Structural basis for RNA recognition by the N-terminal tandem RRM domains of human RBM45.

RBM45 is an RNA-binding protein involved in neural development, whose aggregation is associated with neurodegenerative diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar dementia (FTLD). However, the mechanisms of RNA-binding and aggregation of RBM45 remain unelucidated. Here, we report the crystal structure of the N-terminal tandem RRM domains of human RBM45 in complex with single-stranded DNA (ssDNA). Our structural and biochemical results revealed that both the RRM1 and RRM2 of RBM45 recognized the GAC sequence of RNA/ssDNA. Two aromatic residues and an arginine residue in each RRM were critical for RNA-binding, and the interdomain linker was also involved in RNA-binding. Two RRMs formed a pair of antiparallel RNA-binding sites, indicating that the N-terminal tandem RRM domains of RBM45 bound separate GAC motifs in one RNA strand or GAC motifs in different RNA strands. Our findings will be helpful in the identification of physiologic targets of RBM45 and provide evidence for understanding the physiologic and pathologic functions of RBM45.

Extracellular vesicle-derived microRNA-18b ameliorates preeclampsia by enhancing trophoblast proliferation and migration via Notch2/TIM3/mTORC1 axis.

Preeclampsia (PE), a common disorder of pregnancy, is characterized by insufficient trophoblast migration and inadequate vascular remodelling, such that promotion of trophoblast proliferation might ameliorate PE. In the current study, we sought to study the underlying mechanism of extracellular vesicle (EV)-derived microRNA-18 (miR-18b) in PE. Human umbilical cord mesenchymal stem cells (HUCMSCs) isolated from placental tissues were verified through osteogenic, adipogenic and chondrogenic differentiation assays. Bioinformatics analyses and dual-luciferase reporter gene assay were adopted to confirm the targeting relationship between miR-18b and Notch2. The functional roles of EV-derived miR-18b and Notch2 in trophoblasts were determined using loss- and gain-of-function experiments, and trophoblast proliferation and migration were assayed using CCK-8 and Transwell tests. In vivo experiments were conducted to determine the effect of EV-derived miR-18b, Notch2 and TIM3/mTORC1 in a rat model of PE, with monitoring of blood pressure and urine proteinuria. TUNEL staining was conducted to observe the cell apoptosis of placental tissues of PE rats. We found down-regulated miR-18b expression, and elevated Notch2, TIM3 and mTORC1 levels in the placental tissues of PE patients compared with normal placenta. miR-18b was delivered to trophoblasts and targeted Notch2 and negatively its expression, whereas Notch2 positively mediated the expression of TIM3/mTORC1. EV-derived miR-18b or Notch2 down-regulation enhanced trophoblast proliferation and migration in vitro and decreased blood pressure and 24 hours urinary protein in PE rats by deactivating the TIM3/mTORC1 axis in vivo. In summary, EV-derived miR-18b promoted trophoblast proliferation and migration via down-regulation of Notch2-dependent TIM3/mTORC1.

Crystal structure of histone chaperone Vps75 from Candida albicans.

Vps75 is a histone chaperone that interacts with the fungal-specific histone acetyltransferase Rtt109 and stimulates its acetylation activity on histone H3. Here we report the crystal structure of Vps75 of Candida albicans, one of the most common fungal pathogens. CaVps75 exists as a headphone-like dimer that forms a large negatively charged region on its concave side, showing the potential to bind positively charged regions of histones. The distal ends of the concave side of the CaVps75 dimer are positively charged and each has one more α helix than yeast Vps75. CaVps75 exhibits ionic strength- and concentration-dependent higher oligomerization in solution. In the crystal, two dimers are bound through electrostatic interactions between charged regions on the concave side of their earmuff domains, and this inter-dimer interaction differs from the currently known inter-dimer interactions of Vps75s. Our results will help to understand the role of Vps75 in C. albicans.

Incorporation of heparin/BMP2 complex on GOCS-modified magnesium alloy to synergistically improve corrosion resistance, anticoagulation, and osteogenesis.

