Construction of PARPi Resistance-related Competing Endogenous RNA Network.

Objective: Ovarian cancer is a kind of common gynecological malignancy in women. PARP inhibitors (PARPi) have been approved for ovarian cancer treatment. However, the primary and acquired resistance have limited the application of PARPi. The mechanisms remain to be elucidated. Methods: In this study, we characterized the expression profiles of mRNA and nonconding RNAs (ncRNAs) and constructed the regulatory networks based on RNA sequencing in PARPi Olaparib-induced ovarian cancer cells. Results: We found that the functions of the differentially expressed genes were enriched in "PI3K/AKT signaling pathway," "MAPK signaling pathway" and "metabolic process". The functions of DELs (cis) were enriched in "Human papillomavirus infection""tight junction" "MAPK signaling pathway". As the central regulator of ceRNAs, the differentially expressed miRNAs were enriched in "Human papillomavirus infection" "MAPK signaling pathway" "Ras signaling pathway". According to the degree of interaction, we identified 3 lncRNAs, 2 circRNAs, 7 miRNAs, and 12 mRNA as the key regulatory ceRNA axis, in which miR-320b was the important mediator. Conclusion: Here, we revealed the key regulatory lncRNA (circRNA)-miRNA-mRNA axis and their involved pathways in the PARPi resistant ovarian cancer cells. These findings provide new insights into exploring the ceRNA regulatory networks and developing new targets for PARPi resistance.

Mechanism of One-Step Hydrothermally Synthesized Titanate Catalysts for Ozonation.

A titanate nanotube catalyst for ozonation was synthesized with a simple one-step NaOH hydrothermal treatment without energy-consuming calcination. The synthesized titania catalysts were characterized by X-ray diffraction (XRD), Raman, porosimetry analysis, high-resolution transmission electron microscopy (HR-TEM), Fourier transformed infrared (FTIR), and electron paramagnetic resonance (EPR) analysis. The catalyst treated with a higher concentration of NaOH was found to be more catalytically active for phenol removal due to its higher titanate content that would facilitate more OH groups on its surface. Furthermore, the main active oxidizing species of the catalytic ozonation process were recognized as singlet oxygen and superoxide radical, while the hydroxyl radical may only play a minor role. This work provides further support for the correlation between the properties of titania and catalytic performance, which is significant for understanding the mechanism of catalytic ozonation with titania-based materials.

Self-reduction synthesis and luminescence properties of Eu, Dy co-doped SrMg2 (PO4 )2 phosphor.

A series of SrMg2 (PO4 )2 :Eu2+ -Eu3+ ,Dy3+ phosphors was synthesized successfully using a high-temperature solid-state method in an air atmosphere. The structures were studied in detail using X-ray diffraction (XRD) and the luminescence properties of the samples. SrMg2 (PO4 )2 :Eu2+ -Eu3+ samples can emit adjustable blue-violet light by controlling the proportion of dopant concentration of europium and dysprosium under 340 nm excitation. Dy3+ exhibits typical blue and yellow emission under 350 nm excitation. The energy transferred from Eu3+ to Dy3+ in Dy and Eu co-doped system was determined by comparing the fluorescence spectra of single-doped system. In addition, the colour coordinates of the International Commission on lighting (CIE) indicated that SrMg2 (PO4 )2 :Eu2+ -Eu3+ ,Dy3+ could be considered as a potential blue-purple phosphor for white light-emitting diode applications.

Cell Models for Birth Defects Caused by Chloroethyl Nitrosourea-Induced DNA Lesions.

ABSTRACT: Birth defects have been linked to administration of alkylating agents during pregnancy. The anti-tumor efficacy of alkylating agents correlate with their ability to induce DNA lesions, especially interstrand crosslinks (ICLs). Yet the role of DNA damages in birth defects remains to be clarified, owing, in part, to a lack of cell models. Here we generate DNA lesions in NIH/3T3 cells to mimic defects in fetus triggered by 3-Bis(2-chloroethyl)-1-nitrosourea (BCNU, carmustine). CCK-8 assay suggests that BCNU-induced cell death was dose-dependent. Alkaline comet tests and γ-H2AX staining confirm DNA ICLs and other forms of DNA damages caused by BCNUs. The cell cycle analysis shows cells arrest in G2/M phase until crosslinks repair is complete. Taken together, all these experiments demonstrate we have successfully established normal cell models for birth defects caused by BCNU-mediated DNA damages. The model can not only guide the development of effective and low-toxicity anticancer drugs, but also be of great significance for the study of neonatal malformation triggered by BCNUs.

