Search

Retinal neurodegeneration is an early feature in the pathogenesis of diabetic retinopathy (DR). Autophagy is an intracellular catabolic process involved in protein and organelle degradation that has been linked in DR. Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has beneficial effects in diabetic. however, it is not currently known whether EGCG can regulate Müller cell autophagy. Here, we showed that EGCG increased autophagy by promoting the formation of autophagosomes, increasing lysosomal acidification, and stimulating autophagic flux in Müller cells, while high glucose (HG) induced a decrease in autophagy and an increase in apoptosis. However, retinal Müller cells in HG treated with EGCG showed autophagy machinery activation and reestablishment of cargo degradation, protecting the cells from apoptosis. EGCG could increase the ability of cells to proliferate by increasing autophagy. In an experimental model of diabetic retinopathy, EGCG reduced the reactive gliosis of Müller cells and decreased retinal damage. These results highlight that HG downregulates autophagy and accumulates P62 cargo due to lysosomal dysfunction and then increases apoptosis, which was reversed by treatment with EGCG. This finding might be valuable for developing a novel therapeutic strategy to treat DR. • This experimental drug EGCG is a natural component of green tea. • EGCG induced cell proliferation and decrease apoptosis in Müller cell. • EGCG enhanced autophagic flux through regulating mTOR mediated pathway in HG-treated Müller cells. [ABSTRACT FROM AUTHOR]

The capacity of improving the control accuracy and dynamic performance of a four degree-of-freedom (DOF) permanent magnet biased active magnetic bearing (PMBAMB) system is critical to developing and maintaining a high precision application in a magnetically suspended direct-driven spindle system. The 4-DOF PMBAMB system, however, is a multivariable, strong coupled and nonlinear system with unavoidable and unmeasured external disturbances, in addition to having parameter variations. The satisfactory control performance cannot be obtained by using traditional strategies. Therefore, it is important to present a novel control scheme to construct a robust controller with good closed-loop capability. This paper proposes a new decoupling control scheme for a 4-DOF PMBAMB in a direct-driven spindle system based on the neural network inverse (NNI) and 2- degree-of-freedom (DOF) internal model control method. By combining the inversion of the 4-DOF PMBAMB system with its original system, a new pseudolinear system can be developed. In addition, by introducing the 2-DOF internal model controller into the pseudolinear system to design extra closed-loop controllers, we can effectively eliminate the influence of the unmodeled dynamics to the decoupling control accuracy, as well as adjust the properties of tracking and disturbance rejection independently. The experimental results demonstrate the effectiveness of the proposed control scheme. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is a leading cause of severe vision impairment in the aging population. However, the underlying molecular mechanism remains unclear. Ferroptosis is a novel non-apoptotic programmed cell death pathway, that contributes to AMD. In addition, non-coding RNA-led epigenetic profile was identified in the regulation of AMD progression. Considering that non-coding RNAs are vital regulators of ferroptosis-related genes in various pathological events, we explored and constructed a ferroptosis-associated circRNA-miRNA-mRNA network in AMD. Differential expression of fourteen ferroptosis-associated genes were identified based on our microarray analysis and the FerrDb tool at the threshold of P < 0.05 and log 2 |fold change| ≥ 1, which were subsequently validated by the public datasets. We further screened eight miRNAs via public datasets and the miRNet database. Based on these eight miRNAs, 23 circRNAs were mined using the Starbase tool. Taking all these together, we obtained a ferroptosis-related network with 414 pairs of circRNA-miRNA-mRNA, which are potential targets in future AMD treatments. • Differentially expressed genes (DEGs) in microarray analysis were intersected with ferroptosis related genes to identify promising ferroptosis-associated DEGs in CNV. • Potential circRNAs and miRNAs were mined and validated via public datasets and online tools. • A ferroptosis-associated circRNA-miRNA-mRNA network with 14 ferroptosis-associated genes, 8 miRNA and 23 circRNAs in CNV etiology was constructed for the first time, to our knowledge. [ABSTRACT FROM AUTHOR]

