Asia Pacific Academy of Science Pte. Ltd.
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The Role of Activator Protein-1 in Sepsis-Associated Encephalopathy: Inhibition of Microglial Activation via Transcriptional Regulation of Cold-Inducible RNA-Binding Protein
No full textBackground: Cold-inducible RNA-binding protein (CIRP) promotes inflammatory responses. Activator protein-1 (AP-1) potentially acts as a transcriptional regulator of CIRP. Consequently, this study aims to investigate the impact of the AP-1-CIRP axis on microglial activation to mitigate neural injury in sepsis-associated encephalopathy (SAE). Methods: We employed a Streptococcus pneumoniae-induced mouse SAE model in vivo and lipopolysaccharide (LPS)-induced BV-2 cells for in vitro experiments. The spatial exploration ability of mice was assessed using the Morris water maze assay. Levels of inflammatory factors were determined via enzyme-linked immunosorbent assay. Microglial activation in the cerebral cortex and hippocampus was determined through immunohistochemistry or immunofluorescence. Degenerated neurons were identified using Fluoro-Jade C staining. Quantifications of mRNA and protein levels in tissues, cells, and supernatants were conducted through real-time quantitative polymerase chain reaction and Western blot, respectively. The binding relationship between AP-1 and CIRP was analyzed using JASPAR and chromatin immunoprecipitation. Reactive oxygen species (ROS) levels were measured via 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) assay. Results: Silencing of AP-1 led to reduced levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β levels, as well as a decrease in Iba1+ cells in SAE mice. Cognitive impairment and neuronal degeneration in the brains of SAE mice were partially alleviated by AP-1 silencing. Furthermore, elevated levels of FOS Like 1 (Fosl1), JunB Proto-Oncogene (Junb), Jun Proto-Oncogene (Jun), and CIRP in SAE mice were partially attenuated by AP-1 silencing. We observed that AP-1 is bound to the CIRP promoter region. Inhibition of AP-1 or CIRP reduced levels of inflammatory factors, CD11b+ cells, ROS, pro-apoptosis-related protein, and extracellular CIRP. Conversely, AP-1 overexpression exhibited the opposite effects reversed by CIRP silencing in LPS-induced cells. Conclusion: Inhibition of AP-1 ameliorates neuronal injury in SAE by suppressing microglial activation through transcriptional regulation of CIRP
DEPDC1 Promotes Cell Growth and Reduces Radiosensitivity of Cervical Cancer Cells
No full textBackground: Cervical cancer (CC) is one of the prevalent cancers among females. The DEP domain containing 1 (DEPDC1) has been found to play a crucial role in the progression of cancers by promoting tumorigenesis. However, the regulatory role of DEPDC1 in CC progression remains unclear. Therefore, this study aimed to investigate the regulatory functions of DEPDC1, and its associated pathway in the progression of CC. Methods: Initially, using the UALCAN database, the higher expression level of DEPDC1 was confirmed in both CC and normal tissues. However, the expression levels of proteins were evaluated using immunohistochemistry (IHC) assay and western blot analysis. Moreover, the viability and proliferation capabilities of the cells were determined using cell counting kit-8 (CCK-8) and 5-ethynyl-2′-deoxyuridine (EdU) assays, respectively. Furthermore, the radiosensitivity of CC cells was evaluated using colony formation assay. The level of gamma-H2A histone family member X (γ-H2AX) was assessed within the small interfering RNA-negative control (si-NC), si-DEPDC1#1, si-NC+4 Gray (Gy), and si-DEPDC1#1+4 Gy groups using Immunofluorescence (IF) assay. The cell apoptosis was examined in the si-NC, si-DEPDC1#1, si-NC+4 Gy, and si-DEPDC1#1+4 Gy groups using flow cytometry. Additionally, in vivo assays were utilized to determine the growth of tumors within the short hairpin RNA-negative control (sh-NC), sh-DEPDC1, ionizing radiation (IR), and IR+sh-DEPDC1 groups of mice. Results: It was observed that CC patients with higher DEPDC1 expression level showed poor prognosis. The expression of DEPDC1, both at mRNA and protein level, was significantly elevated in CC tissues (p < 0.05). Moreover, silencing of DEPDC1 suppressed tumor cell growth and proliferation in CC (p < 0.05). Furthermore, radiosensitivity of CC cells was found at 0, 2, 4, 6 Gray-infrared radiation treatment (p < 0.05). However, it was observed that the radiosensitivity of both HeLa-radiation resistant (RR) and SiHa-RR cells was significantly enhanced following DEPDC1 knockdown (p < 0.05). Similarly, inhibition of DEPDC1 enhanced radiation-induced cell apoptosis in CC (p < 0.05) and retarded the forkhead box M1 (FOXM1)/ubiquitin-like plant homeodomain (PHD) and RING finger domain containing 1 (UHRF1) pathway, thereby influencing CC progression (p < 0.05). Additionally, the knockdown of DEPDC1 retarded tumor growth and promoted radiosensitivity in vivo (p < 0.05). Conclusion: The DEPDC1 accelerated cell growth and reduced radiosensitivity in CC by modulating the FOXM1/UHRF1 pathway. These findings suggest that DEPDC1 might be a potential bio-target for the treatment of CC
