Hollow Lindqvist-like-Shaped {V6} Cluster-Based Metal-Organic Framework for the Highly Efficient Detoxification of Mustard Gas Simulant.

A polyoxovanadate-based nickel-organic framework, [Ni(bib)2]{V2O6}({V6}-MOF, bib = 1,4-bis(1H-imidazoly-1-yl)benzene), was facilely prepared under gentle hydrothermal conditions and structurally characterized. Single-crystal X-ray diffraction analysis indicates that the {V6} cluster in the {V6}-MOF is constructed of two VO5 tetragonal pyramids and four VO4 tetrahedrons via the apex sharing of O atoms, presenting a hollow Linqvist-like structure, which is different from these reported hexanuclear vanadium clusters. The {V6}-MOF not only expands the structure of polyoxovanadates (POVs) but also catalyzes the rapid detoxification of mustard gas simulant (2-chloroethyl ethyl sulfide, CEES) at 25 °C. The catalytic results were determined by means of GC, GC-MS, and 1H NMR. Using {V6}-MOF as a heterogeneous catalyst, CEES underwent catalyzed oxidation to only nontoxic product 2-chloroethyl ethyl sulfoxide (CEESO) within 40 min, and the conversion and selectivity were almost 100%. In addition, {V6}-MOF exhibits high sustainability, and no obvious reductions in conversion and selectivity are observed after five runs.

Upregulation of circFLNA contributes to laryngeal squamous cell carcinoma migration by circFLNA-miR-486-3p-FLNA axis.

BACKGROUND: Accumulating evidence shows that circular RNAs (circRNAs) plays vital roles in tumor progression. However, the biological functions of circRNAs in laryngeal squamous cell carcinoma (LSCC) metastasis is still unclear. METHODS: qRT-PCR was used to detect circFLNA, miRNAs and FLNA mRNA expression. Transwell assay and western blot were performed to evaluate cell migration ability and to detect FLNA, MMP2 and MLK1 protein expression, respectively. RNA pull-down analysis was used to find the binding-miRNAs of circFLNA. Luciferase reporter assay was used to examine the effect of circFLNA on miRNAs and miR-486-3p on FLNA expression. RESULTS: In this study, we confirmed that a Filamin A (FLNA)-derived hsa_circ_0092012 known as circFLNA, was upregulated in LSCC, and the higher expression of circFLNA was correlated with LSCC lymph node metastasis. Increased circFLNA facilitates LSCC cell migration ability through upregulating FLNA and MMP2 protein expression. Mechanistically, we find that circFLNA sponges miR-486-3p in LSCC cells, relieving miR-486-3p-induced repression of FLNA which promotes LSCC cell migration. Accordingly, FLNA mRNA is overexpressed in LSCC tissues and a higher FLNA level is correlated with poor survival. Dysregulation of the circFLNA/miR-486-3p/FLNA regulatory pathway contributes to LSCC migration. CONCLUSIONS: In summary, our study sheds light on the regulatory mechanism of circFLNA in LSCC migration via sponging miR-486-3p, which downregulates the FLNA protein expression. Targeting circFLNA/miR-486-3p/FLAN axis provides a potential therapeutic target for aggressive LSCC.

Flavobacterium sharifuzzamanii sp. nov., Isolated from the Sediments of the East China Sea.

A novel bacterial strain A7.6T was isolated from the sediments collected near the Zhairuo Island located in the East China Sea and characterized using a polyphasic approach. Cells were Gram-stain-negative, rod-shaped, non-spore forming, non-flagellated but motile by gliding. The strain was aerobic, positive for oxidase and catalase activities. The strain can grow at 4-35 °C, pH 5.5-9.0, and 0-3% (w/v) NaCl concentration. The major polar lipid was phosphatidylethanolamine, the predominant fatty acids (> 10%) were iso-C15:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). The genomic G+C content was 33.6 mol% and the major respiratory quinone was menaquinone 6. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain A7.6T belonged to the genus Flavobacterium and was closely related to Flavobacterium tistrianum GB 56.1T (98.4% similarity), F. nitrogenifigens NXU-44T (98.4%), F. ginsenosidimutans THG 01T (98.0%) and F. anhuiense D3T (97.7%). Average nucleotide identities and digital DNA-DNA hybridizations values for genomes ranged from 75.9 to 91.4% and 21.4 to 43.9% between strain A7.6T and its closest phylogenetic neighbors. The polyphasic characterization indicated that strain A7.6T represented a novel species of the genus Flavobacterium, for which the name Flavobacterium sharifuzzamanii is proposed. The type strain is A7.6T (= KCTC 62405T = MCCC 1K03485T). The NCBI GenBank accession number for the 16S rRNA gene of A7.6T is MH396692, and for the genome sequence is QJGZ00000000. The digital protologue database (DPD) Taxon Number is TA00643.

