Safety and Tolerability of Direct Ischemic Postconditioning Following Thrombectomy for Acute Ischemic Stroke.

BACKGROUND: Experimental studies have demonstrated the neuroprotection of ischemic postconditioning (IPostC) in acute ischemic stroke by attenuating ischemia-reperfusion injury. This study aimed to investigate the safety and tolerability of direct IPostC in both a dog model and patients with acute ischemic stroke treated with thrombectomy. METHODS: The study involved 2 parts. First, IPostC was induced by repeated balloon inflation and deflation in dogs, where a low-pressure balloon was navigated to the anterior spinal artery, and 4 cycles of 5-minute ischemia followed by 5-minute reperfusion were performed. Vascular injuries were assessed using angiography and vascular tissue specimens. Then, a 3+3 dose-escalation trial was conducted in patients with acute ischemic stroke following successful thrombectomy recanalization. Patients received direct IPostC with ischemia and reperfusion durations in progressive increments of 0, 1, 2, 3, 4, and 5 minutes ×4 cycles. Major adverse responses were defined as vessel perforation, rupture, dissection, reocclusion, severe vasospasm, thrombotic events, and rupture of the balloon. RESULTS: IPostC was investigated in 4 dogs. No vessel perforation or rupture, dissection, or vasospasm was observed under the angiography. Only 1 vessel experienced mild injury between the intima and the internal elastic membrane detected on a histopathologic slide. Then, 18 patients were recruited. The duration of IPostC was progressively escalated with no major response happened. No patient experienced agitation, discomfort, or other tolerability issues. Five patients (27.8%) experienced any intracranial hemorrhage after thrombectomy, and 1 (5.6%) was symptomatic. At 3-month follow-up, no patient died, and 9 patients (50%) achieved functional independence. CONCLUSIONS: Direct IPostC inducing by 4 cycles of 5-minute ischemia followed by 5-minute reperfusion is safe, feasible, and tolerable in patients with acute ischemic stroke treated with thrombectomy. Further investigations are needed to determine the safety and preliminary efficacy of direct IPostC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05153655.

Interleukin-34 deficiency aggravates development of colitis and colitis-associated cancer in mice.

BACKGROUND: Although expression of interleukin (IL)-34 is upregulated in active ulcerative colitis (UC), the molecular function and underlying mechanism are largely unclear. AIM: To investigate the function of IL-34 in acute colitis, in a wound healing model and in colitis-associated cancer in IL-34-deficient mice. METHODS: Colitis was induced by administration of dextran sodium sulfate (DSS), and carcinogenesis was induced by azoxymethane (AOM). Whether the impact of IL-34 on colitis was dependent on macrophages was validated by depletion of macrophages in a murine model. The association between IL-34 expression and epithelial proliferation was studied in patients with active UC. RESULTS: IL-34 deficiency aggravated murine colitis in acute colitis and in wound healing phase. The effect of IL-34 on experimental colitis was not dependent on macrophage differentiation and polarization. IL-34-deficient mice developed more tumors than wild-type mice following administration of AOM and DSS. No significant difference was shown in degree of cellular differentiation in tumors between wild-type and IL-34-deficient mice. IL-34 was dramatically increased in the active UC patients as previously reported. More importantly, expression of IL-34 was positively correlated with epithelial cell proliferation in patients with UC. CONCLUSION: IL-34 deficiency exacerbates colonic inflammation and accelerates colitis-associated carcinogenesis in mice. It might be served as a potential therapeutic target in UC.

Predictive Value of the Serum Matrix Metalloproteinase-9 Level on Hepatic Encephalopathy in Patients with Chronic Liver Disease.

BACKGROUND: Early diagnosis of hepatic encephalopathy (HE) in chronic liver disease (CLD) is difficult clinically. OBJECTIVE: The aim of this study was to evaluate whether serum matrix metalloproteinase-9 (MMP-9) levels could identify early HE in patients with CLD. METHODS: Serum MMP-9 levels in 1,187 patients with CLD were measured at baseline. A total of 1,187 patients with CLD were followed for a mean of 48 months (range: 4-50). The association between MMP-9 and the risk of HE was evaluated by logistic regression analysis and Cox regression analysis. RESULTS: Patients with higher serum MMP-9 levels had higher rates of HE history and HE events during follow-up (all P<0.001). The multivariate logistic regression analysis revealed that MMP-9 (OR=2.84, 95% CI 1.63-7.11, P=0.004) was independently associated with HE history, with an increased grade of aggravation on liver fibrosis at baseline. Multivariate Cox proportional hazard analysis revealed that MMP-9 (HR=2.21, 95% CI 1.09-5.02, P<0.001) was an independent predictor for HE events by sensitivity analysis. The Kaplan-Meier analysis demonstrated that patients with MMP-9 above the median value (176.2 mg/d) had a higher rate of new HE events than patients who had MMP-9 levels below the median value (P<0.001). CONCLUSIONS: Elevated serum RBP4 levels were associated with a higher risk of HE events during follow-up. These results may suggest that serum MMP-9 has good predictive value for detecting HE in patients with CLD, which provides some clinical reference value to clinicians for the early diagnosis of HE.

