c-Cbl induced podocin ubiquitination contributes to the podocytes injury in diabetic nephropathy.

The ubiquitination function in diabetic nephropathy (DN) has attracted much attention, but there is a lack of information on its ubiquitylome profile. To examine the differences in protein content and ubiquitination in the kidney between db/db mice and db/m mice, we deployed liquid chromatography-mass spectrometry (LC-MS/MS) to conduct analysis. We determined 145 sites in 86 upregulated modified proteins and 66 sites in 49 downregulated modified proteins at the ubiquitinated level. Moreover, 347 sites among the 319 modified proteins were present only in the db/db mouse kidneys, while 213 sites among the 199 modified proteins were present only in the db/m mouse kidneys. The subcellular localization study indicated that the cytoplasm had the highest proportion of ubiquitinated proteins (31.87%), followed by the nucleus (30.24%) and the plasma membrane (20.33%). The enrichment analysis revealed that the ubiquitinated proteins are mostly linked to tight junctions, oxidative phosphorylation, and thermogenesis. Podocin, as a typical protein of slit diaphragm, whose loss is a crucial cause of proteinuria in DN. Consistent with the results of ubiquitination omics, the K261R mutant of podocin induced the weakest ubiquitination compared with the K301R and K370R mutants. As an E3 ligase, c-Cbl binds to podocin, and the regulation of c-Cbl can impact the ubiquitination of podocin. In conclusion, in DN, podocin ubiquitination contributes to podocyte injury, and K261R is the most significant site. c-Cbl participates in podocin ubiquitination and may be a direct target for preserving the integrity of the slit diaphragm structure, hence reducing proteinuria in DN.

Sex Differences in Outcomes after Endovascular Thrombectomy for Patients with Acute Ischemic Stroke.

INTRODUCTION: Endovascular thrombectomy (EVT) is the standard of care for patients with large-vessel occlusion acute ischemic stroke (AIS). There may be differing recanalization effectiveness based on patients' sex, and understanding such variations can improve patient outcomes by adjusting for differences. We aimed to assess the sex differences in outcome after EVT for patients with AIS. METHODS: We retrospectively analyzed 250 consecutive AIS patients who underwent EVT from July 2019 to February 2022 across two large comprehensive tertiary care stroke centers in China. Outcomes of male patients were compared to females, where poor outcome was defined as a modified Rankin score (mRS) of 3-6 at 90 days. RESULTS: Male patients had higher rates of symptomatic intracranial hemorrhage (sICH) (12.50% vs. 4.05%, p = 0.042) and higher hospitalization costs (114,541.08 vs. 105,790.27 RMB, p = 0.024). Male patients also had a longer median onset-to-needle time (ONT) (146.00 [104.00, 202.00] versus 120.00 [99.25, 144.75], p = 0.026). However, there were no differences in hospitalization length (p = 0.251), 90-day favorable outcome (p = 0.952), and 90-day mortality (p = 0.931) between the sexes. CONCLUSION: Female patients had lower hospitalization costs and sICH rates than males after EVT for AIS. Identifying such differences and implementing measures, including adaptations to workflow optimization, would help to reduce the ONT and last known normal-to-puncture time seen in males to improve patient outcomes. Despite such variations, favorable outcomes and mortality are similar in female and male AIS patients.

Microplastics' toxic effects and influencing factors on microorganisms in biological wastewater treatment units.

Prior to entering the water body, microplastics (MPs) are mostly collected at the sewage treatment plant and the biological treatment unit is the sewage treatment facility's central processing unit. This review aims to present a comprehensive analysis of the detrimental impacts of MPs on the biological treatment unit of a sewage treatment plant and it covers how MPs harm the effluent quality of biological treatment processes. The structure of microbial communities is altered by MPs presence and additive release, which reduces functional microbial activity. Extracellular polymers, oxidative stress, and enzyme activity are explored as micro views on the harmful mechanism of MPs on microorganisms, examining the toxicity of additives released by MPs and the harm caused to microorganisms by harmful compounds that have been adsorbed in the aqueous environment. This article offers a theoretical framework for a thorough understanding of the potential problems posed by MPs in sewage treatment plants and suggests countermeasures to mitigate those risks to the aquatic environment.

