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D-amino acid oxidase correlation with neurofilament light chain in covid-infectedpatients
No full text[[abstract]]Background: COVID-19, which stands for Coronavirus Disease 2019, is caused by SARS-CoV-2 coronavirus and primarily manifests as a respiratory disease. However, the literature has reported its influence upon brain structure [1] and this observation finds additional support in the brain injury indicator, neurofilament light chain (NFL) [2]. Our NFL analysis in COVID-infected patients has indicated a correlation with the disease’ s severity. Nevertheless, the exact pathological pathway leading to brain neuronal injury remains elusive. Aims & Objectives: In our prior analyses, we presented the findings on the NFL levels and their association with the syndrome observed in COVID-19-infected patients. In this study, we extended our investigation to include the examination of the oxidative stress indicator, D-amino acid oxidase (DAO) [3], in order to assess its correlation with NFL and its potential significance in COVID-infected patients. Method: Plasma samples from 400 COVID-19 patients, drawn from 24 hospitals across Taiwan and sourced from the National Health Research Institutes (NHRI) Biobank, were utilized for the analysis of DAO via immunoassay. The NFL data was incorporated from our previous investigation. Statistical analyses encompassed the Mann-Whitney U test for comparing two groups, Spearman's correlation analysis for assessing bivariate correlations. To address the distribution in plasma DAO and NFL levels, we applied log-transformation before subjecting them to the general linear model, with age and gender adjustment. Results: Among the 391 COVID-infected patients analyzed, the average plasma DAO level was 136 ng/ml. Notably, the 10 patients exhibiting the most severe brain injury (NFL levels above 200 pg/ml) had a significantly higher average plasma DAO level of 568.2 ng/ml, in contrast to the group with less severe brain injury (NFL levels less than 200 pg.ml) composed of 381 patients, who had an average DAO level of 124.7 ng/ml (P=0.002). The DAO level displayed a significant correlation with the NFL level (Spearman’ s r=0.31, P<0.0001). Both the average NFL and DAO levels were significantly higher in patients over 50 years of age (P<0.0001, respectively), indicating a significant age-related trend. Male patients showed higher NFL and DAO levels than females (P=0.0002, and P<0.0001, respectively). The elevation in plasma NFL and DAO levels was most pronounced within the first 1-7 days after the COVID-19 diagnosis was confirmed, subsequently declining over the course of a month. Additionally, the correlation between DAO and NFL levels became more pronounced in patients age 50 and above (Spearman’ s r=0.37, P=0.0001) compared to those under 50 years of age (Spearman’ s r=0.237, P<0.0001). Furthermore, the DAO level exhibited strong correlations with renal function indicators, specifically creatinine (Spearman’ s r=0.30, P=0.0002), and blood urea nitrogen (BUN) (Spearman’ s r=0.23, P=0.008). Discussion & Conclusion: COVID-19 infection may lead to brain neuronal injury, particularly among male patients aged 50 and above. This neuronal injury exhibited a significant correlation with oxidative stress, as indicated by DAO. Furthermore, higher plasma DAO levels were associated with impaired kidney function, as indicated by elevated creatinine and BUN levels in clinical assessments. These results imply the involvement of oxidative stress in the pathological processes underlying brain neuronal injury
Three-dimensional simulations of double-diffusive convection of nanofluids and conjugate heat transfer in an n-shaped cavity with non-uniform boundary conditions using the multigrid method
No full text[[abstract]]Nanofluids are a new type of fluid designed to enhance heat transfer. Brownian motion is one of the key mechanisms by which nanofluids enhance heat transfer. In engineering applications involving double-diffusive convection, the temperature and concentration distributions on the surfaces of objects are often non-uniform. The aim of this study is to develop a fast solver to investigate: (1) the effects of non-uniform heating, non-uniform concentration, and Brownian motion on the heat and mass transfer in nanofluids within a threedimensional n-shaped cavity, and (2) the effects of the composition and arrangement of multi-layer solids on the conjugate heat transfer. The results show that the multigrid method can accelerate the computations by a factor of 1000. Compared to uniform heating and uniform concentration, non-uniform heating and non-uniform concentration can enhance the heat transfer rate by 23.73% and the mass transfer rate by 28.04%. The heat transfer rate of the 5-layer solid is 6.91% higher than that of the 3-layer solid. This study provides important guidance for improving heat and mass transfer efficiency, with potential applications in cooling of electronic devices, solar collectors, and chemical reactors
