The proton exchange membrane water electrolyzer (PEMWE) requires a high operating voltage for hydrogen production to accelerate the decomposition of hydrogen molecules so that the PEMWE ages or ...fails. According to the prior findings of this R&D team, temperature and voltage can influence the performance or aging of PEMWE. As the PEMWE ages inside, the nonuniform flow distribution results in large temperature differences, current density drops, and runner plate corrosion. The mechanical stress and thermal stress resulting from pressure distribution nonuniformity will induce the local aging or failure of PEMWE. The authors of this study used gold etchant for etching, and acetone was used for the lift-off part. The wet etching method has the risk of over-etching, and the cost of the etching solution is also higher than that of acetone. Therefore, the authors of this experiment adopted a lift-off process. Using the flexible seven-in-one (voltage, current, temperature, humidity, flow, pressure, oxygen) microsensor developed by our team, after optimized design, fabrication, and reliability testing, it was embedded in PEMWE for 200 h. The results of our accelerated aging test prove that these physical factors affect the aging of PEMWE.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The voltage, current, temperature, humidity, pressure, flow, and hydrogen in the high-pressure proton exchange membrane water electrolyzer (PEMWE) can influence its performance and life. For example, ...if the temperature is too low to reach the working temperature of the membrane electrode assembly (MEA), the performance of the high-pressure PEMWE cannot be enhanced. However, if the temperature is too high, the MEA may be damaged. In this study, the micro-electro-mechanical systems (MEMS) technology was used to innovate and develop a high-pressure-resistant flexible seven-in-one (voltage, current, temperature, humidity, pressure, flow, and hydrogen) microsensor. It was embedded in the upstream, midstream, and downstream of the anode and cathode of the high-pressure PEMWE and the MEA for the real-time microscopic monitoring of internal data. The aging or damage of the high-pressure PEMWE was observed through the changes in the voltage, current, humidity, and flow data. The over-etching phenomenon was likely to occur when this research team used wet etching to make microsensors. The back-end circuit integration was unlikely to be normalized. Therefore, this study used lift-off process to further stabilize the quality of the microsensor. In addition, the PEMWE is more prone to aging and damage under high pressure, so its material selection is very important.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A novel data-hiding methodology, denoted as digital invisible ink (DII), is proposed to implement secure steganography systems. Like the real-world invisible ink, secret messages will be correctly ...revealed only after the marked works undergo certain prenegotiated manipulations, such as lossy compression and processing. Different from conventional data-hiding schemes where content processing or compression operations are undesirable, distortions caused by prenegotiated manipulations in DII-based schemes are indispensable steps for revealing genuine secrets. The proposed scheme is carried out based on two important data-hiding schemes: spread-spectrum watermarking and frequency-domain quantization watermarking. In some application scenarios, the DII-based steganography system can provide plausible deniability and enhance the secrecy by taking cover with other messages. We show that DII-based schemes are indeed superior to existing plausibly deniable steganography approaches in many aspects. Moreover, potential security holes caused by deniable steganography systems are discussed.