Adsorption of Cu (II) and Zn (II) in aqueous solution by modified bamboo charcoal.

Due to the development of industries such as mining, smelting, industrial electroplating, tanning, and mechanical manufacturing, heavy metals were discharged into water bodies seriously affecting water quality. Bamboo charcoal, as an environmentally friendly new adsorbent material, in this paper, the virgin bamboo charcoal (denoted as WBC) was modified with different concentrations of KMnO4 and NaOH to obtain KMnO4-modified bamboo charcoal (KBC) and NaOH-modified bamboo charcoal (NBC) which was used to disposed of water bodies containing Cu2+ and Zn2+. The main conclusions were as following: The adsorption of Cu2+ by WBC, KBC and NBC was significantly affected by pH value, and the optimum pH was 5.0. Differently, the acidity and alkalinity of the solution doesn't effect the adsorption of Zn2+ seriousely. Meanwhile, surface diffusion and pore diffusion jointly determine the adsorption rate of Cu2+ and Zn2+. The test result of EDS showed that Mn-O groups formed on the surface of K6 (WBC treated by 0.06 mol/L KMnO4) can promote the adsorption of Cu2+ and Zn2+ at a great degree. The O content on N6(WBC treated by 6 mol/L NaOH) surface increased by 30.95% compared with WBC. It is speculated that the increase of carbonyl group on the surface of NBC is one of the reasons for the improvement of Cu2+ and Zn2+ adsorption capacity. Finally, the residual concentrations of Cu2+ and Zn2+ in wastewater are much lower than 0.5 mg/L and 1.0 mg/L, respectively. Thus it can be seen, KBC and NBC could be a promising adsorbent for heavy metals.

Construction of a BiOI/ZnO heterojunction on biomass Juncus effusus fiber for photodegradation of organic pollutants.

Semiconductor heterojunction engineering and three-dimensional (3D) architecture construction have been considered highly desirable strategies to enhance photocatalytic performance. Herein, a BiOI/ZnO composite photocatalyst with a 3D flower-like architecture was successfully prepared, which was stably immobilized on three-dimensional porous lignocellulosic biomass Juncus effusus (JE) fiber. The outstanding photocatalytic performance of the BiOI/ZnO-JE fiber was confirmed by the degradation of tetracycline hydrochloride (TC, 90%), ciprofloxacin (CIP, 79%), and norfloxacin (NOR, 81%). The enhanced photocatalytic activities were mainly attributed to the synergistic absorption performance of the lignocellulosic JE and the effective transfer and separation of charges. Moreover, the hydroxyl (·OH) and superoxide radicals (·O2-) are the main reactive species in the photocatalytic process according to the analysis. This work may provide a novel perspective for constructing high-performance lignocellulosic-based photocatalytic materials.

Compact fiber sensor for pH measurement based on the composite effect of hydrogel deformation and LC refractive index variation.

A novel, to the best of our knowledge, type of compact pH fiber sensor combined with a hydrogel based on the whispering gallery mode (WGM) is proposed and integrates a liquid crystal (LC) microdroplet in a capillary in a compact structure as small as 180 µm. In the research, the hydrogel performs both as a supporting frame and a responsive material that causes morphological deformation of the LC microdroplet with pH variation. Moreover, a new phenomenon of pH-induced LC refractive index variation is observed and applied in the pH measurement, so that the acid itself can also lead the LC microdroplet structure transition. Thus, the WGM method is applied to detect the composite effect simultaneously to improve the sensing capability. The sensitivity of the sensor in the pH range from 4.55 to 6.86 reaches 3.19 nm/pH. The response time is short, within 60 s. The simple and compact structure of the sensor reduces the cost and enhances the stability, which is of great potential for biomedical pH measurement.

Novel Insight into Ferroptosis in Kidney Diseases.