Hierarchical Mesoporous Organosilica-Silica Core-Shell Nanoparticles Capable of Controlled Fungicide Release.

A new class of hierarchically structured mesoporous silica core-shell nanoparticles (HSMSCSNs) with a periodic mesoporous organosilica (PMO) core and a mesoporous silica (MS) shell is reported. The applied one-pot, two-step strategy allows rational control over the core/shell chemical composition, topology, and pore/particle size, simply by adjusting the reaction conditions in the presence of cetyltrimethylammonium bromide (CTAB) as structure-directing agent under basic conditions. The spherical, ethylene- or methylene-bridged PMO cores feature hexagonal (p6mm) or cage-like cubic symmetry (Pm3‾ n) depending on the organosilica precursor. The hexagonal MS shell was obtained by n-hexane-induced controlled hydrolysis of TEOS followed by directional co-assembly/condensation of silicate/CTAB composites at the PMO cores. The HSMSCSNs feature a hierarchical pore structure with pore diameters of about 2.7 and 5.6 nm in the core and shell domains, respectively. The core sizes and shell thicknesses are adjustable in the ranges of 90-275 and 15-50 nm, respectively, and the surface areas (max. 1300 m2 g-1 ) and pore volumes (max. 1.83 cm3 g-1 ) are among the highest reported for core-shell nanoparticles. The adsorption and controlled release of the fungicide propiconazole by the HSMSCSNs showed a three-stage release profile.

Correction: Nano-sized Al2O3 reduces acute toxic effects of thiacloprid on the non-biting midge Chironomus riparius.

[This corrects the article DOI: 10.1371/journal.pone.0176356.].

Nano-sized Al2O3 reduces acute toxic effects of thiacloprid on the non-biting midge Chironomus riparius.

This study focuses on interactions between nanoparticles and a pesticide. The aim was to investigate how nano-sized aluminum oxide (410 nm) can alter the toxic effects of thiacloprid, even if no sorption between particles and the insecticide takes place. Thus, our study investigated a rather unexplored interaction. We conducted our research with larvae of Chironomus riparius and used thiacloprid as test substance as its toxicity to C. riparius is well described. The used nano-Al2O3 particles where chosen due to their suitable properties. For testing the acute effects of the interaction, we exposed larvae to thiacloprid (0.5, 1.0, 2.0, and 5.0 µg/L) and nano-Al2O3 (300 and 1000 mg/L), either solely or in binary mixtures. While thiacloprid resulted in elevated mortality, nano-Al2O3 solely did not exert any effects. Moreover, we observed an aggregation of nano-Al2O3 within the lumen of the intestinal tract of the larvae. Further results showed a significantly reduced mortality of fourth instar larvae when they were exposed to mixtures of nanoparticles and the pesticide, compared to thiacloprid alone. With increasing nano-Al2O3 concentration, this effect became gradually stronger. Additionally, chemical analyses of internal thiacloprid concentrations implicate reduced uptake of thiacloprid in animals exposed to mixtures. However, as larvae exposed to thiacloprid concentrations > 0.5 µg/L showed severe convulsions, independent of the presence or concentration of nano-Al2O3, we assume that nano-Al2O3 leads to a delay of mortality and does not entirely prevent it. As sorption measurements on pristine or defecated nano-Al2O3 did not reveal any sorptive interaction with thiacloprid, we can exclude sorption-based reduction of thiacloprid bioavailability as a mechanism behind our results. Even though we used test substances which might not co-occur in the environment in the tested concentrations, our study gives evidence for an interaction besides adsorption, which is important to generally understand how nanoparticles might affect biota.

Monodisperse mesoporous silica nanoparticles of distinct topology.

