Al8 Cluster-Based Metal Halide Frameworks: Balancing Singlet-Triplet Excited States to Achieve White Light and Multicolor Luminescence.

Luminescent metal clusters have attracted great interest in current research; however, the design synthesis of Al clusters with color-tunable luminescence remains challenging. Herein, an [Al8 (OH)8 (NA)16 ] (Al8 , HNA = nicotinic acid) molecular cluster with dual luminescence properties of fluorescence and room-temperature phosphorescence (RTP) is synthesized by choosing HNA ligand as phosphor. Its prompt photoluminescence (PL) spectrum exhibits approximately white light emission at room temperature. Considering that halogen atoms can be used to regulate the RTP property by balancing the singlet and triplet excitons, different CdX2 (X- = Cl- , Br- , I- ) are introduced into the reactive system of the Al8 cluster, and three new Al8 cluster-based metal-organic frameworks, {[Al8 Cd3 Cl5 (OH)8 (NA)17 H2 O]·2HNA}n (CdCl2 -Al8 ), {[Al8 Cd4 Br7 (OH)8 (NA)16 CH3 CN]·NA·HNA}n (CdBr2 -Al8 ) and {[Al8 Cd8 I16 (OH)8 (NA)16 ]}n (CdI2 -Al8 ) are successfully obtained. They realize the color tunability from blue to yellow at room temperature. The origination of fluorescence and phosphorescence has also been illustrated by structure-property analysis and theoretical calculation. This work provides new insights into the design of multicolor luminescent metal cluster-based materials and develops advanced photo-functional materials for multicolor display, anti-counterfeiting, and encryption applications.

In Situ-Generated Hollow CoFe-LDH/Co-MOF Heterostructure Nanorod Arrays for Oxygen Evolution Reaction.

Assembling a heterostructure is an effective strategy for enhancing the electrocatalytic activity of hybrid materials. Herein, CoFe-layered double hydroxide and Co-metal-organic framework (CoFe-LDH/Co-MOF) hollow heterostructure nanorod arrays are synthesized. First, [Co(DIPL)(H3BTC)(H2O)2]n [named as Co-MOF, DIPL = 2,6-di(pyrid-4-yl)-4-phenylpyridine, H3BTC = 1,3,5-benzenetricarboxylic acid] crystalline materials with a uniform hollow structure were prepared on the nickel foam. The CoFe-LDH/Co-MOF composite perfectly inherits the original hollow nanorod array morphology after the subsequent electrodeposition process. Optimized CoFe-LDH/Co-MOF hollow heterostructure nanorod arrays display excellent performance in oxygen evolution reaction (OER) with ultralow overpotentials of 215 mV to deliver current densities of 10 mA cm-2 and maintain the electrocatalytic activity for a duration as long as 220 h, ranking it one of the non-noble metal-based electrocatalysts for OER. Density functional theory calculations validate the reduction in free energy for the rate-determining step by the synergistic effect of Co-MOF and CoFe-LDH, with the increased charge density and noticeable electron transfer at the Co-O site, which highlights the capability of Co-MOF to finely adjust the electronic structure and facilitate the creation of active sites. This work establishes an experimental and theoretical basis for promoting efficient water splitting through the design of heterostructures in catalysts.

Gradual Size Enlargement of Aluminum-Oxo Clusters and the Photochromic Properties.

Metallic clusters, assembled by functional motifs, possess the attribute of regulating the properties by changing inorganic and organic components. In this work, a series of aluminum-oxo clusters, [Al6O(dmp)4(Hdmp)2]·2iPrOH [Al6-1, H3dmp = 2,2-bis(hydroxymethyl)propionic acid], [Al6(H2thmmg)6]·2DMF·2H2O [Al6-2, H5thmmg = N-tris(hydroxymethyl)methylglycine], [Al8(OH)4(NAP-OH)12(MeO)7(MeOH)]Cl·7MeCN·3MeOH (Al8, HNAP-OH = 3-hydroxy-2-naphthoic acid), and [Al10(NA)10(MeO)20] (Al10, HNA = nicotinic acid), were obtained based on different carboxylic acids, realizing metallic ring size enlargement from 5.91 to 9.32 Å. They all exhibit good chemical stability. Importantly, the Al8 cluster displays obvious photochromic behavior from pale yellow to orange yellow, originating from the generation of photoinduced radicals in the metal-assisted ligand-ligand electron transfer process of 3-hydroxy-2-naphthoic acid (HNAP-OH). This work enriches the metal ring cluster chemistry and reports the example of the aluminum-oxo cluster-based photochromic material, developing a novel system of photochromic materials.