BACKGROUND: Various kidney diseases such as acute kidney injury, chronic kidney disease, polycystic kidney disease, renal cancer, and kidney stones, are an important part of the global burden, bringing a huge economic burden to people around the world. Ferroptosis is a type of nonapoptotic iron-dependent cell death caused by the excess of iron-dependent lipid peroxides and accompanied by abnormal iron metabolism and oxidative stress. Over the past few decades, several studies have shown that ferroptosis is associated with many types of kidney diseases. Studying the mechanism of ferroptosis and related agonists and inhibitors may provide new ideas and directions for the treatment of various kidney diseases. SUMMARY: In this review, we discuss the differences between ferroptosis and other types of cell death such as apoptosis, necroptosis, pyroptosis, cuprotosis, pathophysiological features of the kidney, and ferroptosis-induced kidney injury. We also provide an overview of the molecular mechanisms involved in ferroptosis and events that lead to ferroptosis. Furthermore, we summarize the possible clinical applications of this mechanism among various kidney diseases. KEY MESSAGE: The current research suggests that future therapeutic efforts to treat kidney ailments would benefit from a focus on ferroptosis.

Injectable, Self-Healing and Multiple Responsive Histamine Modified Hyaluronic Acid Hydrogels with Potentialities in Drug Delivery, Antibacterial and Tissue Engineering.

Hydrogels are 3D network structures composed of physically or chemically crosslinked, hydrophilic molecules. Compared with conventional hydrogels with static and permanent network structures, injectable and responsive hydrogels generated from dynamic networks, have attracted increasing attention from various disciplines due to their wide-ranging applications in tissue engineering, drug delivery, soft robotics, etc. Herein, an injectable self-healing and multiple-responsive hyaluronic acid (HA)- histamine (His)/metal hydrogel is developed by modifying His onto HA and the subsequent, dynamic coordination between imidazole and metal ions. The pH-responsive and mechanical behaviors exhibited by the HA-His/metal hydrogels are tunable with the kinds and the concentrations of metal ions. The HA-His/Zr4+ hydrogels demonstrate a moldable capability at a neutral pH and a multi-stimulus-responsive capability when exposed to a weak alkaline environment and hyaluronidase, which inhibits bacterial growth and biofilm formation. Biocompatibilities and accelerated wound healing are demonstrated in vitro and in vivo and are thoroughly investigated and well characterized. The HA-His/Zr4+ hydrogel has great potential in various biomedical applications, such as pH- and hyaluronidase-responsive sustained release, antibacterial, and implantable materials for tissue engineering.

Ultra-low sample consumption consecutive-detection method for biochemical molecules based on a whispering gallery mode with a liquid crystal microdroplet.

Ultra-low sample consumption detection has many applications in molecular biology, bioanalytical chemistry, and medical science. In this Letter, a novel, to the best of our knowledge, simple type of ultra-low sample consumption detection method based on a whispering gallery mode is proposed as a means to realize consecutive detection with a liquid crystal (LC) microdroplet for biochemical molecule detection, using deoxyribonucleic acid (DNA) as a model biomarker. The sensor consists of a 105-µm-core multimode fiber fused with a hollow capillary tube, with the LC microdroplet suspended stably in the testing solution. Its application to the detection of salmon sperm DNA yielded an adjustable measurement range of 3.75-11.25 µg/ml and a sensitivity of 0.33 nm/µg/ml. The test solution required as little as 3 nl of the sample, and the limit of detection was 1.32 µg/ml, which corresponds to the effective detection of as little as 3.96 pg of DNA. This method has great potential for application in the ultra-low sample consumption detection of biochemical molecules.

Inhibition of the glycogen synthase kinase 3ß-hypoxia-inducible factor 1α pathway alleviates NLRP3-mediated pyroptosis induced by high glucose in renal tubular epithelial cells.

