Identification and Functional Mechanism Verification of Novel MicroRNAs Associated with the Fibrosis Progression in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a serious threat to human health worldwide, and its incidence is increasing annually. A growing amount of information is emerging about the role of micoRNAs (miRNAs) in the regulation of renal fibrosis, which has aroused interest in the development of drugs that block pathogenic miRNAs or restore protective miRNAs levels. To clarify the role of miRNAs in CKD, we selected patients with significant renal fibrotic disease (diabetic nephropathy (DN) and focal segmental glomerulosclerosis (FSGS)) as the disease group, and patients with little or no renal fibrotic disease (minimal change disease (MCD) and renal carcinoma adjacent to normal kidney) as controls. Significantly differentially expressed miRNAs were obtained by human kidney tissue sequencing, subsequently verified in mice models of DN and FSGS, and subsequently inhibited or overexpressed in human renal tubular epithelial cells (HK-2) stimulated by high glucose (HG) and TGF-ß1 in vitro. Therefore, the mechanism of its action in renal fibrosis was further elaborated. Finally, the downstream target genes of the corresponding miRNAs were verified by bioinformatics analysis, qRT-PCR, western blot and double luciferase report analysis. Two novel miRNAs, hsa-miR-1470-3p (miR-1470) and hsa-miR-4483-3p (miR-4483), were detected by renal tissue sequencing in the disease group with significant renal fibrosis (DN and FSGS) and the control group with little or no renal fibrosis (MCD and normal renal tissue adjacent to renal carcinoma). Subsequent human renal tissue qRT-PCR verified that the expression of miR-1470 was significantly increased, while the expression of miR-4483 was markedly decreased in the disease group (p < 0.05). Moreover, in vivo DN and FSGS mice models, the expression levels of miR-1470 and miR-4483 were consistent with the results of human kidney tissue. In vitro, miR-4483 was suppressed, whereas miR-1470 was induced by treatment with TGF-ß1 or HG. Inhibition of miR-1470 or overexpression of miR-4483 promoted HG or TGF-ß1-induced fibrosis in HK-2 cells. Further study revealed that MMP-13 and TIMP1 were the target genes ofmiR-1470 and miR-4483, respectively. Our study identifies newly dysregulated miRNA profiles related to fibrosis kidneys. miR-1470 and miR-4483 are demonstrated to participate in kidney fibrosis by regulation of MMP-13, TIMP1 respectively. Our results may represent a promising research direction for renal disorders and help identify new biomarkers and therapeutic targets for CKD.

Ordered Membrane Electrode Assembly with Drastically Enhanced Proton and Mass Transport for Proton Exchange Membrane Water Electrolysis.

In this work, an ordered membrane electrode assembly (MEA) based on a cone Nafion array with gradient Nafion distribution, tightly bonded catalytic layer/proton exchange membrane (CL/PEM) interface, and abundant vertical channels has been engineered by an anodic aluminum oxide template and magnetron sputtering method. Benefiting from a highly efficient CL/PEM interface, plentiful proton transfer highways, and rapid oxygen bubble release, this ordered MEA achieves an ultralow Ir loading of 20.0 µg cm-2 and a high electrochemical active area by 8.7 times compared to traditional MEA with Ir loading of 1.0 mg cm-2. It yields a mass activity of 168 000 mA mgIr-1 cm-2 at 2.0 V, which is superior to most reported PEM electrolyzers. Notably, this ordered MEA maintains excellent durability at a current density of 500 mA cm-2. This work opens a simple, cost-effective, and scalable route to design ordered MEAs for proton exchange membrane water electrolysis.

[Two new isoquinoline alkaloids from Corydalis hendersonii].