Diagnostic Efficacy of Urinary IGFBP7 and TIMP2 Levels in Early Acute Kidney Injury
Get PDFBackground: Acute kidney injury (AKI) is an acute renal insufficiency syndrome, often associated with high morbidity and mortality. Currently, there is a lack of early diagnostic biomarkers. Urine Tissue inhibitor of metalloproteinases 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) serve as markers of G1 cell cycle arrest and foretell AKI development. Therefore, this study aimed to investigate the diagnostic efficacy of these two markers in detecting AKI. Method: We analysed urine and serum samples obtained from the normal control, patients without AKI (NO-AKI), and AKI groups. We assessed the levels of Neutrophil gelatinase-associated lipocalin (NGAL), TIMP2, and IGFBP7 in urine and serum creatinine (Scr) levels utilizing corresponding enzyme linked immunosorbent assay (ELISA) kits. The diagnostic values of urinary NGAL, TIMP2, IGFBP7, and serum Scr were evaluated through receiver operating characteristic (ROC) curve analysis. Moreover, the hypoxia model of renal tubule cells was used to simulate AKI in vitro, and the expression levels of TIMP2 and IGFBP7 were determined at different time following hypoxia induction. Results: There were significant differences in urinary TIMP2, IGFBP7, and NGAL levels as well as Scr levels among the three experimental groups. The urinary TIMP2, IGFBP7, and NGAL levels, as well as Scr levels were significantly higher in the AKI group than those in the normal and the NO-AKI groups (p < 0.01). However, the urinary IGFBP7 and Scr levels were elevated in NO-AKI group compared to the normal group. Moreover, there was no substantial difference in urinary TIMP2 and NGAL levels between the NO-AKI and normal groups (p > 0.05). Additionally, ROC curve analysis revealed that the urinary IGFBP7 had excellent diagnostic performance for AKI, followed by urinary TIMP2, NGAL, and Scr. Furthermore, the TIMP2 and IGFBP7 levels elevated in a time dependent manner, reaching the peak at 120 minutes after hypoxia induction, followed by a gradual decline (p < 0.001). Conclusions: The present study shows that IGFBP7 and TIMP2 have good diagnostic value for early AKI, which are potential biomarkers for early screening of high-risk AKI patients
Angiotensin II Regulates the ROMK Channel in the Renal Distal Convoluted Tubule via the MAPK-dependent Pathway
No full textBackground: Hypertension serves as a significant risk factor for various cardiovascular and renal diseases, necessitating a deeper understanding of its pathogenesis, as well as the identification of potential therapeutic targets. This study aims to investigate the molecular mechanisms underlying hypertension, specifically focusing on the regulation of renal outer medullary potassium (ROMK) channels by the mitogen-activated protein kinase (MAPK) signaling pathway and its impact on water-electrolyte metabolism. Methods: A mouse hypertension model was constructed, and mouse primary renal tubular epithelial cells were stimulated with Angiotensin II (AngII). Differential gene expression, key signaling pathways, and molecules were analyzed utilizing bioinformatics approaches. Furthermore, Western blot and quantitative polymerase chain reaction (qPCR) analyses were used to assess the expression of the ROMK channel both at mRNA and protein levels as well as the signaling molecule MAPK. Additionally, the MAPK inhibitors were applied to further elucidate the involvement of this signaling pathway in hypertension. Results: The contents of sodium, potassium, chloride in mouse blood pressure (BP) and urine were detected. A gradual increase was observed in both mRNA and protein levels of ROMK following AngII stimulation, reaching a peak on day 7. Furthermore, in vitro experiments revealed that following AngII stimulation, ROMK protein and mRNA expression levels were significantly increased compared to the control cells. Similarly, the expression levels of Phospholipase C (PLC), Protein kinase C (PKC), and MAPK proteins were significantly higher. Furthermore, Western blot analysis revealed a significant reduction in the levels of ROMK in renal tubular epithelial cells. Meanwhile, the BP decreased, and the amount of sodium and potassium ions decreased. Conclusion: The study demonstrates the potential significance of AngII regulating the upregulation of ROMK channels through MAPK-dependent pathway to promote potassium excretion and affect water-salt balance, leading to the development of hypertension
