Metformin attenuates lung ischemia-reperfusion injury and necroptosis through AMPK pathway in type 2 diabetic recipient rats.

BACKGROUND: Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats. METHODS: Sprague-Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion. RESULTS: Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C. CONCLUSIONS: Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.

Design and performance analysis of a mid-infrared broadband thermally tunable metamaterial absorption device based on the phase-change effect.

We propose a structurally simple, innovative, and multifunctional mid-infrared broadband thermally tunable metamaterial absorption device. The absorption device consists of a three-layer structure, from bottom to top: Ti substrate, SiO2 dielectric layer, and patterned VO2 layer. Through temperature control, the average absorption intensity of the absorption device can vary between 0.08 and 0.94. The absorption device's absorption mechanism is rooted in the thermal phase-change characteristics exhibited by the topologically patterned VO2. When the temperature is below 340 K, VO2 is in a dielectric state, resulting in near-total reflection performance in the mid-infrared range. When the temperature is above 340 K, VO2 undergoes a dielectric-to-metal transition, enabling the absorption device to achieve an average absorption rate of 94.12% in the ultra-wideband range of 6.26 µm-20.96 µm in the mid-infrared. This absorption range completely covers the atmospheric window wavelengths of 8 µm-14 µm, demonstrating high practical value. We explain the working mechanism of the absorption device from the perspective of the electromagnetic field. Subsequently, we study the variations in the absorption curve of the absorption device at different temperatures of VO2 and use the changes in the electric field at the same wavelength under different temperatures to explain the variations in absorption. Compared to previous work, our structure has only three layers in a single unit, making it easy to process and produce. Additionally, the absorption device's operating bandwidth and average absorption rate in the mid-infrared range have been significantly improved. Furthermore, the absorption device exhibits substantial incident angle tolerance and polarization insensitivity. We believe that this design has broad application potential in future optothermal conversion, infrared stealth, and thermal radiation.

[Retracted] MicroRNA­30a suppresses the proliferation, migration and invasion of human renal cell carcinoma cells by directly targeting ADAM9.

[This retracts the article DOI: 10.3892/ol.2018.8999.].

Sodium butyrate ameliorates sepsis-associated lung injury by enhancing gut and lung barrier function in combination with modulation of CD4+Foxp3+ regulatory T cells.

Sepsis-associated lung injury often coexists with intestinal dysfunction. Butyrate, an essential gut microbiota metabolite, participates in gut-lung crosstalk and has immunoregulatory effects. This study aims to investigate the effect and mechanism of sodium butyrate (NaB) on lung injury. Sepsis-associated lung injury was established in mice by cecal ligation and puncture (CLP). Mice in treatment groups received NaB gavage after surgery. The survival rate, the oxygenation index and the lung wet-to-dry weight (W/D) ratio were calculated respectively. Pulmonary and intestinal histologic changes were observed. The total protein concentration in bronchoalveolar lavage fluid (BALF) was measured, and inflammatory factors in serum and BALF were examined. Diamine oxidase (DAO), lipopolysaccharide (LPS), and surfactant-associated protein D (SP-D) levels in serum and amphiregulin in lung tissue were assessed. Intercellular junction protein expression in the lung and intestinal tissues were examined. Changes in immune cells were analyzed. NaB treatment improved the survival rate, the oxygenation index and the histologic changes. NaB decreased the W/D ratio, total protein concentration, and the levels of proinflammatory cytokines, as well as SP-D, DAO and LPS, while increased the levels of anti-inflammatory cytokines and amphiregulin. The intercellular junction protein expression were improved by NaB. Furthermore, the CD4+/CD8+ T-cell ratio and the proportion of CD4+Foxp3+ regulatory T cells (Tregs) were increased by NaB. Our data suggested that NaB gavage effectively improved the survival rate and mitigated lung injury in CLP mice. The possible mechanism was that NaB augmented CD4+Foxp3+ Tregs and enhanced the barrier function of the gut and the lung.

A High-Entropy Prussian Blue Analog for Aqueous Potassium-Ion Batteries.