The in vivo fast degradation and poor biocompatibility are two major challenges of the magnesium alloys in the field of artificial bone materials. In this study, graphene oxide (GO) was first functionalized by chitosan (GOCS) and then immobilized on the magnesium alloy surface, finally the complex of heparin and bone morphogenetic protein 2 was incorporated on the modified surface to synergistically improve the corrosion resistance, anticoagulation, and osteogenesis. Apart from an excellent hydrophilicity after the surface modification, a sustained heparin and BMP2 release over 14 days was achieved. The corrosion resistance of the modified magnesium alloy was significantly better than that of the control according to the results of electrochemical tests. Moreover, the corrosion rate was also significantly reduced in contrast to the control. The modified magnesium alloy not only had excellent anticoagulation, but also can significantly promote osteoblast adhesion and proliferation, upregulate the expression of alkaline phosphatase and osteocalcin, and enhance mineralization. Therefore, the method of the present study can be used to simultaneously improve the corrosion resistance and biocompatibility of the magnesium alloys targeted for the orthopedic applications.

Hierarchical C/SiO x /TiO2 ultrathin nanobelts as anode materials for advanced lithium ion batteries.

TiO2-based nanomaterials are demonstrated to be a promising candidate for next generation lithium ion batteries due to their stable performance and easy preparation. However, their inherent low capacity impedes their wide application compared to commercial carbon nanomaterials. Here we present a unique in situ grafting-graphitization method to achieve a ternary nanocomposite of C/SiO x /TiO2 ultrathin nanobelts with a core-shell heterostructure. The obtained ternary nanocomposite integrates the merits of high specific capacity of SiO x , the excellent mechanical stability of graphite-like carbon and the high reactivity of TiO2. Cyclic voltammetric curves and cycling performance manifest the optimal ternary nanocomposite and deliver a very high initial specific capacity of ∼1196 mA h g-1 with both good rate capability (∼200 mA h g-1 up to 10 C) and especially enhanced cycle stability. Our work demonstrates that building hierarchical core-shell heterostructures is an effective strategy to improve capacity and cycling performance in other composite anodes for electrochemical energy storage materials.

Supplementing punicalagin reduces oxidative stress markers and restores angiogenic balance in a rat model of pregnancy-induced hypertension.

Pre-eclampsia (PE) is a pregnancy disorder that is characterised by severe hypertension and increased risks of foetal and maternal mortality. The aetiology of PE not completely understood; however, maternal nutrition and oxidative stress play important roles in the development of hypertension. The treatment options for PE are currently limited to anti-hypertensive drugs. Punicalagin, a polyphenol present in pomegranate juice, has a range of bioactive properties. The effects of supplementation with punicalagin on angiogenesis and oxidative stress in pregnant rats with induced hypertension were investigated. The pregnant rats were randomly divided into five experimental groups (n=12 per group). Hypertension was induced using an oral dose of NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day) on days 14-19 of pregnancy. Punicalagin (25, 50 or 100 mg/kg) was given orally on days 14-21 of pregnancy. Punicalagin treatment at the tested doses significantly reduced diastolic, systolic, and mean arterial blood pressure in L-NAME treated rats from day 14. Punicalagin also restored angiogenic balance by increasing the expression of vascular endothelial growth factor and downregulating vascular endothelial growth factor receptor-1/fms-like tyrosine kinase-1. Punicalagin, significantly increased the placental nitric oxide levels as compared to PE group. The increased levels of oxidative stress in rats with PE were markedly decreased by treatment with punicalagin. Punicalagin at the tested doses markedly (p<0.05) enhanced the placental antioxidant capacity in L-NAME-treated rats. The raised catalase activity observed following L-NAME induction was significantly (p<0.05) and restored to normal activity levels in punicalagin treatment. Further, 100 mg dose of punicalagin exhibited higher protective effects as compared to lower doses of 25 and 50 mg. This study shows that supplementation with punicalagin decreased blood pressure and oxidative stress and restored angiogenic balance in pregnant rats with induced PE.

Determination of six polyynes in Oplopanax horridus and Oplopanax elatus using polyethylene glycol modified reversed migration microemulsion electrokinetic chromatography.

A PEG-modified reversed migration MEEKC method was developed for simultaneous determination of six polyynes, including oplopandiol, falcarindiol, oplopandiol acetate, (11S, 16S, 9Z)-9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate, oplopantriol B, and oplopantriol A, in Oplopanax horridus and Oplopanax elatus. The running buffer containing 0.8% v/v ethyl acetate, 3.8% w/v SDS, 6.6% v/v n-butanol in 20 mM phosphate buffer (pH 2.5), followed by mixing with propan-2-ol at 30% v/v and PEG-1000 at 15% w/v, was applied in the analysis. The proposed method was successfully applied to determine the six polyynes in five samples of Oplopanax horridus and one of O. elatus. The result showed that the types and amounts of polyynes present were obviously different when comparing the two herbs. Besides, the developed PEG-modified reversed MEEKC method might be suitable for the analysis of hydrophobic analytes in herbal medicines.

