Acute kidney injury (AKI) is a major public health problem with high incidence and mortality. As a form of programmed cell death (PCD), ferroptosis could be considered as a process of iron ...accumulation and enhanced lipid peroxidation. Recently, the fundamental roles of ferroptosis in AKI have attracted much attention. The network mechanism of ferroptosis in AKI and its roles in the AKI to chronic kidney disease (CKD) transition is complicated and multifactorial. Strategies targeting ferroptosis show great potential. Here, we review the research progress on ferroptosis and its participation in AKI. We hope that this work will provide clues for further studies of ferroptosis in AKI.
A face detection method based on lightweight network and weak semantic segmentation attention mechanism is proposed in this paper, aiming at the problems of low detection accuracy and slow detection ...speed in face detection in complex scenes. K-means++ algorithm is employed to perform clustering analysis on YOLOv4 model prior frames in this paper, and smaller size prior frames are set to capture small face information to solve the missing detection problem of small face targets in scenes. The backbone network structure is improved by introducing Mobile Net lightweight network model, to reduce the number of parameters and calculation of the model and improve the detection speed. The convolutional block attention module model with dual attention mechanism is embedded to improve the sensitivity of the model to target features, which can suppress interference information and improve the accuracy of target detection. A dynamic enhancement attachment based on weak semantic segmentation is added in front of the detector head, whose output is used as the spatial weight distribution to correct the activation area, to suppress the false detection and missed detection caused by the decrease of extraction ability evoked by the pursuit of lightweight. The experimental results on WIDEFACE dataset indicate that this method not only can detect face in real time and with high accuracy, but also has better performance than other existing methods.
Rhodium-catalyzed green synthesis of isoindolin-1-ones via a sequential C–H activation/allene formation/cyclization pathway by applying water as solvent is reported. The reaction is highly ...regioselective, tolerating some potentially useful functional groups.
To test the independent and interactive associations of physical activity (PA) and screen time (ST) with self-reported mental health and sleep quality among Chinese college students.
Data were ...collected in October, 2013. The gender, age, residential background, body mass index (BMI), perceived family economy and perceived study burden were obtained from a total of 4747 college students (41.6% males and 58.4% females). The outcomes were self-reported PA status, ST, anxiety, depression, psychopathological symptoms and sleep quality. Analyses were conducted with logistic regression models.
Overall, 16.3%, 15.9% and 17.3% of the students had psychological problems, such as anxiety, depression and psychopathological symptoms, respectively. The prevalence of poor sleep quality was 9.8%. High ST was significantly positively associated with anxiety (OR=1.38, 95%CI: 1.15-1.65), depression (OR=1.76, 95%CI: 1.47-2.09), psychopathological symptoms (OR=1.69, 95%CI: 1.43-2.01) and poor sleep quality (OR=1.32, 95%CI: 1.06-1.65). High PA was insignificantly negatively associated with anxiety, depression, psychopathological symptoms and poor sleep. Low PA and high ST were independently and interactively associated with increased risks of mental health problems and poor sleep quality (p<0.05 for all).
Interventions are needed to reduce ST and increase PA in the lifestyles of young people. Future research should develop and measure the impacts of interventions and their potential consequences on sleep, health, and well being.
•Circ_0000285 was elevated while miR-654-3p was down-regulated in DN.•Circ_0000285 acted as a sponge of miR-654-3p.•MAPK6 functioned as downstream target of miR-654-3p.