The PTEN/PI3K/Akt signaling pathway mediates HMGB1-induced cell proliferation by regulating the NF-κB/cyclin D1 pathway in mouse mesangial cells.

Our previous experiment confirmed that high-mobility group box chromosomal protein 1 (HMGB1) was involved in the pathogenesis of Lupus nephritis (LN) by upregulating the proliferation of the mouse mesangial cell line (MMC) through the cyclin D1/CDK4/p16 system, but the precise mechanism is still unknown. Therefore, in the present study, we demonstrated that HMGB1 induced the proliferation of MMC cells in a time- and concentration-dependent manner, downregulated phosphatase and tensin homolog deleted on chromosome ten (PTEN) expression, increased the level of Akt serine 473 phosphorylation, and induced p65 subunit nuclear translocation. The overexpression of PTEN prevented the upregulation of HMGB1-induced proliferation by blocking the activation of Akt. The knockdown of Akt by siRNA technology and blocking the nuclear factor-κB (NF-κB) pathway using pyrrolidine dithiocarbamate (PDTC) and SN50, inhibitors of NF-κB, both attenuated the HMGB1-induced proliferation by counteracting the activation of the cyclin D1. In addition, while sh-Akt partly blocked the nuclear translocation of the p65 subunit, PDTC did not affect the activation of the Akt induced by HMGB1 in MMC cells. These findings indicate that HMGB1 induced the proliferation of MMC cells by activating the PTEN/phosphoinositide-3-kinase (PI3K)/Akt/NF-κB signaling pathway.

Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis.

Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate high glucose (HG)-induced podocyte apoptosis remain poorly understood. Conditionally immortalized mouse podocytes were cultured in HG medium. A chemical inhibitor or a specific short-hairpin RNA (shRNA) vector was used to inhibit the activation of the Notch pathway and the PI3K/Akt pathway in HG-treated podocytes. Western blotting and real-time PCR were used to evaluate the levels of Notch, PI3K/Akt, and apoptotic pathway signaling. The apoptosis rate of HG-treated podocytes was assessed by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling and annexin V/propidium iodide staining. In HG-treated podocytes, PI3K/Akt pathway activation prevented podocyte apoptosis in the early stage of HG stimulation and Notch pathway-induced podocyte apoptosis in the late stage of HG stimulation. The inhibition of the Notch pathway or the activation of the PI3K/Akt pathway prevented cell apoptosis in HG-treated podocytes. These findings suggest that the Notch and PI3K/Akt pathways may mediate HG-induced podocyte apoptosis.

Mechanical amplification mechanism of kinesin's ß-domain.

Conventional kinesin's force generation process always takes place on the leading head and the generated force is transmitted to the trailing head through two neck linkers. To guarantee a strong force to be transmitted to the trailing head so that it can be detached from microtubule surface, the neck linker of the leading head must have a large enough forward displacement, which is proposed to be achieved by the amplifying function of the ß-domain. However, the experimental result shows that the forward displacement of the ß-domain itself appears too small. To elucidate the function of the ß-domain, we make a detailed analysis of the mechanical relationship between the two motor heads and, based on the results of molecular dynamics simulation and mechanical analysis, we calculate the forward displacement of the neck linker of the leading head during the ATP binding induced motor head rotation. We show that ß-domain achieves its amplifying function together with ß0, so that neck linker can have a forward displacement during motor head rotation. This displacement of neck linker is large enough to cause detachment of the trailing head. Based on these results, a possible initiation mechanism of neck linker docking is proposed.