Decreased expression of Wiskott-Aldrich syndrome protein family verprolin-homologous protein 2 may be involved in the development of pre-eclampsia.

Wiskott­Aldrich syndrome protein family verprolin-homologous protein 2 (WAVE2) is a protein that mediates actin cytoskeletal reorganization and lamellipodia protrusion formation, which are required for cell migration and invasion. The primary purpose of this study was to determine whether there is an association between reactive oxygen species (ROS) and WAVE2 in pre-eclampsia, and whether WAVE2 expression in trophoblast cells is vulnerable to oxidative stress. This study observed excessive generation of ROS and decreased expression of WAVE2 in pre-eclamptic placentas compared with normotensive controls. Moreover, there was a significant negative correlation between ROS and WAVE2 protein in pre-eclamptic placenta (P < 0.001). An in-vitro model of hypoxia­reoxygenation (H/R) was used to imitate oxidative stress in placental trophoblasts, and it was found that the expression of WAVE2 protein in trophoblasts was decreased after H/R treatment. Additionally, compared with normoxia, decreased cell proliferation, higher cell apoptosis and attenuated cell migration and invasion were detected in trophoblasts exposed to H/R. In conclusion, the findings strongly suggest that excessive oxidative stress can decrease WAVE2 expression in trophoblasts and that the decreased expression of WAVE2 in trophoblast cells may be involved in the development of pre-eclampsia.

[Expression of KLF-8 and MMP-9 in placentas and their relationship with the pathogenesis of preeclampsia].

OBJECTIVE: To evaluate the expression of Krüppel-like factor 8 (KLF-8) and matrix metalloproteinase 9 (MMP-9) in placentas and their relationship with the pathogenesis of preeclampsia (PE). METHODS: Twenty-two women with PE(mild PE:4 cases; severe PE:18 cases) who received cesarean sections in the First Affiliated Hospital of Chongqing Medical University from September 2011 to March 2012 were recruited as the PE group (n = 22). And twenty women who received elective term cesarean section without perinatal complications were chosen as the control group (n = 20). Placentas were collected and immunohistochemical SP method were employed to detect the localization of KLF-8 protein.KLF-8 mRNA level was determined by quantitative real-time PCR technique and western blot analysis was used to quantify KLF-8 and MMP-9 protein levels. RESULTS: (1) There was no difference of KLF-8 protein distribution in placentas of the PE group and the control group.It was mainly located in the nuclear and cytoplasm of syncytiotrophoblasts.KLF-8 immunostaining was apparently decreased in the placentas of preeclamptic women when compared with the control group.(2)The KLF-8 mRNA levels were significantly decreased in placentas of the PE group (0.69 ± 0.08) compared to those of the control group (1.14 ± 0.09, P < 0.01). (3) KLF-8 and MMP-9 protein levels significantly decreased in the PE placentas (0.68 ± 0.05 and 0.21 ± 0.03) when compared to the control group (0.94 ± 0.06 and 0.34 ± 0.03, respectively, P < 0.01).(4) There was a positive correlation between the expression of KLF-8 and MMP-9 protein in the placentas from PE and normal pregnancies (r = 0.64, P < 0.01). CONCLUSIONS: KLF-8 mRNA and protein levels were decreased in placentas of PE patients compared to those of normotensive women.KLF-8 protein was primarily located in the invasion-related trophoblast cells and its expression had a positive correlation with MMP-9 levels.KLF-8 might have an important role in the pathogenesis of PE by regulation of trophoblast invasion.

Human umbilical cord mesenchymal stem cell-derived extracellular vesicles loaded with TFCP2 activate Wnt/ß-catenin signaling to alleviate preeclampsia.

