Mouse serum albumin induces neuronal apoptosis and tauopathies.

The elderly frequently present impaired blood-brain barrier which is closely associated with various neurodegenerative diseases. However, how the albumin, the most abundant protein in the plasma, leaking through the disrupted BBB, contributes to the neuropathology remains poorly understood. We here demonstrated that mouse serum albumin-activated microglia induced astrocytes to A1 phenotype to remarkably increase levels of Elovl1, an astrocytic synthase for very long-chain saturated fatty acids, significantly promoting VLSFAs secretion and causing neuronal lippoapoptosis through endoplasmic reticulum stress response pathway. Moreover, MSA-activated microglia triggered remarkable tau phosphorylation at multiple sites through NLRP3 inflammasome pathway. Intracerebroventricular injection of MSA into the brains of C57BL/6J mice to a similar concentration as in patient brains induced neuronal apoptosis, neuroinflammation, increased tau phosphorylation, and decreased the spatial learning and memory abilities, while Elovl1 knockdown significantly prevented the deleterious effect of MSA. Overall, our study here revealed that MSA induced tau phosphorylation and neuron apoptosis based on MSA-activated microglia and astrocytes, respectively, showing the critical roles of MSA in initiating the occurrence of tauopathies and cognitive decline, and providing potential therapeutic targets for MSA-induced neuropathology in multiple neurodegenerative disorders.

Thrombomodulin reduces α-synuclein generation and ameliorates neuropathology in a mouse model of Parkinson's disease.

The neurotoxic α-synuclein (α-syn) oligomers play an important role in the occurrence and development of Parkinson's disease (PD), but the factors affecting α-syn generation and neurotoxicity remain unclear. We here first found that thrombomodulin (TM) significantly decreased in the plasma of PD patients and brains of A53T α-syn mice, and the increased TM in primary neurons reduced α-syn generation by inhibiting transcription factor p-c-jun production through Erk1/2 signaling pathway. Moreover, TM decreased α-syn neurotoxicity by reducing the levels of oxidative stress and inhibiting PAR1-p53-Bax signaling pathway. In contrast, TM downregulation increased the expression and neurotoxicity of α-syn in primary neurons. When TM plasmids were specifically delivered to neurons in the brains of A53T α-syn mice by adeno-associated virus (AAV), TM significantly reduced α-syn expression and deposition, and ameliorated the neuronal apoptosis, oxidative stress, gliosis and motor deficits in the mouse models, whereas TM knockdown exacerbated these neuropathology and motor dysfunction. Our present findings demonstrate that TM plays a neuroprotective role in PD pathology and symptoms, and it could be a novel therapeutic target in efforts to combat PD. Schematic representation of signaling pathways of TM involved in the expression and neurotoxicity of α-syn. A TM decreased RAGE, and resulting in the lowered production of p-Erk1/2 and p-c-Jun, and finally reduce α-syn generation. α-syn oligomers which formed from monomers increase the expression of p-p38, p53, C-caspase9, C-caspase3 and Bax, decrease the level of Bcl-2, cause mitochondrial damage and lead to oxidative stress, thus inducing neuronal apoptosis. TM can reduce intracellular oxidative stress and inhibit p53-Bax signaling by activating APC and PAR-1. B The binding of α-syn oligomers to TLR4 may induce the expression of IL-1ß, which is subsequently secreted into the extracellular space. This secreted IL-1ß then binds to its receptor, prompting p65 to translocate from the cytoplasm into the nucleus. This translocation downregulates the expression of KLF2, ultimately leading to the suppression of TM expression. By Figdraw.

Construction of ecological network based on MSPA-Conefor-MCR at the county scale: A case study in Yanqing District, Beijing, China.