The zinc finger protein ZFP36L2 inhibits flavivirus infection via the 5′-3′ XRN1-mediated RNA decay pathway in the replication complexes
No full text[[abstract]]BackgroundThe zinc finger protein 36-like (ZFP36L) family is a CCCH-type group consisting of RNA-binding proteins, i.e., ZFP36L1 and ZFP36L2, which regulate cellular mRNA through the RNA decay pathway. ZFP36L1 combats flavivirus infections through the 5 '-3 ' XRN1 and 3 '-5 ' RNA exosome decay pathways. The present study clarified the role of human ZFP36L2 in the defense response of the host against flavivirus infection.MethodsCell lines with overexpression or knockdown of ZFP36L2 were established using lentiviral vectors carrying genes for overexpression and short-hairpin RNA targeting specific genes, respectively. A plaque assay was employed to determine the viral titer. Immunofluorescence and real-time quantitative polymerase chain reaction were used to measure the viral RNA levels. The in vitro-transcribed RNA transcript derived from a replication-dead Japanese encephalitis virus (JEV) replicon containing the renilla luciferase reporter gene (J-R2A-NS5mt) was used to assess the stability of the flavivirus RNA. An RNA immunoprecipitation assay was used to detect the protein-RNA binding ability. Confocal microscopic images were captured to analyze protein colocalization.ResultsZFP36L2 served as an innate host defender against JEV and dengue virus. ZFP36L2 inhibited flavivirus infection solely through the 5 '-3 ' XRN1 RNA decay pathway, whereas ZFP36L1 inhibited JEV infection via the 5 '-3 ' XRN1 and 3 '-5 ' RNA exosome RNA decay pathways. The direct binding between viral RNA and ZFP36L2 via its CCCH-type zinc finger motifs facilitated the degradation of flavivirus RNA mediated by 5 '-3 ' XRN1. Furthermore, ZFP36L2 was localized in processing bodies (PBs), which participate in the 5 '-3 ' XRN1-mediated RNA decay pathway. Nonetheless, the disruption of PBs did not affect the antiviral activity of ZFP36L2, suggesting that its localization is not essential for the function of the protein. Interestingly, the colocalization of ZFP36L2 and XRN1 with viral RNA and NS3 revealed that the antiviral activity of ZFP36L2 occurred within the replication complexes (RCs).ConclusionsIn summary, ZFP36L2 bound to and degraded viral RNA through the XRN1-mediated RNA decay pathway in the RCs, thereby inhibiting flavivirus replication. These findings provide valuable insights into the diverse antiviral mechanisms of the ZFP36-like family of proteins in the innate immune response against flavivirus infection
Real-time and regional analysis of the efficacy of anticancer drugs in a patient-derived intratumoral heterogeneous tumor microenvironment
No full text[[abstract]]Preclinical evaluation of anticancer drug efficacy utilizes 2D cell culture systems, tumoroids or experimental animal models, but it suffers from limitations such as inaccurate simulation of tumor microenvironments in living tumors, difficulty in regional analysis, and low throughput. Therefore, in this study, we developed a system named tumor-microenvironment-on-chip (TMoC) comprising a 3D dynamic tumor tissue culture system, which recreated diverse and heterogeneous cellular tumor microenvironments. In addition to the culture with a dynamic circulation, TMoC allowed users to perform real-time regional analysis, independently assessing the drug response from the normoxic area to the hypoxic area in a gradient manner. Through cell composition analysis and gene analysis, we proved that TMoC has a tumor environment with close resemblance to the original tumor environment. By comparing 15 drug testing results with animal experiments, we proved that TMoC is 93% consistent with the response results of animal experiments. In addition, we confirmed that either mouse- or patient-derived tumor cell lines can be cultured and tested in TMoC, indicating its immense potential for all aspects of preclinical drug evaluation
UV-induced photopatterning of the thermoresponsive properties of a poly(ethylene glycol)methylether acrylate-co-poly(N-isopropylacrylamide) hydrogel