NEW FINDINGS: What is the central question of this study? Activation of the glycogen synthase kinase 3 ß (GSK-3ß)-hypoxia-inducible factor 1 α (HIF-1α) pathway results in stimulation of pyroptosis under high glucose, and exerts actions in a number renal diseases: does this pathway have a role in renal tubular epithelial cells? What is the main finding and its importance? Down-regulation of GSK-3ß can inhibit pyroptosis of renal tubular epithelial cells induced by high glucose and this may be related to down-regulation of HIF-1α. This role of the GSK-3ß-HIF-1α pathway has not previously been reported and identifies a potential new therapeutic target in diabetic nephropathy. ABSTRACT: Diabetic nephropathy (DN) is not only one of the main complications of diabetes, but also has a high incidence rate and a high mortality rate. Glycogen synthase kinase 3 ß (GSK-3ß) and hypoxia-inducible factor 1 α (HIF-1α) have been demonstrated to influence DN by regulating pyroptosis. This study aimed to investigate the effect of the GSK-3ß-HIF-1α pathway on pyroptosis of high-glucose (HG)-induced renal tubular cells. Mouse renal proximal tubular epithelial cells (TKPT cells) were induced by HG to simulate DN cell and we transfected TKPT cells with GSK-3ß knockdown lentivirus. Western blot analysis confirmed the transfection effects and detected the expression of GSK-3ß, HIF-1α, Nod-like receptor protein 3 (NLRP3), cleaved-caspase-1, pro-caspase-1, gasdermin D (GSDMD) and GSDMD-N. The expression of GSDMD-N and HIF-1α were also verified by immunofluorescence. The levels of interleukin (IL)-1ß and IL-18 were measured by enzyme linked immunosorbent assay. Flow cytometric analysis determined the apoptosis rate. Results showed that HIF-1α expression was increased in HG-induced TKPT cells, and GSK-3ß knockdown could decrease the levels of NLRP3, cleaved-caspase-1, GSDMD-N and HIF-1α, verified by immunofluorescence. Moreover, GSK-3ß knockdown suppressed the expression of IL-1ß and IL-18, and reduced the apoptosis rate. Lithium chloride (LiCl) interference could cause the same changes as GSK-3ß knockdown for HG-induced TKPT cells, and dimethyloxallyl glycine could reverse the effect of GSK-3ß-knockdown interference. Our studies definitively demonstrate that the GSK-3ß-HIF-1α signalling pathway mediates HG-stimulated pyroptosis in renal tubular epithelial cells and that down-regulation of GSK-3ß inhibited HG-induced pyroptosis by inhibiting the expression of HIF-1α. These findings suggest a new potential target for the treatment of DN.

Directed genome evolution driven by structural rearrangement techniques.

Directed genome evolution simulates the process of natural evolution at the genomic level in the laboratory to generate desired phenotypes. Here we review the applications of recent technological advances in genome writing and editing to directed genome evolution, with a focus on structural rearrangement techniques. We highlight how these techniques can be used to generate diverse genotypes, and to accelerate the evolution of phenotypic traits. We also discuss the perspectives of directed genome evolution.

Metal-Organic Frameworks Meet Metallic Oxide on Carbon Fiber: Synergistic Effect for Enhanced Photodegradation of Antibiotic Pollutant.

Photodegradation shows a potential strategy for alleviating the excessive antibiotics crisis. The synergistic effect of various metal compounds immobilized on conductive substrates has been considered for wastewater treatment. However, developing a facile and universal approach for rational design and enhancing photocatalytic properties has endured extreme challenges. Herein, we develop a strategy to facilitate the photocatalytic reactions by designing a composite architecture of ZIF-8 ligand binding to the in-situ synthesis ZnO seed layer on carbon fiber. In this architecture, the dissolution and release of the seed layer in the excessive 2-Methylimidazole methanol solution were used as the binder to enhance the interplay between organic ligand and substrate. As an evaluated system for antibiotic contaminants, the photodegradation of tetracycline hydrochloride was performed with a removal efficiency of 88.47% (TC = 50 mg/L, pH = 4, 0.08 g of photocatalyst, illumination within 100 min). Moreover, the photocatalyst exhibited a steady photocatalytic activity (75.0%) after five cycles. The present work demonstrated a strategy for enhancing the photocatalytic performances of carbon fiber and accordingly provided useful perception into the design of the synergistic structure.

Electrospun zirconium oxide embedded in graphene-like nanofiber for aptamer-based impedimetric bioassay toward osteopontin determination.

