LYC inhibits the AKT signaling pathway to activate autophagy and ameliorate TGFB-induced renal fibrosis.

Renal fibrosis is a typical pathological change in chronic kidney disease (CKD). Epithelial-mesenchymal transition (EMT) is the predominant stage. Activation of macroautophagy/autophagy plays a crucial role in the process of EMT. Lycopene (LYC) is a highly antioxidant carotenoid with pharmacological effects such as anti-inflammation, anti-apoptosis and mediation of autophagy. In this study, we demonstrated the specific mechanism of LYC in activating mitophagy and improving renal fibrosis. The enrichment analysis results of GO and KEGG showed that LYC had high enrichment values with autophagy. In this study, we showed that LYC alleviated aristolochic acid I (AAI)-induced intracellular expression of PINK1, TGFB/TGF-ß, p-SMAD2, p-SMAD3, and PRKN/Parkin, recruited expression of MAP1LC3/LC3-II and SQSTM1/p62, decreased mitochondrial membrane potential (MMP), and ameliorated renal fibrosis in mice. When we simultaneously intervened NRK52E cells using bafilomycin A1 (Baf-A1), AAI, and LYC, intracellular MAP1LC3-II and SQSTM1 expression was significantly increased. A similar result was seen in renal tissue and cells when treated in vitro and in vivo with CQ, AAI, and LYC, and the inhibitory effect of LYC on the AAI-activated SMAD2-SMAD3 signaling pathway was attenuated. Molecular docking simulation experiments showed that LYC stably bound to the AKT active site. After intervention of cells with AAI and GSK-690693, the expression of PINK1, PRKN, MAP1LC3-II, BECN1, p-SMAD2 and p-SMAD3 was increased, and the expression of SQSTM1 was decreased. However, SC79 inhibited autophagy and reversed the inhibitory effect of LYC on EMT. The results showed that LYC could inhibit the AKT signaling pathway to activate mitophagy and reduce renal fibrosis.Abbreviation: AA: aristolochic acid; ACTA2/α-SMA: actin alpha 2, smooth muscle, aorta; ACTB: actin beta; AKT/protein kinase B: thymoma viral proto-oncogene; BAF-A1: bafilomycin A1; BECN1: beclin 1, autophagy related; CCN2/CTGF: cellular communication network factor 2; CDH1/E-Cadherin: cadherin 1; CKD: chronic kidney disease; COL1: collagen, type I; COL3: collagen, type III; CQ: chloroquine; ECM: extracellular matrix; EMT: epithelial-mesenchymal transition; FN1: fibronectin 1; LYC: lycopene; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MMP: mitochondrial membrane potential; MTOR: mechanistic target of rapamycin kinase ; PI3K: phosphoinositide 3-kinase; PINK1: PTEN induced putative kinase 1; PRKN/Parkin: parkin RBR E3 ubiquitin protein ligase; PPI: protein-protein interaction; SMAD2: SMAD family member 2; SMAD3: SMAD family member 3; SQSTM1/p62: sequestosome 1; TGFB/TGFß: transforming growth factor, beta; VIM: vimentin.

Curcumin alleviates aristolochic acid nephropathy based on SIRT1/Nrf2/HO-1 signaling pathway.