TRAP-induced PAR1 expression with its mechanism during AMI in a rat model.

BACKGROUND AND OBJECTIVE: Protease-activated receptor 1 (PAR1) is crucial in individuals with acute myocardial infarction (AMI). The continuous and prompt PAR1 activation mainly dependent on PAR1 trafficking is essential for the role of PAR1 during AMI in which cardiomyocytes are in hypoxia. However, the PAR1 trafficking in cardiomyocytes specially during the hypoxia is still unclear. METHODS AND RESULT: A rat AMI model was created. PAR1 activation with thrombin-receptor activated peptide (TRAP) had a transient effect on cardiac function in normal rats but persistent improvement in rats with AMI. Cardiomyocytes from neonatal rats were cultured in a normal CO2 incubator and a hypoxic modular incubator chamber. The cells were then subjected to western blot for the total protein expression and staining with fluorescent reagent and antibody for PAR1 localization. No change in total PAR1 expression following TRAP stimulation was observed; however, it led to increased PAR1 expression in the early endosomes in normoxic cells and decreased expression in the early endosomes in hypoxic cells. Under hypoxic conditions, TRAP restored the PAR1 expression on both cell and endosomal surfaces within an hour by decreasing Rab11A (8.5-fold; 179.93 ± 9.82% of the normoxic control group, n = 5) and increasing Rab11B (15.5-fold) expression after 4 h of hypoxia. Similarly, Rab11A knockdown upregulated PAR1 expression under normoxia, and Rab11B knockdown downregulated PAR1 expression under both normoxic and hypoxic conditions. Cardiomyocytes knocked out of both Rab11A, and Rad11B lost the TRAP-induced PAR1 expression but still exhibited the early endosomal TRAP-induced PAR1 expression under hypoxia. CONCLUSIONS: TRAP-mediated activation of PAR1 in cardiomyocytes did not alter the total PAR1 expression under normoxic conditions. Instead, it triggers a redistribution of PAR1 levels under normoxic and hypoxic conditions. TRAP reverses the hypoxia-inhibited PAR1 expression in cardiomyocytes by downregulating Rab11A expression and upregulating Rab11B expression.

Ligand-Assisted Controllable Growth of Self-Supporting Ultrathin Two-Dimensional Metal-Organic Framework Nanosheet Electrodes for an Efficient Oxygen Evolution Reaction.

Rational design of metal-organic frameworks (MOFs) into ultrathin two-dimensional (2D) nanosheets with controllable thickness is significantly attractive but is also a significant challenge. Herein, the authors report, for the first time, the synthesis of ultrathin 2D nickel-based MOF nanosheets with a thickness of only about 2 nm via a ligand-assisted controllable growth strategy, which cannot be acquired from the exfoliation of their bulky counterparts or the conventional hydrothermal method. The correlation between 2D nanosheets and crystal growth preference was demonstrated through a judicious choice of a specific [Ni(BIP)(p-BDC)(H2O)2]n framework (BIP = (3,5-bis(1-imidazoly)pyridine), p-H2BDC = terephthalic acid) to underlie the geometry of the resultant morphology. Under the modulation by the dosage of terephthalic acid through a corrosion-dissolution-coordination process, the nanosheets of Ni-MOFs with a controllable thickness can be tuned to 50 and 100 nm. Ultrathin 2D Ni-MOF nanosheet-derived N-doped Ni@carbon exhibits a satisfactory electrocatalytic performance with a small overpotential of 170 mV to achieve a current density of 10 mA cm-2, much outperforming the bulk Ni-MOF and the most reported non-noble-metal oxygen evolution reaction electrocatalysts to date. It is believed that this ligand-assisted controllable growth strategy represents a novel and simple path to prepare high-performance MOF-based electrocatalysts for wide applications.

Ultrathin Two-Dimensional Polyoxometalate-Based Metal-Organic Framework Nanosheets for Efficient Electrocatalytic Hydrogen Evolution.