IFN-γ induces lipogenesis in mouse mesangial cells via the JAK2/STAT1 pathway.

The objective is to investigate the effect of high mobility group box-1 (HMGB1) on lipid deposition in γ-interferon (IFN-γ)-stimulated mouse mesangial cell line (MMC) and to determine whether the Janus kinase 2 and signal transducer and activator of transcription 1 (JAK2/STAT1) signaling pathway plays an important role in this process. We employed a control group, an IFN-γ stimulation group, and an IFN-γ + AG490 (JAK2 inhibitor) group. RNA interference aimed at sterol regulatory element-binding protein-1 (SREBP-1) or HMGB1 was used to investigate the effect of these proteins on IFN-γ-induced lipid deposition. Western blotting was used to detect phospho (p)-JAK2, JAK2, p-STAT1, STAT1, SREBP-1, fatty acid synthase (FAS), and HMGB1 protein expression. RT-PCR was used to detect SREBP-1, FAS, and HMGB1 mRNA. Oil Red O staining and the triglyceride assay were used to detect lipid deposition and triglyceride content. Results were as follows: 1) IFN-γ increased MMC cell lipid deposition, triglyceride content, and p-JAK2, p-STAT1, SREBP-1, and FAS expression; 2) SREBP-1 inhibition prevented FAS upregulation and attenuated IFN-γ-induced MMC cell lipid deposition and triglyceride content; 3) HMGB1 upregulated SREBP-1 and FAS mRNA and protein levels, which increased lipid deposition in MMC cells. Small interfering RNA-mediated inhibition of HMGB1 decreased SREBP-1 and FAS expression and lipid accumulation; 4) AG490 decreased upregulation of HMGB1 and p-JAK2/p-STAT1, as well as IFN-γ-induced lipogenesis. In conclusion, the JAK2/STAT1 pathway mediates IFN-γ-induced lipogenesis in MMC cells through regulation of HMGB1/SREBP-1/FAS.

Elimination of grain boundary resistance in vanadoborate electrolyte via the hydrogen-bond interaction of glycerol.

An effective method to eliminate grain boundary resistance of crystalline vanadoborate electrolyte was developed. This method involved the addition of glycerol to result in the formation of many hydrogen bonds between crystal grains, facilitating a rapid transfer of protons across grain boundaries. Using this method, the intrinsic conduction of vanadoborate electrolyte was fully reflected in its bulk materials, valuable for advancing our understanding of vanadoborate electrolytes and for promoting the application of these electrolytes.

A multifunctional cobalt-organic framework for proton conduction and selective sensing of Fe3+ ions.

Developing multifunctional metal-organic frameworks (MOFs) is a new research trend. MOFs have shown remarkable performances in both proton conduction and fluorescence sensing, but the MOFs integrating the two performances are scarce. Herein, a Co-MOF, [Co6(oba)4(Hatz)(atz)(H2O)2(µ3-OH)2(µ2-OH)]·H2O (1, H2oba = 4,4-oxybis(benzoic acid), Hatz = 5-amino-1H tetrazole), has been assembled by Co2+ ions with H2oba and Hatz ligands, providing a unique example of multifunctional MOFs with both proton conduction and fluorescence sensing performances. The framework of 1 displays a pillar-layer structure built by the oba ligand as a pillar and a layer composed of Co-clusters and atz linkers. Because large-scale single crystals of 1 were successfully synthesized, the proton conduction ability of 1 was investigated using single crystal samples. 1 exhibits highly anisotropic conduction with conductivity values of 1.1 × 10-3 S cm-1 along the [001] direction and 9.1 × 10-6 S cm-1 along the [010] direction at 55 °C and 95% RH, respectively. Meanwhile, the fluorescence sensing of 1 towards metal ions was studied in aqueous solutions. Attractively, 1 may sensitively and selectively detect Fe3+ ions in the presence of other interfering ions by fluorescence quenching.