Highlights: [•] DIMEN displays higher anti-proliferative activity than enastron. [•] DIMEN induced mitotic arrest and apoptosis more significantly than enastron. [•] DIMEN blocked the conformational change of ADP-binding pocket more effectively. [•] DIMEN hindered ADP release more potently than enastron. [ABSTRACT FROM AUTHOR]

Abstract: To determine whether high free fatty acids (FFA) could affect the anti-contractile properties of perivascular adipose tissue (PVAT) in rat aortas. Wistar rats were divided into normal, obesity and fenofibrate groups and fed a normal, high-fat, and high-fat plus fenofibrate diet, respectively. Thoracic aortas with or without PVAT (PVAT+ and PVAT−) were prepared with either intact endothelium (E+) or with endothelium removed (E−). Aortas pre-treated with either 500μmol/L of palmitic acid (PA) or physiological salt solution (PSS), as a control, were used for in vitro study. Concentration-dependent responses of aortas to norepinephrine were measured. The anti-contractile effects of PVAT were attenuated in both obese rats with high FFA levels and in the PA group in the presence of endothelium, but not in the absence of endothelium. The attenuation of the anti-contractile effect was restored by reducing FFA levels in the fenofibrate group (P <0.05). Incubation of aortas (PVAT+ E+) with nitric oxide (NO) synthase inhibitor and tumor necrosis factor-alpha (TNF-α) in the normal group caused attenuation of the anti-contractile effect of PVAT (P <0.05). Incubation of aortas (PVAT+ E+) in the obese and PA groups with a NO donor, anti-TNF-α antibodies or free radical scavengers partially restored the anti-contractile effect of PVAT (P <0.05). Under both acute and chronic conditions, high FFA levels could attenuate the anti-contractile properties of PVAT by an endothelium-dependent rather than an endothelium-independent mechanism, in which inflammation and oxidative stress may play important roles. [Copyright &y& Elsevier]

• The operation of a four degree of freedom hybrid magnetic bearing (4-DOF HBM) can be considered as a repetitive process. • Iterative learning control is advantageous to deal with repetitive control problems. • The iteration variant disturbances are considered. • A modified iterative learning controller with an extended state observer (ESO) is presented. • Good performances of anti-disturbance and stability for HMBs system are achieved. Iterative learning control (ILC) is an iterative control strategy which calculates a new input according to the error in previous cycles. It is widely used in industries with repetitive operations. Since magnetic bearing systems can be considered as running in a repetitive task, the ILC could be applied. Hence, this paper proposes a modified iterative learning control (ILC) strategy for a four degree-of-freedom (DOF) hybrid magnetic bearing system to reject the disturbance based on an extended state observer (ESO). The feasibility of applying the ILC to the four-DOF magnetic bearing system is analyzed firstly. It is proved that the tracking error can converge by selecting suitable controller parameters. Secondly, to accurately obtain the uncertainties in the operation process, an ESO is designed. As for a repetitive rotation process, the iteration variant disturbance may have a certain influence on the performance of the system which is not usually considered. Therefore, the iteration variant disturbance is introduced and the effectiveness is derived. Finally, simulations and experiments are carried out to demonstrate the effectiveness of the proposed method. The classical proportion-integration-differentiation (PID) control and an existing proposed neural network inverse (NNI) control are implemented for comparison. The results show that the proposed strategy can achieve better reference tracking and disturbance suppression ability than PID and NNI control. [ABSTRACT FROM AUTHOR]