Recently, increasing evidence ...has reported that circRNAs are non-coding RNAs and they bind with the corresponding miRNAs to modulate the target genes. However, the detailed role of circRNAs in the pathogenesis of DN still remains poorly known. Currently, we aimed to study how circ_0000285 functions in DN development. We found that circ_0000285 was significantly increased in DN mice models and mouse podocytes incubated with HG. Then, circ_0000285 was overexpressed in mouse podocytes and we observed that overexpression of circ_0000285 promoted podocytes injury. Moreover, miR-654-3p was precited as a target of circ_0000285. It was shown that circ_0000285 was strongly pulled down by circ_0000285 specific probe and circ_0000285 specific probe was used to successfully enrich miR-654-3p. In addition, we reported that miR-654-3p was obviously down-regulated in DN. Inhibitors of miR-654-3p greatly reversed the effects of circ_0000285 siRNA on podocytes injury. Moreover, the inflammation release was restrained by loss of circ_0000285, while induced by miR-654-3p inhibitors. IL-6, L-1β and TNF-α level was remarkably depressed by the knockdown of circ_0000285 and miR-654-3p inhibitors induced that. Furthermore, MAPK6 was confirmed as a direct downstream target of miR-654-3p. As shown, MAPK6 was markedly suppressed by circ_0000285 siRNA, which was rescued by the decrease of miR-654-3p. These findings revealed that circ_0000285 promoted podocyte injury via sponging miR-654-3p and activating MAPK6 in DN.
Oxidative and inflammatory damage have been suggested to play important roles in the pathogenesis of diabetic nephropathy (DN). Chlorogenic acid (CGA) is one of the most abundant polyphenols and has ...known immunoprotective, antioxidant and anti-inflammatory properties. In the present study, animal experiments were designed to examine the protective effects of CGA in DN, and cellular experiments were designed to explore the underlying mechanisms. CGA significantly attenuated diabetic renal damage based on histological pathology and molecular biological methods. Pre-treatment with CGA increased the nuclear translocation of nuclear factor erythroid-derived 2-related factor 2 (Nrf2) and the expression of heme oxygenase-1 (HO-1) and reduced the phosphorylation of IĸB and subsequent nuclear translocation of nuclear factor kappa beta (NF-ĸB). Nrf2 small interfering RNA (siRNA) and the HO-1 inhibitor zinc protoporphyrin (ZnPPIX) significantly increased the nuclear translocation of NF-ĸB and the production of pro-inflammatory cytokines in HBZY-1 cells. The NF-ĸB inhibitor pyrrolidine dithiocarbamate (PDTC) increased Nrf2 nuclear translocation and HO-1 expression and antioxidant levels. Thus, these results suggest that CGA is a potential therapeutic agent in the treatment of DN due to its antioxidant and anti-inflammatory effects which are mediated via the modulation of the Nrf2/HO-1 and NF-ĸB pathways. Moreover, CGA-induced the activation of Nrf2/HO-1,which interacts with the inhibition of NF-ĸB, as each begets and amplifies the other.
•Chlorogenic acid mitigates diabetic renal oxidative stress via regulating the Nrf2 pathway.•Chlorogenic acid relieves diabetic renal inflammation by inhibiting NF-ĸB pathway.•CGA-induced activation of Nrf2/HO-1 interacts with the inhibition of NF-ĸB, as each begets and amplifies the other.•CGA could be a potential therapeutic agent in the treatment of diabetic nephropathy.
Abstract
Diabetic kidney disease (DKD) is a major complication for diabetic patients. Adiponectin is an insulin sensitizer and anti-inflammatory adipokine and is mainly secreted by adipocytes. Two ...types of adiponectin receptors, AdipoR1 and AdipoR2, have been identified. In both type 1 and type 2 diabetes (T2D) patients with DKD, elevated adiponectin serum levels have been observed, and adiponectin serum level is a prognostic factor of end-stage renal disease. Renal insufficiency and tubular injury possibly play a contributory role in increases in serum and urinary adiponectin levels in diabetic nephropathy by either increasing biodegradation or elimination of adiponectin in the kidneys, or enhancing production of adiponectin in adipose tissue. Increases in adiponectin levels resulted in amelioration of albuminuria, glomerular hypertrophy, and reduction of inflammatory response in kidney tissue. The renoprotection of adiponectin is associated with improvement of the endothelial dysfunction, reduction of oxidative stress, and upregulation of endothelial nitric oxide synthase expression through activation of adenosine 5′-monophosphate–activated protein kinase by AdipoR1 and activation of peroxisome proliferator-activated receptor (PPAR)-α signaling pathway by AdipoR2. Several single nucleotide polymorphisms in the AdipoQ gene, including the promoter, are associated with increased risk of the development of T2D and DKD. Renin-angiotensin-aldosterone system blockers, adiponectin receptor agonists, and PPAR agonists (e.g., tesaglitazar, thiazolidinediones, fenofibrate), which increase plasma adiponectin levels and adiponectin receptors expression, may be potential therapeutic drugs for the treatment of DKD.