The rational design of 2D polyoxometalate-based metal-organic framework (POMOF) nanosheets on a conductive substrate as a self-supporting electrode is highly attractive but a great challenge. Herein is the first demonstration of POMOF nanopillar arrays consisting of 2D nanosheets as a self-supported electrode for the hydrogen evolution reaction (HER) in acidic conditions. Single-crystal X-ray analysis reveal that our as-prepared 2D [Co2(TIB)2(PMo12O40)]·Cl·4H2O [named CoMo-POMOF; TIB = 1,3,5-tris(1-imidazoly)benzene] crystalline materials are connected by Co-α-Keggin polymolybdate units act as secondary building blocks and TIB as the organic ligands. The 2D CoMo-POMOF nanosheets were successfully arrayed on a conductive nickel foam substrate by a facile CoO nanorod template-assisted strategy. Remarkably, the CoMo-POMOF nanopillar arrays demonstrate superior electrocatalytic performance toward the HER with an overpotential of 137 mV and Tafel slope of 59 mV dec-1 at 10 mA cm-2, which are comparable to those of state-of-the-art POMOF-based electrocatalysts. Density-functional theory (DFT) calculations demonstrate that the exposed bridging oxygen active sites (Oa) of Co-α-Keggin polymolybdate units in CoMo-POMOF optimize the Gibbs free energy of H* adsorption (ΔGH* = -0.11 eV) and increase the intrinsic HER activity.

Statins attenuate cholesterol-induced ROS via inhibiting NOX2/NOX4 and mitochondrial pathway in collecting ducts of the kidney.

BACKGROUND: Statins therapy has been primarily recommended for the prevention of cardiovascular risk in patients with chronic kidney diseases. Statins has also been proved some benefits in lipid-induced kidney diseases. The current study aims to investigate the protection and underlying mechanisms of statins on renal tubular injuries induced by cholesterol overloaded. METHODS: We used tubular suspensions of inner medullary collecting duct (IMCD) cells from rat kidneys and mouse collecting duct cell line mpkCCD cells to investigate the effect of statins on reactive oxygen species (ROS) production induced by cholesterol. Protein and mRNA expression of NADPH oxidase 2 (NOX2) /NOX4 was examined by Western blot and RT-PCR in vitro studies and in rats with 5/6 nephrectomy and high-fat diet. Mitochondrial morphology and membrane potential was observed by Mito-tracker and JC-1. RESULTS: Statins treatment was associated with decreased NOX2 and NOX4 protein expression and mRNA levels in 5/6Nx rats with high-fat diet. Statins treatment markedly reduced the ROS production in IMCD suspensions and mpkCCD cells. Also, statins reduced NOX2 and NOX4 protein expression and mRNA levels in cholesterol overload mpkCCD cells and improved mitochondrial morphology and function. CONCLUSION: Statins prevented ROS production induced by cholesterol in the kidney, likely through inhibiting NOXs protein expression and improving mitochondrial function. Statins may be a therapeutic option in treating obesity-associated kidney diseases.

Activation of TGR5 restores AQP2 expression via the HIF pathway in renal ischemia-reperfusion injury.

Renal ischemia-reperfusion (I/R) injury is associated with markedly reduced protein expression of aquaporins (AQPs). Membrane G protein-coupled bile acid receptor-1 (TGR5) has shown protective roles in some kidney diseases. The purpose of the current study was to investigate whether activation of TGR5 prevented the decreased protein expression of AQPs in rodents with renal I/R injury and potential mechanisms. TGR5 agonist lithocholic acid (LCA) treatment reduced polyuria after renal I/R injury in rats. LCA prevented the decreased abundance of AQP2 protein and upregulated hypoxia-inducible factor (HIF)-1α protein expression, which were associated with decreased protein abundance of NF-κB p65 and IL-1ß. After renal I/R, mice with tgr5 gene deficiency exhibited further decreases in AQP2 and HIF-1α protein abundance and increases of IL-1ß and NF-κB p65 protein expression compared with wild-type mice. In primary cultured inner medullary collecting duct cells with hypoxia/reoxygenation, LCA induced markedly increased protein expression of AQP2 and HIF-1α, which were partially prevented by the PKA inhibitor H89. FG4592, a prolyl-4-hydroxylase domain-containing protein inhibitor, increased HIF-1α and AQP2 protein abundance in association with decreased NF-κB p65 protein expression in inner medullary collecting duct cells with hypoxia/reoxygenation. In conclusion, TGR5 stimulation by LCA prevented downregulation of renal AQPs in kidney with I/R injury, likely through activating HIF-1α signaling and suppressing inflammatory responses.NEW & NOTEWORTHY Stimulation of the membrane G protein-coupled bile acid receptor TGR5 by lithocholic acid (LCA) reduced polyuria in rats with renal ischemia-reperfusion (I/R) injury. LCA increased abundance of aquaporin-2 (AQP2) protein and upregulated hypoxia-inducible factor (HIF)-1α protein expression in association with decreased NF-κB p65 and IL-1ß. After I/R, mice with tgr5 gene deficiency exhibited more severe decreases in AQP2 and HIF-1α protein abundance and inflammatory responses. TGR5 activation exhibits a protective role in acute renal injury induced by I/R.