Rotating shaft instability leading to high amplitude vibration is a key problem with a wide range of industrial applications. The purpose of this study is to identify the response statistics for a conceptual model of a flexible shaft supported on hydrodynamic bearings (HDBs) and propose design strategies to reduce the response. A conceptual model of a flexible shaft with three discs supported on the HDBs is developed. A linearised model of the system is developed using the short bearing assumption. A Campbell diagram is developed for the conceptual model to identify the critical speeds wherein a high response is produced. These high responses occur at the rotor speeds corresponding to the synchronous forward whirl and the oil whip. The identified rotor speeds are validated by carrying out a run-up analysis on the test rig. Since the manufacturing process and operating conditions induce uncertainty by varying the eccentricity and the relative phase of the unbalance mass, the influence of the whirling modes on the response is investigated. The nominal positions of the unbalance masses are such that the predominant mode excited is the first mode. Experimentally a scatter plot on the maximum response at the bearing location is identified using six different positions of the eccentric mass. Further, a stochastic analysis using reduced order nonlinear model of the system is carried out. The probability density obtained is compared with a Monte Carlo simulation and the bounds of the experimental results. A control strategy is designed by altering the relative position of the unbalance masses to reduce the excitation of the first mode. The robustness of the strategy is verified by using a stochastic analysis, which indicates a reduction in the response magnitude. • The dynamic behaviour of a flexible rotating shaft is investigated using a test rig. • High response Rotor speeds due to forward whirl and oil whip are identified • Maximum response statistics is determined using gPC based Stochastic analysis. • Results obtained from gPC and MC simulations are compared with experimental results. • A robust control strategy to reduce the vibration is proposed and tested by using gPC. [ABSTRACT FROM AUTHOR]

Metabolic diseases pose a significant global health challenge, characterized by an imbalance in metabolism and resulting in various complications. Secreted frizzled-related protein 5 (SFRP5), an adipokine known for its anti-inflammatory properties, has gained attention as a promising therapeutic target for metabolic diseases. SFRP5 acts as a key regulator in the Wnt signaling pathway, exerting its influence on critical cellular functions including proliferation, differentiation, and migration. Its significance extends to the realm of adipose tissue biology, where it plays a central role in regulating inflammation, insulin resistance, adipogenesis, lipid metabolism, glucose homeostasis, and energy balance. By inhibiting Wnt signaling, SFRP5 facilitates adipocyte growth, promotes lipid accumulation, and contributes to a decrease in oxidative metabolism. Lifestyle interventions and pharmacological treatments have shown promise in increasing SFRP5 levels and protecting against metabolic abnormalities. SFRP5 is a pivotal player in metabolic diseases and presents itself as a promising therapeutic target. An overview of SFRP5 and its involvement in metabolic disorders and metabolism is provided in this comprehensive review. By elucidating these aspects, valuable insights can be gained to foster the development of effective strategies in combating metabolic diseases. • SFRP5 is involved in maintaining metabolic homeostasis. • The potential of SFRP5 as a therapeutic target for metabolic diseases. • Lifestyle interventions and pharmacological treatments increase SFRP5 levels. [ABSTRACT FROM AUTHOR]

A piezoelectric micropump (PE pump) was proposed featuring a multi-plate cantilever valve (MPCV) and a ramp channel (RC) to deliver high performance in a compact design. Both the MPCV and RC underwent thorough theoretical, simulation-based, and experimental evaluations. A specialized driver plate was then developed to precisely control the PE pump. Key parameters of the PE pump were optimized based on test results. The final phase involved assessing the PE pump's output performance through tests, including a simulated insulin infusion scenario. The findings revealed that the MPCV exhibited a pronounced rectification capability, significantly enhancing the pump's operational efficiency over traditional designs. The RC, on the other hand, effectively minimized fluid resistance, capitalizing on the fluid inertia effect for improved performance. Integrating the MPCV and RC aligned the fluid path from inlet to outlet closely parallel to the PE vibrator. This alignment reduced backflow, thereby improving the micropump's output efficiency. Operating at 240 voltage peak-to-peak (Vpp) and 230 Hz, the PE pump demonstrated a flow rate of 6.8 ml/min and an output pressure of 68.6 kPa while maintaining a compact size of merely 10 × 10 × 1.5 mm3. The precision in flow rate adjustment was refined to 0.15 μl, with the deviation in insulin delivery being approximately ± 3 %. The study presents a prototype for a continuous subcutaneous insulin infusion protocol, leveraging the PE pump's advanced features. [ABSTRACT FROM AUTHOR]