No full text[[abstract]]Photopatterning offers a versatile and precise approach for modifying surface properties, making it a valuable technique in material design. Recent research demonstrates that polymer swelling can significantly enhance photodegradation, facilitating topographical patterning. Herein, this concept in stimuli-responsive hydrogels is explored, focusing on the thermoresponsive poly(ethylene glycol) methylether acrylate-co-poly(N-isopropylacrylamide) (PPEGA-PNIPAM) hydrogel. Surprisingly, it is observed that UV exposure not only partially degrades the hydrogel but also diminishes its thermal responsiveness. This effect enables selective deactivation of responsive properties of the PPEGA-PNIPAM, allowing for spatially defined variations in thermomechanical behavior through photolithography. By using these spatial differences, the hydrogel is programmatically transformed into a thermoresponsive actuator via a single-step photopatterning process, demonstrating a potential application of UV-induced change of thermoresponsiveness. Furthermore, incorporating gelatin methacrylate enhances biocompatibility, suggesting new possibilities for developing thermoresponsive bioactuators. Thus, the results demonstrate the potential of UV-induced modulation of stimuli-responsive properties of hydrogels and present new opportunities for creating multifunctional materials with tailored properties
Inner ear multiple primary cell type detection system
No full text[[abstract]]In vitro inner ear organoids gene therapy has advanced medical development, yet extracting inner ear primary cells (IEP) remains complex and needs to scarify mice. IEP cells contain multiple cell types, including progenitor cells, which can differentiate into hair-progenitor or neuro-progenitor cells. Accurate cell detection is essential to understand cell interactions and optimize culture conditions, ultimately reducing the sacrifice of mice. Current commercial software counts only one cell type at a time, often making errors in aggregated regions and taking at least five minutes per count. This paper proposes the Inner Ear Multiple Primary Cell Type Detection System (IEP-CDS), which addresses data limitations through IEP augmentation, overcomes detection errors in aggregated regions using preprocessing methods for training YOLO models, and achieves an F1-score greater than 20% compared to commercial software, completing counts in under one second. Furthermore, IEP-CDS provides rare IEP image data with expert labels. Overall, IEP-CDS effectively improves the efficiency of IEP detection in developing cell therapy for inner ear organoids
TEMPO-oxidized and carbon dots bound cellulosic nanostructured composite for sustainable fully biobased membranes for separation of nano/micro-sized particles/molecules
No full text[[abstract]]Membrane separation is a highly energy-efficient method for eliminating pollutants, ranging from micrometer- sized particles to angstrom-sized hydrated ions, from water. Nevertheless, the existing membrane technology, which uses costly synthetic materials, has become unsustainable for the most impoverished populations in the society. Thus, in the present study, a fully biobased sustainable functional membrane was developed for the effective separation of impurities from wastewater. A 2,2,6,6-Tetramethylpiperidin-1-oxyl (TEMPO) oxidation and integration of carbon dots (CDs) to cellulose nanofiber (CNF), resulted in significant improvements in the functional properties of membranes. The effectiveness of this modification resulted in a remarkable augmentation in surface zeta-potential as -68.5 mV for pristine CNF to-102 mV for CDs blended CNF. Fourier-transform infrared spectroscopy (FTIR) and X-ray photoelectron spectroscopy (XPS) studies confirmed the existence of essential functional groups that enabled better interactions within the composite membranes. The functionalization of CNF membranes resulted slightly lower in water flux from 1536 L/m2/h for pristine membranes and 1089 L/m2/h for TEMPOoxidized and 1402 L/m2/h for CDs integrated membranes. This hypothesis further confirmed that the tuned membranes were denser with a decreased pore size of 19.96 & Aring; for pristine and 17.49 & Aring; for TEMPO functionalized CNF membranes. We demonstrated that functionalized cellulose nanofiber membranes have high filtration efficiency for heavy metals (Fe3+, Cu2+), dyes (methylene blue and dyes from garment industry wastewater), and protein (bovine serum albumin). Moreover, such biobased composite membranes can be reused, thereby exerting a significant influence on the circular economy
Segmentectomy versus wedge resection for stage IA lung adenocarcinoma-A population-based study
