Prednisolone is involved in glucose homeostasis and has been used for treatment for aristolochic acid (AA) nephropathy (AAN), but its effect on glycolysis in kidney has not yet been clarified. This ...study aims to investigate the effect in terms of altered proteins after prednisolone treatment in a mice model of AAN using a proteomics technique. The six-week C3H/He female mice were administrated AA (0.5 mg/kg/day) for 56 days. AA+P group mice were then given prednisolone (2 mg/kg/day) via oral gavage for the next 14 days, and AA group mice were fed water instead. The tubulointerstitial damage was improved after prednisolone treatment comparing to that of AA group. Kidney homogenates were harvested to perform the proteomics analysis with fluorogenic derivatization-liquid chromatography-tandem mass spectrometry method (FD-LC-MS/MS). On the other hand, urinary methylglyoxal and D-lactate levels were determined by high performance liquid chromatography with fluorescence detection. There were 47 altered peaks and 39 corresponding proteins on day 14 among the groups, and the glycolysis-related proteins, especially glyoxalase 1 (GLO1), fructose-bisphosphate aldolase B (aldolase B), and triosephosphate isomerase (TPI), decreased in the AA+P group. Meanwhile, prednisolone decreased the urinary amount of methylglyoxal (AA+P: 2.004 ± 0.301 μg vs. AA: 2.741 ± 0.630 μg, p < 0.05), which was accompanied with decrease in urinary amount of D-lactate (AA+P: 54.07 ± 5.45 μmol vs. AA: 86.09 ± 8.44 μmol, p < 0.05). Prednisolone thus alleviated inflammation and interstitial renal fibrosis. The renal protective mechanism might be associated with down-regulation of GLO1 via reducing the contents of methylglyoxal derived from glycolysis. With the aid of proteomics analysis and the determination of methylglyoxal and its metabolite-D-lactate, we have demonstrated for the first time the biochemical efficacy of prednisolone, and urinary methylglyoxal and its metabolite-D-lactate might be potential biomarkers for AAN.
Sub-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> wafer thicknesses are an essential enabler for the high-density nano through silicon via (nTSV) in ...design-technology co-optimization (DTCO) and system-technology co-optimization (STCO) scaling options. The measurement and TCAD results prove that decreasing the wafer thickness to 0.3 <inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> is beneficial to latch-up prevention due to lower <inline-formula> <tex-math notation="LaTeX">\beta </tex-math></inline-formula>-gain, which originates from the strong recombination in well-base regions. Moreover, the current flow for sub-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> Si thickness will be impacted and confined in a thinner bulk region. Additionally, the internal guard rings (GRs) efficiency increases by nearly 100% for <inline-formula> <tex-math notation="LaTeX">0.3~\mu \text{m} </tex-math></inline-formula> Si thickness. On the contrary, the holding voltage is unchanged due to the dominant impact of increased well resistances over <inline-formula> <tex-math notation="LaTeX">\beta </tex-math></inline-formula>-gain reduction. Also, the thermal impact on sub-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> Si thickness further increases latch-up risk due to reduced heat dissipation.
Despite Alzheimer’s disease (AD) being the most common neurodegenerative disorder worldwide, no FDA-approved disease-modifying treatments have been approved for this condition since 2003. ...Neuronal-type alpha7 nicotinic acetylcholine receptors (α7nAChRs) play an essential role in cognitive functions, binding with extracellular β-amyloid (Aβ plaques) and inhibiting Aβ-induced neurotoxicity. α7nAChRs are impaired early in the course of AD; drugs targeting α7nAChRs are being hotly pursued as a treatment of AD. Encenicline, a partial selective agonist of α7nAChR and modulator of acetylcholine, failed in phase III trials because of gastrointestinal side effects. We, therefore, evaluated the efficacy of galantamine, a positive allosteric modulator at α7nAChRs and an acetylcholinesterase inhibitor, that has been used since 2000 as first-line treatment of mild-to-moderate dementia. This study highlights an important new benefit with galantamine. We found that galantamine inhibits Aβ
1–42
-induced apoptosis by activating the JNK signaling pathway, thus enhancing α7nAChR expression, and also inhibits the Akt pathway, which further increases autophagosome biogenesis and autophagy. These effects can be reproduced by α7nAChR overexpression in the absence of galantamine. Importantly, the α7 subunit protein sequence of α7nAChRs contains 3 LC3-interacting regions; our immunoprecipitation data show that α7 binds with the autophagosomal marker protein LC3. This is the first report to provide evidence showing that the cell surface receptor α7nAChR acts as a cargo carrier for LC3 binding for Aβ
1–42
sequestration to autophagosomes, suggesting a novel mechanism for the neuroprotective efficacy of galantamine in AD.