High-fat diet causes increased serum insulin and glucose which synergistically lead to renal tubular lipid deposition and extracellular matrix accumulation.

Renal tubular lipid accumulation is associated with renal injury in the metabolic syndrome, but its mechanisms are not fully elucidated. The purpose of the present study was to investigate the exact mechanism of renal tubular lipid accumulation in the diet-induced metabolic syndrome. The in vivo experiments showed that a high-fat diet induced hyperglycaemia, hyperinsulinaemia and hypertriacylglycerolaemia, subsequent increases in sterol regulatory element binding protein-1 (SREBP-1) and transforming growth factor-ß1 (TGF-ß1), lipid droplet deposit in renal tubular cells and interstitial extracellular matrix accumulation in Wistar rats. A human renal proximal tubular epithelial cell line (HKC) was used to determine the direct role of insulin, and the results revealed that insulin induced SREBP-1, fatty acid synthase (FASN), TGF-ß1 expressions, lipid droplet and extracellular matrix deposits. Knockdown of SREBP-1 by RNA interference technology significantly inhibited FASN, TGF-ß1 up-regulation, lipid and extracellular matrix accumulation caused by insulin. In addition, we found that insulin and high glucose could synergistically increase SREBP-1, FASN, TGF-ß1 and fibronectin expressions in HKC cells. These results indicate that high-fat diet-induced increased serum insulin and glucose synergistically cause renal tubular lipid deposit and extracellular matrix accumulation via the SREBP-1 pathway.

[Effects of langchuangping granule on the expression of B lymphocyte activating factor in the peripheral blood B cells of BXSB lupus nephritis mice].

OBJECTIVE: To explore the expressions of B lymphocyte activating factor (BAFF) in the serum and peripheral blood B cells (PBBCs) of BXSB lupus nephritis mice, and to investigate the efficacy of Langchuangping Granule (LG). METHODS: Eighteen 11-week-old male BXSB lupus mice were randomly divided into three groups, i.e., the lupus control group, the hormone treatment group, and the LG treatment group, 6 in each group. Besides, another 6 C57BL/6 male mice were recruited as the normal control group. The mice were given with normal sodium (10 mL/d), methylprednisolone (at the daily dose of 5 mg/kg), LG (at the daily dose of 4 g/kg), and the normal saline (10 mL/d) respectively by gastrogavage for 4 weeks. The urine protein, ds-DNA, and body weight were determined. The serum soluble BAFF (sBAFF), the expressions and changes of BAFF-mRNA in the PBBCs were detected using ELISA and RT-PCR respectively. The activity index (AI) and 24 h urine albumin excretion quantitation of renal pathological activities were observed. The correlation between ds-DNA and sBAFF were analyzed. RESULTS: The level of sBAFF in serum, the BAFF mRNA level in PBBCs, 24 h urinary albumin excretion, and serum ds-DNA content increased more obviously in lupus mice than in the normal mice. After being treated by methylprednisolone or LG, the sBAFF and BAFF mRNA expressions decreased more obviously than before treatment, showing statistical difference (P<0.05). But there was no statistical difference in the sBAFF level or the BAFF mRNA expression (P>0.05). There was positive correlation between sBAFF and AI (r=0.8098, P<0.01), 24 h urinary albumin excretion (r=0.8220, P<0.01), and ds-DNA (r=0.8535, P<0.01). CONCLUSIONS: BAFF plays an important role in the occurrence and development of lupus nephritis. It can be used in monitoring the disease progress and predicting its recurrence. It is one of ideal targets for treating lupus nephritis. LG could attenuate the renal injury via suppressing BAFF level. It is worth further clinical application.

A sodalite-type porous metal-organic framework with polyoxometalate templates: adsorption and decomposition of dimethyl methylphosphonate.

A sodalite-type porous metal-organic framework with polyoxometalate templates, H(3)[(Cu(4)Cl)(3)(BTC)(8)](2)[PW(12)O(40)]·(C(4)H(12)N)(6)·3H(2)O (NENU-11; BTC = 1,3,5-benzenetricarboxylate), was obtained by a hydrothermal reaction. As a reasonable candidate for eliminating nerve gas, NENU-11 displays good adsorption behavior for dimethyl methylphosphonate (15.5 molecules per formula unit). In virtue of the catalytic activity of polyoxometalate guests, this nerve gas mimic could be facilely decomposed by a hydrolysis reaction.