Aqueous potassium-ion batteries (AKIBs) are considered promising electrochemical energy storage systems owing to their high safety and cost-effectiveness. However, the structural degradation resulting from the repeated accommodation of large K-ions and the dissolution of active electrode materials in highly dielectric aqueous electrolytes often lead to unsatisfactory electrochemical performance. This study introduces a high-entropy Prussian blue analog (HEPBA) cathode material for AKIBs, demonstrating significantly enhanced structural stability and reduced dissolution. The HEPBA exhibits a highly reversible specific capacity of 102.4 mAh g-1 , with 84.4% capacity retention after undergoing 3448 cycles over a duration of 270 days. Mechanistic insights derived from comprehensive experimental investigations, supported by theoretical calculations, reveal that the HEPBA features a robust structure resistant to dissolution, a solid-solution reaction pathway with negligible volume variation during charge-discharge, and efficient ion transport kinetics characterized by a reduced band gap and a low energy barrier. This study represents a measurable step forward in the development of long-lasting electrode materials for aqueous AKIBs.

Constructing a Low-Cost Si-NSs@C/NG Composite by a Ball Milling-Catalytic Pyrolysis Method for Lithium Storage.

Silicon-based composites are promising candidates as the next-generation anode materials for high-performance lithium-ion batteries (LIBs) due to their high theoretical specific capacity, abundant reserves, and reliable security. However, expensive raw materials and complicated preparation processes give silicon carbon anode a high price and poor batch stability, which become a stumbling block to its large-scale practical application. In this work, a novel ball milling-catalytic pyrolysis method is developed to fabricate a silicon nanosheet@amorphous carbon/N-doped graphene (Si-NSs@C/NG) composite with cheap high-purity micron-size silica powder and melamine as raw materials. Through systematic characterizations such as XRD, Raman, SEM, TEM and XPS, the formation process of NG and a Si-NSs@C/NG composite is graphically demonstrated. Si-NSs@C is uniformly intercalated between NG nanosheets, and these two kinds of two-dimensional (2D) materials are combined in a surface-to-surface manner, which immensely buffers the stress changes caused by volume expansion and contraction of Si-NSs. Attributed to the excellent electrical conductivity of graphene layer and the coating layer, the initial reversible specific capacity of Si-NSs@C/NG is 807.9 mAh g-1 at 200 mA g-1, with a capacity retention rate of 81% in 120 cycles, exhibiting great potential for application as an anode material for LIBs. More importantly, the simple and effective process and cheap precursors could greatly reduce the production cost and promote the commercialization of silicon/carbon composites.

Radiomics in the diagnosis and treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor. At present, early diagnosis of HCC is difficult and therapeutic methods are limited. Radiomics can achieve accurate quantitative evaluation of the lesions without invasion, and has important value in the diagnosis and treatment of HCC. Radiomics features can predict the development of cancer in patients, serve as the basis for risk stratification of HCC patients, and help clinicians distinguish similar diseases, thus improving the diagnostic accuracy. Furthermore, the prediction of the treatment outcomes helps determine the treatment plan. Radiomics is also helpful in predicting the HCC recurrence, disease-free survival and overall survival. This review summarized the role of radiomics in the diagnosis, treatment and prognosis of HCC.

Identification and Functional Validation of Auxin-Responsive Tabzip Genes from Wheat Leaves in Arabidopsis.

Leaves are an essential and unique organ of plants, and many studies have proved that auxin has significant impacts on the architecture of leaves, thus the manipulation of the three-dimensional structure of a leaf could provide potential strategies for crop yields. In this study, 32 basic leucine zipper transcription factors (bZIP TFs) which responded to 50 µM of indole-acetic acid (IAA) were identified in wheat leaves by transcriptome analysis. Phylogenetic analysis indicated that the 32 auxin-responsive TabZIPs were classified into eight groups with possible different functions. Phenotypic analysis demonstrated that knocking out the homologous gene of the most down-regulated auxin-responsive TabZIP6D_20 in Arabidopsis (AtHY5) decreased its sensitivity to 1 and 50 µM IAA, while the TabZIP6D_20/hy5 complementary lines recovered its sensitivity to auxin as a wild type (Wassilewskija), suggesting that the down-regulated TabZIP6D_20 was a negative factor in the auxin-signaling pathway. These results demonstrated that the auxin-responsive TabZIP genes might have various and vital functions in the architecture of a wheat leaf under auxin response.

Unexplained septic shock after colonoscopy with polyethylene glycol preparation in a young adult: A case report.