The Tri(imidazole)-Derivative Moiety: A New Category of Electron Acceptors for the Design of Crystalline Hybrid Photochromic Materials.

The intermarriage of neutral and tripodal imidazole ligand, tris(4-(1H-imidazol-1-yl)phenyl)amine (TIPA), with zinc phosphite yields two hybrid phosphites, [Zn2 (HPO3 )2 (TIPA)]⋅2 H2 O (1) and [Zn3 (HPO3 )3 (TIPA)]⋅6 H2 O (2). Compound 1 has a hybrid sheet with neutral zinc-phosphite chains as supramolecular building blocks (SBBs), whereas 2 exhibits a 3D hybrid architecture with other neutral zincophosphite chains as supramolecular building blocks. The structural discrepancy between 1 and 2 is mainly due to the distinct linkage modes between organic TIPA ligands and inorganic zincophosphite chains. Interestingly, compounds 1 and 2 feature fast photochromism in response to UV light irradiation under ambient conditions. The discrepancy of photochromic performance between 1 and 2 is mainly due to the different geometrical configuration of the TIPA ligand. Different to majority of reported hybrid photochromic compounds driven by photochromic active units, the photochromism in 1 and 2 is derived from the electron transfer (ET) between phosphite and non-photochromic triimidazole-derivative ligand TIPA. Compared with the widely explored nonphotochromic polypyridine-derivative as electron acceptors (EAs), our work provides a new EA model for the design of hybrid photochromic materials based on the ligand-to-ligand ET mechanism. A multiple anti-counterfeiting application based on 1 and 2 was investigated.

Metal-Organic Complexes@Melamine Foam Template Strategy to Prepare Three-Dimensional Porous Carbon with Hollow Spheres Structures for Efficient Organic Vapor and Small Molecule Gas Adsorption.

Three-dimensional (3D) porous carbon materials have received substantial attention owing to their unique structural features. However, the synthesis of 3D porous carbon, especially 3D porous carbon with hollow spheres structures at the connection points, still pose challenges. Herein, we first develop a metal-organic complexes@melamine foam (MOC@MF) template strategy, by using hot-pressing and carbonization method to synthesize 3D porous carbon with hollow spheres structures (denoted as NOPCs). The formation mechanism of NOPCs can be attributed to the difference in Laplace pressure and surface energy gradient between the carbonized MOC and carbonized MF. These rare 3D porous carbons exhibit high BET surface area (2453.8 m2 g-1), N contents (10.5%), and O contents (16.3%). Moreover, NOPCs show significant amounts of toluene and methanol at room temperature, reaching as high as 1360 and 1140 mg g-1. The adsorption amounts of SO2 and CO2 for NOPCs are up to 93.1 and 445 mg g-1. Theoretical calculation indicates surfaces of porous carbon with N and O coexistence could strongly enhance adsorption with high adsorption energy of -65.83 kJ mol g-1.

Micromesoporous Nitrogen-Doped Carbon Materials Derived from Direct Carbonization of Metal-Organic Complexes for Efficient CO2 Adsorption and Separation.

