ICG-Dimeric Her2-Specific Affibody Conjugates for Tumor Imaging and Photothermal Therapy for Her2-Positive Tumors.

Human epidermal growth factor receptor 2 (Her2) is abundantly expressed in various solid tumors. The Her2-specific Affibody (ZHer2:2891) has been clinically tested in patients with Her2-positive breast cancer and is regarded as an ideal drug carrier for tumor diagnosis and targeted treatment. Indocyanine green (ICG) can be used as a photosensitizer for photothermal therapy (PTT), in addition to fluorescent dyes for tumor imaging. In this study, a dimeric Her2-specific Affibody (ZHer2) based on ZHer2:2891 was prepared using the E. coli expression system and then coupled to ICG through an N-hydroxysuccinimide (NHS) ester reactive group to construct a novel bifunctional protein drug (named ICG-ZHer2) for tumor diagnosis and PTT. In vitro, ICG-ZHer2-mediated PTT selectively and efficiently killed Her2-positive BT-474 and SKOV-3 tumor cells rather than Her2-negative HeLa tumor cells. In vivo, ICG-ZHer2 specifically accumulated in Her2-positive SKOV-3 tumor grafts rather than Her2-negative HeLa tumor grafts; high-contrast tumor optical images were obtained. However, Her2-negative HeLa tumor grafts were not detected. More importantly, ICG-ZHer2-mediated PTT exhibited a significantly enhanced antitumor effect in mice bearing SKOV-3 tumor grafts owing to the good photothermal properties of ICG-ZHer2. Of note, ICG-ZHer2 did not exhibit acute toxicity in mice during short-term treatment. Overall, our findings indicate that ICG-ZHer2 is a promising bifunctional drug for Her2-positive tumor diagnosis and PTT.

The role of Gα protein signaling in the membrane estrogen receptor-mediated signaling.

Estrogens exert rapid, extranuclear effects by their action on the plasma membrane estrogen receptors (mERs). Gα protein associated with the cell membrane is involved in many important processes regulated by estrogens. However, the Gα's role in the mER-mediated signaling and the signaling pathways involved are poorly understood. This review aims to outline the Gα's role in the mER-mediated signaling. Immunoblotting, immunofluorescence, co-immunoprecipitation, and RNA interference were carried out using vascular endothelial cells (ECs) and human breast carcinoma cell lines as experimental models. Electrophysiology and immunocytochemistry were carried out using guinea pigs as animal models. Recent advances suggest that the signaling of mERα through Gα is required for vascular EC migration or endothelial H2S release, while Gα13 is involved in estrogen-induced breast cancer cell invasion. Besides, the Gαq-coupled PLC-PKC-PKA pathway is critical for the neural regulation of energy homeostasis. This review summarizes the contributions of Gα to mER-mediated signaling, including cardiovascular protection, breast cancer metastasis, neural regulation of homeostatic functions, and osteogenesis.

Helium Protects Against Lipopolysaccharide-Induced Cardiac Dysfunction in Mice via Suppressing Toll-Like Receptor 4-Nuclear Factor κB-Tumor Necrosis Factor-Alpha/ Interleukin-18 Signaling.

The nonanesthetic noble gas helium (He) can protect many organs against ischemia and reperfusion injury, such as liver and heart. However, the role of He on cardiac dysfunction during sepsis is not clear. In this study, we established a lipopolysaccharide (LPS)-induced cardiac dysfunction mouse model to examine the influence of He on the impaired cardiac function, and further investigated the possible innate immune mechanisms that may be involved. LPS induced left ventricular dysfunction and cavity enlargement, as indicated by decreased percent ejection fraction, percent fractional shortening, left ventricular anterior wall thickness in systole, and left ventricular posterior wall thickness in systole, while increased left ventricular end-systolic diameter and left ventricular end-systolic volume. He improved the impaired left ventricular function and cavity enlargement in a dose-dependent manner, and it was beneficial at 1.0 mL/100 g. Mechanistically, He inhibited toll-like receptor 4 (TLR4) expression, reduced the phosphorylation of nuclear factor κB (NF-κB), and subsequently alleviated tumor necrosis factor-alpha (TNF-α) and interleukin-18 (IL-18) expression in heart. Therefore, He protects against LPS-induced cardiac dysfunction in mice partially via inhibiting myocardial TLR4-NF-κB-TNF-α/IL-18 signaling.