An impedimetric bioassay was constructed based on a nanohybrid of zirconium oxide nanoparticles and graphene-like nanofiber (denoted by ZrO2@GNF) for the determination of osteopontin (OPN). A series of ZrO2@GNF nanohybrids with different morphologies and nanostructures were derived from zirconium-based metal-organic frameworks (UiO-66) entrapped within the electric spun polyacrylonitrile (PAN) fiber (represented by UiO-66@PAN) by calcination at different temperatures. The basic characterizations revealed that the UiO-66@PAN nanofibers were collapsed into short nanorods. As such, homogeneously distributed ZrO2 nanoparticles were found to be embedded within the GNF nanostructure. This transition in the chemical structure and nanostructure not only can greatly enhance the electrochemical conductivity of the nanohybrid but also can strengthen the adsorbed bioaffinity toward OPN aptamer strands. As compared with bioassays based on ZrO2@GNF calcined at 500 °C and 900 °C, the ZrO2@GNF nanohybrid obtained at 700 °C (ZrO2@GNF700) demonstrated superior sensing performance, showing a determination limit of 4.76 fg mL-1 within a OPN concentration ranging 0.01 pg mL-1 to 2.0 ng mL-1. It also displayed high selectivity, accompanied by  good reproducibility and stability, acceptable applicability, and excellent repeatability. Graphical abstractSchematic representation of an impedimetric aptasensor based on nanohybrids of zirconium oxide nanoparticles and graphene-like nanofiber (ZrO2@CNF) was constructed for osteopontin detection. The ZrO2@CNF700 nanohybrid-based aptasensor demonstrated superior sensing performances, providing a promising tool for detecting cancer markers in biomedical diagnosis.

Midterm Results of Transaxillary Occluder Device Closure of Perimembranous Ventricular Septal Defect Guided Solely by Transesophageal Echocardiography.

BACKGROUND: Perimembranous ventricular septal defect (pmVSD) is a common congenital heart disease. Transaxillary occluder device closure of the pmVSD has been proved effective and an alternative to surgical closure. The study aimed to evaluate the immediate operation outcomes and the early and midterm follow-up outcomes of transaxillary occluder device closure. METHODS: From January 2014 to December 2017, we retrospectively analyzed the patients who underwent transaxillary device closure of the pmVSD. All patients underwent transthoracic echocardiography (TTE), chest x-ray, and electrocardiogram (ECG) before and after the procedure (before discharging). Follow-up evaluation was completed at the time of 3, 6, 12 months and yearly thereafter in outpatient setting with TTE and ECG. RESULTS: A total of 428 patients (216 male, 212 female) underwent transaxillary occluder device closure of the pmVSD under the guidance of transesophageal echocardiography (TEE). The mean age at the operation time was 2.2 ± 1.5 year (range 0.5-16.2 year). The mean weight was 8.5 ± 4.1 kg (range 6-61 kg). The mean size of the occluder implanted in the operation was 5.3 ± 1.4 (range 4-8 mm), matching the mean defect size of 4.2 ± 1.1 (range 3-6 mm). The device closure operation was successfully achieved in 422 pmVSD patients (98.6%), and 6 patients failed in occluding and were converted to open surgery because of a great residual shunt and obvious device-related aortic regurgitation . Immediate complete closure was detected by postoperative TEE in all, but 3 patients had trivial residual shunting. Total early adverse events emerged in 47 patients (11.1%). New mild tricuspid and aortic regurgitation occurred in 17 and 3 patients and disappeared in follow-up. Abnormal atrioventricular conduction events emerged in 23 patients, including left anterior block, complete right bundle branch block (CRBBB), incomplete right bundle branch block (IRBBB), administrated with close follow-up. Pericardial effusion occurred in 2 other patients, managed with puncture drainage. During a median follow-up period of 26.8 months (range 6-48 months), no serious adverse event and later-on complete atrioventricular block were encountered. CONCLUSION: In our experience, transaxillary device closure was performed via right infra-axillary mini-incision (invisible) guided by TEE, with low incidence of postoperative adverse events, confirming that transaxillary device closure of the pmVSD under the guidance of TEE is an effective alternative to surgical closure in well-selected pmVSD patients.

Ecdysone Elicits Chronic Renal Impairment via Mineralocorticoid-Like Pathogenic Activities.