Aristolochic acid I (AA-I), presenting in a variety of natural medicinal plants, which could cause tubular epithelial cell injury. Curcumin (CUR), a polyphenolic substance isolated from turmeric, is a natural antioxidant. The aim of this experiment was to investigate whether CUR attenuated AA-I-induced renal injury in rats through the SIRT1/Nrf2/HO-1 signaling pathway. SD rats were treated with AA-I (10 mg/kg) or/and CUR (200 mg/kg) for 28 days to assess the protective effect of CUR on AA-I-induced renal injury in vivo. NRK-52E cells were treated with AA-I (40 µ M) or/and CUR (20 µ M) for 24 h in vitro. The intervention pathway of CUR against oxidative stress injury induced by AA-I was assessed by observing pathological changes, oxidative stress status, apoptosis and the expression of SIRT1/Nrf2/HO-1 signaling pathway-related factors. The results showed that AA-I exposure increased the contents of BUN, Cr, KIM-1, NGAL, ALT and AST in serum. It increased the content of MDA, decreased the activities of SOD, GST, GSH and the content of ATP in renal tissue. Pathological changes such as inflammatory cell infiltration and mitochondrial injury occurred in renal tissue. AA-I exposure resulted in a substantial rise in the levels of BAX, Ccaspase-9, Cleaved Caspase-9, Caspase-3, Cleaved Caspase-3 and a significant decrease in mRNA and protein expression levels of Bcl-2, SIRT1, Nrf2, NQO1, HO-1 and Keap1. However, these changes were reversed by CUR intervention. In summary, AA-I exposure caused mitochondrial dysfunction and triggered apoptosis through the oxidative stress pathway. However, CUR could reduce AA-I-induced renal injury by activating the SIRT1/Nrf2/HO-1 signaling pathway.

Effect of the Trifunctional Chain Extender on Intrinsic Viscosity, Crystallization Behavior, and Mechanical Properties of Poly(Ethylene Terephthalate).

In this work, poly(ethylene terephthalate) (PET) chain-extending products with different molecular weights were prepared by reactive extrusion using isocyanate trimer (C-HK) as the trifunctional chain extender. The effect of the chain extender C-HK on the intrinsic viscosity, melt flow property, crystallization behavior, crystallization morphology, and mechanical property of PET was investigated. The results showed that when the content of the chain extender was increased from 0.6 to 1.4 wt%, the viscosity average molecular weight of PET was effectively increased from 2.36 × 104 to 5.46 × 104 g·mol-1. After the chain extending, the crystallinity and the time of semicrystallization of PET were significantly decreased. After the isothermal crystallization at 220 °C for 5 min, the spherulites formed by pure PET became larger. With the increase in molecular weight of PET after chain extension, its spherulite size was significantly decreased without changing the crystalline structure. The chain-extended PET also exhibited more excellent bending-resistant and impact-resistant properties. While the tensile strength of PET after chain extension was slightly decreased, the bending strength was increased by a maximum value of 56.8%, and the impact strength was increased by a maximum value of five times.

Surface Laser-Marking and Mechanical Properties of Acrylonitrile-Butadiene-Styrene Copolymer Composites with Organically Modified Montmorillonite.

In this study, organically modified montmorillonite (OMMT) was prepared by modifying MMT with a cationic surfactant cetyltrimethylammonium bromide (CTAB). The obtained OMMT of different loading contents (1, 2, 4, 6, and 8 wt %) was melt-blended with poly(acrylonitrile-co-butadiene-co-styrene) (ABS) to prepare a series of ABS/OMMT composites, which were laser marked using a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser beam of 1064 nm under different laser current processes. X-ray diffraction (XRD), color difference spectrometer, optical microscope, water contact angle tests, scanning electron microscope (SEM), and Raman spectroscopy were carried out to characterize the morphology, structure, and properties of the laser-patterned ABS composites. The effects of the addition of OMMT and the laser marking process on the mechanical properties of ABS/OMMT composites were investigated through mechanical property tests. The results show that the obtained ABS/OMMT composites have enhanced laser marking performance, compared to the ABS. When the OMMT content is 2 wt % and the laser current intensity is 9 A, the marking on ABS composites has the highest contrast (ΔE = 36.38) and sharpness, and the quick response (QR) code fabricated can be scanned and identified with a mobile app. SEM and water contact angle tests showed that the holes, narrow cracks, and irregular protrusion are formed on the composite surface after laser marking, resulting in a more hydrophobic surface and an increased water contact angle. Raman spectroscopy and XRD indicate that OMMT can absorb the near-infrared laser energy, undergo photo thermal conversion, and cause the pyrolysis and carbonization of ABS to form black marking, and the crystal structure itself does not change significantly. When the 2 wt % of OMMT is loaded, the tensile strength, elongation at break, and impact strength of ABS/OMMT are increased by 15, 20, and 14%, respectively, compared to ABS. Compared with the unmarked ABS/OMMT, the defects including holes and cracks generated on the surface of the marked one lead to the decreased mechanical property. The desirable combination of high contrast laser marking performance and mechanical properties can be achieved at an OMMT loading content of 2 wt % and a laser current intensity of 9 A. This research work provides a simple, economical, and environmentally friendly method for laser marking of engineering materials such as ABS.