IMPORTANCE: The incidence of inflammatory bowel disease (IBD) is increasing in newly industrialized countries but disease etiologies remain unclear. OBJECTIVE: To investigate the association between ...physical fitness and subsequent IBD risk among children and adolescents in Taiwan. DESIGN, SETTING, AND PARTICIPANTS: This nationwide cohort study was conducted between January 1, 2010, and December 31, 2018. Data sources included the Taiwan National Health Insurance Research Database, the National Student Fitness Tests Database, and the Air Quality Monitoring System Database. This study included students who were aged 10 years, completed physical fitness tests between grades 4 and 13, and had at least 1 year of follow-up. Data analysis was last performed on January 15, 2023. EXPOSURES: Physical fitness tests included cardiorespiratory endurance (CE; number of minutes to complete an 800-m run), musculoskeletal endurance (ME; number of bent-leg curl-ups in 1 minute), musculoskeletal power (MP; standing broad jump distance), and flexibility fitness (FF; 2-leg sit-and-reach distance). MAIN OUTCOMES AND MEASURES: Subsequent risk of IBD was compared among students based on physical fitness test results. Six-year cumulative incidences and hazard ratios (HRs) were calculated after adjusting for competing mortality. Performance was reported in quantiles, ranging from 1 (best) to 4 (poorest). RESULTS: There were 4 552 866 students who completed physical fitness tests between grades 4 and 13; among these students, 1 393 641 were aged 10 years and were included in the analysis. Six-year cumulative incidence of IBD risk was lowest among students in the best-performing quantile of CE (quantile 1, 0.74% 95% CI, 0.63%-0.86%; P < .001), ME (0.77% 0.65%-0.90%; P < .001), and MP (0.81% 0.68%-0.93%; P = .005) compared with students in quantiles 2 through 4, respectively; however, no association was observed for quantiles of FF. After adjusting for competing HRs for mortality and other confounders, better CE was inversely associated with IBD risk (adjusted HR, 0.36 95% CI, 0.17-0.75; P = .007). Other measures of physical fitness were not independently associated with IBD risk. CONCLUSIONS AND RELEVANCE: The results of this study suggest that CE was inversely associated with IBD risk among children and adolescents, but ME, MP, and FF were not independently associated with IBD risk. Future studies that explore the mechanisms are needed.
Hepatopulmonary syndrome (HPS) is characterized by hypoxia in patients with chronic liver disease. The mechanism of HPS includes pulmonary vasodilatation, inflammation, and angiogenesis. ...Prostaglandins synthesized by cyclooxygenases (COX) participate in vascular responsiveness, inflammation and angiogenesis, which can be modulated by COX inhibitors. We therefore evaluated the impact of COX inhibition in rats with common bile duct ligation (CBDL)-induced liver cirrhosis and HPS.
Cirrhotic rats were randomly allocated to receive non-selective COX inhibitor (indomethacin), selective COX-1 inhibitor (SC-560), or COX-2 inhibitor (celecoxib) for 14 days. After that, hemodynamic parameters, severity of hypoxia and intrapulmonary shunts, liver and renal biochemistry parameters, histological finding and protein expressions were evaluated.
Non-selective COX inhibition by indomethacin improved hepatic fibrosis and pulmonary inflammation in cirrhotic rats with HPS. It also decreased mean arterial blood pressure, portal pressure, and alleviated hypoxia and intrapulmonary shunts. However, indomethacin increased mortality rate. In contrast, selective COX inhibitors neither affected hemodynamics nor increased mortality rate. Hypoxia was improved by SC-560 and celecoxib. In addition, SC-560 decreased intrapulmonary shunts, attenuated pulmonary inflammation and angiogenesis through down-regulating COX-, NFκB- and VEGF-mediated pathways.
Selective COX-1 inhibitor ameliorated HPS by mitigating hypoxia and intrapulmonary shunts, which are related to anti-inflammation and anti-angiogenesis.