Metal-organic complexes (MOCs) are considered as excellent precursors to prepare carbon materials, due to the fact that heteroatoms and functional groups can be naturally reserved in the resulting carbon materials through the carbonization. Herein, micromesoporous nitrogen-doped carbons MPNC-1 and MPNC-2 are successfully obtained by direct carbonization (800 °C, KOH activation) of metal-organic complexes DQA-1 and DQA-2. MPNC-1 and MPNC-2 exhibit high BET surface area (2368.9 and 2327.6 m2 g-1), pore volume (1.95 and 1.89 cm3 g-1), and N contents (17.2% and 12.3%). At 25 °C and 1 bar, MPNC-1 and MPNC-2 show high CO2 adsorption of 7.53 and 6.58 mmol g-1, the estimated CO2/N2 selectivity are 20.5 and 22.6, indicating excellent promise for practical CO2 adsorption and separation applications. Theoretical calculation indicates carbon surfaces with pyridinic-N, pyrrolic-N, and graphitic-N coexistence could strongly change the local electronic distribution and electrostatic surface potential, enhancing the CO2 adsorption with adsorption energy of -58.96 kJ mol g-1. Theoretical calculation also highlights that CO2 adsorption mechanism is electrostatic interaction with a large green isosurface between CO2 molecules and the carbon surface.

A Dual Associated-Functional Fluorescent Switch: From Alternate Detection Cycle for Fe(III) and pH to Molecular Logic Operations.

With the expansion and deepening of scientific research, dual-functional or multifunctional materials are urgently needed to replace those for single application. Herein, a fluorescence sensing system based on an In(III)-organic complex with in situ Lewis acid sites has been constructed, exhibiting high sensitivity for the detection of Fe(III) ions with a low detection limit of 3.95 µM and a short response time of within 10 s. It is noteworthy that the quenched fluorescence of the Fe(III)-incorporated sample could be reopened linearly with an increase of alkalinity, followed by the reactivation of its functionality to identify Fe(III) ions, forming an alternate detection cycle for Fe(III) and pH with off-on-off fluorescent switch characteristics. Considering its unique molecular recognition capability, an advanced three-input (Fe(III), EDTA, and OH-) and two-output (B440 and G489) Boolean logic operation comprising BUFF, NOT, OR, and AND logic gates was integrated, possessing potential applications in intelligent multianalyte sensing systems.

A new insight into the SO2 adsorption behavior of oxidized carbon materials using model adsorbents and DFT calculations.

Heteroatom-doped carbon materials have been proven to be very effective for gas adsorption. Herein, edge-carboxylated graphene nanoplatelets with gradient oxygen contents and consistent pore structures were used as model adsorbents to independently determine the effects of the oxygen functionalization of carbon materials on the SO2 adsorption. The OGnPs were obtained by employing a simple ball milling method using dry ice by which an oxygen content as high as 14.06 wt% could be achieved, resulting in a 20 times increase in SO2 adsorption capacity as compared to that of oxygen-free graphene nanoplatelets. Both the experiments and density functional theory calculations demonstrated that the enhanced SO2 adsorption on the oxygenated carbon surface had a physisorption nature, which provided new insights into the development of advanced carbon materials with heteroatom doping for gas molecule adsorption.

Research on the Mechanism of Aggregation-Induced Emission through Supramolecular Metal-Organic Frameworks with Mechanoluminescent Properties and Application in Press-Jet Printing.

This study investigates the mechanism of AIE in the solid state through supramolecular metal-organic frameworks and mechanoluminescent materials for the first time. Herein, four novel differently substituted Schiff base building blocks, SB1-SB4, exhibit typical AIE properties with various fluorescence emissions from yellow to green. SB1-SB4 are linked through C-H···O hydrogen bonding interactions to construct supramolecular metal-organic frameworks (SMOFs): namely, SMOFSB1-SMOFSB4. Particularly, among these SMOFs, SMOFSB3 is observed to have micropores in the 3D supramolecular structure and exhibits mechanoluminescent properties (grinding). An emission turn-on mechanism occurs with destruction of micropores by grinding and blockage of intramolecular rotations of the methyl and acetonitrile in the micropores, resulting in emission turn-on in SMOFSB3. Single-crystal X-ray structures, powder X-ray diffraction, emission spectra at room temperature, temperature-dependent emission spectra, DFT calculations, and a charge separation hypothesis well demonstrate the emission turn-on mechanism, which is consistent with the mechanism of AIE. More importantly, the molecules demonstrated potential application for press-jet printing.

The influence of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms on prostate cancer risk.