Heart diseases are a major cause of morbidity and mortality worldwide. Understanding the molecular mechanisms underlying these diseases is essential for the development of effective diagnostic and therapeutic strategies. The FHL family consists of five members: FHL1, FHL2, FHL3, FHL4, and FHL5/Act. These members exhibit different expression patterns in various tissues including the heart. FHL family proteins are implicated in cardiac remodeling, regulation of metabolic enzymes, and cardiac biomechanical stress perception. A large number of studies have explored the link between FHL family proteins and cardiac disease, skeletal muscle disease, and ovarian metabolism, but a comprehensive and in-depth understanding of the specific molecular mechanisms targeting FHL on cardiac disease is lacking. The aim of this review is to explore the structure and function of FHL family members, to comprehensively elucidate the mechanisms by which they regulate the heart, and to explore in depth the changes in FHL family members observed in different cardiac disorders, as well as the effects of mutations in FHL proteins on heart health. • FHL and cardiac metabolism enzyme regulation. • Structure and function of FHL proteins. • FHL proteins and various heart diseases. [ABSTRACT FROM AUTHOR]

Highlights • A compact reflective fiber laser refractometer is demonstrated. • The sensing system is power modulation. • The structure is suitable for precise localized measurement. • The temperature cross-sensitivity can be effectively compensated. Abstract A temperature-compensated fiber laser refractometer based on compact hybrid S fiber taper (SFT)/fiber Bragg grating (FBG) structure is proposed. The SFT is used as a sensing component as well as a band-pass filter (BPF) to tailor the FBG reflection, which has the micro size of 0.78 mm. Owing to the RI-dependence intra-cavity loss, the output power of the erbium-doped fiber ring laser (FRL) can be modulated by the surrounding refractive index (SRI). During the measurement range of 1.3330–1.4060, the refractometer provides a high sensitivity of 269.76 dB/RIU. By using the sensing matrix containing the SRI as well as temperature sensitivities for the output power and lasing wavelength, the temperature cross-sensitivity problem can be effectively resolved. [ABSTRACT FROM AUTHOR]

Age-associated dysfunction of retinal pigment epithelial cells (RPEs) is considered to be the initial trigger of retinal diseases such as age-related macular degeneration. Although autophagy is upregulated in RPEs during the course of aging, little is known about how autophagy is regulated and its functional role in RPEs. In this study, we found that expression of Sirtuin 6 (SIRT6) and autophagic markers are upregulated in RPEs of aged mice where subretinal deposition of amyloid-β is accumulated and in amyloid-β stimulated RPEs. In addition, gain and loss-of-function studies confirmed the positive role of SIRT6 in regulating autophagy. Interesting, inhibition of autophagy attenuates amyloid-β stimulated inflammatory response in RPEs. Collectively, our findings uncover the autophagy modulated by SIRT6 may be a proinflammatory mechanism for amyloid-β induced RPE dysfunction. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a leading cause of vision impairment and blindness among diabetics. We aimed to explore whether long-term exposure to residential greenness was beneficial to DR. We used data from a large-scale, cross-sectional screening survey conducted in 129 cities of 27 provincial regions of China from 2018 to 2021 among patients with diabetes. We measured residential greenness exposure as the 3-year average of annual maximum Normalized Difference Vegetation Index (NDVI) at a spatial resolution of 250 m. DR was assessed by ophthalmologists based on fundus photographs. The primary outcome was DR, and secondary outcome included DR severity status (i.e., nonproliferative and proliferative), hallmarks of retinal lesions and macular oedema. A total of 484,380 adult participants with diabetes were included in the current analysis, and 15.7% of them were diagnosed with DR. NDVI was inversely and linearly associated with DR prevalence, and an increment of 0.1 NDVI was associated with a 10% (9%–10%) decrease in DR prevalence. Significant and inverse associations were further found for nonproliferative and proliferative DR, hallmarks of lesions and macular oedema. The association between greenness and DR was stronger among participants who were older, obese, lived in the south, had longer duration of diabetes or did not take antidiabetic medications. This large-scale nationwide study provides the first-hand epidemiological evidence on the associations of residential greenness with DR. Our findings highlight the importance of residential greenness in alleviating DR risk especially in an era of aging and urbanization. • The first to examine the relationship between greenness and diabetic retinopathy (DR). • Greenness exposure was almost linearly associated with decreased odds of DR. • Greenness was inversely associated with nonproliferative and proliferative DR. • Greenness was inversely associated with hallmarks of DR and macular oedema. [ABSTRACT FROM AUTHOR]