Notopterol Inhibits TNF-α-Induced C2C12 Myoblast Apoptosis by Stimulating the PI3K/AKT Pathway
Get PDFBackground: Qianghuo is the root and rhizome of the umbelliferae plant Notopterygium incisum Ting ex H.T. Chang (NI) or N. franchetii H. de Boiss. Notopterol (linear furocoumarin) is the most effective component of Notopterygium incisum. Notopterol exhibits antipyretic, analgesic, anti-inflammatory, anti-oxidation, and anti-apoptosis effects. However, the effects of notopterol on skeletal muscle cells are unclear. This study aims to evaluate the influence of notopterol on the activity of myoblast as well as its inhibiting effect on apoptosis induced by tumor necrosis factor-alpha (TNF-α). Method: We assessed the effect of notopterol on TNF-α-induced C2C12 apoptosis and its underlying mechanisms. Cell viability and apoptosis were evaluated using the CCK-8 and Annexin V-FITC/PI, respectively. The expressions of apoptosis-related proteins and pathways were assessed utilizing western blot (WB) analysis. Additionally, the role of notopterol in the phosphatidylinositol 3-kinases/AKT (PI3K/AKT) pathway was explored using specific inhibitors of PI3K. Results: We observed that notopterol increased the activity of TNF-α-treated myoblasts (p < 0.05). Furthermore, flow cytometry, Hoechst-33258 staining, and WB analysis revealed that notopterol reduced TNF-α-induced apoptosis of C2C12 myoblasts by increasing B Cell Lymphoma 2 (BCL-2) levels and decreasing BCL-2-associated X protein (BAX), caspase-3, and caspase-9 levels (p < 0.05). Additionally, notopterol can activate the PI3K/AKT pathway in the first place, then can increase AKT phosphorylation and BCL-2 expression and decrease BAX and caspase-3 expression sequentially. These effects were reversed with the introduction of LY294002, which is a specific inhibitor of PI3K (p < 0.05). Conclusions: Notopterol can affect C2C12 through PI3K/AKT, thus protecting against TNF-α-induced C2C12 myoblast apoptosis. Therefore, notopterol can be used to treat amyotrophy, providing insights into Sarcopenia prevention and treatment
Deciphering avian emotions: A novel AI and machine learning approach to understanding chicken vocalizations
Get PDFIn this groundbreaking study, we present a novel approach to interspecies communication, focusing on the understanding of chicken vocalizations. Leveraging advanced mathematical models in artificial intelligence (AI) and machine learning, we have developed a system capable of interpreting various emotional states in chickens, including hunger, fear, anger, contentment, excitement, and distress. Our methodology employs a cutting-edge AI technique we call Deep Emotional Analysis Learning (DEAL), a highly mathematical and innovative approach that allows for the nuanced understanding of emotional states through auditory data. DEAL is rooted in complex mathematical algorithms, enabling the system to learn and adapt to new vocal patterns over time. We conducted our study with a sample of 80 chickens, meticulously recording and analyzing their vocalizations under various conditions. To ensure the accuracy of our system’s interpretations, we collaborated with a team of eight animal psychologists and veterinary surgeons, who provided expert insights into the emotional states of the chickens. Our system demonstrated an impressive accuracy rate of close to 80%, marking a significant advancement in the field of animal communication. This research not only opens up new avenues for understanding and improving animal welfare but also sets a precedent for further studies in AI-driven interspecies communication. The novelty of our approach lies in its application of sophisticated AI techniques to a largely unexplored area of study. By bridging the gap between human and animal communication, we believe our research will pave the way for more empathetic and effective interactions with the animal kingdom
Walking the Camino de Santiago: A case study of endurance and wearable technology
Get PDFThis case study examines the use of wearable technology to monitor physiological and performance metrics during a 100+ km pilgrimage on the Camino de Santiago. The subject, a 34-year-old female amateur triathlete recovering from an ankle injury, used a Garmin Enduro device to track key data over five days. The study focuses on heart rate, speed, cadence, caloric expenditure, and environmental factors, shedding light on how wearable devices can provide valuable insights into endurance performance. Correlation analysis highlights significant relationships between physical performance and physiological markers, offering a deeper understanding of how such technology can enhance both athletic performance and the overall pilgrimage experience
