A novel interleaved high step-up DC-DC converter based on voltage multiplier cell and voltage-stacking techniques is proposed for the power conversion in renewable energy power systems. The circuit ...configuration incorporates an input-parallel output-series boost converter with coupled inductors, clamp circuits and a voltage multiplier cell stacking on the output side to extend the voltage gain. The converter achieves high voltage conversion ratio without working at extreme large duty ratio. The voltage stresses on the power switches are significantly lower than the output voltage. As a result, the low-voltage-rated metal-oxide-semiconductor field-effect transistors (MOSFETs) can be employed to reduce the conduction losses and higher conversion efficiency can be expected. The interleaved operation reduces the input current ripple. The leakage inductances of the coupled inductors act on mitigating the diode reverse recovery problem. The operating principle, steady-state analysis and design guidelines of the proposed converter are presented in detail. Finally, a 1-kW prototype with 28-V input and 380-V output voltages was implemented and tested. The experimental results are presented to validate the performance of the proposed converter.
Obesity is a worldwide epidemic problem and correlates to varieties of acute or chronic lung diseases such as acute respiratory distress syndrome, chronic obstructive pulmonary disease, and pulmonary ...fibrosis. An increase of leptin, a kind of adipokine, in lean mice plasma has been found to impair immune responses and facilitate the infection of
, resulting in increased pneumonia severity. Also, a higher leptin level is found in exhaled breath condensates of obese or asthmatic subjects, compared to healthy ones, suggesting that leptin is involved in the occurrence or exacerbation of lung injury. In previous studies, we showed that leptin stimulated cytosolic phospholipase A2-α (cPLA2α) gene expression in lung alveolar type II cells via mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB)-activated coactivator p300. Herein, we show that the in vivo application of leptin in the respiratory system upregulated the expression of inflammatory proteins cPLA2α and cyclooxygenase-2 (COX-2) together with leukocyte infiltration. Treatment with an ROS scavenger (
-acetylcysteine, NAC), an NADPH oxidase inhibitor (apocynin), or an activating protein (AP)-1 inhibitor (tanshinone IIA) attenuated leptin-mediated cPLA2α/COX-2 expression and leukocyte recruitment in the lung. Leptin increased intracellular oxidative stress in a leptin receptor (OB-R) and NADPH oxidase-dependent manner, leading to the phosphorylation of the AP-1 subunit c-Jun. In summation, leptin increased lung cPLA2α/COX-2 expression and leukocyte recruitment via the NADPH oxidase/ROS/AP-1 pathway. Understanding the inflammatory effects of leptin on the pulmonary system provides opportunities to develop strategies against lung injury related to metabolic syndrome or obesity.
Background Hepatitis C virus (HCV) infection not only links closely to systemic inflammation but also has numerous extrahepatic manifestations. Chronic inflammation also increases the risk of ...new-onset atrial fibrillation (AF). However, little is known regarding the clinical association between HCV infection and new-onset AF. Methods and Results We conducted a population-based cohort study using Taiwan's National Health Insurance Research Database during 1997 to 2013. A total of 11 771 HCV-infected patients were included in this study, and each of them was matched in a ratio of 1:4. Because of higher mortality among HCV cohorts, we used both Cox proportional hazard regression and competing risk regression models to compute the hazard ratios accompanying 95% CIs after adjustment for relevant confounder. The results demonstrated that the patients with chronic HCV infection had significantly higher incidence rate (332.0 versus 265.8 in 100 000 person-years,
<0.0001) of new-onset AF compared with the non-HCV population. The adjusted hazard ratio of HCV for new-onset AF was 1.32 (95% CI, 1.20-1.44;
<0.0001) and 1.20 (95% CI, 1.10-1.31;
=0.0001) while calculated with Cox proportional hazard regression model and competing risk model, respectively. Intriguingly, we observed that the patients with HCV treated with antiviral agents had significantly lower incidental AF than those without anti-HCV treatment (1.2% versus 6.0%;
<0.0001). Conclusions Chronic HCV infection was associated with an increased risk of incidental AF probably through sharing common pathology of chronic inflammation. Furthermore, a well-designed study is needed to clarify whether anti-HCV therapy can provide protection against the occurrence of AF.
This study tested the hypothesis that exendin-4 and sitagliptin can effectively protect kidney from acute ischemia-reperfusion (IR) injury.
Adult SD-rats (n = 48) equally divided into group 1 (sham ...control), group 2 (IR injury), group 3 IR + sitagliptin 600 mg/kg at post-IR 1, 24, 48 hr), and group 4 IR + exendin-4 10 μm/kg at 1 hr after procedure were sacrificed after 24 and 72 hrs (n = 6 at each time from each group) following clamping of bilateral renal pedicles for 60 minutes (groups 2-4).