In this study, flaxseed oil was used as embedding material and flaxseed gum as sole emulsifier to prepare flaxseed oil nanoemulsions. The storage temperature (4–37 °C, pH 5.8, 0 mmol/L), pH (3–11, 4 °C, 0 mmol/L), NaCl (100–500 mmol/L, pH 5.8, 4 °C) on the stability of flaxseed oil nanoemulsions were investigated in terms of particle size, ζ -potential, creaming index, microscopy, rheological characteristics, surface tension, and nanoemulsion color as characterization. The results showed that temperature significantly affected the stability of flaxseed oil nanoemulsions, and the stability decreased with increasing temperature. The characteristics of flaxseed oil nanoemulsion were relatively stable at pH 5 and pH 7, while the stability was poor under pH 3 and alkaline conditions. As the strength of the ionic increased, unstable aggregation occurred (NaCl >200 mmol/L). In conclusion, the stability of flaxseed oil nanoemulsion was better at 4 °C, pH 5–7, and NaCl <200 mmol/L. These results provide useful information to facilitate the design and preparation of stable package delivery systems for flaxseed oil in food and other industries. [Display omitted] • Flaxseed oil nanoemulsions (FON) were prepared based on homologous flaxseed gum. • Multi-indicator evaluation of the impact of environmental changes on FON stability. • Temperature significantly affected characterizations and stability of FON. • FON droplets were more aggregated at high NaCl concentrations and alkaline pH. [ABSTRACT FROM AUTHOR]

Retinal Müller glial dysfunction and intracellular edema are important mechanisms leading to diabetic macular edema (DME). Aquaporin 11 (AQP11) is primarily expressed in Müller glia with unclear functions. This study aims to explore the role of AQP11 in the pathogenesis of intracellular edema of Müller glia in diabetic retinopathy (DR). Here, we found that AQP11 expression, primarily located at the endfeet of Müller glia, was down-regulated with diabetes progression, accompanied by intracellular edema, which was alleviated by intravitreal injection of lentivirus-mediated AQP11 overexpression. Similarly, intracellular edema of hypoxia-treated rat Müller cell line (rMC-1) was aggravated by AQP11 inhibition, while attenuated by AQP11 overexpression, accompanied by enhanced function in glutamate metabolism and reduced cell death. The down-regulation of AQP11 was also verified in the Müller glia from the epiretinal membranes (ERMs) of proliferative DR (PDR) patients. Mechanistically, down-regulation of AQP11 in DR was mediated by the HIF-1α-dependent and independent miRNA-AQP11 axis. Overall, we deciphered the AQP11 down-regulation, mediated by miRNA-AQP11 axis, resulted in Müller drainage dysfunction and subsequent intracellular edema in DR, which was partially reversed by AQP11 overexpression. Our findings propose a novel mechanism for the pathogenesis of DME, thus targeting AQP11 regulation provides a new therapeutic strategy for DME. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims To determine whether irisin could improve perivascular adipose tissue (PVAT) dysfunction via regulation of the heme oxygenase-1 (HO-1)/adiponectin axis in obesity. Materials and methods C57BL/6 mice were given chow or a high-fat diet (HFD) with or without treatment with irisin. The concentration-dependent responses of the thoracic aorta with or without PVAT (PVAT + or PVAT −) to phenylephrine were studied in an organ bath. Protein levels of HO-1 and adiponectin were determined by western blot. UCP-1, Cidea, and TNF-α gene expression in PVAT were analyzed by real-time PCR. Results Treatment of obese mice with irisin improved glucose and lipid metabolism, reduced plasma levels of TNF-α and malondialdehyde, and increased plasma adiponectin levels ( P < 0.01). The anti-contractile effects of PVAT were attenuated in HFD mice and this attenuation was restored in HFD mice treated with irisin ( P < 0.05). Incubation of aortas (PVAT +) with the HO-1 inhibitor and adiponectin receptor blocking peptide in irisin-treated HFD mice abolished the beneficial effects of irisin on PVAT function. The same results were also observed in HFD mice treated with irisin ex vivo. Treatment of HFD mice with irisin significantly enhanced protein levels of HO-1 and adiponectin, and reduced superoxide production and TNF-α expression in PVAT. Irisin treatment enhanced brown adipocyte markers UCP-1 and Cidea expression in PVAT from HFD mice. Conclusion Irisin improved the anti-contractile properties of PVAT from the thoracic aorta in diet-induced obese mice. The mechanism for protective effects of irisin appeared to be related to upregulation of the HO-1/adiponectin axis in PVAT and browning of PVAT. [ABSTRACT FROM AUTHOR]