BACKGROUND: Failures in invasive extravillous trophoblasts (EVTs) migration into the maternal uterus have been noticed in preeclampsia (PE). Human umbilical cord mesenchymal stem cell (hUCMSC)-derived extracellular vesicles (EVs) have been highlighted for the role as a potential therapeutic method in PE. This study intends to investigate the mechanistic basis of hUCMSCs-derived EVs loaded with bioinformatically identified TFCP2 in the activities of EVTs of PE. METHODS: Primary human EVTs were exposed to hypoxic/reoxygenation (H/R) to mimic the environment encountered in PE. The in vivo PE-like phenotypes were induced in mice by reduced uterine perfusion pressure (RUPP) surgery. CCK-8, Transwell and flow cytometry assays were performed to detect proliferation, migration, invasion and apoptosis of H/R-exposed EVTs. More importantly, EVs were extracted from hUCMSCs and transduced with ectopically expressed TFCP2, followed by co-culture with EVTs. RESULTS: TFCP2 was found to be down-regulated in the preeclamptic placental tissues and in H/R-exposed EVTs. hUCMSCs-EVs loaded with TFCP2 activated the Wnt/ß-catenin pathway, thereby promoting the proliferative, migratory, and invasive potential of EVTs. Furthermore, overexpression of TFCP2 alleviated PE-like phenotypes in mice, which was associated with activated Wnt/ß-catenin pathway. CONCLUSION: From our data we conclude that hUCMSCs-EVs overexpressing TFCP2 may be instrumental for the therapeutic targeting and clinical management of PE.

Altered distribution of fatty acid exerting lipid metabolism and transport at the maternal-fetal interface in fetal growth restriction.

INTRODUCTION: Fetal growth restriction (FGR) is a common complication of pregnancy. Lipid metabolism and distribution may contribute to the progression of FGR. However, the metabolism-related mechanisms of FGR remain unclear. The aim of this study was to identify metabolic profiles associated with FGR, as well as probable genes and signaling pathways. METHODS: Metabolomic profiles at the maternal-fetal interface (including the placenta, maternal and fetal serum) from pregnant women with (n = 35) and without (n = 35) FGR were analyzed by gas chromatography-mass spectrometry (GC-MS). Combined with differentially expressed genes (DEGs) from the GSE35574 dataset, analysis was performed for differential metabolites, and identified by the Metabo Analyst dataset. Finally, the pathology and screened DEGs were further identified. RESULTS: The results showed that fatty acids (FAs) accumulated in the placenta and decreased in fetal blood in FGR cases compared to controls. The linoleic acid metabolism was the focus of placental differential metabolites and genes enrichment analysis. In this pathway, phosphatidylcholine can interact with PLA2G2A and PLA2G4C, and 12(13)-EpOME can interact with CYP2J2. PLA2G2A and CYP2J2 were elevated, and PLA2G4C was decreased in the FGR placenta. DISCUSSION: In conclusion, accumulation of FAs in the placental ischemic environments, may involve linoleic acid metabolism, which may be regulated by PLA2G2A, CYP2J2, and PLA2G4C. This study may contribute to understanding the underlying metabolic and molecular mechanisms of FGR.

Cascade Tumor Therapy Platform for Sensitized Chemotherapy and Penetration Enhanced Photothermal Therapy.

As a stand-alone therapy strategy may not be sufficient for effective cancer treatment and a combination of chemotherapy with other therapies is a main trend in cancer treatment. A combination of chemotherapy and photothermal therapy (PTT) is reported here to achieve the goal of cascade multistage cancer treatment. A thermally responsive amphiphilic copolymer is designed and then a CuS nanoparticles (NPs)-based carbon monoxide (CO) photoinduced release system and doxorubicin (Dox) are encapsulated to construct the nanomedicine. The large-sized nanomedicine can accumulate in tumors after long circulation in vivo and will generate heat to act as a photothermal therapeutic agent by near infrared (NIR) light. Moreover, synergically release of CO and Dox is achieved and acted as a sensitized chemotherapeutic agent. The combination of PTT and chemotherapy sensitization can effectively eliminate active tumor cells in the periphery of the tumor. CuS NPs are also released after the degradation of nanomedicine and small-sized CuS NPs possess better tumor penetration and achieve penetration-enhanced PTT by further NIR irradiation, thereby effectively eliminating tumor cells inside solid tumors. Hence, cascade multistage cancer treatment of "combined PTT and chemotherapy sensitization"-"penetration-enhanced PTT" is achieved, and tumor cells are comprehensively and effectively eliminated.

