Pioglitazone Protects Against Renal Ischemia-Reperfusion Injury via the AMP-Activated Protein Kinase-Regulated Autophagy Pathway

Renal ischemia-reperfusion injury (IRI) is a major cause of acute renal failure. Our previous studies have shown that pioglitazone, a peroxisome proliferators-activated receptor (PPAR)-γ agonist used in type 2 diabetes, protects against renal IRI; however, the molecular mechanism underlying the renoprotective effects of pioglitazone is still unclear. In this study, we investigated the role of AMP-activated protein kinase (AMPK)-regulated autophagy in renoprotection by pioglitazone in IRI. To investigate whether pioglitazone protects renal cells from IRI, an in vivo renal IRI model was used. Cell apoptosis in the kidneys was determined by TUNEL staining. Western blotting was used to determine the expression of AMPK, autophagy-related proteins, and caspase-3/8 proteins in the kidneys. In a rat model of IRI, pioglitazone decreased the increased serum creatinine and urea nitrogen, improved renal histological score, and decreased the cell injury. Pioglitazone also increased AMPK phosphorylation, inhibited p62 and cleaved caspase-3/8 proteins, and activated autophagy-related proteins LC3 II and Beclin-1 in the kidneys of IRI rats. Moreover, GW9662, as a selective inhibitor of PPAR-γ, inhibited the protective effects of pioglitazone. These results suggest that pioglitazone exerts its protective effects in renal IRI via activation of an AMPK-regulated autophagy signaling pathway

Antiviral activity of the host defense peptide piscidin 1: investigating a membrane-mediated mode of action

Outbreaks of viral diseases are on the rise, fueling the search for antiviral therapeutics that act on a broad range of viruses while remaining safe to human host cells. In this research, we leverage the finding that the plasma membranes of host cells and the lipid bilayers surrounding enveloped viruses differ in lipid composition. We feature Piscidin 1 (P1), a cationic host defense peptide (HDP) that has antimicrobial effects and membrane activity associated with its N-terminal region where a cluster of aromatic residues and copper-binding motif reside. While few HDPs have demonstrated antiviral activity, P1 acts in the micromolar range against several enveloped viruses that vary in envelope lipid composition. Notably, it inhibits HIV-1, a virus that has an envelope enriched in cholesterol, a lipid associated with higher membrane order and stability. Here, we first document through plaque assays that P1 boasts strong activity against SARS-CoV-2, which has an envelope low in cholesterol. Second, we extend previous studies done with homogeneous bilayers and devise cholesterol-containing zwitterionic membranes that contain the liquid disordered (Ld; low in cholesterol) and ordered (Lo, rich in cholesterol) phases. Using dye leakage assays and cryo-electron microscopy on vesicles, we show that P1 has dramatic permeabilizing capability on the Lo/Ld, an effect matched by a strong ability to aggregate, fuse, and thin the membranes. Differential scanning calorimetry and NMR experiments demonstrate that P1 mixes the lipid content of vesicles and alters the stability of the Lo. Structural studies by NMR indicate that P1 interacts with the Lo/Ld by folding into an α-helix that lies parallel to the membrane surface. Altogether, these results show that P1 is more disruptive to phase-separated than homogenous cholesterol-containing bilayers, suggesting an ability to target domain boundaries. Overall, this multi-faceted research highlights how a peptide that interacts strongly with membranes through an aromatic-rich N-terminal motif disrupt viral envelope mimics. This represents an important step towards the development of novel peptides with broad-spectrum antiviral activity

Defect engineering in N-doped OMC for lightweight and high-efficiency electromagnetic wave absorption