Abstract: Progesterone (Pg) is an essential steroid hormone during mammary gland development and tumorigenesis, including the maintenance of epithelial stem/progenitor cells. Pg functions through interaction with the progesterone receptors (PR) and Pg-PR signaling is thought to be mediated by key transcription factors, which are largely unidentified. In this study, we have identified the ATBF1 transcription factor as a transcriptional target of Pg-PR signaling in mammary epithelial cells. Pg treatment dramatically increased ATBF1 expression at both mRNA and protein levels in cultured cells and mammary tissues. As expected, the induction of ATBF1 was PR-dependent, as it only occurred in PR-positive but not in PR-negative cells, and pretreatment with the Pg antagonist RU-486 or RNAi-mediated knockdown of PR abolished the upregulation of ATBF1 by Pg. Promoter-reporter and ChIP assays further showed that Pg-activated PR directly binds to the ATBF1 promoter to induce its transcription. Prevention of ATBF1 induction inhibited the function of Pg in promoting progenitor cell transition, as indicated by colony formation in a Matrigel culture assay and expression of stem cell markers CD49f and CD44. These findings suggest that ATBF1 plays a crucial role in the Pg-PR signaling pathway in mammary epithelial cells. [Copyright &y& Elsevier]

Proliferative retinopathies, such as proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP) are major causes of visual impairment and blindness in industrialized countries. Prostaglandin E 2 (PGE 2) is implicated in cellular proliferation and migration via E-prostanoid receptor (EP 4 R). The aim of this study was to investigate the role of PGE 2 /EP 4 R signaling in the promotion of retinal neovascularisation. In a streptozotocin (STZ)-induced diabetic model and an oxygen-induced retinopathy (OIR) model, rats received an intravitreal injection of PGE 2 , cay10598 (an EP 4 R agonist) or AH23848 (an EP 4 R antagonist). Optical coherence tomography, retinal histology and biochemical markers were assessed. Treatment with PGE 2 or cay10598 accelerated pathological retinal angiogenesis in STZ and OIR-induced rat retina, which was ameliorated in rats pretreated with AH23848. Serum VEGF-A was upregulated in the PGE 2 -treated diabetic rats vs non-treated diabetic rats and significantly downregulated in AH23848-treated diabetic rats. PGE 2 or cay10598 treatment also significantly accelerated endothelial tip-cell formation in new-born rat retina. In addition, AH23848 treatment attenuated PGE 2 -or cay10598-induced proliferation and migration by repressing the EGF receptor (EGFR)/Growth factor receptor bound protein 2-associated binder protein 1 (Gab1)/Akt/NF-κB/VEGF-A signaling network in human retinal microvascular endothelial cells (hRMECs). PGE 2 /EP 4 R signaling network is thus a potential therapeutic target for pathological intraocular angiogenesis. [Display omitted] • Prostaglandin E 2 is a crucial growth-factor inducer and a potent proangiogenic mediator. • PGE 2 /EP 4 R cascade actually mediates retinal angiogenesis via transactivation of EGFR. • The PGE 2 /EP 4 R pathway could be a therapeutic target for pathological angiogenesis prevention and treatment in the retina. [ABSTRACT FROM AUTHOR]