Movements and behaviors during spontaneous arousals in healthy young adults: an intermediary stage between wakefulness and sleep?

BACKGROUND: Arousals are common, sudden and transient elevations of the vigilance level during normal sleep, but arousal-associated behaviors have not yet been studied. OBJECTIVE: We aimed to describe the duration as well as motor and autonomic patterns associated with arousals across sleep stages in normal subjects. METHODS: The spontaneous arousals of 25 healthy young adults were randomly analyzed on polysomnography with body- and face-oriented video cameras. The duration of the heart rate response as well as the frequency, amplitude, speed, body segment and semiology of associated movements were measured. RESULTS: Among 624 arousals (258 in N2, 140 in N3 and 226 in REM sleep), REM sleep arousals had the shortest duration, and N3 arousals were associated with greater heart rate acceleration. Movements and behaviors (mostly involving the head and neck, then the upper limbs, with rare eyes opening and no turning in bed) were frequent during arousals (69.4% during N2 sleep, 89.3% during N3 and 93.8% during REM sleep). Arousals more frequently included ample, prolonged and whole-body movements during N3 sleep and fast movements and facial expressions during REM sleep. During N2 arousals, chewing was the most prevalent behavior. Some movements resembled orientation and comfort behaviors (flexing/rotating the neck and trunk, scratching, pulling the sheets, rubbing the nose, yawning, smiling, frowning and speaking), whereas others resembled sleep-associated automatisms (swallowing, chewing). CONCLUSION: In contrast with previous assumptions, most arousals are associated with movements. The type of movements suggests that arousal is an intermediary state between wakefulness and sleep.

Immobilization of bioactive complex on the surface of magnesium alloy stent material to simultaneously improve anticorrosion, hemocompatibility and antibacterial activities.

Magnesium alloy represents one of the most potential biodegradable vascular stent materials due to its good biodegradability, biocompatibility and suitable mechanical properties, whereas the rapid degradation in physiological environment and the limited biocompatibility remain the challenges. In this study, graphene oxide (GO) was firstly functionalized by chitosan (GOCS), followed by loading zinc ions and propranolol to obtain GOCS@Zn/Pro complex, which was finally covalently immobilized on the self-assembled modified magnesium alloy surface to enhance the corrosion resistance and biocompatibility. The multi-functional coating can significantly improve the corrosion resistance and reduce the degradation rate of the magnesium alloy. Furthermore, the coating can significantly inhibit platelet adhesion and activation, reduce hemolysis rate, prolong activated partial thromboplastin time (APTT), and thus improve the blood compatibility of the magnesium alloy. In addition, the modified magnesium alloy can not only significantly promote the endothelial cell adhesion and proliferation, up-regulate the expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO), but also endow the materials with good antibacterial properties. Therefore, the method of the present study can be used to modify magnesium alloy stent materials to simultaneously enhance corrosion resistance and blood compatibility, promote endothelialilization, and inhibit infections.

LncRNA GAS5 inhibits the proliferation and invasion of ovarian clear cell carcinoma via the miR-31-5p/ARID1A axis.

To investigate the role of the lncRNA growth arrest special 5 (GAS5) in ovarian clear cell carcinoma (OCCC), we measured the expression of GAS5 and miR-31-5p in OCCC tissue samples and OCCC cell lines using RT-qPCR. MTT and colony formation assays were used to measure cell viability and colony formation ability. Cell invasion was determined by Transwell assays. The binding between GAS5 and miR-31-5p as well as miR-31-5p and ARID1A was determined by dual-luciferase reporter assays. The ARID1A protein levels were detected using western blotting. Kaplan-Meier curves were used for the analysis of the 5-year survival rate of patients with OCCC. GAS5 and ARID1A levels were significantly decreased, while miR-31-5p levels were strongly elevated in the OCCC tissues and cell lines. Patients with lower GAS5/ARID1A levels had shorter overall survival times. Overexpression of GAS5 or inhibition of miR-31-5p suppressed cell viability and invasion of OCCC cells and upregulated the protein levels of ARID1A. Moreover, overexpression of miR-31-5p reversed the effects of overexpression of GAS5. Cotransfection with pcDNA3.1-GAS5 and miR-31-5p inhibitor led to the lowest cell viability and cell invasion rates. A dual-luciferase reporter assay was performed to confirm the target relationship between GAS5 and miR-31-5p, as well as between miR-31-5p and ARID1A. LncRNA GAS5 inhibited cell viability and invasion of OCCC through activation of ARID1A by sponging miR-31-5p.