Developing low density and efficient dielectric loss materials has become a research hotspot, which can greatly meet the demands of modern radars and settle the problem of electromagnetic wave pollution. Herein, a series of N-doped ordered mesoporous carbon (OMC) materials with different nitrogen content were prepared via a modified self-assembly method and defect engineering in subsequent calcination treatment. It was discovered that the content and type of nitrogen doping can be effectively modulated by the amount of precursor dicyandiamide, resulting in the changes in porous structure, carbon defects, electromagnetic properties, microwave absorption (MA) performance and radar cross section (RCS) reduction values. Remarkably, as-fabricated OMC/N2.5 displays ideal MA performance, whose minimum reflection loss (RL(min)) value reaches −35.3 dB at 7.76 GHz (3.0 mm) and its effective absorption bandwidth reaches 3.52 GHz (10.64–14.16 GHz, 2.0 mm). Furthermore, the optimal RCS reduction values can be obtained as 12.01 dB·m2 when the detection theta is 30°, which validly reduces the chances of being detected by radar. Thus, this work opens up a novel way for the development of lightweight and high-efficiency MA materials

Modeling and Design of Graphene GaAs Junction Solar Cell

Graphene based GaAs junction solar cell is modeled and investigated by Silvaco TCAD tools. The photovoltaic behaviors have been investigated considering structure and process parameters such as substrate thickness, dependence between graphene work function and transmittance, and n-type doping concentration in GaAs. The results show that the most effective region for photo photogenerated carriers locates very close to the interface under light illumination. Comprehensive technological design for junction yields a significant improvement of power conversion efficiency from 0.772% to 2.218%. These results are in good agreement with the reported experimental work

Two-Dimensional Modeling of Silicon Nanowires Radial Core-Shell Solar Cells

Silicon nanowires radial core-shell solar cells have recently attracted significant attention as promising candidates for low cost photovoltaic application, benefit from its strong light trapping, and short radial carrier collection distances. In order to establish optics and electricity improvement, a two-dimensional model based on Shockley-Read-Hall recombination modes has been carried out for radial core-shell junction nanowires solar cell combined with guided resonance modes of light absorption. The impact of SiNWs diameter and absorption layer thickness on device electrical performance based on a fixed nanowires height and diameter-over-periodicity were investigated under illumination. The variation in quantum efficiency indicated that the performance is limited by the mismatch between light absorption and carriers’ collection length

Surgery combined with anlotinib for local control of patients with resectable extremity desmoid fibromatosis: a retrospective study

Background: Desmoid fibromatosis (DF) is a pathological intermediate fibroblastoma that is difficult to control locally due to its invasive nature, especially in the extremities. Although anlotinib demonstrated efficacy in treating DF with tolerable safety, the impact of surgical intervention in conjunction with anlotinib administration on local control in patients with extremity DF remains undetermined.Methods: We conducted a retrospective examination of the clinical medical documentation belonging to patients with resectable DF of the extremities who were treated with surgery between January 2010 and June 2022. The patients were divided into two cohorts: surgery alone cohort and surgery combined with anlotinib group (surgery plus anlotinib cohort), crossover to surgery plus anlotinib cohort was admissible for patients in the surgery alone cohort who experienced disease recurrence postoperatively. Clinical data such as basic information, tumor location, anlotinib toxicity, time to recurrence, surgical complications, follow-up time, visual analogue scale (VAS) score and Musculoskeletal Tumor Society (MSTS) score at the last follow-up were collected.Results: In total, 48 consecutive patients (19 males and 29 females) with resectable DF of the extremities, including 25 patients in the surgery alone cohort, 23 patients in the surgery plus anlotinib cohort, and 10 patients who were transferred from the surgery alone cohort to the surgery plus anlotinib cohort. The VAS score at the last follow-up was 5 (IQR, 3–6) in the surgery alone cohort and 2 (IQR, 1–3) in the surgery plus anlotinib cohort, respectively; the MSTS score at the last follow-up was 19 (IQR, 16.5–24) in the surgery alone cohort and 27 (IQR, 25–28) in the surgery plus anlotinib cohort, respectively; these characteristics were statistically different between the two cohorts. The 3-year recurrence-free survival (RFS) of the surgery alone cohort and the surgery plus anlotinib cohort were 37.7% and 72.6%, respectively, and the difference was statistically significant (p = 0.022).Conclusion: Surgery combined with anlotinib appears to be effective in controlling local recurrence in patients with resectable DF of the extremities, and the side effects were acceptable