Corydalis hendersonii(CH) is a Tibetan folk medicine with the functions of clearing heat, detoxifying, cooling blood, checking diarrhea, and lowering blood pressure. It is often used to treat high altitude polycythemia, vasculitis, peptic ulcer, and diarrhea. Nine compounds were separated from the ethanol extract of CH by silica gel, ODS, Sephadex LH-20 chromatography and semi-preparative HPLC. Their structures were identified as hendersine H(1),hendersine I(2), dehydrocheilanthifoline(3), protopine(4), izmirine(5), 6,7-methylenedioxy-1(2H)-isoquinolinone(6), icariside D_2(7), ethyl 4-(ß-D-glucopyranosyloxy)-3-methoxybenzoate(8), 3-hydroxy-4-methoxybenzoic acid(9), respectively, by the spectroscopic data analysis and comparison with those in the literature. Among them, compounds 1 and 2 are new isoquinoline alkaloids, and compounds 7-9 are reported the first time for Corydalis. The hypoglycemic model of H9c2 cardiomyocytes and the inflammatory model of H9c2 cardiomyocytes induced by conditional supernatant were employed to determine the activities of the above compounds. The results showed that 20 µmol·L~(-1) compound 1 had a protective effect on H9c2 cardiomyocytes and 10 µmol·L~(-1) compounds 4 and 5 inhibited H9c2 cardiomyocyte inflammation induced by conditional supernatant.

Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde.

Crotonaldehyde (CRA)-one of the major environmental pollutants from tobacco smoke and industrial pollution-is associated with vascular injury (VI). We used proteomics to systematically characterize the presently unclear molecular mechanism of VI and to identify new related targets or signaling pathways after exposure to CRA. Cell survival assays were used to assess DNA damage, whereas oxidative stress was determined using colorimetric assays and by quantitative fluorescence study; additionally, cyclooxygenase-2, mitogen-activated protein kinase pathways, Wnt3a, ß-catenin, phospho-ErbB2, and phospho-ErbB4 were assessed using ELISA. Proteins were quantitated via tandem mass tag-based liquid chromatography-mass spectrometry and bioinformatics analyses, and 34 differentially expressed proteins were confirmed using parallel reaction monitoring, which were defined as new indicators related to the mechanism underlying DNA damage; glutathione perturbation; mitogen-activated protein kinase; and the Wnt and ErbB signaling pathways in VI based on Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and protein-protein interaction network analyses. Parallel reaction monitoring confirmed significant (p < 0.05) upregulation (> 1.5-fold change) of 23 proteins and downregulation (< 0.667-fold change) of 11. The mechanisms of DNA interstrand crosslinks; glutathione perturbation; mitogen-activated protein kinase; cyclooxygenase-2; and the Wnt and ErbB signaling pathways may contribute to VI through their roles in DNA damage, oxidative stress, inflammation, vascular dysfunction, endothelial dysfunction, vascular remodeling, coagulation cascade, and the newly determined signaling pathways. Moreover, the Wnt and ErbB signaling pathways were identified as new disease pathways involved in VI. Taken together, the elucidated underlying mechanisms may help broaden existing understanding of the molecular mechanisms of VI induced by CRA.

The role of microRNA-155 in glomerular endothelial cell injury induced by high glucose.

OBJECTIVE: To investigate the role of microRNA-155-5p on apoptosis and inflammatory response in human renal glomerular endothelial cells (HRGEC) cultured with high glucose. METHODS: The primary HRGEC were mainly studied, light microscopy was used to detect changes in cell morphology. Quantitative Real Time-Polymerase Chain Reaction, Western Blot, immunofluorescence were aimed to observe the mRNA and protein expression levels of target gene ETS-1, downstream factors VCAM-1, MCP-1 and cleaved caspase-3 in each group after high glucose treatment as well as transfection with miR-155 mimics or inhibitor. RESULTS: The expression of inflammatory factors and apoptosis of HRGEC cells increased under high glucose treatment. Compared with normal-glucose treatment, the expression of microRNA-155 markedly increased in HRGECs treated with high-glucose, as well as the mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3. Overexpression of microRNA-155 remarkably downregulated mRNA and protein levels of ETS-1, VCAM-1, MCP-1 and cleaved caspase-3, whereas miRNA-155 knockdown upregulated their levels. In addition, HRGEC cells were transfected with miR-155 mimics and ETS-1 siRNA with high glucose stimulation. The expression of ETS-1 was positively correlated with the expression of downstream factors VCAM-1 and MCP-1. These results suggest that ETS-1 can mediate endothelial cell inflammation by regulating VCAM-1 and MCP-1. CONCLUSION: MiR-155 can negatively regulate the expression of target gene ETS-1 and its downstream factors VCAM-1, MCP-1 and cleaved caspase-3, thus mediating the inflammatory response and apoptosis of HRGEC.