BACKGROUND: Colonoscopy has become a routine physical examination as people's health awareness has increased. Polyethylene glycol (PEG) is greatly used in bowel preparation before colonoscopy due to its price and safety advantages. Septic shock after colonoscopy with PEG preparation is extremely rare, with only very few cases in critically ill patients. Herein, we describe a case of septic shock in a healthy young adult immediately following colonoscopy with PEG preparation. CASE SUMMARY: A 33-year-old young adult presented to our hospital for colonoscopy with PEG bowel preparation due to recurrent diarrhea for 7 years. The male's previous physical examination showed no abnormal indicators, and colonoscopy results were normal; however, he exhibited septic shock and markedly elevated white blood cell, C-reactive protein, and procalcitonin levels on the second day after colonoscopy. Immediate resuscitation and intensive care with appropriate antibiotics improved his condition. However, the blood and stool cultures did not detect the pathogen. CONCLUSION: Septic shock after colonoscopy is rare, especially in young adults. The authors considered the possibility of opportunistic infections after PEG bowel preparation, and clinicians should monitor patients for the possibility of such complications.

Discovery of novel heterocyclic derivatives as potential glycogen phosphorylase inhibitors with a cardioprotective effect.

The purpose of this study was to evaluate the effect of GP inhibitor as a potential pharmaceutical target on MI/R injury. Four different structural types of novel compounds (I, II, III, and IV) were designed and synthesized, obtaining 31 novel GP inhibitors. SAR studies revealed that the conjugates of 5-chloroindole with benzo six-membered heterocyclic were found to elevate the activity. In particular, compound IIIh (IC50 = 0.21 ± 0.03 µM) emerged as a potent derivative against RMGPa, being approximately 2-fold less potent than that of PSN-357. In order to screen out a compound for in vivo activity test, we further conducted an experiment of inhibition against three different subtypes of GPa (HLGPa, HMGPa and HBGPa) and the corresponding affinity experiment. As a result, compound IIIh showed strong inhibitory activity against the above three subtypes of GP, especially on HBGPa (IC50 = 0.09 ± 0.002 µM), which was relatively close to that of positive control ingliforib (IC50 = 0.16 ± 0.02 µM). The affinity of compound IIIh to HBGPa was 4.3 times higher than that of HLGPa, and 1.1 times higher than that of HMGPa. This fact further proved that compound IIIh has a higher inhibitory effect on HMGPa than the other two subtypes. Besides, in vivo activity evaluation demonstrated that compound IIIh exhibited obviously cardioprotective effect on MI/R injury mice. The discovery of compound IIIh provides a new strategy for developing novel GP inhibitors with myocardial ischemia protection.

Malignancy Suspicious Region Guided Deep Neural Networks for Gastric Ulcer Classification.

Malignant transformation of gastric ulcer can result in gastric cancer, hence an accurate gastric ulcer classification method is of vital importance. Despite marvelous progress has been achieved in recent years, there are still many challenges in diagnosis of gastric ulcer. In this paper, we propose a mechanism to mimic gastroenterologist's behaviours based on deep learning techniques, by integrating the segmented malignancy suspicious masks with gastroscopic images for gastric ulcer classification, which instructs the model to focus on the area where symptoms occur for gastric ulcer diagnosis. Specifically, a U-Net-type deep neural network is built to segment the suspicious pathological regions from gastroscopic images, then the segmented regions are treated as an attention channel of gastroscopic images for the gastric ulcer classification by a ResNet-type deep neural network. Experiments on a real gastroscopic dataset with 900+ patient cases demonstrate that our proposed approach achieves much better performance for gastric ulcer diagnosis, compared with standard method with only gastroscopic images.

Experimental Study on Effects of Aging Time on Dry Shrinkage Cracking of Lime Soils.