Estrogen receptor 1 (ESR1) and estrogen receptor 2 (ESR2) may play a role in the development of prostate cancer. Many studies focused on ESR1 rs9340799 and ESR2 rs1256049 polymorphisms to explore associations with prostate cancer risk. These studies showed inconsistent and conflicting results. The aim of this meta-analysis was to investigate the pooled association of ESR1 rs9340799 and ESR2 rs1256049 polymorphisms with prostate cancer risk. A systematic literature search was conducted to identify related studies (up to February 2014) in several online databases including PubMed, Google Scholar, CNKI and Wanfang online libraries. A total of 16 eligible articles were enrolled in this updated meta-analysis. The result suggested that ESR1 rs9340799 polymorphism was significantly associated with prostate cancer in overall populations (GG+GA vs. AA: P = 0.002; G vs. A: P = 0.004), Caucasians (GG+GA vs. AA: P = 0.008; G vs. A: P = 0.016) and Africans (GG+GA vs. AA: P = 0.005; G vs. A: P = 0.006), but not in Asians (GG+GA vs. AA: P = 0.462; G vs. A: P = 0.665). The result also showed that there was a significant association between ESR2 rs1256049 polymorphism and prostate cancer in Caucasians (AA+AG vs. GG: P = 0.016; A vs. G: P = 0.005), but no association in overall populations (AA+AG vs. GG: P = 0.826; A vs. G: P = 0.478), Asians (AA+AG vs. GG: P = 0.177; A vs. G: P = 0.703) and Africans (AA+AG vs. GG: P = 0.847; A vs. G: P = 0.707). The cumulative meta-analysis and sensitivity analysis showed the results were robust. In conclusion, this meta-analysis indicated that ESR1 rs9340799 polymorphism was associated with prostate cancer risk in overall populations, Caucasians and Africans, while ESR2 rs1256049 polymorphism was associated with prostate cancer risk in Caucasians. However, the biological mechanisms need to be further investigated.

Hollow Carbon Nanopillar Arrays Encapsulated with Pd-Cu Alloy Nanoparticles for the Oxygen Evolution Reaction.

Delicate design and bottom-up synthesis of hollow nanostructures for oxygen evolution electrocatalysts is a promising way to accelerate the reaction kinetics of overall water splitting. Herein, an efficient and versatile strategy for the controllable preparation of Pd-Cu alloy nanoparticles encapsulated in carbon nanopillar arrays (PD-Cu@HPCN) is developed. Core-shell structured MOF@imidazolium-based ionic polymers (ImIPs) have been prepared and adopted as a template, along with the decomposition of the inner Cu-MOFs when an anion exchange occurs between sodium tetrachloropalladate in solution and bromides in the external ImIP shell. Pd nanoparticles will be highly dispersed in the resulting Pd-Cu@HO-ImIP array, and subsequent topotactic transformation generates Pd-Cu@HNPC. No hazardous reagents or tedious steps are used to remove the inner Cu-MOF templates in contrast to the traditional top-down methods. Remarkably, the Pd-Cu@HPCN catalyst possesses outstanding oxygen evolution reaction (OER) activity, including small overpotential with 10 mA cm-2 at an overpotential of 188 mV, a large double layer capacitance (73.8 mF cm-2), and high stability (20 h). This simple, green, and efficient synthesis methodology represents a new way to design metal alloys for OER electrocatalysts or other electrocatalytic devices.

Valsartan Attenuated Homocysteine-Induced Impaired Autophagy and ER Stress in Human Umbilical Vein Endothelial Cells.

Hyperhomocysteinemia is a risk factor for various cardiovascular diseases. However, the mechanism underlying homocysteine- (Hcy-) induced vascular injury remains unclear. The purpose of the present study was to examine a potential mechanism by which Hcy induced injury in human umbilical vascular endothelial cells (HUVEC). The protein abundance of autophagy-related markers was markedly decreased after Hcy treatment, which was associated with endoplasmic reticulum (ER) stress and apoptosis in HUVECs. Protein expression level of angiotensin II type 1 receptor (AT1 receptor) was dramatically increased in response to Hcy. Valsartan, an AT1 receptor blocker, improved autophagy and prevented ER stress and apoptosis in HUVECs treated with Hcy. Consistent with this, silence of AT1 receptor with siRNA decreased the protein abundance of ER stress markers, prevented apoptosis, and promoted autophagy in HUVECs. Inhibition or knockdown of AT1 receptor was shown to be associated with suppression of p-GSK3ß/GSK3ß-p-mTOR/mTOR signaling pathway. Additionally, inhibition of autophagy by 3-MA aggravated Hcy-induced apoptosis, while amelioration of ER stress by 4-PBA prevented Hcy-induced injury in HUVECs. Hcy-induced HUVEC injury was likely attributed to AT1 receptor activation, leading to impaired autophagy, ER stress, and apoptosis.

