomposition hazard of PAA was beneficial to proactive safety protocol for the industrial process, storage, as well as transportation.
Peracetic acid (PAA) is potentially harmful because of its thermal hazards in industrial processes. Attention must be paid to the preparation, manufacturing, transportation, and storage because PAA ...may readily cause a thermal runaway reaction under various upset scenarios. PAA is classified an explosive substance in the governmental regulation in Taiwan. Here, 20 mass% of PAA was used to estimate the thermokinetic parameters by using differential scanning calorimetry. Heating rates employed were 1.0, 2.0, 4.0, and 8.0 °C min
−1
. We compared the four heating rates of thermal safety assessment with regard to process safety parameters, such as exothermic initial temperature (
T
0
) and heat of decomposition (Δ
H
d
). Finally, five kinetic analysis methods, along with differential isoconversional kinetic analysis, were used to estimate the apparent activation energy (
E
a
). The experimental results could be used helpful during the manufacturing process, transportation, and storage as the process safety parameter considerations to forestall thermal damage from happening, and to reach zero-disaster purposes as the ultimate goals.
Isoprene monomer (IPM) is a colorless, volatile liquid obtained from petroleum or coal tar that occurs naturally in many process plants. It is used chiefly to make synthetic rubber. Our study used ...calorimetric approaches to conduct thermal analysis and hazard assessment of aluminum oxide (Al
2
O
3
) and IPM relevant studies. Differential scanning calorimetry, thermal activity monitor III, thermogravimetry, and vent sizing package 2 were used to discuss thermal instability reaction of Al
2
O
3
, which adsorbed IPM, and find every possible reason for cases of fire to prevent any future recurrence of the package store and transport related hazards. By means of calorimetric analysis technology, we can observe thermal decomposition or mass loss for different adsorbed concentrations of IPM and Al
2
O
3
to discuss the related thermal stability parameters, such as exothermic onset temperature (
T
0
), heat of decomposition (Δ
H
d
), self-accelerating exothermic rate (d
T
d
t
−1
), pressure rise rate, and maximum reaction temperature (
T
max
). Then, we can understand the potential hazard factors that contribute to disasters related to processing, transport, and storage of security controls and reaction process design.
碩士
國立雲林科技大學
環境與安全衛生工程系碩士班
101
Peracetic acid (PAA) is widely used as an epoxidation agent for olefins. It is also commonly used as disinfection in various industries, even wastewater handling, due to ...its excellent virucidal and fungicidal effectiveness. In addition, PAA at low concentrations is also used to disinfect in medical categories, food-processing, and beverage industries. However, PAA is instable upon heat and has potential hazard because of its thermal runaway potentiality in the process of manufacturing, storaging, and transporting. Concentration of PAA was decayed, in this research, high performance liquid chromatography (HPLC) was used to confirm concentration. Furthermore, this investigation employed three calorimeters as differential scanning calorimetry (DSC), thermal activity monitor III (TAM III), and vent sizing package 2 (VSP2) were employed to receive and elucidate the kinetic data for thermal decomposition of PAA. Therefore, thermal instabilities of PAA were investigated exclusively for
Endogenous signals, namely nitric oxide (NO) and electrons, play a crucial role in regulating cell fate as well as the vascular and neuronal systems. Unfortunately, utilizing NO and electrical ...stimulation in clinical settings can be challenging due to NO's short half‐life and the invasive electrodes required for electrical stimulation. Additionally, there is a lack of tools to spatiotemporally control gas release and electrical stimulation. To address these issues, an “electromagnetic messenger” approach that employs on‐demand high‐frequency magnetic field (HFMF) to trigger NO release and electrical stimulation for restoring brain function in cases of traumatic brain injury is introduced. The system comprises a NO donor (poly(S‐nitrosoglutathione), pGSNO)‐conjugated on a gold yarn‐dynamos (GY) and embedded in an implantable silk in a microneedle. When subjected to HFMF, conductive GY induces eddy currents that stimulate the release of NO from pGSNO. This process significantly enhances neural stem cell (NSC) synapses' differentiation and growth. The combined strategy of using NO and electrical stimulation to inhibit inflammation, angiogenesis, and neuronal interrogation in traumatic brain injury is demonstrated in vivo.
An “electromagnetic messenger” approach utilizing high‐frequency magnetic fields (HFMF) to trigger nitric oxide (NO) release and electrical stimulation is developed for restoring brain function in traumatic brain injury. Upon exposure to HFMF, in vivo experiments demonstrated the combined strategy's effectiveness in inhibiting inflammation, angiogenesis, and neuronal interrogation in traumatic brain injury.
Abstract
Traumatic brain injury (TBI) triggers inflammatory response and glial scarring, thus substantially hindering brain tissue repair. This process is exacerbated by the accumulation of activated ...immunocytes at the injury site, which contributes to scar formation and impedes tissue repair. In this study, a mussel‐inspired nitric oxide‐release microreservoir (MINOR) that combines the features of reactive oxygen species (ROS) scavengers and sustained NO release to promote angiogenesis and neurogenesis is developed for TBI therapy. The injectable MINOR fabricated using a microfluidic device exhibits excellent monodispersity and gel‐like self‐healing properties, thus allowing the maintenance of its structural integrity and functionality upon injection. Furthermore, polydopamine in the MINOR enhances cell adhesion, significantly reduces ROS levels, and suppresses inflammation. Moreover, a nitric oxide (NO) donor embedded into the MINOR enables the sustained release of NO, thus facilitating angiogenesis and mitigating inflammatory responses. By harnessing these synergistic effects, the biocompatible MINOR demonstrates remarkable efficacy in enhancing recovery in mice. These findings benefit future therapeutic interventions for patients with TBI.
The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulting in the emergence of new variants that are resistant to existing vaccines and therapeutic antibodies, ...has raised the need for novel strategies to combat the persistent global COVID-19 epidemic. In this study, a monoclonal anti-human angiotensin-converting enzyme 2 (hACE2) antibody, ch2H2, was isolated and humanized to block the viral receptor-binding domain (RBD) binding to hACE2, the major entry receptor of SARS-CoV-2. This antibody targets the RBD-binding site on the N terminus of hACE2 and has a high binding affinity to outcompete the RBD. In vitro, ch2H2 antibody showed potent inhibitory activity against multiple SARS-CoV-2 variants, including the most antigenically drifted and immune-evading variant Omicron. In vivo, adeno-associated virus (AAV)-mediated delivery enabled a sustained expression of monoclonal antibody (mAb) ch2H2, generating a high concentration of antibodies in mice. A single administration of AAV-delivered mAb ch2H2 significantly reduced viral RNA load and infectious virions and mitigated pulmonary pathological changes in mice challenged with SARS-CoV-2 Omicron BA.5 subvariant. Collectively, the results suggest that AAV-delivered hACE2-blocking antibody provides a promising approach for developing broad-spectrum antivirals against SARS-CoV-2 and potentially other hACE2-dependent pathogens that may emerge in the future.
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Tao and colleagues developed AAV-mediated delivery of hACE2-blocking monoclonal antibody ch2H2, which enables sustained high-level antibody presence in mice. This approach offers broad-spectrum protection against SARS-CoV-2 variants infection while also ameliorating pulmonary histopathology. It holds promise as a solution to combat upcoming COVID-19 waves and emerging hACE2-dependent pathogens.
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