Metal Emulsion-Based Synthesis, Characterization, and Properties of Sn-Based Microsphere Phase Change Materials.

A comparative study of the metal emulsion-based synthesis of Sn-based materials in two different types of molten salts (namely LiCl-KCl-CsCl and LiNO3-NaNO3-KNO3 eutectics) is presented, and the properties of Sn, Sn-Cu and Sn-Cu-Zn microsphere phase change materials prepared in chloride salts are evaluated by differential scanning calorimetry (DSC) to understand the effect of element doping. Despite a high ultrasonic power (e.g., 600 W or above) being required for dispersing liquid Sn in the chloride system, well-shaped Sn microspheres with a relatively narrow size range, e.g., about 1 to 15 µm or several micrometers to around 30 µm, can be prepared by adjusting the ultrasonic power (840-1080 W), sonication time (5-10 min) and the volume ratio of salts to metal (25:1-200:1). Such a method can be extended to the synthesis of Sn-based alloy microspheres, e.g., Sn-Cu and Sn-Cu-Zn microspheres. In the nitrate system, however, a very low ultrasonic power (e.g., 12 W) can be used to disperse liquid Sn, and the particles obtained are much smaller. At low ultrasonic power (e.g., 12 W), the particle size is generally less than 10 or 4 µm when the sonication time reaches 2 or 5 min, and at high ultrasonic power, it is typically in the range of hundreds of nanometers to 2 µm, regardless of the change in ultrasonic power (480-1080 W), irradiation time (5-10 min), or volume ratio of salts to metal (25:1-1000:1). In addition, the appearance of a SnO phase in the products prepared under different conditions hints at the occurrence of a reaction between Sn droplets and O2 in situ generated by the ultrasound-induced decomposition of nitrates, and such an interfacial reaction is believed to be responsible for these differences observed in two different molten salt systems. A DSC study of Sn, Sn-Cu, and Sn-Cu-Zn microspheres encapsulated in SiO2 reveals that Cu (0.3-0.9 wt.%) or Cu-Zn (0.9 wt.% Cu and 0.6% Zn) doping can raise the onset freezing temperature and thus suppress the undercooling of Sn, but a broad freezing peak observed in these doped microspheres, along with a still much higher undercooling compared to those of reported Sn-Cu or Sn-Cu-Zn solders, suggests the existence of a size effect, and that a low temperature is still needed for totally releasing latent heat. Since the chloride salts can be recycled by means of the evaporation of water and are stable at high temperature, our results indicate that the LiCl-KCl-CsCl salt-based metal emulsion method might also serve as an environmentally friendly method for the synthesis of other metals and their alloy microspheres.

Clinical characteristics of hospitalized patients with SARS-CoV-2 infection: A single arm meta-analysis.

OBJECTIVE: We aim to summarize reliable evidence of evidence-based medicine for the treatment and prevention of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by analyzing all the published studies on the clinical characteristics of patients with SARS-CoV-2. METHODS: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of SARS-CoV-2 infection were collected for meta-analysis. RESULTS: Ten studies were included in Meta-analysis, including a total number of 50466 patients with SARS-CoV-2 infection. Meta-analysis shows that, among these patients, the incidence of fever was 0.891 (95% CI: 0.818, 0.945), the incidence of cough was 0.722 (95% CI: 0.657, 0.782), and the incidence of muscle soreness or fatigue was 0.425 (95% CI: 0.213, 0.652). The incidence of acute respiratory distress syndrome (ARDS) was 0.148 (95% CI: 0.046, 0.296), the incidence of abnormal chest computer tomography (CT) was 0.966 (95% CI: 0.921, 0.993), the percentage of severe cases in all infected cases was 0.181 (95% CI: 0.127, 0.243), and the case fatality rate of patients with SARS-CoV-2 infection was 0.043 (95% CI: 0.027, 0.061). CONCLUSION: Fever and cough are the most common symptoms in patients with SARS-CoV-2 infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare. The case fatality rate of patients with SARS-CoV-2 infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This meta-analysis also has limitations, so the conclusions of this Meta-analysis still need to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size.