No full text[[abstract]]BACKGROUND: Sublobar resection (SLR), including segmentectomy and wedge resection (WR), is an alternative to lobectomy for early-stage lung cancer due to its potential benefits in preserving lung function. However, the comparative outcomes between segmentectomy and WR for stage IA lung adenocarcinoma are equivocal. This population-based study aimed to compare overall survival between segmentectomy and WR. METHODS: Data on patients with clinical stage IA lung adenocarcinoma were collected from the Taiwan Cancer Registry between 2011 and 2018. The primary endpoint was overall survival. Further subgroup survival analyses were conducted based on tumor size. Propensity score matching (PSM) was used to balance baseline differences such as age and tumor stage between the two groups. Predictors of survival other than the surgical procedure were analyzed using a Cox regression model. RESULTS: In total, 6598 patients with stage IA lung adenocarcinoma undergoing SLR between 2011 and 2018 were enrolled, including 2061 and 4537 receiving segmentectomy and WR, respectively. The mean age was 60.3 ± 11.7 years, 66.2% were female, and 81.5% never smoked. After PSM, segmentectomy was associated with significantly better overall survival than WR (p = 0.019), especially for tumors larger than 2 cm (p < 0.001). Aside from segmentectomy, age ≤ 75 years, well-differentiated tumors, small tumor size, and the absence of nodal metastasis were associated with better overall survival. CONCLUSIONS: Segmentectomy offered superior overall survival for patients with tumors larger than 2 cm. For tumors smaller than 2 cm, the outcomes of segmentectomy and WR were comparable, offering flexibility in surgical decision-making. These findings highlight the need for individualized surgical approaches based on tumor characteristics
[[alternative]]Hypoxia amplifies arecoline-induced invasion and metastasis in oral squamous cell carcinoma-Insights into TGF-β1 signaling and collagen production
No full text[[abstract]]Background/Purpose: Betel quid chewing is a major risk factor for oral squamous cell carcinoma (OSCC), largely due to arecoline, a key alkaloid. Hypoxia, common in the tumor microenvironment, also influences cancer progression. This study investigated the combined effects of arecoline and hypoxia on proliferation, migration, and protein expression in tongue squamous cell carcinoma (SCC-25) cells, focusing on the TGF-b1 signaling pathway and type I collagen production. Materials and methods: SCC-25 cells were treated with arecoline and incubated for 24 h under normoxia or hypoxia. Cytotoxicity assays and Western blotting were performed to assess cell viability and protein expression. Results: At 2.5 mg/mL, arecoline enhanced SCC-25 cell proliferation under normoxia, while hypoxia suppressed this effect. Arecoline significantly promoted cell migration that was further amplified by hypoxia. Western blotting revealed that arecoline upregulated TGF-b1, Smad2/3, phosphorylated Smad2/3, and type I collagen. Under hypoxia, HIF1-a expression increased along with TGF-b 1 and type I collagen, indicating that hypoxia enhances arecoline-induced collagen production through TGF-b1 signaling. Conclusion: Arecoline stimulates SCC-25 cell proliferation and migration, with hypoxia amplifying these effects by promoting TGF-b1 signaling and type I collagen production. These findings suggest that betel quid consumption, in combination with hypoxia, may exacerbate the invasion and metastasis of OSCC
Crohn's disease but not ulcerative colitis elevated risk of end-stage renal disease and mortality: A Taiwan retrospective cohort study
No full text[[abstract]]Inflammatory bowel disease (IBD) is an autoinflammatory disease which may affect extraintestinal organs, including kidney. However, rare research showed that patients with IBD have higher risk of end-stage renal disease (ESRD). Furthermore, lack of studies compared the potential risk of ESRD and mortality among patients with ulcerative colitis (UC) and Crohn disease (CD). We conducted a nationwide cohort study using the National Health Insurance database in Taiwan, from January 2008 to December 2018. A total of 3204 patients diagnosed with IBD were enrolled. IBD cases were identified through the presence of a catastrophic illness certificate, including CD and UC. The study outcomes were the incidence of ESRD and mortality. ESRD diagnosis required a serious illness certificate and was identified using the corresponding ICD-10-CM codes. Mortality was recorded in the Taiwan Death Registry linked with the National Health Insurance database, Cox proportional hazards models were used to estimate the risk factors for ESRD and mortality among IBD patients. CD patients had a significantly higher risk of ESRD (adjust hazard ratio: 2.32, 95% confidence interval: 1.28-4.18) and mortality (adjust hazard ratio: 1.80, 95% confidence interval: 1.37-2.35) compared to healthy individuals. UC patients showed no difference in the risk of ESRD compared to healthy individuals. Instead, among IBD patients, UC poses a relatively lower risk for ESRD compared to other factors like age and other comorbidities. Elevated risk of ESRD and mortality was only noted in patients with CD but not UC. Surprisingly, UC patients had lower risk of ESRD and mortality than CD patients. These findings highlight distinctive patterns of risk associated with CD and UC, emphasizing the importance of considering disease subtype when assessing outcomes such as ESRD and mortality