Serum creatinine level and urine protein to creatinine ratio were highest in group 2 and lowest in group 1 (all p < 0.001) without notable differences between groups 3 and 4. Kidney injury score, expressions of inflammatory biomarkers at mRNA (MMP-9, TNF-α, IL-1β, PAI-1), protein (TNF-α, NF-κB and VCAM-1), and cellular (CD68+) levels in injured kidneys at 24 and 72 hr showed an identical pattern compared to that of creatinine level in all groups (all p < 0.0001). Expressions of oxidized protein, reactive oxygen species (NOX-1, NOX-2), apoptosis (Bax, caspase-3 and PARP), and DNA damage marker (γH2AX+) of IR kidney at 24 and 72 hrs exhibited a pattern similar to that of inflammatory mediators among all groups (all p < 0.01). Renal expression of glucagon-like peptide-1 receptor, and anti-oxidant biomarkers at cellular (GPx, GR) and protein (NQO-1, HO-1, GPx) levels at 24 and 72 hr were lowest in group 1, significantly lower in group 2 than in groups 3 and 4 (all p < 0.01).
Exendin-4 and sitagliptin provided significant protection for the kidneys against acute IR injury.
Peritoneal dialysis (PD) possesses multiple advantages for end stage renal disease. However, long-term PD triggers peritoneal fibrosis (PF). From the nationwide analysis of diabetic PD patients (n = ...19,828), we identified the incidence of PD failure was significantly lower in diabetic patients treated with dipeptidyl peptidase 4 (DPP4) inhibitors. Experimental study further showed high concentration of glucose remarkably enhanced DPP4 to promote epithelial-mesenchymal transition (EMT) in the mesothelial cells. In chlorhexidine gluconate (CG)-induced PF model of rats, DPP4 expression was enriched at thickening peritoneum. Moreover, as to CG-induced PF model, DPP4 deficiency (F344/DuCrlCrlj strain), sitagliptin and exendin-4 treatments significantly inhibited DPP4 to reverse the EMT process, angiogenesis, oxidative stress, and inflammation, resulting in the protection from PF, preservation of peritoneum and the corresponding functional integrity. Furthermore, DPP4 activity was significantly correlated with peritoneal dysfunction. Taken together, DPP4 caused peritoneal dysfunction/PF, whereas inhibition of DPP4 protected the PD patients against PD failure.
This study traced intravenously administered induced pluripotent stem cell (iPSC)‐derived mesenchymal stem cells (MSC) and assessed the impact of iPSC‐MSC on preserving renal function in SD rat after ...5/6 nephrectomy. The results of in vitro study showed that FeraTrack™Direct contrast particles (ie intracellular magnetic labelling) in the iPSC‐MSC (ie iPS‐MSCSPIONs) were clearly identified by Prussian blue stain. Adult‐male SD rats (n = 40) were categorized into group 1 (SC), group 2 SC + iPS‐MSCSPIONs (1.0 × 106cells)/intravenous administration post‐day‐14 CKD procedure, group 3 (CKD), group 4 CKD + iPS‐MSCSPIONs (0.5 × 106cells) and group 5 CKD + iPS‐MSCSPIONs (1.0 × 106cells). By day‐15 after CKD induction, abdominal MRI demonstrated that iPS‐MSCSPIONs were only in the CKD parenchyma of groups 4 and 5. By day 60, the creatinine level/ratio of urine protein to urine creatinine/kidney injury score (by haematoxylin and eosin stain)/fibrotic area (Masson's trichrome stain)/IF microscopic finding of kidney injury molecule‐1 expression was lowest in groups 1 and 2, highest in group 3, and significantly higher in group 4 than in group 5, whereas IF microscopic findings of podocyte components (ZO‐1/synaptopodin) and protein levels of anti‐apoptosis ((Bad/Bcl‐xL/Bcl‐2) exhibited an opposite pattern to creatinine level among the five groups (all P < .0001). The protein expressions of cell‐proliferation signals (PI3K/p‐Akt/m‐TOR, p‐ERK1/2, FOXO1/GSK3β/p90RSK), apoptotic/DNA‐damage (Bax/caspases8‐10/cytosolic‐mitochondria) and inflammatory (TNF‐α/TNFR1/TRAF2/NF‐κB) biomarkers displayed an identical pattern to creatinine level among the five groups (all P < .0001). The iPS‐MSCSPIONs that were identified only in CKD parenchyma effectively protected the kidney against CKD injury.