Polymeric hybrid aerogels and their biomedical applications.

Aerogels are a class of porous materials that possess extremely high specific surface area, high pore volume, high porosity, and variable chemical structures. They have been widely applied in the fields of aerospace, chemical engineering, construction, electrotechnics, and biomedicine. In recent years a great boom in aerogels has been observed, where various new aerogels with novel physicochemical properties and functions have been synthesized. Nevertheless, native aerogels with a single component normally face severe problems such as low mechanical strength and lack of functions. One strategy to solve the problems is to construct hybrid aerogels. In this study, a comprehensive review on polymer based hybrid aerogels is presented, including polymer-polymer, polymer-carbon material, and polymer-inorganic hybrid aerogels, which will be introduced and discussed in view of their chemical structures and hybrid structures. Most importantly, polymeric hybrid aerogels are classified into three different composition levels, which are molecular-level, molecular-aggregate-level, and aggregate-level, due to the fact that hybrid aerogels with the same chemical structures but with different composition levels might show quite different functions or properties. The biomedical applications of these hybrid aerogels will also be reviewed and discussed, where the polymeric components in the hybrid aerogels provide the main contribution. This review would provide creative design principles for aerogels by considering both their chemical and physical structures.

In-air self-reduction synthesis and colour tunable luminescence from SrBPO5 :Eu2+ -Eu3+ excited using ultraviolet light.

SrBPO5 :Eu2+ -Eu3+ phosphors were synthesized using a conventional solid self-reduction reaction in an air atmosphere. Samples were characterized using thermogravimetry analysis (TGA), differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectra, fluorescence spectra and Commission International de l'Eclairage (CIE) data. The results of TGA and DSC showed that the raw materials could completely react at 1000°C. FTIR spectra and XRD results displayed that europium ions of different concentrations do not effect the structure of the hosts. Fluorescence spectra displayed that europium ions exist in bivalent and trivalent forms, and that the emission peak at 403 nm was attributed to the typical 5d-4f transition for Eu2+ ; 597 nm and 620 nm emissions were assigned to the characteristic transitions of 5 D0 -7F1, 2 for Eu3+ . CIE results depicted that the colour tone of the phosphors could be macro-controlled from blue to purple by controlling the doping amount of Eu3+ .Therefore, relative luminescence intensity between Eu2+ and Eu3+ could be adjusted by controlling the doping concentration of europium to tune the luminescence colour of SrBPO5 .

Analysis of trace organics and its correlation with COD in condensate from natural gas to hydrogen production.

Qualitative and quantitative analysis of trace organics in the condensate and its correlation with chemical oxygen demand (COD) is the key to the research on the reuse technology of condensate (condensate) from natural gas to hydrogen production process. The contents of anions, COD, total organic carbon (TOC) and total nitrogen (TN) were measured by ion chromatography and the TOC analyzer. Trace organics in the condensate and its correlation with COD was investigated in this paper. Results show that the contents of COD and TOC is 74.1 and 17.81 mg/L, respectively, and the anions in the condensate are mainly Cl-, I-, and SO4 2-, etc. The condensate mainly contains small molecule organics including methanol, ethanol and formic acid with the content of 41.4, 2.1 and 3.2 mg/L, respectively. The spiked recovery of methanol, ethanol and formic acid is 96.1%, 100.2% and 103.9% by high performance liquid chromatography (HPLC) and gas chromatography (GC), respectively. Methanol is the main source of COD in the condensate, and the contribution rate reaches up to 83.8%. The removal of trace methanol can significantly reduce the COD of the condensate. This work might provide basic data for reasonable recovery and utilization of condensate in the hydrogen production process.

A study on the protective effects of CpG oligodeoxynucleotide-induced mucosal immunity against lung injury in a mouse acute respiratory distress syndrome model.