Diabetic retinopathy (DR) is a neurovascular complication of diabetes mellitus that leads to blindness in the working-age population. Retinal Müller cells proliferate and produce pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via the reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NACHT, LRR and PYD domain-containing protein 3 (NLRP3) inflammasome axis to promote proliferative DR. Epigallocatechin-3-gallate (EGCG) plays anti-oxidant, anti-inflammatory, anti-proliferative and anti-angiogenic roles in Müller cells. A prodrug of EGCG (pro-EGCG) enhances the bioavailability of EGCG. In an in vitro model of high glucose-stimulated Müller cells, pro-EGCG inhibited proliferation and pro-angiogenic factor production by down-regulating the activity of the ROS/TXNIP/NLRP3 inflammasome axis. In a mouse DR model, pro-EGCG reduced ROS accumulation, NLRP3 inflammasome activation, Müller cell proliferation, and production of the pro-angiogenic factors VEGF and HGF. In summary, pro-EGCG mitigated hyperglycaemia-challenged Müller cell proliferation and pro-angiogenic factor production by inhibiting ROS/TXNIP/NLRP3 inflammasome signalling, implying a potential therapeutic strategy for DR. • Müller cells proliferate and produce pro-angiogenic factors, including vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF), via the reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome axis to promote proliferative DR. • In an in vitro model of high glucose-stimulated Müller cells, pro-EGCG inhibited proliferation and pro-angiogenic factor production by downregulating ROS/TXNIP/NLRP3 inflammasome axis activity. • In a mouse DR model, pro-EGCG reduced ROS accumulation, NLRP3 inflammasome activation, Müller cell proliferation, and production of the pro-angiogenic factors VEGF and HGF. • Pro-EGCG mitigated hyperglycaemia-challenged Müller cell proliferation and pro-angiogenic factor production by inhibiting ROS/TXNIP/NLRP3 inflammasome signalling. [ABSTRACT FROM AUTHOR]

• Bioinformatics data disclosed the central targets of calycosin for anti-fatty liver. • All top bio-functional process and pathway of calycosin for anti-fatty liver were highlighted. • The biochemical data of human samples were used to validate the predictive findings. • The biochemical experiments in vivo were used to validate the predictive findings. • The bioinformatic and biochemical findings disclosed the anti-fatty liver mechanism of calycosin. As revealed in previous reports, calycosin is a functional flavonoid characterized with identified pharmacological activities. Most of evidences are used to demonstrate the anti-cancer benefits of calycosin, however, the existing study of anti-fatty liver medicated by calycosin is limitedly reported. Recently, an emerging avenue based on network pharmacology may contribute to excavate the biological targets and molecular mechanisms of calycosin for anti-fatty liver. In confirmatory experiments, the human and animal studies were subjected to verify some of bioinformatic results. Accordingly, bioinformatic data based on network pharmacology suggested that discoverable biotargets of calycosin for anti-fatty liver were aldehyde dehydrogenase (ALDH2), Niemann pick C1 (NPC1), high mobility group protein 1 (HMGB1), bilirubin UDP glucuronosyltransferase 1 (UGT1A1), mitogen-activated protein kinase 3 (MAPK3), epidermal growth factor receptor (EGFR), hydroxytryptamine receptor 2 (HTR2), migration inhibitory factor (MIF), cytochrome P450, family 19A1 (CYP19A1). Furthermore, all significant biological characteristics and mechanisms of to treat fatty liver were revealed in several. In human findings, the blood tests showed changed glucose and lipid contents, elevated insulin resistance and inflammatory stress. And fatty liver sections from patients resulted in negative expressions of ALDH2, NPC1, and positive HMGB1 expression. In a study in vivo , calycosin-treated high fat diet (HFD)-fed mice exhibited reduced liver weights, decreased fasting serum glucose and insulin, liver functional transaminases, blood lipids, metabolic enzymes, and inflammatory cytokines. And the data in gene tests displayed up-regulations of ALDH2, NPC1 mRNAs, and down-regulation of HMGB1 mRNA in calycosin-treated liver samples. Together, the current bioinformatic data demonstrate biological targets, functions and mechanisms of calycosin for anti-fatty liver. Interestingly, these bioinformatic findings can be partially verified with clinical and animal samples. [ABSTRACT FROM AUTHOR]