[Langohuangping granule down-regulated monocyte chemoattractant protein-1 via suppressing nuclear factor kappa B signaling pathway in BXSB lupus nephritis mice].

OBJECTIVE: To study whether Langchuangping granule (LG) could exert its renal protection by down-regulating monocyte chemoattractant protein-1 (MCP-1) via suppressing nuclear factor kappa B (NF-kappaB) signaling pathway in BXSB lupus nephritis (LN) mice. Methods Eighteen male 11-week-old BXSB LN mice were randomly divided into three groups, i.e., the model group, the hormone group, and the Chinese medicine group, 6 in each. They were administered by gastrogavage with normal saline, methylprednisolone, and LG, respectively. Another six C57BL/6 male mice of the same age was taken as the normal control group, which was administered with normal saline by gastrogavage. All mice were treated once daily, for 4 successive weeks. The 24-h urine protein was determined. The mRNA and protein expressions of MCP-1 in the renal tissue were detected using RT-PCR and Western blot. The expression of NF-kappaB p65 in the renal tissue was detected using immunohistochemical assay. Activity index (AI) of the renal tissue was counted using PAS stain. The content of ds-DNA antibody was detected using ELISA. The correlations of the aforesaid indices were analyzed. RESULTS: The 24-h urine protein level, serum ds-DNA antibody content, protein and mRNA expressions of MCP-1, NF-kappaB p65 expression level, and AI count were obviously higher in the model group than in the normal control group (P < 0.01). The aforesaid indices all obviously decreased after medication in the Chinese medicine group and the hormone group (P < 0.05). MCP-1 protein expression level was positively correlated with MCP-1 mRNA, NF-kappaB p65, AI, 24-h urine protein, and ds-DNA antibody of all LN mice (r= 0.984, 0.936, 0.887, 0.698, 0.679, all P < 0.01). CONCLUSIONS: LG possibly played renal protection by down-regulating NF-kappaB-mediated MCP-1 expression levels. MCP-1 played important roles in the occurrence and development of LN, being one of ideal targets for LN treatment.

Origin of the Surprising Mechanical Stability of Kinesin's Neck Coiled Coil.

Kinesin-1 is a motor protein moving along a microtubule with its two identical motor heads dimerized by two neck linkers and a coiled-coil stalk. When both motor heads bind the microtubule, an internal strain is built up between the two heads, which is indispensable to ensure proper coordination of the two motor heads during kinesin-1's mechanochemical cycle. The internal strain forms a tensile force along the neck linker that tends to unwind the neck coiled coil (NCC). Experiments showed that the kinesin-1's NCC has a high antiunwinding ability compared with conventional coiled coils, which was mainly attributed to the enhanced hydrophobic pressure arising from the unconventional sequence of kinesin-1's NCC. However, hydrophobic pressure cannot provide the shearing force which is needed to balance the tensile force on the interface between two helices. To find out the true origin of the mechanical stability of kinesin-1's NCC, we perform a novel and detailed mechanical analysis for the system based on molecular dynamics simulation at an atomic level. We find that the needed shearing force is provided by a buckle structure formed by two tyrosines which form effective steric hindrance in the presence of tensile forces. The tensile force is balanced by the tensile direction component of the contact force between the two tyrosines which forms the shearing force. The hydrophobic pressure balances the other component of the contact force perpendicular to the tensile direction. The antiunwinding strength of NCC is defined by the maximum shearing force, which is finally determined by the hydrophobic pressure. Kinesin-1 uses residues with plane side chains, tryptophans and tyrosines, to form the hydrophobic center and to shorten the interhelix distance so that a high antiunwinding strength is obtained. The special design of NCC ensures exquisite cooperation of steric hindrance and hydrophobic pressure that results in the surprising mechanical stability of NCC.