The acceleration of urbanization and the frequent occurrence of natural disasters have led to increasingly fragmented habitats and decreased ecological connectivity, which in turn hinder rural sustainable development. Constructing ecological networks is a key direction in the spatial planning. By strengthening source protection, corridor construction, and ecological control, it can effectively alleviate the contradiction between regional ecological and economic development imbalance and promote biodiversity enhancement. With Yanqing District as an example, we constructed the ecological network by means of the morphological spatial pattern analysis, the connectivity analysis software, and the minimum cumulative resistance model. We analyzed various network elements from a county perspective, and provide suggestions for the development of towns. The results showed that the ecological network of Yanqing District as a whole presented the distribution characteristics of "the Mountain and the Plain". A total of 12 ecological sources were identified, covering an area of 1085.54 km2, accounting for 54.4% of the total area. 66 ecological corridors were screened with a total length of 1057.18 km, including 21 important corridors and 45 general corridors, with the length of which accounting for 32.6% and 67.4%, respectively. 27 first-class ecological nodes and 86 second-class ecological nodes were identified, which were concentrated in "the Mountain" such as Qianjiadian and Zhenzhuquan. The distribution of ecological networks in different towns was closely related to their geographical environment and development orientation. The towns such as Qianjiadian and Zhenzhuquan were located in "the Mountain", covering a wide range of ecological sources and corridors. Strengthening protection of ecological source was the focus of network construction, which can promote the coordinated development of ecology and tourism in towns. The towns such as Liubinbao and Zhangshanying were located at the junction of "the Mountain-Plain", hence strengthening corridor connectivity was the main direction of network construction, which could promote the construction of ecological landscape in towns. The towns such as Yanqing and Kangzhuang were located in the "the Plain", with serious landscape fragmentation due to the lack of ecological sources and corridors. Those towns need to build green livable towns through increasing ecological nodes and strengthening ecological restoration. This study enriched the construction of ecological networks at the county scale, explored the interface with spatial planning, strengthened ecological restoration and ecological control, which had reference value for promoting the sustainable development of towns and the construction of a multi-scale ecological network.

Comparison of effects of aminosalicylic acid, glucocorticoids and immunosuppressive agents on the expression of multidrug-resistant genes in ulcerative colitis.

To compare the effects of aminosalicylic acid, glucocorticoids and immunosuppressants on the expression levels of multidrug resistance genes in patients with ulcerative colitis (UC), with the aim of providing a theoretical and therapeutic basis for the diagnosis, treatment, and prevention of UC. Fresh colonic mucosal tissues or postoperative pathological biopsies from 148 UC patients were collected, and the distribution sites and morphology of P-glycoprotein (P-gp) were detected using immunohistochemical staining. RT-PCR was used to quantify the expression levels of multidrug resistance gene (MDR1) mRNA before and after the corresponding treatment, and the effects of aminosalicylic acid, glucocorticoids and immunosuppressive drugs on P-gp were compared. In addition, the effects of the three drugs on MDR1 mRNA were analyzed. Administration of 5-aminosalicylic acid (5-ASA) drugs did not correlate with MDR1 expression in UC, whereas administration of glucocorticoids and immunosuppressive drugs was positively correlated with MDR1 expression profile. The expression levels of MDR1 mRNA and its product P-gp were significantly upregulated in patients who did not respond to glucocorticoids and immunosuppressive drugs. 5-ASA had no effect on the expression levels of MDR1 and its product P-gp in patients with a confirmed diagnosis of UC. However, the use of glucocorticoids and immunosuppressants can increase the expression level of MDR1.

Frequency controlled beam scanning characteristic realized using a compact slow wave transmission line.

To simplify the design of a beam scanning device, we present a simple and compact structure to realize the frequency scanning characteristic based on a hybrid waveguide consisting of a spoof surface plasmon polariton (SSPP) transmission line and half-mode substrate integrated waveguide (HMSIW). Additionally, the radiation characteristic is implemented using periodically modulated slots. The scanning angle range covers backward to forward directions without an open stop band at the broadside. The results from both simulations and measurements show that the total scanning angle reaches 117° for a frequency range of 9-11.4 GHz. Owing to the inherent features of the HMSIW and the unique design of the SSPP transmission line, the entire structure is only 139.2mm×15mm in size. Moreover, the average gain is approximately 6.5 dBi. Overall, the compact size and good performance ensure that the proposed design is favorable for planar integrated communication systems.

Efficient conversion from spoof surface plasmon polaritons to radiation mode.

A direct conversion from spoof surface plasmon polaritons (SSPPs) to radiation mode is proposed. A modified parallel two-wire SSPP transmission line is the key to the conversion, which is composed of traditional unit cells with slots among them. Taking advantages of the slots, the phase velocity of electromagnetic waves is larger than that of light, leading to the radiation. Both simulated and measured results show that the radiation occurs from 7.6 to 11 GHz, and the radiation angle keeps nearly stable in the whole operating frequency band, which can be predicted by theoretical calculation. The average gain and efficiency is 6.41 dBi and around 90%, respectively. The simple structure with flexibly tunable operating frequency makes the proposed design promising in planar integrated communication systems.