Tumor Cell Distinguishable Nanomedicine Integrating Chemotherapeutic Sensitization and Protection.

Theoretically, with a high enough drug dosage, cancer cells could be eliminated. However, the dosages that can be administered are limited by the therapeutic efficacy and side effects of the given drug. Herein, a nanomedicine integrating chemotherapeutic sensitization and protection was developed to relieve the limitation of administration dosage and to improve the efficacy of chemotherapy. The nanomedicine was endowed with the function of synergistically controlled release of CO and drugs under near-infrared (NIR) light irradiation. CO photo-induced release system (COPIRS) was synthesized by constructing an electron excitation-electron transfer group-electron-induced CO release structure and was used as the hydrophobic part, and then hydrophilic polymer (polyethylene glycol; PEG) was introduced by a thermal-responsive groups (DA group), forming a near-infrared-induced burst-release nanocarrier. In vitro and in vivo experiments showed that the nanomedicine can distinguish between tumor and normal cells and regulates the resistance of these different cells through the controlled release of carbonic oxide (CO), simultaneously enhancing the efficacy of chemotherapy drugs on tumor cells and chemotherapeutic protection on normal cells. This strategy could solve the current limitations on dosages due to toxicity and provide a solution for tumor cure by chemotherapy.

Loading Gentamicin and Zn2+ on TiO2 Nanotubes to Improve Anticoagulation, Endothelial Cell Growth, and Antibacterial Activities.

Titanium and its alloys are widely used in blood-contacting implantable and interventional medical devices; however, their biocompatibility is still facing great challenges. In the present study, in order to improve the biocompatibility and antibacterial activities of titanium, TiO2 nanotubes were firstly in situ prepared on the titanium surface by anodization, followed by the introduction of polyacrylic acid (PAA) and gentamicin (GS) on the nanotube surface by layer-by-layer assembly, and finally, zinc ions were loaded on the surface to further improve the bioactivities. The nanotubes displayed excellent hydrophilicity and special nanotube-like structure, which can selectively promote the albumin adsorption, enhance the blood compatibility, and promote the growth of endothelial cells to some degree. After the introduction of PAA and GS, although the superhydrophilicity cannot be achieved, the results of platelet adhesion, cyclic guanosine monophosphate (cGMP) activity, hemolysis rate, and activated partial thromboplastin time (APTT) showed that the blood compatibility was improved, and the blood compatibility was further enhanced after zinc ion loading. On the other hand, the modified surface showed good cytocompatibility to endothelial cells. The introduction of PAA and zinc ions not only promoted the adhesion and proliferation of endothelial cells but also upregulated expression of vascular endothelial growth factor (VEGF) and nitric oxide (NO). The slow and continuous release of GS and Zn2+ over 14 days can significantly improve the antibacterial properties. Therefore, the present study provides an effective method for the surface modification of titanium-based blood-contacting materials to simultaneously endow with good blood compatibility, endothelial growth behaviors, and antibacterial properties.

Molecular Antenna-Sensitized Upconversion Nanoparticle for Temperature Monitored Precision Photothermal Therapy.

BACKGROUND: Photothermal therapy with accurate and real-time temperature detection is desired in clinic. Upconversion nanocrystals (UCNs) are candidate materials for simultaneous temperature detection and photothermal agents carrying. However, the weak luminescence and multiple laser excitations of UCNs limit their application in thermal therapy. MATERIALS AND METHODS: NaYF4:Yb3+,Er3+,Nd3+, PL-PEG-NH2, IR-806 and folic acid are selected as structural components. A nanoprobe (NP) integrated with efficient photothermal conversion and sensitive temperature detection capabilities is synthesized for precise photothermal therapy. The probes are based on near-infrared upconversion nanocrystals doped with Yb, Er and Nd ions, which can be excited by 808 nm light. IR-806 dye molecules are modified on the surface as molecular antennas to strongly absorb near-infrared photons for energy transfer and conversion. RESULTS: The results show that under an 808 nm laser irradiation upconversion luminescence of the nanocrystals is enhanced based on both the Nd ion absorption and the FRET energy transfer of IR-806. The luminescence ratio at 520 and 545 nm is calculated to accurately monitor the temperature of the nanoparticles. The temperature of the nanoprobes increases significantly through energy conversion of the molecular antennas. The nanoparticles are found successfully distributed to tumor cells and tumor tissue due to the modification of the biocompatible molecules on the surface. Tumor cells can be killed efficiently based on the photothermal effect of the NPs. Under the laser irradiation, temperature at mouse tumor site increases significantly, tissue necrosis and tumor cell death can be observed. CONCLUSION: Precision photothermal therapy can thus be achieved by highly efficient near-infrared light absorption and accurate temperature monitoring, making it promising for tumor treatment, as well as the biological microzone temperature detection.