BACKGROUND/AIMS: Ecdysteroids are steroidal insect molting hormones that also exist in herbs. Ecdysteroid-containing adaptogens have been popularly used to improve well-being and by bodybuilders for muscle growth. However, the use of ecdysone in mammals is also associated with kidney growth and enlargement, indications of disturbed kidney homeostasis. The underlying pathogenic mechanism remains to be clarified. METHODS: Virtual screening tools were employed to identify compounds that are homologous to ecdysone and to predict putative ecdysone-interacting proteins. The kidney effect of ecdysone was examined in vitro and in vivo and compared with that of aldosterone. Cellular apoptosis was estimated by terminal deoxynucleotidyl transferase dUTP nick end labeling. Cell motility was assessed by scratch-wound cell migration assay. Blood urea nitrogen was measured to evaluate renal function. Western immunblot analysis was employed to determine the expression profile of interested proteins. RESULTS: Computational molecular structure analysis revealed that ecdysone is highly homologous to aldosterone. Moreover, virtual screening based on compound-protein interaction profiles identified the Mineralocorticoid Receptor (MR) to potentially interact with ecdysone. Accordingly, to assess potential biological functions of ecdysone in mammals, ecdysone was applied to mineralocorticoid-sensitive inner medullar collecting duct cells. Ecdysone induced mesenchymal accumulation of extracellular matrix and epithelial dedifferentiation characterized by de novo expression of α-smooth muscle actin. In addition, ecdysone elicited cellular apoptosis and retarded cell motility, akin to the effect of aldosterone. In vivo, daily treatment of mice with ecdysone increased cell apoptosis in the kidney, impaired renal function and elicited early signs of renal fibrogenesis, marked by deposition of collagen and fibronectin in tubulointerstitium, reminiscent of the action of aldosterone. The MR signaling pathway is likely responsible for the cellular and pathobiological effects of ecdysone, as evidenced by strong ecdysone-induced MR nuclear translocation in renal tubular cells both in vitro and in vivo, while blockade of MR by concomitant spironolactone treatment largely abolished the detrimental effects of ecdysone. CONCLUSION: Our findings suggest that ecdysone induces mineralocorticoid-dependent activities that impair renal function and elicit renal injury.

Three-dimensional printing enhances preparation for repair of double outlet right ventricular surgery.

OBJECTIVE: To assess the clinical value of three-dimensional (3D) printing technology for treatment strategies for complex double outlet right ventricle (DORV). METHODS: Twenty-five patients with complex double outlet right ventricle were enrolled in this study. The patients were divided into two groups: 3D printing group (eight patients) and a non-3-D printing control group (17 patients). The cardiac images of patients in the 3D printing group were transformed to Digital Imaging and Communications and were segmented and reconstructed to create a heart model. No cardiac models were created in the control group. A Pearson coefficient analysis was used to assess the correlation between measurements of 3D printed models and computed tomography angiography (CTA) data. Pre-operative assessment and planning were performed with 3D printed models, and then operative time and recovery time were compared between the two groups. RESULTS: There was good correlation (r = 0.977) between 3D printed models and CTA data. Patients in the 3D printing group had shorter aortic cross-clamp time (102.88 vs 127.76 min, P = 0.094) and cardiopulmonary bypass time (151.63 vs 184.24 min; P = 0.152) than patients in the control group. Patients with 3D printed models had significantly lower mechanical ventilation time (56.43 vs 96.76 h, P = 0.040) and significantly shorter intensive care unit time (99.04 vs 166.94 h, P = 0.008) than patients in the control group. CONCLUSIONS: 3D printed models can accurately demonstrate anatomic structures and are useful for pre-operative treatment strategies in DORV.

Genetic and Pharmacologic Targeting of Glycogen Synthase Kinase 3ß Reinforces the Nrf2 Antioxidant Defense against Podocytopathy.