This study tested the hypothesis that abrogated dipeptidyl peptidase-4 (DPP4) activity played a crucial role on reducing stroke volume and preserving neurological function in rodent after acute ...hemorrhagic stroke (AHS). Animals (n=6/each group) were categorized into group 1 (sham-control of F344 rat), group 2 (sham-control of DPP4-deficiency rat), group 3 AHS by right cerebral injection of autologous blood (100 µL) in F344 rat, group 4 (AHS + sitagliptin/600 mg/kg 3 h prior to and at 3 h then once per day after AHS) and group 5 (AHS in DPP4-deficiency rat). The results of corner test showed the neurological function was significantly improved from days 3, 7, and 14 in groups 4 and 5 than in group 3 (all
<0.001). By days 1 and 14 after AHS procedure, the circulating levels of SDF-1α and GLP-1 were significantly increased from groups 1/2 to group 5 (all
<0.001), whereas circulating DPP4 activity was significantly increased in group 3 than other groups (all
<0.001). The brain ischemic area (BIA) was highest in group 3, lowest in groups 1/2 and significantly lower in group 5 than in group 4 (all
<0.0001). The protein expressions of oxidative-stress/inflammatory/apoptotic/cell-proliferation signaling, and the cellular expressions of inflammatory/DNA-damaged biomarkers exhibited a similar pattern to BIA among the groups (all
<0.01). In conclusion, deprivation of DPP4 activity protected the brain from AHS damage and preserved neurological function.
Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and ...empagliflozin (EMPA) in DKD rats.
Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 DKD + ADMSCs (6.0 × 105/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 106/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration) and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction.
The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p < 0.0001). The protein levels of inflammation (NF-κB/FNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized protein/p22-phox)/apoptosis (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax)/fibrosis (TGF-β/Smad 3)/mitochondrial/DNA-damaged (p-DRP1/γ-H2AX) biomarkers revealed a similar manner of creatinine level among the groups (all p < 0.0001). Kidney injury score/fibrotic area/oxidative-stress score (8-OHdG) and cellular levels of kidney-damaged biomarkers (KIM-1/γ-H2AX) showed a unanimous manner. In contrast, the cellular expressions of podocyte components (ZO-1/synaptopodin) revealed an antithetical manner of creatinine among the groups (all p < 0.0001).
Combined ADMSCs-EMPA was superior to just one therapy for protecting kidney function and ultra-structural integrity in DKD rodents.
Diesel generators (DGs) are used to provide electrical power to consumers because their power outputs can be scheduled, and they offer stable operating characteristics in a standalone or microgrid ...system. The parameters for DGs are set to ensure reliable and accurate simulation for distributed energy resources (DERs), which increases system reliability, maintains power supply quality and reduces operational costs. There are many parameters that must be estimated for a DG. These parameter settings such as system gains and time constants may vary, as facilities are run for a few days. Parameters for a DG must then be re-estimated to ensure accurate simulation in a microgrid system. The proposed method uses a sensitivity analysis to classify parameters into three different categories. A hierarchical optimization method combined with an enhanced whale optimization algorithm (EWOA) is then used to estimate the parameter settings for a DG using actual measurement data. The proposed method is applied to a practical microgrid system, and the results show that the proposed method determines the optimal parameter settings for a DG that enables accurate simulation and robust implementation for a microgrid system.
We tested whether combined melatonin (Mel) and exendin‐4 (Ex4) treatment can better preserve glomerular structural integrity after ischemia–reperfusion (IR) injury compared with either alone. Adult ...male Sprague Dawley rats (n = 50) were equally divided into sham control (SC), IR, IR‐Ex4 (10 μg/kg subcutaneously 30 min after reperfusion and daily for 5 days), IR‐Mel (20 mg/kg intraperitoneally at 30 min postreperfusion and 50 mg/kg at 6 and 18 hr), and IR‐Ex4‐Mel were euthanized at day 14. Serum creatinine level and urine protein‐to‐creatinine ratio at days 3 and 14 were highest in IR group and lowest in SC, significantly higher in IR‐Ex4 and IR‐Mel groups than in IR‐Ex4‐Mel group (all P < 0.001) without significant difference between IR‐Ex4 and IR‐Mel groups. Changes in podocyte injury score (PIS) and kidney injury score were highest in IR group and lowest in SC, significantly higher in IR‐Ex4 and IR‐Mel groups than in IR‐Ex4‐Mel, and significantly higher in IR‐Mel group than in IR‐Ex4 group (all P < 0.001). Immunohistochemical microscopic findings of the expressions of FSP‐1 and WT‐1 (two glomerular damage indicators) and KIM‐1 and snail (two renal tubular‐damaged indicators) showed an identical pattern, whereas the expressions of ZO‐1, p‐cadherin, podocin, dystroglycan, fibronectin, and synaptopodin (six indices of glomerular integrity) demonstrated an opposite pattern compared to that of PIS among five groups (all P < 0.001). Protein expressions of inflammatory (TNF‐α/NF‐κB/MMP‐9) and oxidative stress (NOX‐1, NOX‐2, oxidized protein) biomarkers exhibited an identical pattern to that of PIS among five groups (all P < 0.001). Combined melatonin–exednin‐4 therapy further protected glomerulus from IR injury.
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