This study aims to determine the feasibility of using oligodeoxynucleotides with unmethylated cytosine-guanine dinucleotide sequences (CpG ODN) as an immunity protection strategy for a mouse model of acute respiratory distress syndrome (ARDS). This is a prospective laboratory animal investigation. Twenty-week-old BALB/c mice in Animal research laboratory were randomized into groups. An ARDS model was induced in mice using lipopolysaccharides (LPSs). CpG ODN was intranasally and transrectally immunized before or after the 3rd and 7th days of establishing the ARDS model. Mice were euthanized on Day 7 after the second immunization. Then, retroorbital bleeding was carried out and the chest was rapidly opened to collect the trachea and tissues from both lungs for testing. CpG ODN significantly improved the pathologic impairment in mice lung, especially after the intranasal administration of 50 µg. This resulted in the least severe lung tissue injury. Furthermore, interleukin-6 (IL-6) and IL-8 concentrations were lower, which was second to mice treated with the rectal administration of 20 µg CpG ODN. In contrast, the nasal and rectal administration of CpG ODN in BALB/c mice before LPS immunization did not appear to exhibit any significant protective effects. The intranasal administration of CpG ODN may be a potential treatment approach to ARDS. More studies are needed to further determine the protective mechanism of CpG ODN.

Melatonin improves functional recovery in female rats after acute spinal cord injury by modulating polarization of spinal microglial/macrophages.

Spinal cord injury (SCI) is a devastating neurological disorder, but few drugs have proven to be effective for its treatment. Neuroinflammation exaggerates the secondary injury subsequent to trauma. Emerging evidence suggests that melatonin may help protect neural tissue against secondary injury after SCI, but the underlying mechanisms remain elusive. Microglial/macrophages polarization plays an important role in regulating immune responses. To examine whether melatonin exerts neuroprotective effects after acute SCI by regulating microglial/macrophages polarization in the spinal cord, we administered intraperitoneal injections of melatonin (50 mg/kg) in female rats immediately after SCI and then daily for seven consecutive days (n = 6). Compared with the vehicle-treated group (n = 6), the melatonin-treated group exhibited a greater Basso, Beattie, and Bresnahan locomotor rating score, smaller spinal cavity, and less cleaved caspase 3 immunofluorescence staining in the injured spinal segments. Real-time PCR data revealed decreases in the expression levels of M1 microglia phenotypic markers and increases in M2 markers in the spinal cord of melatonin-treated SCI rats, as compared to levels in the vehicle-treated group. Melatonin increased the number of CD206+ and Arg1+ cells, decreased the number of CD16+ and iNOS+ cells and reduced the levels of pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in the spinal cord tissue of female SCI rats. Current findings suggest that melatonin may inhibit pro-inflammatory responses and promote M2 polarization of microglial/macrophages in the spinal cord in the early stage of SCI, facilitating functional recovery. Accordingly, melatonin may represent a promising therapeutic candidate for acute SCI.

Catalytic Performance of Nitrogen-Doped Activated Carbon Supported Pd Catalyst for Hydrodechlorination of 2,4-Dichlorophenol or Chloropentafluoroethane.

Nitrogen-doped activated carbon (N-AC) obtained through the thermal treatment of a mixture of HNO3-pretreated activated carbon (AC) and urea under N2 atmosphere at 600 °C was used as the carrier of Pd catalyst for both liquid-phase hydrodechlorination of 2,4-dichlorophenol (2,4-DCP) and gas-phase hydrodechlorination of chloropentafluoroethane (R-115). The effects of nitrogen doping on the dispersion and stability of Pd, atomic ratio of Pd/Pd2+ on the surface of the catalyzer, the catalyst's hydrodechlorination activity, as well as the stability of N species in two different reaction systems were investigated. Our results suggest that, despite no improvement in the dispersion of Pd, nitrogen doping may significantly raise the atomic ratio of Pd/Pd2+ on the catalyst surface, with a value of 1.2 on Pd/AC but 2.2 on Pd/N-AC. Three types of N species, namely graphitic, pyridinic, and pyrrolic nitrogen, were observed on the surface of Pd/N-AC, and graphitic nitrogen was stable in both liquid-phase hydrodechlorination of 2,4-DCP and gas-phase hydrodechlorination of R-115, with pyridinic and pyrrolic nitrogen being unstable during gas-phase hydrodechlorination of R-115. As a result, the average size of Pd nanocrystals on Pd/N-AC was almost kept unchanged after liquid-phase hydrodechlorination of 2,4-DCP, whereas crystal growth of Pd was clearly observed on Pd/N-AC after gas-phase hydrodechlorination of R-115. The activity test revealed that Pd/N-AC exhibited a much better performance than Pd/AC in liquid-phase hydrodechlorination of 2,4-DCP, probably due to the enhanced stability of Pd exposed to the environment resulting from nitrogen doping as suggested by the higher atomic ratio of Pd/Pd2+ on the catalyst surface. In the gas-phase hydrodechlorination of R-115, however, a more rapid deactivation phenomenon occurred on Pd/N-AC than on Pd/AC despite a higher activity initially observed on Pd/N-AC, hinting that the stability of pyridinic and pyrrolic nitrogen plays an important role in the determination of catalytic performance of Pd/N-AC.