Efficient light redirection via stretched field resonance in dielectric meta-resonator.

Light redirection plays an important role in photonic integrated circuit system, which attracts much attention on account of thriving application prospects from microwave to visible frequency. By treating a two-dimensional photonic crystal array as a dielectric resonator with low effective index neff << 1, a new strategy of one-direction semi-enclosed meta-resonator is proposed for light redirection and splitting with a high efficiency beyond 90%. Instead of zero-index material, the phenomenon of significant collimating radiations with zero phase delay can also be achieved through a meta-resonator of low effective index to stretch the internal resonant field with a wavelength much longer than that in air. The geometrical dimensions and structural parameters of the meta-resonator offer a great design flexibility for modulating the operating frequency. The numerical simulation and experimental results perfectly coincide with the theoretical predictions. This strategy can also be extended to other artificial metamaterials and three-dimensional cases, which may offer fantastic possibilities to the development of integrated photonics.

Dual novel mutations in SLC26A2 in two siblings with multiple epiphyseal dysplasia 4 from a Chinese family: a case report.

BACKGROUND: Multiple epiphyseal dysplasia (MED) is a heterogeneous genetic condition characterized by variable phenotypes, such as short stature (mild to moderate), joint deformities, abnormal gait, scoliosis, and brachydactyly. Recessive mutations in the SLC26A2 gene cause a phenotype of multiple epiphyseal dysplasia-4 (MED-4). In the present study, we identified novel compound heterozygous mutations in the SLC26A2 gene in a Chinese family with two affected sibs with MED-4. CASE PRESENTATION: Radiographs revealed hip dysplasia, brachydactyly and scoliosis in patient 1. Radiological examinations in patient 2 also showed hip dysplasia recently. Both of them were diagnosed with MED-4. SLC26A2 c.824 T > C and SLC26A2 c.1198C > T were identified in two siblings in this family, which were inherited from both parents, one mutation from each. CONCLUSIONS: This is the first Chinese MED-4 family attributed to SLC26A2 mutations, and these results show that these novel compound heterozygous mutations in SLC26A2 contribute to MED-4.

17ß-Estradiol inhibits vascular smooth muscle cell migration via up-regulation of striatin protein.

Striatin, an estrogen receptor (ER)-interacting protein, plays an important role in estrogen's nongenomic actions in vascular endothelial cells. However, the role of striatin in VSMCs is unknown. Here, we investigated the role of striatin in estrogen-regulated VSMCs migration. 17ß-Estradiol (E2) at 10 nM largely inhibited VSMCs migration, which was reversed by the silencing of striatin expression. E2 increased striatin protein expression in a dose- and time-dependent manner. ERα agonist PPT, but not ERß agonist DPN, mimicked the regulatory effect of E2. The regulatory effect of E2 on striatin protein expression was blocked by the pure ER antagonist ICI 182,780 or the mitogen-activated protein kinase inhibitor PD98059, but not by the phosphatidylinositol-3 kinase inhibitor wortmannin or Src inhibitor PP2, suggesting that E2 increased striatin protein expression via extracellular-signal regulated kinase 1/2 (ERK1/2). E2 resulted in phosphorylation of ERK1/2 in a time-dependent manner. The silencing of ERK1/2 largely abolished E2-enhanced striatin expression. Finally, the inhibitory effect of E2 on VSMC migration was reversed by ICI 182,780 or PD98059. Taken together, our results indicate that E2 inhibits VSMC migration by increasing striatin expression via ERα to ERK1/2 pathway, which maybe helpful to understand estrogen's anti-atherogenic effect in VSMCs.

17ß-estradiol induces vasorelaxation by stimulating endothelial hydrogen sulfide release.