Henri Lefebvre and planetary urbanization: Progress and prospect
Get PDFHenri Lefebvre, a key Marxist urban theorist, introduced the concept of ‘Planetary Urbanization,’ a cutting-edge theory addressing emerging global forms of capitalist urbanization, where traditional urban theories have limited explanatory power. This paper reviews studies on planetary urbanization over the past 20 years in relation to Lefebvre’s urban theories. The report categorizes planetary urbanization’s contributions to urban theory into two primary aspects. First, it innovatively incorporates the processes of urbanization and the extended operational landscapes within urban research. Second, it proposes new trajectories for urban politics by reshaping Lefebvre’s concept of ‘the right to the city.’ However, by tracing Lefebvre’s theories, the report argues that planetary urbanization overlooks his emphasis on ‘everyday life’ while aligning with his views on generality and universality. Consequently, this dehumanized approach fails to uncover the significant political potential embedded in urban daily life. Additionally, by neglecting the differences among urban populations, the theory adopts a naive perspective on the subaltern’s capacity to articulate their ‘right to the city.’ Moreover, as a Eurocentric theory rooted in Western urbanization history, it inadequately explains context-specific events occurring in the urbanization of the Global South. Thus, this paper suggests that future research on planetary urbanization should incorporate considerations of urban everyday life, recognize social differences, and account for context-specific dependencies
Research on interdisciplinary project-based geography fieldwork in education for sustainable development
Get PDFThe ability to solve real-world problems for a sustainable future has become a worldwide consensus, and interdisciplinary competencies and project-based learning (PBL) have become the focus of curriculum reform in China. This study investigates the effectiveness of interdisciplinary PBL fieldwork in geography education for sustainable development, focusing on the perceptions of students from a junior high school in Chongming, Shanghai, of the interdisciplinary effectiveness of PBL fieldwork. Over a one-month pilot program, the results suggest that the new fieldwork approach did not achieve the expected benefits. The significant gains of students can be grouped into four perspectives, namely, understanding of nature and classroom knowledge; problem-solving skills and environmental action; scientific spirit, environmental awareness, and interest in geography; and understanding of local needs and sustainable development issues, which increased their interest in learning. The students generally accepted the ability to collect information and data and the thinking ability of circular development. The influencing factors of activity effectiveness include the time and difficulty of the activity, cognitive and knowledge levels, learning habits of students, student participation, and teaching experience of teachers. The study offers valuable insights for improving fieldwork in other regions and for future research
A novel tucker decomposition driven taxi travel demand forecasting algorithm
Get PDFThis research aims to enhance taxi travel demand forecasting for sustainable urban traffic management and planning. We extend the Seasonal Autoregressive Integrated Moving Average model into a high-dimensional tensor form by treating the urban transport network as a Euclidean space and introducing Tucker decomposition. This novel approach, both theoretically significant and practically applicable, represents time series data as tensors to better capture multimodal structures and correlations, improving predictive accuracy. Tucker decomposition reduces computational complexity and memory requirements, making it ideal for large-scale urban traffic network prediction. Experiments on six real-world datasets show that the model’s MAE and RMSE are reduced by about 39.43% and 27.01% on average, respectively, compared to the baseline model. Notably, the model is computationally very efficient and takes only a relatively short time to train., suitable for real-time traffic management, congestion mitigation, and resource optimization. In summary, this work innovates time series analysis, providing an efficient and precise tool for urban traffic management and planning, contributing to sustainable urban transportation advancement