The Role of α-Synuclein Oligomers in Parkinson's Disease.

α-synuclein (α-syn) is a protein associated with the pathogenesis of Parkinson's disease (PD), the second most common neurodegeneration disease with no effective treatment. However, how α-syn drives the pathology of PD remains elusive. Recent studies suggest that α-syn oligomers are the primary cause of neurotoxicity and play a critical role in PD. In this review, we discuss the process of α-syn oligomers formation and the current understanding of the structures of oligomers. We also describe seed and propagation effects of oligomeric forms of α-syn. Then, we summarize the mechanism by which α-syn oligomers exert neurotoxicity and promote neurodegeneration, including mitochondrial dysfunction, endoplasmic reticulum stress, proteostasis dysregulation, synaptic impairment, cell apoptosis and neuroinflammation. Finally, we investigate treatment regimens targeting α-syn oligomers at present. Further research is needed to understand the structure and toxicity mechanism of different types of oligomers, so as to provide theoretical basis for the treatment of PD.

Coronary embolism causing acute inferior wall and ventricular myocardial infarction in a patient with rheumatic valvular heart disease: treatment with thrombus aspiration.

An elderly man with rheumatic valvular heart disease and atrial fibrillation presented with acute myocardial infarction. A coronary angiogram revealed complete occlusion of the right coronary artery (RCA), and we therefore considered that a thrombus might have obstructed the ostium of the RCA. We used a guiding catheter and the syringe of an aspiration device to remove two large dark red thrombi. A subsequent angiogram revealed that blood flow through the RCA had recovered, and the endomembrane of the RCA was smooth, with no evidence of stenosis or residual thrombus. In this case, thrombus aspiration via a guiding catheter was efficacious for treating this type of coronary embolism.

The proto-oncogene c-src is involved in primordial follicle activation through the PI3K, PKC and MAPK signaling pathways.

BACKGROUND: C-src is an evolutionarily conserved proto-oncogene that regulates cell proliferation, differentiation and apoptosis. In our previous studies, we have reported that another proto-oncogene, c-erbB2, plays an important role in primordial follicle activation and development. We also found that c-src was expressed in mammalian ovaries, but its functions in primordial follicle activation remain unclear. The objective of this study is to investigate the role and mechanism of c-src during the growth of primordial follicles. METHODS: Ovaries from 2-day-old rats were cultured in vitro for 8 days. Three c-src-targeting and one negative control siRNA were designed and used in the present study. PCR, Western blotting and primordial follicle development were assessed for the silencing efficiency of the lentivirus c-src siRNA and its effect on primordial follicle onset. The expression of c-src mRNA and protein in primordial follicle growth were examined using the PCR method and immunohistochemical staining. Furthermore, the MAPK inhibitor PD98059, the PKC inhibitor Calphostin and the PI3K inhibitor LY294002 were used to explore the possible signaling pathways of c-src in primordial folliculogenesis. RESULTS: The results showed that Src protein was distributed in the ooplasmic membrane and the granulosa cell membrane in the primordial follicles, and c-src expression level increased with the growth of primordial follicle. The c-src -targeting lentivirus siRNAs had a silencing effect on c-src mRNA and protein expression. Eight days after transfection of rat ovaries with c-src siRNA, the GFP fluorescence in frozen ovarian sections was clearly discernible under a fluorescence microscope, and its relative expression level was 5-fold higher than that in the control group. Furthermore, the c-src-targeting lentivirus siRNAs lowered its relative expression level 1.96 times. We also found that the development of cultured primordial follicles was completely arrested after c-src siRNA knockdown of c-src expression. Furthermore, our studies demonstrated that folliculogenesis onset was inhibited by Calphostin, PD98059 or LY294002 treatment,but none of them down-regulated c-src expression. In contrast, the expression levels of p-PKC, p-ERK1/2 and p-PI3K in the follicles were clearly decreased by c-src siRNA transfection. Correspondingly, both Calphostin and LY294002 treatment resulted in a decrease in the p-PKC level in follicles, but no change was observed in the PD98059 group. Finally, LY294002 treatment decreased the p-PI3K expression level in the follicles, but no changes were observed in the PD98059 and Calphostin groups. CONCLUSIONS: C-src plays an important role in regulating primordial follicle activation and growth via the PI3K-PKC- ERK1/2 pathway.