Estrogen exerts vascular protective effects, but the underlying mechanisms remain to be understood fully. In recent years, hydrogen sulfide (H(2)S) has increasingly been recognized as an important signaling molecule in the cardiovascular system. Vascular H(2)S is produced from L-cysteine, catalyzed by cystathionine γ-lyase (CSE). In our study, apolipoprotein E (ApoE)-deficient mice were ovariectomized and implanted with placebo (OVX mice) or 17ß-estradiol (E(2)) pellets (OVX + E(2) mice). Compared with OVX mice, OVX + E(2) mice showed increased plasma H(2)S levels (P = 0.012) and decreased aortic lesion area (P = 0.028). These effects were largely reversed when supplementing with the irreversible CSE inhibitor DL-propargylglycine (PPG) in the OVX + E(2) + PPG mice. Meanwhile, the nitric oxide and prostacyclin-resistant responses to cumulative application of acetylcholine (ACh) were studied among all the three groups of femoral arteries. Compared with the arteries in the OVX group, the vasodilator sensitivity of arteries to ACh was increased in the OVX + E(2) group and attenuated in the OVX + E(2) + PPG group. E(2) and estrogen receptor (ER) α agonist 4',4″,4'″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol rapidly increased H(2)S release in human endothelial cells, but not partially selective ERß agonist 2,3-bis-(4-hydroxyphenyl)-propionitrile. These effects were inhibited by ER antagonist ICI 182780 or by protein kinase G (PKG) inhibitor KT5823. Furthermore, endothelial PKG activity was increased by E(2) (P = 0.003) and E(2)-induced vasodilation was inhibited by KT5823 (P = 0.009). In conclusion, the endothelial CSE/H(2)S pathway is activated by E(2) through PKG, which leads to vasodilation. These actions may be relevant to estrogen's anti-atherogenic effect.

Common variation in with no-lysine kinase 1 (WNK1) and blood pressure responses to dietary sodium or potassium interventions- family-based association study.

BACKGROUND: Common variations in the gene with no-lysine kinase 1 (WNK1) are associated with hypertension, but because of gene-environment interaction, it is difficult to fully identify the genetic contribution of WNK1 gene polymorphism to blood pressure (BP) variability. The aim of this study was to identify the effect of common WNK1 variants on the shift of BP during strict dietary interventions of salt or potassium intake. METHODS AND RESULTS: A total of 342 subjects from 126 families were selected and sequentially maintained on normal diet for 3 days at baseline, a low-salt diet for 7 days (3g/day, NaCl), then a high-salt diet for 7 days (18 g/day), and high-salt diet with potassium supplementation for another 7 days (4.5 g/day, KCl). Five single nucleotide polymorphisms (SNPs) were selected from the WNK1 gene. rs880054 and rs12828016 were associated with diastolic BP (DBP) response during the low-or high-sodium intervention, and rs2301880 was significantly associated with systolic BP, DBP and mean arterial pressure responses to the high-sodium intervention (all P<0.05). Unfortunately, no associations for WNK1 SNPs and the constructed haplotype blocks of WNK1 with BP responses to high-salt-and-potassium supplement intervention reached nominal statistical significance. CONCLUSIONS: The WNK1 gene might be mechanistically involved in the variation in BP response to dietary sodium and potassium intake among individuals, and might contribute to the variation of this complex phenotype.

Excellent Magnetocaloric Performance of the Fe87Ce13-xBx (x = 5, 6, 7) Metallic Glasses and Their Composite.

The novel Fe87Ce13-xBx (x = 5, 6, 7) metallic glass (MG) ribbons were fabricated in this work. The compositional dependence of glass forming ability (GFA), magnetic and magnetocaloric properties of these ternary MGs, and the mechanism involved was investigated. The GFA and Curie temperature (Tc) of the MG ribbons were found to improve with the boron content, and the peak value of magnetic entropy change (-ΔSmpeak) reaches a maximum of 3.88 J/(kg × K) under 5 T when x = 6. Based on the three results, we designed an amorphous composite that exhibits a table-shape magnetic entropy change (-ΔSm) profile with a rather high average -ΔSm (-ΔSmaverage~3.29 J/(kg × K) under 5 T) from 282.5 K to 320 K, which makes it a potential candidate for the highly efficient refrigerant in a domestic magnetic refrigeration appliance.

Progesterone enhances vascular endothelial cell migration via activation of focal adhesion kinase.