The effect of aging on the internal mechanism of the dry shrinkage cracking of lime soil was studied from the perspective of macroscopic cracking phenomenon and microscopic composition change, and the reasonable aging time of lime soil was determined. Large numbers of cracks often occur in buildings constructed using lime soil, which impacts sustainable development and building environmental protection. This study explored the influence of aging time on the mechanical properties and shrinkage cracking of lime soil. The influence of aging time was evaluated using a triaxial compression test; using the dry-wet cycle, sieving, pH, and other tests, the influence of aging time on volume crack rate, expansion shrinkage rate, particle size distribution, and pH was analyzed. Scanning electron microscopy and X-ray diffraction experiments were used to analyze changes in the lime soil particle structure for different aging times and the formation of new substances. The results show that as aging time increases, the stress-strain curve of the soil softens significantly, shear strength deteriorates, and cohesion decreases. When the aging time is 6 h, the expansion rate and shrinkage rate at the center of the soil sample are the maximum. The volume fracture and expansion shrinkage rates decrease first, and then plateau with aging time, with the changes remaining stable after 72 h; these rate decreases are positively correlated with the change rate of pH. The formation of Ca(OH)2 affects the sample pH, and the changes in pH, Ca(OH)2, and CaO tend to be stable. With an increase in aging time, the proportion of particles of a size less than 0.1 mm decreases, and that of particles of size 0.1-0.5 mm increases. After 72 h of aging, the particle size proportion remains unchanged. Reasonable aging time can, thus, reduce the hydration reaction of lime, improve particle agglomeration effects, and reduce the crack development of the soil.

Experimental Study on the Effect of Carbonation Reaction on the Properties of Imitation Site Soil.

In this study, sodium methylsilicate and lime were selected to prepare the same proportion of Imitation Site Soil, and according to the principle of carbonation reaction of restoration materials, the effect of carbonation reaction on the performance of restoration soil of earthen sites was studied. The study has good significance for the conservation and restoration of earthen sites. The samples were cured with CO2 concentration and curing age as variables. After curing, the samples were tested to determine their water-resistant properties, uniaxial compressive strength, and pH value and a micro scanning electron microscope was used. The results indicated that the carbonation reaction can quickly improve the water resistance and compressive strength of imitation site soil, and reduced the water absorption by 16.67% compared to the specimens conditioned at 0.03% CO2 concentration. The UCS of specimens at 5%, 10%, and 15% CO2 concentrations increased by 72.22%, 131.19%, and 219.27%, respectively, compared with those at 0.03% CO2 concentration after the specimens were environmentally maintained in the carbonation chamber at 0.03%, 5%, 10%, and 15% CO2 concentrations for 120 h, respectively. The internal particle gradation of the imitation site soil improved after carbonation. These results provide a basis for improving the restoration technology of earthen sites.

Mapping of Level I Axillary Lymph Nodes in Patients with Newly Diagnosed Breast Cancer: Optimal Target Delineation and Treatment Techniques for Breast and Level I Axilla Irradiation.

PURPOSE: To map the locations of level I axilla (Ax-L1) lymph nodes (LNs), evaluate the clinical target volume (CTV) coverage defined by the Radiation Therapy Oncology Group (RTOG) Breast Cancer Atlas, and assess the optimal techniques for whole-breast and Ax-L1 irradiation (WBI + Ax-L1). METHODS AND MATERIALS: We identified 76 patients newly diagnosed with breast cancer with 1 to 4 positive LNs confirmed by axillary dissection. The locations of 116 involved Ax-L1 LNs on diagnostic computed tomography (CT) were mapped onto simulated CT images of a standard patient. Ax-L1 LN coverage by the RTOG atlas was evaluated, and a modified Ax-L1 CTV with better coverage was proposed. Treatment plans were designed for WBI + Ax-L1 with high tangential simplified intensity modulated radiation therapy (HT-sIMRT) and volumetric modulated arc therapy (VMAT) and for WBI + RTOG Ax-L1 with VMAT with a prescription dose of 50 Gy in 25 fractions, respectively. The differences in dosimetric parameters were compared. RESULTS: The RTOG Atlas missed 29.3% of LNs. Modification by extending 1 cm caudal and 0.5 cm anterior to the RTOG-defined CTV borders allowed the modified Ax-L1 CTV to encompass 90.5% of LNs. All plans met the required prescription dose to WBI and Ax-L1. The mean dose and the V20 and V5 (percentage volume receiving 20 Gy and 5 Gy) of the ipsilateral lung were 11.7 Gy, 23.0%, and 38.1% for HT-sIMRT WBI + Ax-L1 and 8.9 Gy, 16.4%, and 32.5% for VMAT WBI + Ax-L1 plans, respectively. The mean heart doses in the left-sided plans were 3.2 Gy and 3.0 Gy, respectively. The V30 of the humeral head and the minimum dose to the axillary-lateral thoracic vessel junction were 2.0% versus 1.8% and 45.5 Gy versus 45.7 Gy for VMAT WBI + Ax-L1 and VMAT WBI + RTOG Ax-L1 plans, respectively. CONCLUSIONS: A modified Ax-L1 CTV with expansion of the caudal and anterior borders might provide better coverage. Compared with HT-sIMRT WBI + Ax-L1, VMAT WBI + Ax-L1 provided an adequate dose to the Ax-L1 while decreasing the doses to most normal tissues. Coverage of the modified Ax-L1 did not increase the dose to organs at risk compared with coverage of RTOG Ax-L1.