We point out a new phenomenon which seems to be generic in 4d effective theories of scalar fields coupled to Einstein gravity, when applied to cosmology. A lift of such theories to a Weyl-invariant ...extension allows one to define classical evolution through cosmological singularities unambiguously, and hence construct geodesically complete background spacetimes. An attractor mechanism ensures that, at the level of the effective theory, generic solutions undergo a big crunch/big bang transition by contracting to zero size, passing through a brief antigravity phase, shrinking to zero size again, and re-emerging into an expanding normal gravity phase. The result may be useful for the construction of complete bouncing cosmologies like the cyclic model.
Extracorporeal membrane oxygenation (ECMO) can be used as a salvage therapy, but the effectiveness is controversial. The aim of this study was to investigate the predictors of mortality and the ...influence of organ dysfunction scores in severe acute respiratory distress syndrome (ARDS) patients treated with ECMO.
The records of adult severe ARDS patients receiving ECMO support from May 2006 to December 2011 at Chang Gung Memorial Hospital were retrospectively analyzed.
The records of 65 patients with severe ARDS who received venovenous ECMO were analyzed. The hospital survival rate was 47.7%. Survivors were younger than nonsurvivors (41.4 ± 15.4 versus 54.1 ± 16.9 years, respectively; p = 0.002) and had shorter duration of mechanical ventilation before ECMO (52.7 ± 51.1 versus 112.1 ± 101.0 hours, respectively; p = 0.01). Before ECMO, Acute Physiology and Chronic Health Evaluation II, Sequential Organ Failure Assessment, and Multiple Organ Dysfunction scores were significantly lower for survivors than for nonsurvivors. Mortality rate increased with rising predictive score. During 7 days of ECMO use, organ dysfunction scores were significantly lower for survivors than nonsurvivors.
Severe ARDS patients who are younger, have shorter duration of mechanical ventilation, and lower organ dysfunction scores before ECMO initiation have more favorable survival outcome. Early application of ECMO, especially if predictive score is below 2, may improve survival. Organ dysfunction scores before and during ECMO support are correlated with survival.
Coix lacryma-jobi var. ma-yuen L. Gramineae is widely cultivated in Taiwan. Literature regarding the molecular action mechanism of coixol on tyrosinase and the application of coicis seed extracts to ...the processing of facial masks is still lacking. Solvent extractability analysis revealed that most of the polyphenolics in coicis seeds were water soluble (3.17 ± 0.12 to 3.63 ± 0.07 μg/mLGAE). In contrast, the methanolic extract contained the most flavonoids (0.06 ± 0.00~0.26 ± 0.03 μg/mL QE) and coixol (11.43 ± 0.13~12.83 ± 0.14 μg/mL), showing potent antioxidant capability. Additionally, the contents of coixenolide (176.77 ± 5.91 to 238.60 ± 0.21 μg/g), phytosterol (52.45 ± 2.05 to 58.23 ± 1.14 mg/g), and polysaccharides (3.42 ± 0.10 to 4.41 ± 0.10 mg/g) were rather high. The aqueous extract (10 μg/mL) and the ethanolic extract (1 mg/mL) showed no cytotoxicity to B16F10 melanocytes. More attractively, the ethanolic extract at 1 mg/mL caused 48.4% inhibition of tyrosinase activity in B16F10 melanocytes, and 50.7% on human tyrosinase (hTyr) fragment 369–377. Conclusively, the coicis seed extracts containing abundant nutraceuticals with promising anti-hTyr activity and moisturizing capability can serve as good ingredients for facial mask processing.
Background and Objectives
In patients with lymphedema, the disruption of the lymphatic network increases skin turgor and fibrosis of subcutaneous tissue, delays wound healing, causing recurrent ...ulcerations and infections. In these cases, management of ulcers can be challenging.
Methods
Between January 2016 and June 2018, patients presenting with lymphedema were enrolled at our Institution. We selected patients with severe lymphedema and ulcers of lower limbs and we performed a surgical approach, involving free gastroepiploic lymph nodes and omentum flap, harvested through laparoscopy.