Alashanoids O-S, seco-Humulane and Eremophilane Sesquiterpenoids from Syringa pinnatifolia.

Five new sesquiterpenoids, alashanoids O-S (1-5), along with three known analogs (6-8) were isolated from the peeled stems of Syringa pinnatifolia. Their structures were elucidated by analysis of extensive spectroscopic data including ESI-MS, 1D, 2D NMR. The absolute configurations were determined by comparing its experimental and calculated electronic circular dichroism, calculated OR, calculated NMR, and single crystal X-ray diffraction data analysis. Compounds 1 and 2 belong to the seco-humulane type and possess a rare 13-membered oxygen heterocycle framework, and 3-5 belong to eremophilane-type. Compounds 1, 2, and 5 showed inhibitory effects against NO production in LPS-induced RAW264.7 macrophage cells with its IC50 values of 11.86±2.34, 72.08±7.72, and 69.22±15.29 µM, respectively, compared with the positive control indomethacin (IC50 =31.52 µM).

Single-Nanoparticle Coulometry Method with High Sensitivity and High Throughput to Study the Electrochemical Activity and Oscillation of Single Nanocatalysts.

To explore nanocatalysts with high electro-catalytic performance and less loading of precious metals, efforts have been made to develop electrochemical methods with high spatial resolution at the single nanoparticle level. Herein, a highly sensitive single-nanoparticle coulometry method is successfully developed to study the electrochemical activity and oscillation of single PtTe nanocatalysts. Based on microbattery reactions involving the formic acid electro-oxidation and the deposition of Ag on the single PtTe nanocatalyst surface, this method enables the transition from the undetectable sub-fA electric signal of the formic acid electro-oxidation into strong localized surface plasmon resonance scattering signal of Ag detected by dark-field microscopy. The lowest limiting current for a single nanocatalyst is found to be as low as 25.8 aA. Different trends of activity versus the formic acid concentration and types of activity of the single nanocatalyst have been discovered. Unveiled frequency-amplitude graph shows that the two electrochemical oscillation modes of low frequency with high amplitude and vice versa coexist in a single PtTe nanocatalyst, indicating the abundantly smooth surfaces and defects of nanocatalysts. This conducted study will open up the new avenue for further behavioral and mechanistic investigation of more types of nanocatalysts in the electrochemistry community.

Three Pairs of Enantiomeric Sesquiterpenoids from Syringa pinnatifolia.

Three pairs of enantiomeric sesquiterpenoids, (∓)-syringanoid A (1a and 1b) and (±)-pinnatanoids A (2a and 2b) and B (3a and 3b), that represent an unprecedented 5/4/6 tricyclic backbone and a rare 6/7 bicyclic backbone, respectively, were isolated from the peeled stems of Syringa pinnatifolia. The structures were elucidated by extensive spectroscopic analysis, single-crystal X-ray diffraction, a modified Mosher's method, and quantum chemical calculations. A plausible biotransformation pathway for 1-3 was proposed, and their cardiomyocyte-protective and anti-inflammatory activities were evaluated.

(+/-)-Alashanoid N, Two Enantiomeric Sesquiterpenes from Syringa pinnatifolia.

Two enantiomeric humulane sesquiterpenes, namely (+)-alashanoid N (1a) and (-)-alashanoid N (1b), along with two known analogs ((2R,3R,5R)-2,3-epoxy-6,9-humuladien-5-ol-8-one (2) and (2R,3S,5R)-2,3-epoxy-6,9-humuladien-5-ol-8-one (3)), were described from the peeled stems of a folk Mongolian herbal medicine Syringa pinnatifolia. Their structures were characterized based on UV, IR, NMR, and HR-ESI-MS data analyses, and the absolute configurations were determined by data analysis of X-ray diffraction and quantum chemical calculations. (+/-)-Alashanoid N showed inhibition against NO production in RAW 264.7 macrophage cells with IC50 values of 90.1 µM and 71.7 µM, and protective effect against oxygen-glucose deprivation injury to H9c2 cells at a concentration of 20 µM and 5 µM, respectively.

[Effect of total phenolic part of Rhus chinensis against myocardial ischemia in mice].

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.

[Network pharmacology study of Tibetan medicine Corydalis Herba against acute myocardial ischemia].

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.

lncRNA LIFR-AS1 suppresses invasion and metastasis of non-small cell lung cancer via the miR-942-5p/ZNF471 axis.

BACKGROUND: MicroRNA 942-5p (miR-942-5p) has been reported to promote migration and invasion in non-small cell lung cancer (NSCLC), but the underlying mechanism is not completely understood. The interplay between long non-coding RNAs (lncRNAs) and miRNAs plays a crucial role in tumor progression. METHODS: In the present study, we performed bioinformatic and biochemical analyses to identify miR-942-5p-interacting lncRNAs. The function and clinical significance of the candidate lncRNA(s) in NSCLC were determined. RESULTS: We identified LIFR-AS1 as a pivotal miR-942-5p-interacting lncRNA. Overexpression of miR-942-5p caused a reduction of LIFR-AS1 in NSCLC cells. LIFR-AS1 showed the ability to sponge miR-942-5p, leading to derepression of ZNF471. Functionally, LIFR-AS1 overexpression inhibited NSCLC cell migration and invasion, whereas LIFR-AS1 silencing yielded an opposite effect. In vivo studies confirmed that LIFR-AS1 overexpression suppressed lung metastasis of NSCLC cells. Rescue experiments demonstrated that enforced expression of miR-942-5p or depletion of ZNF471 restored the migration and invasion capacity of LIFR-AS1-overexpressing cells. Moreover, overexpression of ZNF471 restrained NSCLC cell invasion. Clinically, LIFR-AS1 downregulation was significantly correlated with TNM stage, lymph node metastasis, and reduced overall survival in NSCLC patients. CONCLUSIONS: we provide first evidence for the involvement of the LIFR-AS1/miR-942-5p/ZNF471 axis in NSCLC invasion and metastasis. LIFR-AS1 may represent a novel target for the treatment of NSCLC.

The Evi5 oncogene promotes laryngeal cancer cells proliferation by stabilizing c-Myc protein.

BACKGROUND: The Ecotropic viral integration site 5 (Evi5) is recognized as a potential oncogene and a cell cycle regulator. Evi5 regulates the abundance of Emi1, an inhibitor of the anaphase-promoting complex/cyclosome, to govern mitotic fidelity. Evi5 has been shown to be dysregulated in several cancer types. However, the expression and biological function of Evi5 in human laryngeal squamous cell carcinoma (LSCC) are still unknown. METHODS: Clustered regularly interspaced short palindromic repeats (CRISPR)-based gene editing was used to generate Evi5 knockout (KO) LSCC cells. The proliferation and cell cycle distribution of LSCC cells was determined. The effect of Evi5 on LSCC tumor growth in vivo was studied in a tumor xenograft model in mice. The interaction between Evi5 and c-Myc was detected by immunoprecipitation (IP) assay. Luciferase assay was used to determine the transcriptional activity of c-Myc. RESULTS: Here, we show that Evi5 controls LSCC tumorigenesis via the stabilization of c-MYC oncogene. CRISPR-mediated knockout (KO) of Evi5 decreased the proliferation and decreased colony formation ability of LSCC cells. Knockout of Evi5 caused increased G1 phase and decreased S phase cells. In the tumor-bearing nude mice, The transplanted tumors originated from Evi5-KO TU212 cells were significantly decreased when compared with control TU212 cells. At the molecular level, we found that Evi5 interacted with c-MYC and Evi5 antagonized E3 ligase FBXW7-mediated ubiquitination and degradation of c-Myc protein, and promoted c-Myc-dependent transactivation. CONCLUSION: Given the critical role of c-Myc in tumorigenesis, our data suggest that Evi5 is a potential therapeutic target in LSCC, and inhibition of Evi5 should be a prospective strategy for LSCC therapy.

Identifying risk factors for chronic kidney disease stage 3 in adults with acquired solitary kidney from unilateral nephrectomy: a retrospective cohort study.

BACKGROUND: We aimed to examine the risk factors for chronic kidney disease (CKD) stage 3 among adults with ASK from unilateral nephrectomy. METHODS: We retrospectively collected data from adult patients with ASK between January, 2009 and January, 2019, identified from a tertiary hospital in China. The clinical data were compared between patients who developed CKD stage 3 and those who did not develop CKD stage 3 during follow-up. RESULTS: In total, 172 patients with ASK (110 men; median 58.0 years) were enrolled, with a median follow-up duration of 5.0 years. During follow-up, 91 (52.9%) and 24 (14.0%) patients developed CKD stage 3 and end-stage renal disease, respectively. Multiple regression analyses showed that age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.039-1.115, p < 0.001), diabetes (OR 4.401, 95% CI 1.693-11.44, p = 0.002), hyperuricemia (OR 2.733, 95% CI 1.104-6.764, p = 0.03), a history of cardiovascular disease (CVD) (OR 5.583, 95% CI 1.884-18.068, p = 0.002), and ASK due to renal tuberculosis (OR 8.816, 95% CI 2.92-26.62, p < 0.001) were independent risk factors for developing CKD stage 3 among patients with ASK. CONCLUSIONS: Regular follow-up of renal function is needed among adult patients with ASK. Optimal management of diabetes, hyperuricemia, and CVD may reduce their risk of CKD stage 3, especially among those that undergo unilateral nephrectomy for renal tuberculosis.

Alashanoids K-M, bioactive eremophilane sesquiterpenoids from Syringa pinnatifolia.

Three new eremophilane-type sesquiterpenoids, alashanoids K-M (1-3), and one known analogue (4) were isolated from the peeled stems of Syringa pinnatifolia. All the compounds were isolated from the genus Syringa for the first time. Structures of these compounds were established using 1D and 2D NMR and MS data. The absolute configurations were determined by experimental and calculated electronic circular dichroism analysis, a modification of Mosher's method, and X-ray diffraction. Compounds 2 and 3 inhibited NO production in LPS-induced RAW264.7 macrophage cells with IC50 values of 14.23 and 12.20 µM, respectively, and showed cytotoxic activities against HepG2 cells with the IC50 values of 34.41 and 40.86 µM, respectively.

[Advances on network pharmacology in ethnomedicine research].

Ethnomedicine is the precious wealth left by ethnic minorities in their struggle against diseases. It is similar to traditional Chinese medicine in a narrow sense and has the characteristics of multi-component,multi-target and multi-channel synergy. Under the guidance of the theory of ethnomedicine,the combination of ethnomedicine and network pharmacology will help to understand the essence of the prevention and treatment of ethnomedicines in a dynamic and holistic manner. This paper reviews the research progress of network pharmacology applied in ethnomedicine,analyses the problems and challenges existing in the application of network pharmacology in ethnomedicine research at present,such as inaccurate data and information,lack of network analysis platform for effective analysis of dose-effect relationship of chemical constituents and weak basic research of ethnomedicine,and puts forward corresponding prospects.

Nanobubbles: An Effective Way to Study Gas-Generating Catalysis on a Single Nanoparticle.

Gas-generating catalysis is important to many energy-related research fields, such as photocatalytic water splitting, water electrolysis, etc. The technique of single-nanoparticle catalysis is an effective way to search for highly active nanocatalysts and elucidate the reaction mechanism. However, gas-generating catalysis remains difficult to investigate at the single-nanoparticle level because product gases, such as H2 and O2, are difficult to detect on an individual nanoparticle. Here, we successfully find that nanobubbles can be used to study the gas-generating catalysis, i.e., H2 generation from formic acid dehydrogenation on a single Pd-Ag nanoplate, with a high time resolution (50 ms) via dark-field microscopy. The research reveals that the nanobubble evolution process includes nucleation time and lifetime. The nucleation rate of nanobubbles is proportional to the catalytic activity of a single nanocatalyst. The relationship between the catalytic activity and the nucleation rate is quantitatively described by a mathematical model, which shows that an onset reaction rate (ronset) exists for the generation of nanobubbles on a single Pd-Ag nanoplate. The research also reveals that a Pd-Ag nanoplate with larger size usually has a higher activity. However, some large-sized ones still have low activities, indicating the size of the Pd-Ag nanoplate is not the only key factor for the activity. Notablely, further research shows that Pd content is the key factor for the activity of single Pd-Ag nanoplates with similar size. The methodology and knowledge acquired from this research are also applicable to other important gas-generating catalysis reactions at the single-nanoparticle level.

Massively Screening the Temporal Spectra of Single Nanoparticles to Uncover the Mechanism of Nanosynthesis.

Nanosynthesis is the basis of nanotechnology and its applications. It is necessary to understand the growth mechanism of nanoparticles and the functions of growth factors. An effective way to study the synthesis is at the single nanoparticle level. This study reports a single nanoparticle spectrometer, which is based on a commercial dark-field microscopy and a group of narrowband filters. This spectrometer has many advantages, such as high light transparency (35%-75%), low cost (<$1500), massive screening (≈200 nanoplates at a time), and a high time resolution (<5 s). By using this spectrometer, the galvanic replacement reaction (GRR) is studied on single Ag nanoplates in situ and in real time. The research reveals that GRR on single Ag nanoplates has three different types according to the change of peak wavelength during reaction. Such diverse reaction types can be attributed to the different relative reaction rates of GRR on the faces and edges of Ag nanoplate with different facets. Further research shows that the relative reaction rates of different facets vary a lot under different concentrations of tri-sodium citrate. This research successfully demonstrates that the new single nanoparticle spectrometer can study the growth of single nanoparticles and the effect of growth factors.

Fractional transfer of a free unpaired electron to overcome energy barriers in the formation of Fe(4+) from Fe(3+) during the core contraction of macrocycles: implication for heme distortion.

The free unpaired electron in Fe(3+) ions cannot be directly removed, and needs a transfer pathway with at least four steps to overcome the high energy barriers to form Fe(4+) ions. Fine changes in the electronic structure of Fe(3+) ions on spin conversion were identified through a deeper analysis of the diffraction, spectral and electrochemical data for six non-planar iron porphyrins. Fe(3+) ions can form four d electron tautomers as the compression of the central ion is increased. This indicates that the Fe(3+) ion undergoes a multistep electron transfer where the total energy gap of electron transfer is split into several smaller gaps to form high-valent Fe(4+) ions. We find that the interchange of these four electron tautomers is clearly related to the core size of the macrocycle in the current series. The large energy barrier to produce iron(iv) complexes is overcome through a gradient effect of multiple energy levels. In addition, a possible porphyrin Fe(3+)˙ radical may be formed from its stable isoelectronic form, porphyrin Fe(3+), under strong core contraction. These results indicate the important role of heme distortion in its catalytic oxidation functions.

Differential proteome analysis of the cell differentiation regulated by BCC, CRH, CXCR4, GnRH, GPCR, IL1 signaling pathways in Chinese fire-bellied newt limb regeneration.

Following amputation, the newt has the remarkable ability to regenerate its limb, and this process involves dedifferentiation, proliferation and differentiation. To investigate the potential proteome during a dynamic network of Chinese fire-bellied newt limb regeneration (CNLR), two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrum (MS) were applied to examine changes in the proteome that occurred at 11 time points after amputation. Meanwhile, several proteins were selected to validate their expression levels by Western blot. The results revealed that 1476 proteins had significantly changed as compared to the control group. Gene Ontology annotation and protein network analysis by Ingenuity Pathway Analysis 9.0 (IPA) software suggested that the differentially expressed proteins were involved in 33 kinds of physiological activities including signal transduction, cell proliferation, cell differentiation, etc. Among these proteins, 407 proteins participated in cell differentiation with 212 proteins in the differentiation of skin cell, myocyte, neurocyte, chondrocyte and osteocyte, and 37 proteins participated in signaling pathways of BCC, CRH, CXCR4, GnRH, GPCR and IL1 which regulated cell differentiation and redifferentiation. On the other hand, the signal transduction activity and cell differentiation activity were analyzed by IPA based on the changes in the expression of these proteins. The results showed that BCC, CRH, CXCR4, GnRH, GPCR and IL1 signaling pathways played an important role in regulating the differentiation of skin cell, myocyte, neurocyte, chondrocyte and osteocyte during CNLR.