The mechanisms of progesterone on endothelial cell motility are poorly investigated. Previously we showed that progesterone stimulated endothelial cell migration via the activation of actin-binding protein moesin, leading to actin cytoskeleton remodelling and the formation of cell membrane structures required for cell movement. In this study, we investigated the effects of progesterone on the formation of focal adhesion complexes, which provide anchoring sites for cell movement. In cultured human umbilical endothelial cells, progesterone enhanced focal adhesion kinase (FAK) phosphorylation at Tyr(397) in a dose- and time-dependent manner. Several signalling inhibitors interfered with progesterone-induced FAK activation, including progesterone receptor (PR) antagonist ORG 31710, specific c-Src kinase inhibitor PP2, phosphatidylinosital-3 kinase (PI3K) inhibitor wortmannin as well as ρ-associated kinase (ROCK-2) inhibitor Y27632. It suggested that PR, c-Src, PI3K and ROCK-2 are implicated in this action. In line with this, we found that progesterone rapidly promoted c-Src/PI3K/Akt activity, which activated the small GTPase RhoA/ρ-associated kinase (ROCK-2) complex, resulting in FAK phosphorylation. In the presence of progesterone, endothelial cells displayed enhanced horizontal migration, which was reversed by small interfering RNAs abrogating FAK expression. In conclusion, progesterone promotes endothelial cell movement via the rapid regulation of FAK. These findings provide new information on the biological actions of progesterone on human endothelial cells that are relevant for vascular function.

Estrogen improved metabolic syndrome through down-regulation of VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.

Metabolic syndrome (MBS), a cluster of metabolic abnormalities and visceral fat accumulation, increases cardiovascular risks in postmenopausal women. In addition to visceral fat, perivascular adipose tissue has been recently found to play an important role in vascular pathophysiology. Hence, the present study investigates the effects of estrogen on both intra-abdominal fat (visceral fat) and periaortic fat (perivascular fat) accumulation as well as hypoxia in ovariectomized female rats. Female rats were divided into sham operation, ovariectomy and ovariectomy with 17ß-estradiol supplementation groups. Twelve weeks later, we found that estrogen improved MBS via reducing body weight gain, the weight of periaortic and intra-abdominal fat, hepatic triglyceride, and total serum cholesterol levels. Estrogen also increased insulin sensitivity through restoring glucose and serum leptin levels. For periaortic fat, western blot showed estrogen inhibited hypoxia by reducing the levels of VEGF and HIF-1α, which is consistent with the results from immunohistochemical staining. The correlation analysis indicated that perivascular fat had a positive correlation with body weight, intra-abdominal fat or serum total cholesterol, but a negative correlation with insulin sensitivity index. For intra-abdominal fat, real-time fluorescent RT-PCR showed estrogen improved fat dysfunction via reducing the levels of relative leptin, MCP-1 but increasing adiponectin mRNA. Estrogen reduced the levels of VEGF and HIF-1α to inhibit hypoxia but restored the levels of PPARγ and Srebp-1c, which are important for lipid capacity function of intra-abdominal fat. These results demonstrated estrogen improved MBS through down-regulating VEGF and HIF-1α to inhibit hypoxia of periaortic and intra-abdominal fat in ovariectomized female rats.

Evolution of blood pressure from adolescents to youth in salt sensitivies: a 18-year follow-up study in Hanzhong children cohort.

BACKGROUND: Essential hypertension mostly originates from children. Salt Sensitivity (SS) is regarded as the intermediate phenotype of essential hypertension. The present study investigated the effects of salt-sensitivity on evolution of blood pressure (BP) and development to hypertension from adolescents to youth. METHODS: A baseline survey was carried out in 4,623 adolescents aged 6-15 years old in Hanzhong rural areas in 1987, 310 of whom (mean 9.2 years) were randomly recruited for determination of salt sensitivity using the tests of oral saline load and furosemide sodium-volume depletion. SS was diagnosed in 101 subjects while 209 were determined as non-salt-sensitive (NSS). We made a 18-year followed-up of the cohort in 2005. RESULTS: The response rate for surviving baseline adolescents was 71.9%. At follow up, BP in youth with baseline SS was higher than that in NSS (SBP:122.9 ± 13.1 VS 117.3 ± 12.4, P < 0.01; DBP: 78.2 ± 10.4 VS 74.7 ± 10.8, P < 0.05). Longitudinal analysis of 18-year BP evolution, subjects in SS had greater Systolic BP change than subjects in NSS(19.6 ± 12.714.7 ± 12.2, P < 0.01). The incidence of hypertension in salt sensitive group was higher than that in NSS group (15.5% VS 6.3%, RR = 2.34, P < 0.05). CONCLUSION: Our findings indicate that adolescents with higher BP salt-sensitivity have a higher rate of incident hypertension in youth. Salt sensitivity could be at high risk predisposing to development of hypertension from adolescents to youth.