Retinal detachment (RD) results in disruption of retinal physiology and visual function. Although surgical intervention has been well-developed to restore the retinal anatomic structure, post-op progression of visual function decline is prominent in a large proportion of patients. Therefore, the establishment of a disease model that accurately mimics RD pathogenesis is crucial to mechanistic study and drug screening. General protocols to induce RD in mice are frequently associated with complications leading to model instability and reduced reproducibility. In this study, we established a stable and reproducible mice RD model with a detached area of over 90% and rare complications. Briefly, the modified method was realized by vitreous humor extraction to reduce intraocular pressure, followed by directly-visible hyaluronic acid injection into subretinal space. The detachment of retina was confirmed by fundus photography, and progressive thinning of the outer nuclear layer (ONL) was determined by HE staining. Apoptotic signals were prominent in the ONL. Consistently, visual function was significantly compromised as determined by ERG. Moreover, retinal vasculature appeared to remodel and acquired winding, twisted and dilated structures illustrated by 3D reconstruction. In addition, activation of Müller cells and microglia, and infiltration of blood-derived macrophages were detected locally. Collectively, we have established a modified protocol to model RD with increased stability, reproducibility and fewer complications, and 3D high-resolution imaging and reconstruction of vasculature could provide new tools to evaluate this model. • A modified model of retinal detachment in mice was established to better mimic pathogenesis. • Vitreous humor extraction followed by visible hyaluronic acid injection increased the stability of model. • Retinal vasculature after retinal detachment was evaluated by 3D imaging and reconstruction. [ABSTRACT FROM AUTHOR]

In this study, the effects of Rhodopseudomonas capsulata present in wastewater effluent on the biodegradation of carbaryl in soil and improvement of soil fertility were investigated. Compared to control treatment, carbaryl was removed efficiently and soil fertility was remediated with the addition of effluent containing R. capsulata. Molecular analysis revealed that carbaryl induced carbaryl hydrolase gene expression to synthesize carbaryl hydrolase through activating MAPKKKs , MAPKKs , MAPKs genes in MAPK signal transduction pathway. The induction and secretion of carbaryl hydrolase occur after one day in R. capsulata , which can be attributed to its characteristics as an ancient bacteria, which require acclimatization to carbaryl before gene induction. However, lack of organics in soil and control treatment could not maintain R. capsulata growth for over one day. The residual organics in the effluent provided sufficient carbon source and energy for R. capsulata under four effluent treatments. This new method resulted in the remediation of carbaryl pollution and improvement of soil fertility and soybean processing wastewater treatment simultaneously, as well as the reutilization of wastewater and R. capsulata as sludge. Meanwhile, the high-order non-linear mathematical model about carbaryl removal rate was established. • Soil carbaryl removal by R. capsulata in effluent was proposed. • Carbaryl biodegradation, improvement of soil fertility by R. capsulata in effluent was feasible. • Gene cehA and hydrolase were induced after inoculation 24 h. • Residual COD in effluent provided energy for R. capsulata growth over 24 h. • Soil bioremediation, wastewater treatment were completed simultaneously by new method. [ABSTRACT FROM AUTHOR]