Fabricating polyoxometalates-stabilized single-atom site catalysts in confined space with enhanced activity for alkynes diboration.

Effecting the synergistic function of single metal atom sites and their supports is of great importance to achieve high-performance catalysts. Herein, we successfully fabricate polyoxometalates (POMs)-stabilized atomically dispersed platinum sites by employing three-dimensional metal-organic frameworks (MOFs) as the finite spatial skeleton to govern the accessible quantity, spatial dispersion, and mobility of metal precursors around each POM unit. The isolated single platinum atoms (Pt1) are steadily anchored in the square-planar sites on the surface of monodispersed Keggin-type phosphomolybdic acid (PMo) in the cavities of various MOFs, including MIL-101, HKUST-1, and ZIF-67. In contrast, either the absence of POMs or MOFs yielded only platinum nanoparticles. Pt1-PMo@MIL-101 are seven times more active than the corresponding nanoparticles in the diboration of phenylacetylene, which can be attributed to the synergistic effect of the preconcentration of organic reaction substrates by porous MOFs skeleton and the decreased desorption energy of products on isolated Pt atom sites.

One-pot mechanochemical synthesis to encapsulate functional guests into a metal-organic framework for proton conduction.

Through one-pot mechanochemical synthesis, a series of guests [imidazole, (aminomethyl)phosphonic acid, urea and sulfamic acid] are rapidly encapsulated into the pores of MOF NENU-3 while the MOF is formed. The synthesis of a MOF loaded with functional guests that used to take several days and require a multistep procedure can now be completed in one step within several minutes. The proton conductivities of the obtained composites increased by 2-3 orders of magnitude compared with NENU-3.

Reactivity of polyoxoniobates in acidic solution: controllable assembly and disassembly based on niobium-substituted germanotungstates.

The reactivity of polyoxoniobates has been studied in acidic solution by grafting niobium onto trivacant Keggin-type germanotungstates. Four niobium-containing compounds were obtained in the course of this study. Cs(6.5)K(0.5)[GeW(9)(NbO(2))(3)O(37)]·6H(2)O (Cs(6.5)K(0.5)-1) synthesized by the reaction of K(7)H[Nb(6)O(19)] and A-α-Na(10)[GeW(9)0(34)] in H(2)O(2) solution is a tris(peroxoniobium)-substituted A-α-GeW(9) derivative. Cs(6.5)K(0.5)[GeW(9)Nb(3)O(40)]·10H(2)O (Cs(6.5)K(0.5)-2) is a peroxo-free compound obtained by eliminating the peroxo groups in 1. Monomers 1 and 2 as precursors can each afford two nanoscale POMs, dimer Cs(5)[H(15)Ge(2)W(18)Nb(8)O(88)]·18H(2)O (Cs(5)-3) and tetramer Cs(8)K(3)H(9)[Ge(4)W(36)Nb(16)O(166)]·27H(2)O (Cs(8)K(3)H(9)-4), through the formation of Nb-O-Nb bridges. Disassembly through the cleavage of Nb-O-Nb bonds from 4 to 2 and 1 was achieved by controlling the pH and by adding H(2)O(2), respectively. The transition from 1 to 2 can be achieved by simply adding H(2)O(2) to a solution of 1. All four compounds were characterized in the solid state by elemental analysis, infrared spectroscopy, thermogravimetry, and single-crystal X-ray diffraction. (183)W NMR analysis proved that the solid-state structures of polyanions 1-4 were retained after dissolution. Disassembly from 4 to 1 and 2 in solution was observed by (183)W NMR spectroscopy. The UV/Vis spectra of 1 at different pH confirmed that it is stable in the pH range of 0.1-14.0 at room temperature.

[The effect of Janus kinase 2 inhibitor AG490 on renal tubular epithelial-myofibroblast transdifferentiation induced by interleukin-1ß].