[Preliminary study about the role of c-src in the initiation of primordial follicle in rat ovary].

OBJECTIVE: To explore the role of c-src on the initiation of primordial follicles. METHODS: 2-days-old female SD rats' ovaries were cultured in Waymouth culture system and were used HE staining and immunohistochemy to observe the number of follicles after 0, 4, 8 days cultured. Use chemically synthesized small interference RNA (siRNA) transfected into ovarian tissue in cultured for RNA interference, and use HE staining and RT-PCR to detect the best siRNA and packaging it by lentiviruses to test the interference effect. RESULTS: With the increase of culturing days, the nummber of the primordial follicles in ovarian gradually reduced. We packed the best siRNA by lentiviruses to doing RNA interference and found comparing with the blank control group and blank vector group, c-src mRNA of the best interference group were significantly decreased. The total number of primordial follicles was relatively greater and the development of primordial folliculars was inhibited. CONCLUSION: c-src plays an important role in primordial follicle development and folliculogenesis initiation.

[Role of MAPK and PKC signaling pathways in the regulation of c-erbB2 in the primordial follicles onset].

Our previous studies showed that the proto-oncogene c-erbB2 played an important role in primordial follicles growth. The present study was conducted to investigate the role of MAPK and PKC signaling pathways in the primordial follicle onset in neonatal rats, and the relationship between c-erbB2 and MAPK/PKC signaling pathways. Ovaries collected from 2-day-old Sprague-Dawley rats were cultured in the Waymouth culture system in vitro. Ovaries were transfected with c-erbB2 siRNA, or treated with PD98059 (50 mumol/L) or Calphostin (0.5 mumol/L) in the culture medium. RT-PCR was performed to measure the expression of c-erbB2 mRNA, and Western blot analysis was performed to measure the expression of ErbB2, MAPK and PKC protein after the neonatal rat ovaries were cultured for 8 d. The quantities of every-stage follicles of ovaries cultured for 8 d were obtained in histological section stained with hematoxylin eosin. The results showed that c-erbB2 siRNA reduced the levels of c-erbB2 mRNA (P<0.01) and the levels of ErbB2, MAPK and PKC protein (P<0.01) significantly. But the levels of c-erbB2 mRNA and ErbB2 protein exhibited no change (P>0.05) in the ovaries cultured with PD98059 or Calphostin. After the ovaries were transfected with c-erbB2 siRNA or cultured with PD98059 or Calphostin for 8 d, the quantities of primary follicles and second follicles were lower than those in the control group (P<0.05 or P<0.01), but the quantity of the primordial follicles was higher than that in the control group (P<0.01). These results suggest that proto-oncogene c-erbB2 promotes the initiation of primordial follicle growth through the MAPK and PKC signal transduction, and c-erbB2 is possibly the upstream of PKC and MAPK signaling pathway in the regulation of primordial follicle onset.

Detection of deoxynivalenol based on a single-chain fragment variable of the antideoxynivalenol antibody.

Immunological detection of low molecular weight toxins, such as deoxynivalenol using single-chain antibody fragment (scFv), is a potentially novel and safe method of diagnosing fungal infection and food contamination. To develop a deoxynivalenol detection procedure based on scFv, deoxynivalenol was first conjugated to horseradish peroxidase (HRP) for immunoassay. Deoxynivalenol was initially activated using N-[p-maleimidophenyl] isocyanate and subsequently conjugated to S-acetyl thioglycolic acid N-hydroxysuccinimide-activated HRP. Sodium dodecylsulphate polyacrylamide gel electrophoresis and enzyme-linked immunosorbent assay (ELISA) analysis confirmed covalent attachment of deoxynivalenol to HRP successfully. Competitive direct-ELISA based on antideoxynivalenol scFv was used to detect deoxynivalenol in spiked and natural contaminated wheat samples, and the results showed that scFv is applicable in deoxynivalenol detection of contaminated wheat samples. This work confirms that sensitive and specific scFv against fungal toxins can be applicable in diagnosis of fungal infection.