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Angiogenesis in liver cirrhosis leads to splanchnic hyperemia, increased portal inflow, and portosystemic collaterals formation, which may induce lethal complications, such as gastroesophageal ...variceal hemorrhage and hepatic encephalopathy. Cannabinoids (CBs) inhibit angiogenesis, but the relevant influences in cirrhosis are unknown. In this study, Spraque‐Dawley rats received common bile duct ligation (BDL) to induce cirrhosis. BDL rats received vehicle, arachidonyl‐2‐chloroethylamide (cannabinoid receptor type 1 CB1 agonist), JWH‐015 (cannabinoid receptor type 2 CB2 agonist), and AM630 (CB2 antagonist) from days 35 to 42 days after BDL. On the 43rd day, hemodynamics, presence of CB receptors, severity of portosystemic shunting, mesenteric vascular density, vascular endothelial growth factor (VEGF), VEGFR‐1, VEGFR‐2, phospho‐VEGFR‐2, cyclooxygenase (COX)‐1, COX‐2, and endothelial nitric oxide synthase (eNOS) expressions as well as plasma VEGF levels were evaluated. Results showed that CB1 and CB2 receptors were present in left adrenal veins of sham rats, splenorenal shunts (the most prominent intra‐abdominal shunts) of BDL rats, and mesentery of sham and BDL rats. CB2 receptor was up‐regulated in splenorenal shunts of BDL rats. Both acute and chronic JWH‐015 treatment reduced portal pressure and superior mesenteric arterial blood flow. Compared with vehicle, JWH‐015 significantly alleviated portosystemic shunting and mesenteric vascular density in BDL rats, but not in sham rats. The concomitant use of JWH‐015 and AM630 abolished JWH‐015 effects. JWH‐133, another CB2 agonist, mimicked the JWH‐015 effects. JWH‐015 decreased mesenteric COX‐1, COX‐2 messenger RNA expressions, and COX‐1, COX‐2, eNOS protein expressions. Furthermore, JWH‐015 decreased intrahepatic angiogenesis and fibrosis. Conclusions: CB2 agonist alleviates portal hypertension (PH), severity of portosystemic collaterals and mesenteric angiogenesis, intrahepatic angiogenesis, and fibrosis in cirrhotic rats. The mechanism is, at least partly, through COX and NOS down‐regulation. CBs may be targeted in the control of PH and portosystemic collaterals. (HEPATOLOGY 2012;56:248–258)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Thrombosis, characterized by blood clot formation within vessels, poses a significant medical challenge. Despite extensive research, the development of effective thrombosis therapies is hindered by ...substantial costs, lengthy development times, and high failure rates in medication commercialization. Conventional pre-clinical models often oversimplify cardiovascular disease, leading to a disparity between experimental results and human physiological responses. In response, we have engineered a photothrombosis-on-a-chip system. This microfluidic model integrates human endothelium, human whole blood, and blood flow dynamics and employs the photothrombotic method. It enables precise, site-specific thrombus induction through controlled laser irradiation, effectively mimicking both normal and thrombotic physiological conditions on a single chip. Additionally, the system allows for the fine-tuning of thrombus occlusion levels
via
laser parameter adjustments, offering a flexible thrombus model with varying degrees of obstruction. Additionally, the formation and progression of thrombosis noted on the chip closely resemble the thrombotic conditions observed in mice in previous studies. In the experiments, we perfused recalcified whole blood with Rose Bengal into an endothelialized microchannel and initiated photothrombosis using green laser irradiation. Various imaging methods verified the model's ability to precisely control thrombus formation and occlusion levels. The effectiveness of clinical drugs, including heparin and rt-PA, was assessed, confirming the chip's potential in drug screening applications. In summary, the photothrombosis-on-a-chip system significantly advances human thrombosis modeling. Its precise control over thrombus formation, flexibility in the thrombus severity levels, and capability to simulate dual physiological states on a single platform make it an invaluable tool for targeted drug testing, furthering the development of organ-on-a-chip drug screening techniques.
A photothrombosis-on-a-chip system with precise site-specific thrombus formation, controllable thrombus severity, and dual physiological environments for drug testing and thrombosis research.
Background and Aim
Hypo‐perfusion resulting from intense renal vasoconstriction is traditionally contributed to renal dysfunction in advanced liver disease, although cumulative studies demonstrated ...renal vasodilatation with impaired vascular contractility to endogenous vasoconstrictors in portal hypertension and compensated liver cirrhosis. The pathophysiology of altered renal hemodynamics remains unclear. This study, using a rat model of portal hypertension with superimposed endotoxemia, was designed to delineate the evolution of renal vascular reactivity and vaso‐regulatory gene expression during liver disease progression.
Methods
Rats were randomized into sham surgery (SHAM) or partial portal vein ligation (PVL). Endotoxemia was induced by intraperitoneal injection of lipopolysaccharide (LPS) on the seventh day following surgery. Isolated kidney perfusion was performed at 0.5 h or 5 h after LPS to evaluate renal vascular response to endothelin‐1.