Monodisperse and uniform high-quality MCM(Mobil Composition of Matter)-48-type CMSNs (Cubic Mesoporous Silica Nanoparticles) are readily prepared by simply optimizing the molar ratio of ethanol and surfactant in the system TEOS-CTAB-NaOH-H2O-EtOH (TEOS=tetraethyl orthosilicate, CTAB=cetyltrimethylammonium bromide, EtOH=ethanol). In the absence of ethanol only hexagonal mesoporous silica with ellipsoidal and spherical morphology are obtained. The presence of ethanol drives a mesophase transformation from hexagonal to mixed hexagonal/cubic, further to purely cubic, and finally to a mixed cubic/lamellar. This is accompanied by a morphology evolution involving a mixture of ellipses/spheres, regular rods, uniform spheres, and finally a mixture of spheres/flakes. Preserving the three-dimensional (3D) cubic MCM-48 structure, use of a small amount of ethanol is beneficial to the improvement of the monodispersity of the CMSNs. Moreover, the quality of the CMSNs can also be controlled by changing the surfactant concentration or adjusting the stirring rate. All MSNs were characterized using powder X-ray diffraction, transmission electron microscopy, scanning electron microscopy, and N2 physisorption, indicating highly long-range ordered pore arrays, high specific surface areas (max. 1173 m2g-1) as well as high pore volumes (max. 1.14 cm3g-1). The monodispersity of the CMSNs was verified by statistical particle size distribution from SEM (scanning electron microscopy)/TEM (transmission electron microscopy) images and DLS (dynamic light scattering). The mesophase transformation can be rationalized on the basis of an ethanol-driven change of the surfactant packing structure and charge matching at the surfactant/silicate interface. The corresponding morphology evolution can be elucidated by an ethanol-controlled hydrolysis rate of TEOS and degree of condensation of oligomeric silicate species via a nucleation and growth process.

Synthesis and characterization of visible light driven mesoporous nano-photocatalyst MoO3/TiO2.

A novel mesoporous-structured photocatalyst MoO3/TiO2 was synthesized through a modified sol-gel method by using P123 as the template, and the resulting nano-photocatalysts were characterized by X-ray diffraction (XRD), N2 adsorption measurements, transmission electron microscope (TEM), UV-vis spectroscopy, XPS and Raman techniques. Low-angle XRD and TEM images show the lack of long-range order in the as-prepared MoO3/TiO2, but the Mo species are homogenously dispersed on the anatase matrix. According to the results of N2 ads-desorption, the calcined products possess the high surface area and the pore size distribution centered between 4-7 nm. The calcined meso-MoO3/TiO2 materials exhibit the high photocatalytic activity for the degradation of MB (methylene blue) under visible light radiation.

Hyperbranched polymeric N-oxide: a novel kind of metal-free photocatalyst.

A N-O bond is introduced into hyperbranched polyimide photocatalysts for the first time to change their polarity and modulate electronic structure. Both of the changes help improve the photocatalytic ability of the polyimide. This strategy shows great prospect for synthesizing effective organic photocatalysts.

An efficient visible light controlled protein delivery system.

A visible light triggered protein delivery system has been assembled through hydroxyl coordinated onto titania nanoparticles. Biomolecules such as hemoglobin (Hb) can be controlled-released from the hybrid material TiO(2)-DB-Hb by switching visible light on/off. The released Hb not only retains its senior structure but also can fulfil the enzymatic bioactivity. Controlled delivery of Hb stems from the scission of the Ti-O coordination bond with the aid of photo-inducing electron transfer property of titania.

Serum APRIL, a potential tumor marker in pancreatic cancer.

BACKGROUND: A proliferation-inducing ligand (APRIL) is a newly-found member in the tumor necrosis factor (TNF) superfamily. Our previous studies have already confirmed that APRIL is overexpressed in pancreatic cancer tumors, however, it is not expressed or has a weak expression in normal pancreatic gland tissues. Furthermore, there is no report on serum APRIL in patients with pancreatic diseases. Herein, in order to explore the clinical implication of serum APRIL in patients with pancreatic cancer, serum APRIL, together with carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9, was examined. METHODS: Serum APRIL was tested by ELISA in patients with pancreatic cancer. Meanwhile, two other conventional serum tumor markers, CEA and CA19-9, were measured by Elecsys 2010 Chemistry Analyzer. RESULTS: Serum APRIL increased in patients with pancreatic cancer, which proved a positive correlation with CEA and CA19-9. When the diagnosis of benign or malignant condition was examined by one tumor marker, the sensitivity of APRIL alone (70.1%) was greater than that of CEA alone (56.7%), and the specificity of APRIL alone (85.5%) was higher than that of CA19-9 alone (83.6%). When examined by a combination of two markers, the sensitivity of the combination of APRIL and CA19-9 was the highest (88.1%), as it was compared with that of APRIL alone, CEA alone and APRIL+CEA, p<0.05. In addition, serum APRIL also correlated with the tumor stage and postoperative survival in patients with pancreatic cancer. CONCLUSIONS: Our results indicate that serum APRIL, as a potential biomarker, has a positive diagnosis and prognosis value for pancreatic cancer. Moreover, the combination assay of APRIL and CA19-9 is highly sensitive to pancreatic cancer.