A Self-Supported CuO/Cu Nanowire Electrode as Highly Efficient Sensor for COD Measurement.

A self-supported CuO/Cu nanowire electrode (CuO/CuNWE), which was prepared by annealing Cu nanowires to form a porous Cu nanowire electrode (CuNWE) and then anodizing the as-prepared CuNWE in alkaline medium to generate Cu(OH)2 nanowires followed by calcination, was employed for chemical oxygen demand (COD) determination using cyclic voltammetry (CV). The structure and electrochemical behavior of the CuO/CuNWE were investigated by scanning electron microscopy, X-ray diffraction, and CV. The results indicated that the as-synthesized CuO/CuNWE, in which CuO nanowires with a length of several micrometers and a diameter of 100 to 300 nm could be found, was stable in alkaline medium and more electrocatalytically active for oxidizing a wide range of organic compounds in comparison with the CuNWE. Under optimized alkaline concentration and scan rate, the CuO/CuNWE exhibited a good performance for COD measurement, with a linear range of 5 to 1153 mg L-1, a sensitivity of 2.46× 10-2 mA /(mg L-1), and a detection limit of about 2.3 mg L-1. In addition, an excellent correlation was observed in COD values obtained by our method and the classic dichromate method (r = 0.9995, p < 0.01, n = 11). Finally, our method was successfully used to measure the COD values in real water samples, showing great potential for practical application in water pollution control.

Splenic responses play an important role in remote ischemic preconditioning-mediated neuroprotection against stroke.

BACKGROUND: Remote ischemic preconditioning (RIPC) of a limb has been reported to protect against ischemic stroke. Our previous results demonstrated that the RIPC-mediated neuroprotection is associated with alterations in circulating immune cell populations. Here, we evaluated the effect of the spleen, the largest reservoir of immune cells, on RIPC-mediated neuroprotection against stroke. METHODS: Noninvasive RIPC was achieved by four repeated cycles of 5-min blood flow constriction in the hindlimbs using a tourniquet. The blood and spleens were collected before and 1 h and 3 days after preconditioning to analyze the effect of RIPC on the spleen and the correlation between splenic and peripheral lymphocytes. Moreover, spleen weight and splenic lymphocytes were compared in stroke rats with or without RIPC. Finally, splenectomy was made 1 day or 2 weeks before RIPC and 90-min middle cerebral artery occlusion (MCAO). The infarct areas and deficits were assessed. Blood was collected 1 h after RIPC and 3 days after MCAO to explore the impact of splenectomy on RIPC-induced neuroprotection and immune changes. The contralateral and ipsilateral hemispheres were collected 3 days after MCAO to detect the infiltration of immune cells after RIPC and splenectomy. RESULTS: Flow cytometry analysis demonstrated that the RIPC promptly increased the percentages of CD3+CD8+ cytotoxic T (Tc) cells in the spleen with a relatively delayed elevation in CD3+CD161+ natural killer T (NKT) and CD3-CD45RA+ B lymphocytes. The percentages of circulating lymphocytes are positively correlated with the percentages of splenic lymphocytes in normal rats. Interestingly, RIPC resulted in negative correlations between the percentages of splenic and circulating T lymphocytes, while the correlation between splenic and circulating B lymphocytes remained positive. For animals subjected to RIPC followed by MCAO, RIPC increased splenic volume with an expansion of splenic lymphocytes 3 days after MCAO. Furthermore, the removal of the spleen 1 day or 2 weeks before RIPC and MCAO reduced the protective effect of RIPC on ischemic brain injury and reversed the effects of RIPC on circulating immune cell composition. RIPC significantly reduced brain infiltration of Tc and NKT cells. Prior splenectomy showed no effect on immune cell infiltration after RIPC and stroke. CONCLUSION: These results reveal an immunomodulatory effect of the spleen, effecting mainly the spleen-derived lymphocytes, during RIPC-afforded neuroprotection against cerebral ischemia.