Results
In contrast to impaired vascular contractility of SHAM rats, PVL rats displayed enhanced renal vascular reactivity to endothelin‐1 at 5 h following endotoxemia. There were extensive upregulations of inducible nitric oxide synthase in kidney tissues of endotoxemic rats. The changes of renal endothelin receptor type A (ETA) level paralleled with the changes of renal vascular reactivity in LPS‐treated rats. Compared with SHAM rats, PVL rats showed increased renal ETA and phosphorylated extracellular‐signal‐regulated kinases 1/2 (p‐ERK1/2) at 5 h after LPS.
Conclusion
LPS‐induced systemic hypotension induces a paradoxical change of renal vascular response to endothelin‐1 between SHAM and PVL rats. LPS‐induced renal vascular hyperreactivity in PVL rats was associated with upregulation of renal ETA and subsequent activation of ERK1/2 signaling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The hepatopulmonary syndrome (HPS) is characterized by hypoxia and increased intrapulmonary shunts in cirrhotic patients. Emerging evidence showed promising results of treating HPS by abolishment of ...intrapulmonary inflammation and angiogenesis. Rosuvastatin is a kind of 3-hydroxy-methyl-3-glutamyl coenzyme A reductase inhibitor. In addition to lipid-lowering effects, it has anti-inflammation and anti-angiogenesis properties. We postulated that rosuvastatin treatment can ameliorate HPS. Common bile duct ligation (CBDL) was applied in an experimental HPS animal model. CBDL rats received 2-week rosuvastatin (20 mg/kg/day) treatments from the fifteenth day after operation. The haemodynamic data, blood gas analysis, liver biochemistries, tumour necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) were examined after rosuvastatin treatment. The liver and lung tissues were dissected for histopathological studies and protein analyses. In the parallel groups, intrapulmonary shunts were determined. The haemodynamic and liver biochemistries were not changed after rosuvastatin treatment in CBDL rats, but the alveolar-arterial oxygen pressure gradient was significantly decreased, implying that HPS-induced hypoxia was reversed after rosuvastatin treatment. In addition, rosuvastatin treatment reduced intrapulmonary shunts and plasma levels of VEGF and TNF-α. Besides, the intrapulmonary protein expression of nuclear factor kappa B (NF-κB), VEGF receptor (VEGFR)-1,2 and Rho-associated A kinase were significantly down-regulated and the intrapulmonary angiogenesis was ameliorated. We concluded that rosuvastatin alleviates experimental HPS through blockade of pulmonary inflammatory angiogenesis via TNF-α/NF-κB and VEGF/Rho-associated A kinase pathways down-regulation.
This study investigated the impact of implementing ventilator-associated pneumonia (VAP) bundle care on the rates of VAP in intensive care units (ICUs) in Taiwan.
A total of 10 ICUs (bed number, ...170), including surgical (SICUs) (n = 7), cardiovascular/surgical (CV/S-ICUs) (n = 1), and medical ICUs (MICUs) (n = 2) from 10 hospitals (7 medical center hospitals and 3 regional hospitals) were enrolled in this quality-improvement project. This study was divided into the pre-intervention phase (1st January, 2012–31st July, 2013) and the intervention phase (1st August, 2013–31st October, 2014).
Among the 10 hospitals, the overall rates (cases per 1000 ventilator-days) of VAP declined significantly (p = 0.005; rate ratio, 0.71) from 1.9 in the pre-intervention period to 1.5 in the intervention period. Significant difference in VAP rates between these periods was found in the regional hospitals (from 1.6 to 0.7; p < 0.001) and the SICUs (from 2.1 to 1.4; p < 0.001), but not in the medical centers (2.0 vs. 1.9; p = 0.0667) or CV/S-ICUs (4.5 vs. 4.5; p = 0.5391). However, VAP rate increased significantly (cases per 1000 ventilator-days) in the MICUs between the two periods (from 0.5 to 1.0; p = 0.0489). For the VAP bundle care elements, the overall compliance rate was 87.7% with 83.6% and 97.9% in the medical centers and regional hospitals, respectively.
Implementing VAP bundle care has effectively reduced VAP in Taiwanese ICUs, but differences in performance and compliance rates of VAP bundle care among the different ICUs and hospital categories did exist.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP