Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

Introduction: Early diagnosis of Parkinson's disease (PD) remains challenging. It has been suggested that abnormal brain iron metabolism leads to excessive iron accumulation in PD, although the mechanism of iron deposition is not yet fully understood. Ferritin and transferrin receptor (TfR) are involved in iron metabolism, and the exosome pathway is one mechanism by which ferritin is transported and regulated. While the blood of healthy animals contains a plentiful supply of TfR-positive exosomes, no studies have examined ferritin and TfR in plasma neural-derived exosomes. Methods: Plasma exosomes were obtained from 43 patients with PD and 34 healthy controls. Neural-derived exosomes were isolated with anti-human L1CAM antibody immunoabsorption. Transmission electron microscopy and western blotting were used to identify the exosomes. ELISAs were used to quantify ferritin and TfR levels in plasma neural-derived exosomes of patients with PD and controls. Receivers operating characteristic (ROC) curves were applied to map the diagnostic accuracy of ferritin and TfR. Independent predictors of the disease were identified using logistic regression models. Results: Neural-derived exosomes exhibited the typical exosomal morphology and expressed the specific exosome marker CD63. Ferritin and TfR levels in plasma neural-derived exosomes were significantly higher in patients with PD than controls (406.46 ± 241.86 vs. 245.62 ± 165.47 ng/µg, P = 0.001 and 1728.94 ± 766.71 vs. 1153.92 ± 539.30 ng/µg, P < 0.001, respectively). There were significant positive correlations between ferritin and TfR levels in plasma neural-derived exosomes in control group, PD group and all the individuals (rs = 0.744, 0.700, and 0.752, respectively). The level of TfR was independently associated with the disease (adjusted odds ratio 1.002; 95% CI 1.000-1.003). ROC performances of ferritin, TfR, and their combination were moderate (0.730, 0.812, and 0.808, respectively). However, no relationship was found between the biomarkers and disease progression. Conclusion: It is hypothesized that ferritin and TfR in plasma neural-derived exosomes may be potential biomarkers for PD, and that they may participate in the mechanism of excessive iron deposition in PD.

Corrigendum: Evaluation of ferritin and TfR level in plasma neural-derived exosomes as potential markers of Parkinson's disease.

[This corrects the article DOI: 10.3389/fnagi.2023.1216905.].

Complete Genome Sequence of Ralstonia syzygii subsp. indonesiensis Strain LLRS-1, Isolated from Wilted Tobacco in China.

Here, we present the complete genome sequence and annotation of Ralstonia syzygii subsp. indonesiensis strain LLRS-1, which caused bacterial wilt on flue-cured tobacco in Yunnan Province, southwest China. Strain LLRS-1 is the first R. syzygii strain identified to be pathogenic to tobacco in China. The completely assembled genome of strain LLRS-1 consists of a 3,648,314-bp circular chromosome and a 2,046,405-bp megaplasmid with 5,190 protein-coding genes, 55 transfer RNAs, 28 small RNAs, 3 structural RNAs (5S, 16S, and 23S), and a G+C content of 67.05%.

Midkine Inhibits Cholesterol Efflux by Decreasing ATP-Binding Membrane Cassette Transport Protein A1 via Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling in Macrophages.

BACKGROUND: Midkine (MK), a heparin-binding protein, participates in multiple cellular processes, such as immunity, cellular growth and apoptosis. Overwhelming evidence indicates that MK plays an important role in various pathological processes, including chronic inflammation, autoimmunity, cancer, and infection. Recent studies demonstrated that MK may be involved in the development of atherosclerosis, yet the mechanism has not been fully explored. Therefore, this study aims to investigate the effect and mechanism of MK on macrophage cholesterol efflux.Methods and Results:Using Oil Red O staining, NBD-cholesterol fluorescence labeling and enzymatic methods, it observed that MK markedly promoted macrophage lipid accumulation. Liquid scintillation counting (LSC) showed that MK decreased cholesterol efflux. Moreover, cell immunofluorescence, western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) showed that MK downregulated ATP-binding membrane cassette transport protein A1 (ABCA1) expression. Functional promotion of ABCA1 expression attenuated the inhibitory effects of MK on cholesterol efflux, which reduced lipid accumulation. Additionally, intervention of adenosine monophosphate activated protein (AMPK)-mammalian target of rapamycin (mTOR) signaling molecule by the AMPK activator, AICAR, increased p-AMPK and ABCA1 expression, decreased p-mTOR expression and promoted cholesterol efflux, resulting in an obvious reduction in intracellular lipid content. CONCLUSIONS: These data suggest that MK reduces the expression of ABCA1, inhibits the efflux of cholesterol and promotes the accumulation of lipids in RAW264.7 macrophages, and AMPK-mTOR signaling is involved in MK-mediated regulation of cholesterol metabolism in RAW264.7 macrophages.

[Effect of Electroacupuncture on Ultrastructure of Oligodendrocytes and Expression of the Related Marker Proteins in the Marginal Zone of Cerebral Ischemia Locus in Rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) on changes of ultrastructure of oligodendrocytes in the marginal zone of the cerebral ischemia (CI) locus in rats with cerebral infarction so as to reveal its mechanism underlying improving ischemic cerebral diseases. METHODS: Ninety male SD rats were randomized into sham operation, model and electroacupuncture (EA) groups which were further divided into five subgroups: 1 h, 1 d, 3 d, 7 d, and 21 d after CI (n = 6 in each subgroup). The CI model was established by occlusion of the middle cerebral artery. EA (1 - 3 mA) was applied to "Baihui" (GV 20) and "Dazhui" (GV 14) for 30 min, once a day for 1 h, 1 d, 3 d, 7 d and 21 d, respectively. The ultrastructural changes of oligodendrocytes in the marginal zone of the ischemic cerebral tissue were observed by transmission electron microscope. The immunoactivity levels of A2B5, O4 and 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase) for labeling the oligodendrocyte precursor cells, immature oligodendrocytes, and mature oligodendrocytes respectively were detected by immunohistochemistry. RESULTS: The oligodendrocytes were swelling in structure and increased in number after cerebral ischemia. Compared with the model group, the degree of swelling of oligodendrocytes was obviously decreased and new oligodendrocyte proliferation was found in the EA group. In comparison with the sham group, the immunoactivity levels of cerebral A2B5 and CNPase proteins on day 3 and 7 were significantly higher in the model group (P<0. 05), while those of O4 on day 1, 3, 7 and 21 were obviously lower in the model group (P<0. 01). Following EA intervention, the immunoactivity levels of cerebral A2B5, O4 and CNPase proteins were significantly up-regulated in the EA group in comparison with the model group (P<0. 0 1 , P<0. 05). CONCLUSION: EA intervention may reduce the structural damage of oligodendrocytes in CI rats, which may be associated with its effects in promoting the expression of cerebral A2B5, O4 and CNPase proteins, suggesting an involvement of glial cells in the protective effect of EA.

Retrieval and analysis of atmospheric XCO2 using ground-based spectral observation.

Atmospheric CO2 column concentration (column-averaged dry air mole fractions of atmospheric carbon dioxide) data obtained by ground-based hyperspectral observation is an important source of data for the verification and improvement of the results of CO2 retrieval based on satellite hyperspectral observation. However, few studies have been conducted on atmospheric CO2 column concentration retrieval based on ground-based spectral hyperspectral observation in China. In the present study, we carried out the ground-based hyperspectral observation in Xilingol Grassland, Inner Mongolia of China by using an observation system which is consisted of an optical spectral analyzer, a sun tracker, and some other elements. The atmospheric CO2 column concentration was retrieved using the observed hyperspectral data. The effect of a wavelength shift of the observation spectra and the meteorological parameters on the retrieval precision of the atmospheric CO2 concentration was evaluated and analyzed. The results show that the mean value of atmospheric CO2 concentration was 390.9 microg x mL(-1) in the study area during the observing period from July to September. The shift of wavelength in the range between -0.012 and 0.042 nm will generally lead to 1 microg x mL(-1) deviation in the CO2 retrievals. This study also revealed that the spectral transmittance was sensitive to meteorological parameters in the wavelength range of 6 357-6 358, 6 360-6 361, and 6 363-6 364 cm(-1). By comparing the CO2 retrievals derived from the meteorological parameters observed in synchronous and non-synchronous time, respectively, with the spectral observation, it was showed that the concentration deviation caused by using the non-synchronously observed meteorological parameters is ranged from 0.11 to 4 microg x mL(-1). These results can be used as references for the further improvement of retrieving CO2 column concentration based on spectral observation.

A new sesquiterpene from endophytic fungus Aspergillus sp.

A fungal strain named YLF-14 was isolated from the leaf of Altingia yunnunensis. Based on the sequence at the internal transcribed spacer (ITS) region, the strain was identified as an Aspergillus sp.. A new sesquiterpene 5ß,8aß-dimethyl-3,4,4aß,5,6,7,8,8a-octahydronaphthalene-1,2,5α-trimethanol (1) and a known compound 12-N-methylcyclo-(L-tryptophyl-L-phenylalanyl) (2) were isolated from the culture of this strain. Bioassay experiments showed that the two compounds had no obvious effect on the growth of tested bacteria and nematodes.

[A new type of iridium (III) phenylpyrazole complexes: synthesis, photophysical characterization].

New heteroleptic iridium(III) complexes (ppz)2Ir(LX), which consist of two cyclometalated ligands ppz(1-phenylpyrazole) together with an ancillary ligand LX (LX= 2-(2'-hydroxylphenyl)benzothiazole (BTZ), 2-(3'-methyl-2'-hydroxylphenyl) benzothiazole (3-MeBTZ), 2-(4'-methyl-2'-hydroxylphenyl) benzothiazole (4-MeBTZ) and 2-(4'-Trifluoromethyl-2'hydroxylphenyl) benzothiazole (4-tfmBTZ)), were synthesized and characterized. The molecular structures and photophysical properties were characterized and analyzed comparatively. The results show that the four complexes have basically similar UV-Vis absorption spectra, fluorescence excitation and emission spectra. Their maximum emission peaks are located at 583-615 nm, and accompanied by a lower intensity emission band around 400 nm. The weak emissions around 400 nm are ascribed to the radi ation transition of single state excition from ancillary ligand BTZ perturbed by metallic ion, and light emission around long-wave-length to the radiation transition of 3MLCT of Ir(BTZ) fragment. While the triplet state 3 MLCT of Ir(ppz)2 fragment might be quenched at room temperature. For all complexes, the excitations with maximum efficiency are located at 250-310 nm, which indicates that main contributor to light emitting is ligand-centered absorption (1pi-pi*) of ppz and BTZ rather than 3MLCT transitions, and thus provides a striking evidence that there is intersystem crossing from 1pi-pi* state to 3MLCT state in these complexes. Compared with Ir(ppz)3, these complexes not only have stronger phosphorescence at room temperature but also their emission color can be tuned by modifying ancillary ligand.

[Nonlinear finite element analysis for compression behavior of intravascular stents].

The implantation of intravascular stents has become a new method to cure stenosis in arteries with its low injury and high efficiency. The mechanical behavior of the stents is studied by the finite element method. The compression behavior is simulated with stent models of different sizes and geometry structures whose material is cobalt-chromium alloy. Experiments are also carried out to verify the simulation method, which shows that the finite element model can substitute the stent to some extent in which its mechanical behavior is studied. The results show that the reaction stress of the stent increases with the thickness of the strut. Besides, the smaller metal surface area ratio will result in a smaller elongation ratio. All these are helpful and instructive to the proper designs and actual operation of intravascular stents.

[Prokaryotic expression of an antigen gene of Trichinella spiralis and identification of the recombinant protein].

OBJECTIVE: To obtain the recombinant protein of an antigen gene Ts88 of Trichinella spiralis and identify the characteristics of the recombinant protein. METHODS: Ts88 cDNA obtained by immunoscreening the cDNA library of adult T. spiralis was subcloned into the pET-28c(+) expression vector and expressed in E. coli. Mice were immunized with the fusion protein incorporated into Freund' s adjuvant and the immune sera were collected. The titers of the Ts88 immune sera and the antigenicity of the recombinant protein were detected by ELISA and Western blotting. Immuno-fluorescence test was performed in order to confirm the distribution of Ts88 protein in the worm. RESULTS: The fragment of Ts88 gene was expressed successfully in E. coli and a highly purified fusion protein was obtained. Immunization with the recombinant protein in mice produced high titers of antibodies, which recognized some components of native antigens of soluble proteins from adult worm of T. spiralis. Western blotting analysis showed that Ts88 recombinant antigen was recognized by all the positive sera, such as the sera from infected or immunized rabbits, from infected swine and from patients of trichinosis. Immuno-fluorescence test confirmed that Ts88 protein mainly distributed in the cuticle surface of the worm. CONCLUSION: The Ts88 antigen gene from T. spiralis was successfully expressed. The recombinant protein presented antigenicity.