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The fluorescent nanoparticles with aggregation-induced emission have caused tremendous research interest. In this work, the polycarbonates-based fluorescent nanoparticles with aggregation-induced emission (AIE) have been prepared by a facile and efficient approach of ring-opening polymerization and click chemistry. The tetraphenylethylene moieties that feature the AIE characteristics can be facilely grafted onto the polymer main chain by click reaction between azide-terminated tetraphenylethene derivative and alkyne-bearing amphiphilic block copolymer poly(ethylene glycol)-block-poly(5-methyl-5-propargylxycarbonyl-1,3-dioxane-2-one). The resulted tetraphenylethylene substituted block copolymers possess amphiphilic properties and are able to self-assemble into fluorescent polymeric nanoparticles. Based on cellular imaging experiments, we demonstrated that these fluorescent nanoparticles have great potential for cells imaging applications due to their attractive properties including strong fluorescence intensity, great water dispersibility, excellent biocompatibility and high cellular uptake efficiency.

pH-sensitive betulinic acid (BA) polymer prodrug nanoparticles, have been proposed. The carboxyl group-terminated poly[2-(3-butenyl)-2-oxazoline] (PBuOx-COOH) is prepared by cationic ring-opening p...

ObjectiveThe physical and neuromental development of infants remains uncertain after fetal exposure to tenofovir disoproxil fumarate (TDF) for the prevention of mother-to-child transmission of HBV. We aimed to investigate the safety of TDF therapy during the third trimester of pregnancy.DesignInfants from a previous randomised controlled trial were recruited for our long-term follow-up (LTFU) study. Mothers with chronic hepatitis B were randomised to receive TDF therapy or no treatment during the third trimester. Infants’ physical growth or malformation, bone mineral density (BMD) and neurodevelopment, as assessed using Bayley-III assessment, were examined at 192 weeks of age.ResultsOf 180 eligible infants, 176/180 (98%) were enrolled and 145/176 (82%) completed the LTFU (control group: 75; TDF-treated group: 70). In the TDF-treated group, the mean duration of fetal exposure to TDF was 8.57±0.53 weeks. Congenital malformation rates were similar between the two groups at week 192. The mean body weight of boys in the control and TDF-treated groups was significantly higher (19.84±3.46 kg vs. 18.47±2.34 kg; p=0.03) and within the normal range (18.48±2.35 kg vs. 17.80±2.50 kg; p=0.07), respectively, when compared with the national standard. Other prespecified outcomes (head circumference, height, BMD, and cognitive, motor, social–emotional, and adaptive behaviour measurements) were all comparable between the groups.ConclusionInfants with fetal exposure to TDF had normal physical growth, BMD and neurodevelopment at week 192. Our findings provide evidence on the long-term safety of infants after fetal exposure to maternal TDF therapy for preventing hepatitis B transmission.Trial registration numberNCT01488526.

An interesting activatable fluorescent imaging probe based on a graphene oxide–coumarin derivative conjugate with high sensitivity in cancer cell visualization was proposed. The nanoprobe has a fluorescence off–on response for intracellular imaging via covalently linking coumarin derivatives to graphene oxide (GO) through disulfide bonds. The obtained nanoprobe shows no or weak fluorescence (OFF) most likely due to the fluorescence resonance energy transfer from the coumarin moiety to GO. It becomes activated (ON) inside the cells by glutathione initiated dissociation, showing remarkably enhanced fluorescence. More significantly, the present activatable nanoprobe can be efficiently taken up by cells. Two-photon induced fluorescence imaging of the proposed nanoprobe was also clearly observed by utilizing femtosecond pulse laser excitation, and affords a powerful alternative candidate for near-infrared (NIR) fluorescence imaging of tumors. Similar fluorescence was visualized in a tumor-bearing mouse model using this probe. These results demonstrate the potential of using this activatable nanoprobe for the detection of cancer.

Few data are available regarding the use of tenofovir disoproxil fumarate (TDF) during pregnancy for the prevention of mother-to-child transmission of hepatitis B virus (HBV).In this trial, we included 200 mothers who were positive for hepatitis B e antigen (HBeAg) and who had an HBV DNA level higher than 200,000 IU per milliliter. Participants were randomly assigned, in a 1:1 ratio, to receive usual care without antiviral therapy or to receive TDF (at an oral dose of 300 mg per day) from 30 to 32 weeks of gestation until postpartum week 4; the participants were followed until postpartum week 28. All the infants received immunoprophylaxis. The primary outcomes were the rates of mother-to-child transmission and birth defects. The secondary outcomes were the safety of TDF, the percentage of mothers with an HBV DNA level of less than 200,000 IU per milliliter at delivery, and loss or seroconversion of HBeAg or hepatitis B surface antigen at postpartum week 28.At delivery, 68% of the mothers in the TDF group (66 of 97 women), as compared with 2% in the control group (2 of 100), had an HBV DNA level of less than 200,000 IU per milliliter (P0.001). At postpartum week 28, the rate of mother-to-child transmission was significantly lower in the TDF group than in the control group, both in the intention-to-treat analysis (with transmission of virus to 5% of the infants [5 of 97] vs. 18% [18 of 100], P=0.007) and the per-protocol analysis (with transmission of virus to 0 vs. 7% [6 of 88], P=0.01). The maternal and infant safety profiles were similar in the TDF group and the control group, including birth-defect rates (2% [2 of 95 infants] and 1% [1 of 88], respectively; P=1.00), although more mothers in the TDF group had an increase in the creatine kinase level. After the discontinuation of TDF, alanine aminotransferase elevations above the normal range occurred more frequently in mothers in the TDF group than in those in the control group (45% [44 of 97 women] vs. 30% [30 of 100], P=0.03). The maternal HBV serologic outcomes did not differ significantly between the groups.In a cohort of HBeAg-positive mothers with an HBV DNA level of more than 200,000 IU per milliliter during the third trimester, the rate of mother-to-child transmission was lower among those who received TDF therapy than among those who received usual care without antiviral therapy. (Funded by Gilead Sciences; ClinicalTrials.gov number, NCT01488526.).