OBJECTIVE: To investigate the effect of AG490, a Janus kinase 2 inhibitor, on epithelial-myofibroblast transdifferentiation induced by interleukin-1ß (IL-1ß). METHODS: Cultured human renal tubular epithelial cell line (HKCs) were divided into three groups: blank control group, IL-1ß (5 ng/ml) group and AG490 group (IL-1ß 5 ng/ml+AG490 10 µmol/L). The cells in all groups were collected at 24, 48, 72 hours after intervention. Immunocytochemistry and Western blotting analysis were used to determine the expressions of cytokeratin-18 (CK-18) and α-smooth muscle actin (α-SMA). RESULTS: The higher expression of CK-18 (1.25±0.08) and mild expression of α-SMA (0.17±0.01) were found in blank control group. In IL-1ß group, the protein level of CK-18 was gradually decreased with prolongation of stimulus (24 hours : 0.69±0.04, 48 hours: 0.52±0.03, 72 hours: 0.30±0.01), while the expression level of α-SMA was gradually increased (24 hours: 0.56±0.04, 48 hours: 1.05±0.07, 72 hours: 1.43±0.07), and the difference between blank control group and IL-1ß group was statistically significant (all P<0.05). The administration of AG490 could restore the expression of CK-18 (24 hours: 1.07±0.07, 48 hours: 0.93±0.06, 72 hours: 0.83±0.06), and inhibit the expression of α-SMA induced by IL-1ß (24 hours: 0.33± 0.01, 48 hours: 0.52±0.01, 72 hours: 0.61±0.04). There was significant difference between AG490 group and IL-1ß group (all P<0.05). The results of immunocytochemistry and that of Western blotting were identical. CONCLUSION: IL-1ß can induce the transdifferentiation of renal tubular epithelial cells, up-regulate the expression of α-SMA, induce the renal tubular epithelial cells to transform to myofibroblast, while AG490 can inhibit the effect of IL-1ß.

Complement factor B knockdown by short hairpin RNA inhibits laser-induced choroidal neovascularization in rats.

AIM: To evaluate whether recombinant complement factor B (CFB) short hairpin RNA (shRNA) reduces laser-induced choroidal neovascularization (CNV) in rats. METHODS: Laser-induced rat CNV model was established, and then the animals underwent fundus fluorescence angiography (FFA) and hematoxylin and eosin (HE) staining. On day 3 and 7 after photocoagulation, the expression of CFB and membrane attack complex (MAC) was detected by immunhischemistry. A recombinant CFB-shRNA plasmid was constructed. CFB and scrambled shRNA plasmids were intravenous injected into rats via the tail vein on the day of laser treatment, respectively. On day 7, the incidence of CNV was determined by FFA, and the expression of CFB and vascular endothelial growth factor (VEGF) in retinal pigment epithelium (RPE)/choroidal tissues was detected by immunhischemistry, Western blot and/or semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in CFB and scrambled shRNA groups. The possible adverse effects of CFB-shRNA injection were assessed by transmission electron microscopy and electroretinography. RESULTS: FFA and HE results indicated that a laser-induced rat CNV model was successfully established on day 7 after photocoagulation. The expression of CFB and MAC was extremely weak in normal retina and choroid, and increased on day 3 after photocoagulation. However, it started to reduce on day 7. CFB shRNA plasmid was successfully constructed and induced CFB knockdown in the retinal and choroidal tissues. FFA showed CFB knockdown significantly inhibited incidence of CNV in rats. Moreover, CFB knockdown significantly inhibited the expression of VEGF in RPE/choroidal tissues. CFB shRNA caused no obvious side effects in eyes. CONCLUSION: CFB knockdown significantly inhibits the formation and development of CNV in vivo through reducing the expression of VEGF, which is a potential therapy target. The alternative pathway of complement activation plays an important role in CNV formation.

Purely inorganic frameworks based on polyoxometalate clusters with abundant phosphate groups: single-crystal to single-crystal structural transformation and remarkable proton conduction.

A pure-inorganic framework based on {P4MoV4MoVI2} clusters with rich phosphate groups has been synthesized. It underwent a single crystal to single crystal conversion in air to form a new framework with changes both in the metal valent state and coordination environment. The new framework exhibits an ultra-high proton conductivity of 1.33 × 10-2 S cm-1 at 95 °C and 98% relative humidity and excellent stability.