Study on Deterioration of Gray Brick with Different Moisture Contents under Freeze-Thaw Environment.

Generally, brick buildings are in the open-air environment year round, and damage to them is aggravated by the effect of repeated freezing and thawing cycles. In order to determine freeze-thaw damage and deterioration mechanism, the initial moisture content of gray brick specimens was set as 20%, 40%, 60%, 80%, 100%. The effects of moisture content and the number of freeze-thaw cycles on the quality, mechanical properties and microstructure of gray brick were investigated by uniaxial compression tests and scanning electron microscopy (SEM) tests. Numerical simulations were applied to model the freezing and thawing process. The results showed that: as the number of freeze-thaw cycles increased, the mass loss rate and peak strength reduction rate of gray brick both increased. The initial moisture content had a greater impact on damage to gray brick due to freeze-thaw; ω = 80% was defined as the limit moisture content of gray brick. Under the repeated action of freeze-thaw cycles, the areas affected by thermal stress were mainly concentrated in the center of the outer surface and the center of the side of gray bricks. The maximum thermal stress after 55 freeze-thaw cycles was 1.522 × 10-2 MPa. This research results provide a theoretical basis for the prevention and protection of frost damage of brick buildings in a freeze-thaw environment.

Complete photonic bandgap in silicon nitride slab assisted by effective index difference between polarizations.

The slab effective index difference between the transverse-electric (TE) and transverse-magnetic (TM) polarizations was utilized to obtain complete photonic bandgap (CPBG) in a silicon nitride (SixNy) photonic crystal slab. For this, coincident frequency range in the TE photonic bandgap (PBG) and TM PBG, which denotes the CPBGs of the slab, must be found with the same structure. Through adjusting the effective index pair of TE and TM polarizations by changing the thickness of the SixNy core layer, and also optimizing the structure parameters within the photonic crystal plane, a large normalized CPBG of 5.62% was theoretically obtained in a slab of SixNy with a refractive index of 2.5. Moreover, based on the obtained CPBG, a microcavity which could support both TE and TM polarization was theoretically demonstrated. The cavity modes for different polarizations were both well confined, which proved the reliability of the CPBG. In addition, using the same method, the lowest refractive index of SixNy on silica slab for a CPBG could be extended to as low as 2. The results indicate that there is potential for development of various high-performance CPBG devices based on SixNy slab technology.

A network meta-analysis on the efficacy of HER2-targeted agents in combination with taxane-containing regimens for treatment of HER2-positive metastatic breast cancer.

PURPOSE: We performed a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of HER2-targeted agents in combination with taxanes and to identify the best strategy for HER2+ metastatic breast cancer (MBC). METHODS: Pubmed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for randomized controlled trials that evaluated any taxanes+HER2-targeted agents in the treatment of HER2+ MBC. The primary outcome was overall survival (OS). The secondary outcomes included overall response rate (ORR) and progression-free survival (PFS). RESULTS: A total of 13 RCTs were eligible, involving 4941 patients and 10 regimens. The result showed that single-HER2-targeted agent+a taxane did improve the effect on ORR and PFS than taxane alone, but only trastuzumab+a taxane had a significant improvement in OS outcomes. Single-HER2-targeted agent (trastuzumab) combined with taxane-based doublets (taxane+carboplatin/capecitabine/doxorubicin/bevacizumab) showed no further benefit than trastuzumab+a taxane. Doublet-HER2-targeted agents combined with a taxane(trastuzumab+pertuzumab+a taxane) showed further improvement in ORR, PFS, and all OS outcomes than single-HER2-targeted agent+a taxane. Ranking analysis based on their P-scores suggested that trastuzumab+pertuzumab+a taxane was the best combination treatment for all the efficacy outcomes. CONCLUSIONS: These findings demonstrate that combining two HER2-targeted agents (trastuzumab+pertuzumab) with a taxane is much more beneficial for the treatment of HER2+ MBC. Dual HER2-targeted agents combined with a taxane appears to be the preferred application of HER2+ MBC.