Evidence suggests that the glycogen synthase kinase 3 (GSK3)-dictated nuclear exclusion and degradation of Nrf2 is pivotal in switching off the self-protective antioxidant stress response after injury. Here, we examined the mechanisms underlying this regulation in glomerular disease. In primary podocytes, doxorubicin elicited cell death and actin cytoskeleton disorganization, concomitant with overactivation of GSK3ß (the predominant GSK3 isoform expressed in glomerular podocytes) and minimal Nrf2 activation. SB216763, a highly selective small molecule inhibitor of GSK3, exerted a protective effect that depended on the potentiated Nrf2 antioxidant response, marked by increased Nrf2 expression and nuclear accumulation and augmented production of the Nrf2 target heme oxygenase-1. Ectopic expression of the kinase-dead mutant of GSK3ß in cultured podocytes reinforced the doxorubicin-induced Nrf2 activation and prevented podocyte injury. Conversely, a constitutively active GSK3ß mutant blunted the doxorubicin-induced Nrf2 response and exacerbated podocyte injury, which could be abolished by treatment with SB216763. In murine models of doxorubicin nephropathy or nephrotoxic serum nephritis, genetic targeting of GSK3ß by doxycycline-inducible podocyte-specific knockout or pharmacologic targeting by SB216763 significantly attenuated albuminuria and ameliorated histologic signs of podocyte injury, including podocytopenia, loss of podocyte markers, podocyte de novo expression of desmin, and ultrastructural lesions of podocytopathy (such as foot process effacement). This beneficial outcome was likely attributable to an enhanced Nrf2 antioxidant response in glomerular podocytes because the selective Nrf2 antagonist trigonelline abolished the proteinuria-reducing and podocyte-protective effect. Collectively, our results suggest the GSK3ß-regulated Nrf2 antioxidant response as a novel therapeutic target for protecting podocytes and treating proteinuric glomerulopathies.

Perventricular device closure of doubly committed sub-arterial ventricular septal defects via a left infra-axillary approach.

BACKGROUND: This study sought to evaluate the feasibility, safety, and efficacy of perventricular device closure of a doubly committed sub-arterial ventricular septal defect (dcVSD) through a left infra-axillary approach. METHOD: Forty-five patients, with a dcVSD of less than 8 mm in diameter, were enrolled in this study. The pericardium was exposed and opened through a left infra-axillary mini-incision. Two parallel purse-string sutures were placed on the right ventricle outflow tract and under transesophageal echocardiography guidance, a delivery sheath loaded with the device was inserted into the right ventricle and advanced through the defect into the left ventricle. The device, connected to a delivery cable, was then deployed. RESULTS: Forty-one patients achieved successful device closure. In four patients, the device failed to occlude the VSD due to device dislodgement, device-related aortic regurgitation, and residual shunts, and open surgical repair was required. The mean dcVSD diameter was 4.5 ± 1.0 mm (range, 3.0-8.0 mm). The implanted device size was 6.0 ± 1.5 mm (range, 4-10 mm). All patients were implanted with an eccentric device. The mean intracardiac manipulation time was 20.9 ± 7.1 min (range, 9-45 min). The procedure time was 62.5 ± 19.5 min (range 34-105 min). There were no severe adverse events. CONCLUSIONS: Perventricular device closure of a dcVSD through a left infra-axillary approach is feasible, safe, and efficacious in selected patients with dcVSD.

Transjugular closure of secundum atrial septal defects.

OBJECTIVE: This study reports the results of a steerable delivery system under the guidance of transesophageal echocardiography (TEE) for the treatment of transjugular closure of secundum atrial septal defects (ASD). METHODS: From July 2015 to May 2016, 33 patients underwent transjugular closure of a secundum ASD under general anesthesia with TEE guidance. The right internal jugular vein was punctured and a FuStar™ steerable sheath was implanted into the right atrium and aligned vertically with the septum, and a closure device was deployed to close the defect. RESULTS: Thirty-two patients with an ASD were successfully occluded; one patient required ASD closure on cardiopulmonary bypass. Procedure time ranged from 5 to 15 (8.2 ± 3.8) min. The length of stay was three to five days after the operation. The follow-up time ranged from 1.1 to 11.0 (5.5 ± 1.5) months. There was no valve regurgitation, no malignant arrhythmias, no device dislocation, or other serious complications. CONCLUSIONS: A steerable delivery system under the guidance of TEE is a safe, effective, and cosmetic method for the transjugular closure of secundum ASDs.