Ultrasound-guided bilateral superficial cervical plexus blocks enhance the quality of recovery in patients undergoing thyroid cancer surgery: A randomized controlled trial.

STUDY OBJECTIVE: Regional anesthesia can improve postoperative analgesia and enhance the quality of recovery (QoR) after surgery. This trial evaluates the effects of ultrasound-guided bilateral superficial cervical plexus block (SCPB) on QoR in patients undergoing thyroid cancer surgery. DESIGN: Prospective, randomized, double-blinded, placebo-controlled trial. SETTING: Operating room. PATIENTS: Seventy-four ASA I-II female patients scheduled for thyroid cancer surgery were included to the study. INTERVENTIONS: Patients were randomly allocated to receive pre-operative ultrasound-guided bilateral SCPB with 10 ml of ropivacaine 0.5% or normal saline on each side. MEASUREMENTS: The primary endpoint was the quality of recovery, which was assessed using the 15-item quality of recovery questionnaire (QoR-15). Secondary endpoints were acute postoperative pain, time to first rescue analgesia, the number of patients requiring rescue analgesia, length of post-anesthesia care unit (PACU) stay, the incidence of postoperative nausea or vomiting (PONV) and dizziness, and patient satisfaction. MAIN RESULTS: The global QoR-15 score at 24 h postoperatively was significantly higher in the SCPB group (Median [IQR], 118 [115-120]) than the control group (110 [106-112]) with a median difference of 8 (95% CI: 6 to 10, P < .001). Compared with the control group, pre-operative ultrasound-guided bilateral SCPB reduced postoperative pain up to 24 h and the incidence of PONV, as well as the length of PACU stay. Additionally, the patient satisfaction scores were improved in the SCPB group (P = .024). CONCLUSION: Pre-operative ultrasound-guided bilateral SCPB with ropivacaine enhances the quality of recovery, postoperative analgesia and patient satisfaction, alleviates the incidence of PONV, and accelerates the PACU discharge following thyroid cancer surgery.

Photoinduced charge flow inside an iron porphyrazine complex.

Tracking inorganic photochemistry with high resolution poses considerable challenges. Here, sub-picosecond electronic and structural motions and MLCT/d-d intersystem crossing in a cationic iron-porphyrazine are probed using ultrafast transient absorption, stimulated Raman spectroscopy, and quantum calculations. By delineating photoinduced energy relaxation, strategies for extending the lifetime of MLCT state are discussed.

Fast Hydrogen Atom Abstraction by a Hydroxo Iron(III) Porphyrazine.

A reactive hydroxoferric porphyrazine complex, [(PyPz)FeIII(OH) (OH2)]4+ (1, PyPz = tetramethyl-2,3-pyridino porphyrazine), has been prepared via one-electron oxidation of the corresponding ferrous species [(PyPz)FeII(OH2)2]4+ (2). Electrochemical analysis revealed a pH-dependent and remarkably high FeIII-OH/FeII-OH2 reduction potential of 680 mV vs Ag/AgCl at pH 5.2. Nernstian behavior from pH 2 to pH 8 indicates a one-proton, one-electron interconversion throughout that range. The O-H bond dissociation energy of the FeII-OH2 complex was estimated to be 84 kcal mol-1. Accordingly, 1 reacts rapidly with a panel of substrates via C-H hydrogen atom transfer (HAT), reducing 1 to [(PyPz)FeII(OH2)2]4+ (2). The second-order rate constant for the reaction of [(PyPz)FeIII(OH) (OH2)]4+ with xanthene was 2.22 × 103 M-1 s-1, 5-6 orders of magnitude faster than other reported FeIII-OH complexes and faster than many ferryl complexes.