A general asymmetric copper-catalysed Sonogashira C(sp3)-C(sp) coupling.

Continued development of the Sonogashira coupling has made it a well established and versatile reaction for the straightforward formation of C-C bonds, forging the carbon skeletons of broadly useful functionalized molecules. However, asymmetric Sonogashira coupling, particularly for C(sp3)-C(sp) bond formation, has remained largely unexplored. Here we demonstrate a general stereoconvergent Sonogashira C(sp3)-C(sp) cross-coupling of a broad range of terminal alkynes and racemic alkyl halides (>120 examples) that are enabled by copper-catalysed radical-involved alkynylation using a chiral cinchona alkaloid-based P,N-ligand. Industrially relevant acetylene and propyne are successfully incorporated, laying the foundation for scalable and economic synthetic applications. The potential utility of this method is demonstrated in the facile synthesis of stereoenriched bioactive or functional molecule derivatives, medicinal compounds and natural products that feature a range of chiral C(sp3)-C(sp/sp2/sp3) bonds. This work emphasizes the importance of radical species for developing enantioconvergent transformations.

Neuroprotective Effects of Ginsenoside Rg1 against Hyperphosphorylated Tau-Induced Diabetic Retinal Neurodegeneration via Activation of IRS-1/Akt/GSK3ß Signaling.

We have recently demonstrated that tau hyperphosphorylation causes diabetic synaptic neurodegeneration of retinal ganglion cells (RGCs), which might be the earliest affair during the pathogenesis of diabetic retinopathy (DR). Thus, there is a pressing need to seek therapeutic agents possessing neuroprotective effects against tau hyperphosphorylation in RGCs for arresting the progression of DR. Here, using a well-characterized diabetes model of db/db mouse, we discovered that topical ocular application of 10 mg/kg/day of ginsenoside Rg1 (GRg1), one of the major active ingredients extracted from Panax ginseng and Panax notoginseng, ameliorated hyperphosphorylated tau-triggered RGCs synaptic neurodegeneration in diabetic mice. The neuroprotective effects of GRg1 on diabetic retinae were abrogated when retinal IRS-1 or Akt was suppressed by intravitreal injection with si-IRS-1 or topically coadministered with a specific inhibitor of Akt, respectively. However, selective repression of retinal GSK3ß by intravitreal administration of si-GSK3ß rescued the neuroprotective properties of GRg1 when Akt was inactivated. Therefore, the present study showed for the first time that GRg1 can prevent hyperphosphorylated tau-induced synaptic neurodegeneration of RGCs via activation of IRS-1/Akt/GSK3ß signaling in the early phase of DR. Moreover, our data clarify the potential therapeutic significance of GRg1 for neuroprotective intervention strategies of DR.

MicroRNA-30a suppresses the proliferation, migration and invasion of human renal cell carcinoma cells by directly targeting ADAM9.

An increasing number of studies reported that microRNA (miR)-30a was dysregulated in several types of human cancer and may contribute to cancer carcinogenesis and progression. However, its expression and roles in renal cell carcinoma (RCC) remain unknown. In the present study, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to quantify miR-30a expression in RCC tissues and cell lines. The cell counting kit-8 assay, migration and invasion assays were used to evaluate the roles of miR-30a on the proliferation, migration and invasion of RCC cells. The target gene of miR-30a was identified by luciferase reporter assays, RT-qPCR and western blotting. The results indicated that miR-30a was downregulated in RCC tissues and cell lines compared with corresponding noncancerous tissues and normal renal cell line, respectively. Re-expression of miR-30a inhibited the proliferation, migration and invasion of RCC cells. Additionally, ADAM metallopeptidase domain 9 (ADAM9) was validated as a direct target of miR-30a. Furthermore, the knockdown of ADAM9 by small interfering RNAs was able to mimic the effects of miR-30a overexpression in RCC cells. These results highlight the important role for miR-30a in the occurrence and development of RCC, and the restoration of miR-30a might be investigated as a potential strategy for treating RCC.