Layer-by-layer deposition of bioactive layers on magnesium alloy stent materials to improve corrosion resistance and biocompatibility.

Magnesium alloy is considered as one of the ideal cardiovascular stent materials owing to its good mechanical properties and biodegradability. However, the in vivo rapid degradation rate and the insufficient biocompatibility restrict its clinical applications. In this study, the magnesium alloy (AZ31B) was modified by combining the surface chemical treatment and in-situ self-assembly of 16-phosphonyl-hexadecanoic acid, followed by the immobilization of chitosan-functionalized graphene oxide (GOCS). Heparin (Hep) and GOCS were alternatively immobilized on the GOCS-modified surface through layer by layer (LBL) to construct the GOCS/Hep bioactive multilayer coating, and the corrosion resistance and biocompatibility were extensively explored. The results showed that the GOCS/Hep bioactive multilayer coating can endow magnesium alloys with an excellent in vitro corrosion resistance. The GOCS/Hep multilayer coating can significantly reduce the hemolysis rate and the platelet adhesion and activation, resulting in an excellent blood compatibility. In addition, the multilayer coating can not only enhance the adhesion and proliferation of the endothelial cells, but also promote the vascular endothelial growth factor (VEGF) and nitric oxide (NO) expression of the attached endothelial cells on the surfaces. Therefore, the method of the present study can be used to simultaneously control the corrosion resistance and improve the biocompatibility of the magnesium alloys, which is expected to promote the application of magnesium alloys in biomaterials or medical devices, especially cardiovascular stent.

miR-326 inhibits the cell proliferation and cancer stem cell-like property of cervical cancer in vitro and oncogenesis in vivo via targeting TCF4.

BACKGROUND: Cervical cancer ranks as one of the most prevalent female malignancies globally, and its treatment with new targets has been the focus of current research. The present study set out to investigate the function of microRNA-326 (miR-326) in vitro and in vivo and to verify the direct targeting of transcription factor 4 (TCF4) by miR-326. METHODS: The detection of messenger RNA (mRNA) expressing miR-326 and TCF4 in cervical cancer cell lines and tumor samples was conducted using quantitative real-time polymerase chain (qRT-PCR). A dual-luciferase reporter assay was carried out to detect the target relationship of miR-326 with TCF4. A Cell Counting Kit-8 (CCK-8) assay was employed to detect the effect of miR-326 on CasKi cell viability. Flow cytometry and western blotting were employed to examine the effects of miR-326 on cancer stem cell (CSC)-like property. Tumor weight was measured in orthotopic xenograft mouse models. Immunohistochemistry was employed to analyze the protein expression levels of Ki-67, proliferating cell nuclear antigen (PCNA), CD44, and SRY-box 4 (SOX4). RESULT: Downregulation of the mRNA expression levels of miR-326 was observed in cervical cancer cell lines and tumor tissue, while the levels of TCF4 were upregulated. The dual-luciferase reporter assay revealed binding of miR-326 to the three prime untranslated region (3'-UTR) of TCF4. In vitro assays demonstrated that miR-326 inhibited CasKi cell proliferation through regulating TCF4. miR-326 also suppressed the CSC-like property of CasKi cells by targeting TCF4. Furthermore, the protein expression levels of cyclin D1, ß-catenin, and c-Myc were decreased when miR-326 was added to TCF4-transfected cells. In vivo assays demonstrated that miR-326 inhibited tumor weight, growth, and the protein expression levels of Ki-67, PCNA, CD44, SOX4, and ß-catenin. CONCLUSIONS: miR-326 acted in a tumor-suppressive manner through its regulation of TCF4, and has potential as a biomarker or therapeutic target for cervical cancer.