Palladium-Catalyzed Regioselective Hydroaminocarbonylation of Alkynes to α,ß-Unsaturated Primary Amides with Ammonium Chloride.

α,ß-Unsaturated primary amides have found numerous applications in drug development, organic materials, and polymer sciences. However, the catalytic synthesis of α,ß-unsaturated primary amides via carbonylation of alkynes has long been an elusive endeavor. Here, we report a novel palladium-catalyzed hydroaminocarbonylation of alkynes with NH4Cl as the amine source, enabling the highly chemo- and regioselective synthesis of α,ß-unsaturated primary amides. A variety of alkynes, including aromatic alkynes, aliphatic alkynes, terminal alkynes, internal alkynes, as well as diynes with various functional groups, react well. The method turns the parasitic noncoordination ability of ammonium salts into a strategic advantage, enabling the gram-scale reaction to be performed in the presence of 0.05 mol % of catalyst with excellent selectivity.

Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke.

Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia. This study assessed the impact of regulatory T cells in the context of tPA-induced brain haemorrhage and investigated the underlying mechanisms of action. The number of circulating regulatory T cells in stroke patients was dramatically reduced soon after stroke onset (84 acute ischaemic stroke patients with or without intravenous tPA treatment, compared to 115 age and gender-matched healthy controls). Although stroke patients without tPA treatment gradually repopulated the numbers of circulating regulatory T cells within the first 7 days after stroke, post-ischaemic tPA treatment led to sustained suppression of regulatory T cells in the blood. We then used the murine suture and embolic middle cerebral artery occlusion models of stroke to investigate the therapeutic potential of adoptive regulatory T cell transfer against tPA-induced haemorrhagic transformation. Delayed administration of tPA (10 mg/kg) resulted in haemorrhagic transformation in the ischaemic territory 1 day after ischaemia. When regulatory T cells (2 × 106/mouse) were intravenously administered immediately after delayed tPA treatment in ischaemic mice, haemorrhagic transformation was significantly decreased, and this was associated with improved sensorimotor functions. Blood-brain barrier disruption and tight junction damages were observed in the presence of delayed tPA after stroke, but were mitigated by regulatory T cell transfer. Mechanistic studies demonstrated that regulatory T cells completely abolished the tPA-induced elevation of MMP9 and CCL2 after stroke. Using MMP9 and CCL2 knockout mice, we discovered that both molecules partially contributed to the protective actions of regulatory T cells. In an in vitro endothelial cell-based model of the blood-brain barrier, we confirmed that regulatory T cells inhibited tPA-induced endothelial expression of CCL2 and preserved blood-brain barrier integrity after an ischaemic challenge. Lentivirus-mediated CCL2 knockdown in endothelial cells completely abolished the blood-brain barrier protective effect of regulatory T cells in vitro. Altogether, our studies suggest that regulatory T cell adoptive transfer may alleviate thrombolytic treatment-induced haemorrhage in stroke victims. Furthermore, regulatory T cell-afforded protection in the tPA-treated stroke model is mediated by two inhibitory mechanisms involving CCL2 and MMP9. Thus, regulatory T cell adoptive transfer may be useful as a cell-based therapy to improve the efficacy and safety of thrombolytic treatment for ischaemic stroke.

Molecular and Bioinformatics Analyses Identify 7 Circular RNAs Involved in Regulation of Oncogenic Transformation and Cell Proliferation in Human Bladder Cancer.