Her3-specific affibody mediated tumor targeting delivery of ICG enhanced the photothermal therapy against Her3-positive tumors.

Photothermal therapy (PTT), mediated by tumor-targeted drug delivery of indocyanine green (ICG), is a promising strategy for cancer therapy. Human epidermal growth factor receptor 3 (Her3) is highly expressed in several solid tumors and is an ideal target for tumor diagnosis and therapy. This study prepared a Her3-specific dimeric affibody (ZHer3) using an Escherichia coli expression system. The affibody could bind explicitly to Her3-positive MCF7 and LS174T cells, rather than to Her3-negative SKOV-3 cells in vitro. ICG was coupled with the ZHer3 affibody (ICG-ZHer3) through an N-hydroxysuccinimide (NHS) ester reactive group for tumor-targeted delivery. As expected, Her3-positive cells were selectively and efficiently killed by ICG-ZHer3-mediated PTT in vitro. In vivo, ICG-ZHer3 preferentially accumulated in Her3-positive LS174T tumor grafts because of the tumor-targeting ability of the ZHer3 affibody. As a result of the local generation of cytotoxic reactive oxygen species and hyperthermia, the growth rates of LS174T tumor grafts were significantly inhibited by ICG-ZHer3-mediated PTT, and ICG-ZHer3 showed good safety performance during short-term treatment. In conclusion, these results demonstrated that ICG-ZHer3 is a promising photosensitizer for PTT against Her3-positive tumors.

Efficacy of generic teriparatide and alendronate in Chinese postmenopausal women with osteoporosis: a prospective study.

The efficacy of generic teriparatide in improving BMD at lumbar spine in patients with osteoporosis was similar to that of alendronate. It provided a new choice for osteoporosis treatment in Chinese population. INTRODUCTION: To determine whether the efficacy of generic teriparatide is noninferior to alendronate for Chinese postmenopausal women with osteoporosis. METHODS: Eligible patients were randomly assigned (2:1) in a 48-week, open-label design to receive 20 µg sc daily teriparatide or 70 mg oral weekly alendronate. Primary outcome was percentage change in BMD at the lumbar spine from baseline to 48 weeks and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. RESULTS: Three hundred ninety-one and 196 participants were randomly assigned to the teriparatide or alendronate group, of whom 379 and 194 receiving at least one dose of teriparatide and alendronate treatment were eligible for the efficacy analysis. Teriparatide was non-inferior to alendronate for BMD change at lumbar spine (treatment difference: 0.7%, 95% CI: - 0.3 to 1.7%), which excluded the predefined non-inferiority margin of - 1.5%. However, teriparatide was not statistically superior to alendronate in improving BMD at lumbar spine (P = 0.169). At 48 weeks, changes in BMD at total hip were - 1.0% and 2.2% in teriparatide and alendronate group, respectively (P < 0.001). The incidence of new fracture showed no statistical difference between groups (P = 0.128). Serum P1NP and ß-CTX levels significantly increased in the teriparatide group and markedly decreased in alendronate group (all P < 0.001 vs baseline). The adverse events (AEs) and serious AEs were more common in the teriparatide group than in the alendronate group, which were mainly teriparatide-related hypercalcemia, elevated alkaline phosphatase or parathyroid hormone, dizziness, and arthralgia. CONCLUSIONS: Teriparatide was not inferior to alendronate in increasing BMD at lumbar spine in Chinese postmenopausal women, and they achieved these effects through different mechanisms.

Involvement of the lymphatic system in salt-sensitive hypertension in humans.