Changing epidemiology of chronic kidney disease as a result of type 2 diabetes mellitus from 1990 to 2017: Estimates from Global Burden of Disease 2017.

AIMS/INTRODUCTION: Type 2 diabetes mellitus has been a leading cause of chronic kidney disease (CKD), with a heterogeneous distribution worldwide. Optimal healthcare planning requires an understanding of how the burden of CKD as a result of type 2 diabetes mellitus has changed over time and geographic location, as well as the potential roles of sociodemographic, clinical and behavioral factors in these changes. MATERIALS AND METHODS: We used the Global Burden of Disease data from 1990 to 2017 at the global, regional and national levels to investigate changes in the incidence, death and disability-adjusted life years of CKD as a result of type 2 diabetes mellitus, incorporating both epidemiological research and risk factor monitoring. RESULTS: The incident cases of CKD as a result of type 2 diabetes mellitus worldwide in 2017 had increased by 74% compared with 1990; total disability-adjusted life years had increased by 113%, mainly attributable to population expansion and demographic transition. The Sociodemographic Index was significantly and negatively correlated with overall CKD as a result of type 2 diabetes mellitus burden. However, in 82 countries and territories, the burden was not alleviated in parallel with socioeconomic development. CONCLUSIONS: CKD as a result of type 2 diabetes mellitus has been the main contributor to the increasing burden of CKD over the past several decades. We suggest a more pragmatic approach focusing on early diagnosis, primary care and adequate follow up to reduce mortality and the long-term burden in low-to-middle Sociodemographic Index regions. Interventions should address high systolic blood pressure, as well as overweight and obesity problems, especially in high-income regions.

EWI-2 controls nucleocytoplasmic shuttling of EGFR signaling molecules and miRNA sorting in exosomes to inhibit prostate cancer cell metastasis.

Early and accurate diagnosis of prostate cancer (PCa) is extremely important, as metastatic PCa remains hard to treat. EWI-2, a member of the Ig protein subfamily, is known to inhibit PCa cell migration. In this study, we found that EWI-2 localized on both the cell membrane and exosomes regulates the distribution of miR-3934-5p between cells and exosomes. Interestingly, we observed that EWI-2 is localized not only on the plasma membrane but also on the nuclear envelope (nuclear membrane), where it regulates the nuclear translocation of signaling molecules and miRNA. Collectively, these functions of EWI-2 found in lipid bilayers appear to regulate PCa cell metastasis through the epidermal growth factor receptor-mitogen-activated protein kinase-extracellular-signal-regulated kinase (EGFR-MAPK-ERK) pathway. Our research provides new insights into the molecular function of EWI-2 on PCa metastasis, and highlights EWI-2 as a potential PCa biomarker.

Specific MiRNAs in naïve T cells associated with Hepatitis C Virus-induced Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common type of cancer and the second leading cause of cancer-associated mortality worldwide. Hepatitis C virus (HCV) infection is the primary cause of hepatic fibrosis and cirrhosis, which in turn, notably increase the risk of developing HCC. The systematic immune response plays a vital role in protecting eukaryotic cells from exogenous antigens. In the present study, to determine the association between T cells and miRNAs in HCV-induced HCC (HCV-HCC), bulk mRNA and miRNA sequencing data from HCV-HCC tissues were combined, along with single-cell RNA sequencing (RNA-seq) data from T cells. Deconvoluted bulk RNA-seq data and miRNA profiles enabled the identification of naive CD4+ T cell-associated miRNAs, which may help to elucidate the underlying mechanism of the anti-HCV immune response. Using bulk RNA-seq data, the current analysis presents a feasible method for assessing the relationship between miRNAs and cell components, providing valuable insights into the effects of T cell-associated miRNAs in HCV-HCC.