BACKGROUND Circular RNAs (circRNAs) have emerged as important regulators in carcinogenesis and metastasis. However, the knowledge of circRNAs in bladder cancer remains limited. This study aimed to investigate the role and mechanism of circRNAs in the development and progression of bladder cancer. MATERIAL AND METHODS Three pairs of bladder carcinomas (including high- and low-grade tumors) and adjacent normal tissues were collected from patients. The total RNAs were extracted from these samples and subjected to Clariom D microarray assays to detect the differentially expressed circRNAs and mRNAs. The mRNA targets for these circRNAs were predicted by miRanda in combination with stringent differential mRNA filters. The interaction network for the circRNA-mRNA pairs was generated by Cytoscape. RESULTS Among the 1038 circRNAs detected by the Clariom D microarray assay, we identified 7 significantly differentially expressed circRNAs in the tumors (fold change >2, FDR <0.05). Principal component analysis of the differential circRNAs confirmed that the tumor samples were separated from the normal samples. Hierarchical clustering analyses on these RNAs and their predicted mRNA targets showed that the majority of differentially expressed circRNAs and mRNAs had been up-regulated in the bladder tumors. KEGG signaling pathway analysis has indicated that genes involved in cell proliferation, oncogenic transformation, and metastasis are potentially regulated by these circRNAs. CONCLUSIONS The current study provides a molecular basis for further investigating the mechanisms by which circRNAs regulate bladder cancer. The clinical significance of the identified circRNAs is highlighted by their potentials as diagnostic and prognostic biomarkers for bladder cancer patients.

Effect of the grafting ratio of poly(N-isopropylacrylamide) on thermally responsive polymer brush surfaces.

Four kinds of poly(N-isopropylacrylamide)-grafted silicas with different grafting ratios and the same grafting density were prepared by atom transfer radical polymerization. The chemical groups in the stationary phase was verified by FTIR spectroscopy, and the content of elements was measured by elemental analysis. The grafting ratio of thermoresponsive chromatographic materials was measured by thermogravimetric analysis and was 2.36-21.10% mg/m2 . The retention behaviors of the stationary phase with different grafting ratios were evaluated by separating five kinds of steroids and ten kinds of different hydrophobic properties compounds. With the increase in grafting ratio, the retention time of analytes was prolonged in high-performance liquid chromatography. The results showed that grafting ratio had a significant influence on the separation effect under the same grafting density. And the optimal grafting ratio of poly(N-isopropylacrylamide) was 5.81-13.15%.

Ethanol and normobaric oxygen: novel approach in modulating pyruvate dehydrogenase complex after severe transient and permanent ischemic stroke.

BACKGROUND AND PURPOSE: Ischemic stroke induces metabolic disarray. A central regulatory site, pyruvate dehydrogeanse complex (PDHC) sits at the cross-roads of 2 fundamental metabolic pathways: aerobic and anaerobic. In this study, we combined ethanol (EtOH) and normobaric oxygen (NBO) to develop a novel treatment to modulate PDHC and its regulatory proteins, namely pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase, leading to improved metabolism and reduced oxidative damage. METHODS: Sprague-Dawley rats were subjected to transient (2, 3, or 4 hours) middle cerebral artery occlusion followed by 3- or 24-hour reperfusion, or permanent (28 hours) middle cerebral artery occlusion without reperfusion. At 2 hours after the onset of ischemia, rats received either an intraperitoneal injection of saline, 1 dose of EtOH (1.5 g/kg) for 2- and 3-hour middle cerebral artery occlusion, 2 doses of EtOH (1.5 g/kg followed by 1.0 g/kg in 2 hours) in 4 hours or permanent middle cerebral artery occlusion, and EtOH+95% NBO (at 2 hours after the onset of ischemia for 6 hours) in permanent stroke. Infarct volumes and neurological deficits were examined. Oxidative metabolism and stress were determined by measuring ADP/ATP ratio and reactive oxygen species levels. Protein levels of PDHC, pyruvate dehydrogenase kinase, and pyruvate dehydrogenase phosphatase were assessed. RESULTS: EtOH induced dose-dependent neuroprotection in transient ischemia. Compared to EtOH or NBO alone, NBO+EtOH produced the best outcomes in permanent ischemia. These therapies improved brain oxidative metabolism by decreasing ADP/ATP ratios and reactive oxygen species levels, in association with significantly raised levels of PDHC and pyruvate dehydrogenase phosphatase, as well as decreased pyruvate dehydrogenase kinase. CONCLUSIONS: Both EtOH and EtOH+NBO treatments conferred neuroprotection in severe stroke by affecting brain metabolism. The treatment may modulate the damaging cascade of metabolic events by bringing the PDHC activity back to normal metabolic levels.