BACKGROUND: The mechanisms of salt sensitivity as an important intermediate phenotype of essential hypertension remain elusive. A novel theory proposes that lymphatic vessels regulate sodium and fluid homeostasis. Since vascular endothelial growth factor C (VEGF-C) plays a vital role in lymphatic capillary hyperplasia, we hypothesized that VEGF-C was involved in salt-sensitive hypertension. We therefore investigated its plasma concentration in salt-sensitive subjects. MATERIAL/METHODS: Twenty-seven subjects (BP ≤ 160/100 mmHg; age range 25-50 years) from a rural community of northern China were enrolled in this study. The baseline BP of volunteers was monitored for 3 days, followed by a low-salt diet for 7 days (3 g/day, NaCl) and a high-salt diet for 7 days (18 g/day, NaCl). Those who exhibited a BP increase of 10% from low-salt period to high-salt period were diagnosed as salt-sensitive subjects. The concentration of plasma VEGF-C was measured by an immunoenzyme method (ELISA). RESULT: High salt intake significantly increased the plasma VEGF-C level. It was higher in the salt-sensitive subjects (3642.2 ± 406.1 pg/ml) than in the salt-resistant subjects (2249.8 ± 214.6 pg/ml). The comparison of VEGF-C levels between the 2 groups had significant statistical difference (P<0.01). CONCLUSIONS: The VEGF-C level increases significantly in the salt-sensitive subjects after high salt intake. VEGF-C could be used as a biomarker of salt sensitivity.

Potassium supplement ameliorates salt-induced haemostatic abnormalities in normotensive subjects.

BACKGROUND: Dietary high salt or low potassium is always associated with an increased incidence of death or cardiovascular complications, but the mechanisms remain elusive. We hypothesize that haemostatic abnormalities may play an important role in the phenomenon. METHODS: Twenty normotensive subjects (aged 25 to 50 years) were selected from a rural community of Northern China. All of the people were sequentially maintained on a 3-day baseline investigation, 7 days on a low-salt diet (51.3 mmol or 3 g of NaCI per day), 7 days on a high-salt diet (307.7 mmol or 18 g of NaCl per day), and another 7 days on a high-salt diet with potassium supplementation (4.5 g/day, KCI). The concentrations of fibrinogen, D-dimer and von Willebrand factor (vWF) in plasma were assessed, and these data represent the systemic haemostatic state. RESULTS: Plasma levels of fibrinogen, fibrin D-dimer and vWF were significantly higher in the high-salt diet than in the low-salt diet (P < 0.05). In contrast, potassium supplement could convert the sodium-dependent haemostatic abnormalities to normal (P < 0.05). CONCLUSIONS: Dietary high salt intake could stimulate the production of haemostatic factors, which may ultimately lead to cardiovascular events. Inversely, potassium supplementation could ameliorate the sodium-induced haemostatic abnormalities.

Hydrogen Gas: A Novel Type of Antioxidant in Modulating Sexual Organs Homeostasis.

Sex is a science of cutting edge but bathed in mystery. Coitus or sexual intercourse, which is at the core of sexual activities, requires healthy and functioning vessels to supply the pelvic region, thus contributing to clitoris erection and vaginal lubrication in female and penile erection in male. It is well known that nitric oxide (NO) is the main gas mediator of penile and clitoris erection. In addition, the lightest and diffusible gas molecule hydrogen (H2) has been shown to improve erectile dysfunction (ED), testis injuries, sperm motility in male, preserve ovarian function, protect against uterine inflammation, preeclampsia, and breast cancer in female. Mechanistically, H2 has strong abilities to attenuate excessive oxidative stress by selectively reducing cytotoxic oxygen radicals, modulate immunity and inflammation, and inhibit injuries-induced cell death. Therefore, H2 is a novel bioactive gas molecule involved in modulating sexual organs homeostasis.

[Synthesis and properties of nanorod-long afterglow BaAl2O4:Eu2+, Dy3+ phosphor].