This article reviews the role and underlying molecular mechanisms of adiponectin and its receptors, AdipoR1 and AdipoR2, in diabetic kidney disease (DKD).
Cisplatin (DDP) was reported to improve pathological complete response (pCR) rates in triple-negative breast cancer (TNBC) patients, however, the molecular mechanism still remains largely unknown. ...Emerging evidence suggested that some chemotherapeutic drugs played anti-tumor effects by inducing cell pyroptosis. Nevertheless, whether pyroptosis contributes to the DDP-induced anti-tumor effect in TNBC remains unexploited. In the present study, NLRP3/caspase-1/GSDMD pyroptosis pathway was involved in the DDP-induced anti-tumor effect of TNBC
and
, providing evidence that DDP might induce pyroptosis in TNBC. Moreover, DDP activated NLRP3/caspase-1/GSDMD pyroptosis pathway by up-regulating the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3). Furthermore, knockdown of MEG3 not only partly abolished the activation effect of DDP on NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis, but also reversed the suppression of DDP on tumor growth and metastasis ability
and
further confirming that MEG3 may partially mediate the pyroptotic signaling upon DDP treatment. Thus, our data uncovered a novel mechanism that DDP induced pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in TNBC to exert anti-tumor effects, which may help to develop new strategies for the therapeutic interventions in TNBC.
Abstract
Sodium/glucose cotransporter-2 inhibitors (SGLT2i) are a new type of glucose-lowering drug that can reduce blood glucose by inhibiting its reabsorption in proximal tubules and by promoting ...urinary glucose excretion. SGLT2i are widely used in the clinical treatment of type 2 diabetes mellitus (T2DM). In recent studies, SGLT2i were found to not only reduce blood glucose but also protect the heart and kidney, which can significantly reduce cardiovascular events, delay the progression of renal failure, greatly improve the quality of life of patients, and reduce medical expenses for families and society. As adverse cardiac and renal events are the most common and serious complications of T2DM, it is very important to understand the cardio- and renoprotective mechanisms of SGLT2i. This article reviews the historical development, pharmacological mechanism, heart and kidney protection and safety of SGLT2i. The information presented provides a theoretical basis for the clinical prevention and treatment of diabetes and its complications and for the development of new glucose-lowering drugs.
Abstract
The industrial yeast Pichia pastoris has been harnessed extensively for production of proteins, and it is attracting attention as a chassis cell factory for production of chemicals. However, ...the lack of synthetic biology tools makes it challenging in rewiring P. pastoris metabolism. We here extensively engineered the recombination machinery by establishing a CRISPR-Cas9 based genome editing platform, which improved the homologous recombination (HR) efficiency by more than 54 times, in particular, enhanced the simultaneously assembly of multiple fragments by 13.5 times. We also found that the key HR-relating gene RAD52 of P. pastoris was largely repressed in compared to that of Saccharomyces cerevisiae. This gene editing system enabled efficient seamless gene disruption, genome integration and multiple gene assembly with positive rates of 68–90%. With this efficient genome editing platform, we characterized 46 potential genome integration sites and 18 promoters at different growth conditions. This library of neutral sites and promoters enabled two-factorial regulation of gene expression and metabolic pathways and resulted in a 30-fold range of fatty alcohol production (12.6–380 mg/l). The expanding genetic toolbox will facilitate extensive rewiring of P. pastoris for chemical production, and also shed light on engineering of other non-conventional yeasts.
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