Results
We enrolled 135 patients presenting for lymphedema. Among them, 10 eligible cases underwent excision of the ulcer and reconstruction with omentum flap. Mean age was 57.8 years and average follow‐up 24.1 months. Circumferences and skin tonicity significantly decreased from the preoperative period. Lymphoscintigraphy showed improvement of the lymphatic drainage and restoration of lymphatic network. No episodes of infection were recorded in the postoperative period.
Conclusions
Our combined procedure merges free flap techniques and lymphedema surgery: omentum covers the defect while providing a new source of lymph nodes, improving the lymphatic networks of the affected limb. This technique can highly increase the quality of life of the patient in a single‐stage operation with fast recovery and low donor site morbidity.
Different body weight-supported gait-training strategies are available for improving ambulation in individuals with spinal cord injury (SCI). These include body weight-supported overground training ...(BWSOGT), body weight-supported treadmill training (BWSTT), and robot-assisted gait training (RAGT). We conducted a network meta-analysis of randomised controlled trials (RCTs) to assess the effect and priority of each training protocol. We searched the PubMed, Cochrane Library, Scopus, and Embase databases from inception to 6 August 2022. The eligibility criteria were as follows: (1) being RCTs, (2) recruiting participants with SCI diagnosis and requiring gait training, (3) comparing different body weight-supported gait training strategies, and (4) involving ambulatory assessments. We conducted a network meta-analysis to compare different training strategies using the standard mean difference and its 95% credible interval. To rank the efficacy of training strategies, we used the P score as an indicator. Inconsistency in network meta-analysis was evaluated using loop-specific heterogeneity. We included 15 RCTs in this analysis. RAGT was had significantly more favourable performance than had the control intervention. The ranking probabilities indicated that the most effective approach was RAGT, followed by BWSOGT, BWSTT, and the control intervention. No significant inconsistency was noted between the results of the direct and indirect comparisons.
Radiomics, which extract large amount of quantification image features from diagnostic medical images had been widely used for prognostication, treatment response prediction and cancer detection. The ...treatment options for lung nodules depend on their diagnosis, benign or malignant. Conventionally, lung nodule diagnosis is based on invasive biopsy. Recently, radiomics features, a non-invasive method based on clinical images, have shown high potential in lesion classification, treatment outcome prediction.
Lung nodule classification using radiomics based on Computed Tomography (CT) image data was investigated and a 4-feature signature was introduced for lung nodule classification. Retrospectively, 72 patients with 75 pulmonary nodules were collected. Radiomics feature extraction was performed on non-enhanced CT images with contours which were delineated by an experienced radiation oncologist.
Among the 750 image features in each case, 76 features were found to have significant differences between benign and malignant lesions. A radiomics signature was composed of the best 4 features which included Laws_LSL_min, Laws_SLL_energy, Laws_SSL_skewness and Laws_EEL_uniformity. The accuracy using the signature in benign or malignant classification was 84% with the sensitivity of 92.85% and the specificity of 72.73%.
The classification signature based on radiomics features demonstrated very good accuracy and high potential in clinical application.
We report a new efficient exciplex-forming system consisting of a biscarbazole donor and a triazine-based acceptor. The new exciplex was characterized with a high photoluminescence quantum yield up ...to 68% and effective thermally activated delayed fluorescence behavior. The BCzPh:3P-T2T (2:1, 30 nm) blend was examined not only as an emitting layer (device D1) but also a reliable co-host of fluorescent and phosphorescent emitters for giving highly efficient exciplex-based organic light-emitting diodes (OLEDs) with a high maximum external quantum efficiency of 15.5 and 29.7% for devices doped with 1 wt % C545T (device D2) and 8 wt % Ir(ppy)2(acac) (device D4), respectively. More strikingly, a strongly enhanced lifetime (T 75 = 16 927 min.) of the C545T-doped device was obtained. The transient electroluminescence measurement as well as capacitance–voltage and impedance–voltage correlations were utilized to explore the factors governing the high efficiency and stability. The obtained results clearly show that the energy transfer and charge transport is highly efficient; they also show the photoelectric semiconducting characteristics of exciplex-based OLEDs, which are significantly different from those of unipolar host-based reference devices D3 (Alq3: 1 wt % C545T) and D5 (CBP: 8 wt % Ir(ppy)2(acac)). Our works have established a systematic protocol to shed light on the mechanisms behind exciplex-based devices. The combined results also confirm the bright prospect of the exciplex-forming system as the co-host for highly efficient and stable OLEDs.
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