The present paper mainly reports a new method to synthesize long afterglow photoluminescent material BaAl2O4:Eu2+, Dy3+. Al(NO3)3.9H2O, Ba(NO3)2, urea, RE(NO3) 3(RE==Eu, Dy) were employed as raw materials, the admixture of H2O/n-butanol and H2O/n-butanol/SBS were used as medium, then BaAl2O4:Eu2+, Dy3+ phosphor was achieved by calcining the precursor, which was synthesized by hydrothermal method, at 130 degrees C under reduction atmosphere. The TEM and SEM were used to analyse the morphology and BaAl2O4:Eu2+, Dy3+ synthesized by annealing at 1300 degrees C are all nanorods. The excitation and emission spectra of the phosphor indicated that all of them are broad band, and the main emission peak is around 498 nm, which is due to 5d-->4f transition of Eu2+. The state-solid synthesis of the long afterglow phosphor BaAl2O4:Eu2+, Dy3+ generally requires a high calcination temperature, so the products are easily agglomerated, and in this paper the hydrothermal solvothermal synthesis was used, so the synthesized products calcined at 130 degrees degrees C still present well-dispersed rod structure, need not milling, and display well luminescence performance. The authors compared the two different conditions of experiment, and found that under the condition without surfactant the authors can still get well-dispersed rod structure of BaAl2O4:Eu2+, Dy3+. The method is hopeful to be used in synthesizing other alkali-earth aluminate and silicate and other luminescent materials.

The FTO/miR-181b-3p/ARL5B signaling pathway regulates cell migration and invasion in breast cancer.

BACKGROUND: N6-methyladenosine (m6 A) RNA modification has been demonstrated to be a significant regulatory process in the progression of various tumors, including breast cancer. Fat mass and obesity-associated (FTO) enzyme, initially known as the obesity-related protein, is the first identified m6 A demethylase. However, the relationship between FTO and breast cancer remains controversial. In this study, we aimed to elucidate the role and clinical significance of FTO in breast cancer and to explore the underlying mechanism. METHODS: We first investigated the expression of FTO in breast cancer cell lines and tissues by quantitative reverse transcription-PCR (qRT-PCR), Western blotting, and immunohistochemistry. Wound healing assay and Transwell assay were performed to determine the migration and invasion abilities of SKBR3 and MDA-MB453 cells with either knockdown or overexpression of FTO. RNA sequencing (RNA-seq) was conducted to decipher the downstream targets of FTO. qRT-PCR, luciferase reporter assay, and Western blotting were employed to confirm the existence of the FTO/miR-181b-3p/ARL5B axis. The biological function of ADP ribosylation factor like GTPase 5B (ARL5B) in breast cancer cells was evaluated by wound healing assay and Transwell invasion assay. RESULTS: High FTO expression was observed in human epidermal growth factor receptor 2 (HER2)-positive breast cancer, predicting advanced progression (tumor size [P < 0.001], nuclear grade [P = 0.001], peritumoral lymphovascular invasion [P < 0.001), lymph node metastasis [P = 0.002], and TNM stage [P = 0.001]) and poor prognosis. Moreover, FTO promoted cell invasion and migration in vitro. Mechanistically, RNA-seq and further confirmation studies suggested that FTO up-regulated ARL5B by inhibiting miR-181b-3p. We further verified that ARL5B also displayed carcinogenic activity in breast cancer cells. CONCLUSION: Our work demonstrated the carcinogenic activity of FTO in promoting the invasion and migration of breast cancer cells via the FTO/miR-181b-3p/ARL5B signaling pathway.

Migrasome and Tetraspanins in Vascular Homeostasis: Concept, Present, and Future.

Cell migration plays a critical role in vascular homeostasis. Under noxious stimuli, endothelial cells (ECs) migration always contributes to vascular repair, while enhanced migration of vascular smooth muscle cells (VSMCs) will lead to pathological vascular remodeling. Moreover, vascular activities are involved in communication between ECs and VSMCs, between ECs and immune cells, et al. Recently, Ma et al. (2015) discovered a novel migration-dependent organelle "migrasome," which mediated release of cytoplasmic contents, and this process was defined as "migracytosis." The formation of migrasome is precisely regulated by tetraspanins (TSPANs), cholesterol and integrins. Migrasomes can be taken up by neighboring cells, and migrasomes are distributed in many kinds of cells and tissues, such as in blood vessel, human serum, and in ischemic brain of human and mouse. In addition, the migrasome elements TSPANs are wildly expressed in cardiovascular system. Therefore, TSPANs, migrasomes and migracytosis might play essential roles in regulating vascular homeostasis. In this review, we will discuss the discoveries of migration-dependent migrasome and migracytosis, migrasome formation, the basic differences between migrasomes and exosomes, the distributions and functions of migrasome, the functions of migrasome elements TSPANs in vascular biology, and discuss the possible roles of migrasomes and migracytosis in vascular homeostasis.