Poly(2-oxazoline)-based nanoparticles with AIE feature were prepared for targeted cell imaging. First, P(EtOx-BuOx) was fabricated by subsequent cationic ring-opening polymerization (CROP). Then, the folate was attached to the end chains of P(EtOx-BuOx). AIE-active TPEMN was conjugated to the side chains of P(EtOx-BuOx) through ‘‘thio-ene’’ click reactions. Cellular experiments demonstrated that the nanocomposites had well dispersity in the physiological environment and could be internalized by folate receptor (FR)-positive cells. We envision that this research endows a simple approach to the fabrication of stable fluorescent polymeric nanocomposites, which display favorable biocompatibility and immense potential for applications in biological imaging and cell detection.

Combination of chemotherapy with photothermal therapy (PTT) demonstrate highly desirable for efficient medical treatment of tumor. At present works, camptothecin (CPT)-containing polymeric prodrug (PCPT) were fabricated by polymerization of a pH-sensitive camptothecin (CPT) prodrug monomer and MPC using reversible addition-fragmentation transfer (RAFT) strategy. The pH-sensitive polymeric prodrug was tethered onto surface of polydopamine (PDA) nanoparticles by amidation chemistry for combination of chemotherapy with photothermal therapy. Specifically, the active CPT quickly released from the multifunctional nanoparticles in acidic microenvironment ascribe to the cleavage of bifunctional silyl ether linkage. Meanwhile, the PDA could convert the near infrared (NIR) light energy into heat with high efficiency, which makes the resulted nanoparticles an effective platform for photothermal therapy. In vitro analysis confirmed that the PDA@PCPT nanoparticles could be efficiently uptaked by HeLa cells and deliver CPT into the nuclei of cancer cells. The cell viability assays indicated an evident in vitro cytotoxicity to HeLa cancer cells under 808 nm light irradiation. Significant tumor regression was also observed in the tumor-bearing mice model with the combinational therapy provided from the PDA@PCPT nanoparticles. The PDA@PCPT multifunctional system which was achieved by a facile route should be a potential candidate in the anti-cancer field due to the synergistic therapeutic effect, which is superior to any single approach.

A robust redox-responsive block copolymer was proposed and prepared as drug vehicle based on disulfide linked poly(2-methacryloyloxyethyl phosphorylcholine) and poly(trimethylene carbonate) (PMPC-ss-PTMC). The size and morphology of the polymer nanoparticles were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The profile of drug release response to glutathione (GSH) was monitored in vitro. Upon 10 mM GSH, mimicking the intracellular microenvironments such as cytosol and the cell nucleus, the resulted drug carrier was destructed ascribe to abruption of the disulfide bonds, followed by accelerated drug release from the nanoparticles. MTT assay showed that the blank micelles did not reveal cytotoxicity to the human cervical cancer HeLa cells and mouse connective tissue fibroblast L929 cells even up to 500 μg/mL. On the other hand, the Doxorubicin-loaded (DOX-loaded) micelles that contained disulfide bonds exhibit a higher cytotoxicity against HeLa cells than that of no disulfide bonds, but there was no significant difference in cytotoxicity against the L929 cells. Confocal laser scanning microscopy and flow cytometry investigation showed that the DOX-loaded micelles can be swiftly internalized, and effectively transmitted the drugs into nuclei. These results suggested that the copolymer as a robust and effective redox-responsive nanocarrier to augment drug efficacy for cancer cells.

The title compound, C9H8ClN2O2 +·Cl−, is a hydrochloric acid salt of 2-methyl-3-chloro-9- hydroxy-4H-pyrido[1,2-a]pyrimidine-4-one, which is an important intermediate for the synthesis of biologically active heterocyclic compounds. The synthesized compound was characterized by 1H NMR and X-ray crystallography. The structure was solved in monoclinic, space group P21/n with a = 11.8295 (12), b = 6.2214 (6), c = 13.8133 (15) A, β = 97.7860 (10)°, V = 1007.23 (18) A3, Z = 4, and with R int = 0.077. The cation of the title compound, as shown by the single-crystal structure determination, has two conjugated aromatic rings that are almost coplanar with a dihedral angle of 0.230°. The crystal packing is stabilized by intermolecular N–H···Cl, O–H···Cl hydrogen bonds, which link the molecules into centrosymmetric dimers, and by weak π–π stacking interactions (average distance 3.352 A). The interaction of native calf thymus DNA (ctDNA) with the compound at physiological pH was monitored by UV–Vis spectroscopy and viscosimetric techniques. It was found that the compound might interact with ctDNA by a groove mode of binding via hydrogen bonds. The title compound, C9H8ClN2O2 +·Cl−, is a hydrochloric acid salt of 2-methyl-3- chloro-9-hydroxy-4H-pyrido[1,2-a]pyrimidine-4-one, which is an important inter-mediate for the synthesis of biologically active heterocyclic compounds. It was found that the compound might interact with ctDNA by a groove mode of binding.

Single crystals of N-(2-hydroxybenzylidene)acetohydrazide were grown by evaporating the solvents from a methanol solution. The single crystal X-ray structure solution confirmed the monoclinic system of the compound with P21/n space group. The functional groups were identified using FT-IR spectroscopic technique. 1H NMR spectral analysis were carried out to identify the position of protons. The optical properties such as UV–vis in transmittance mode and second harmonic generation (SHG) conversion efficiency were investigated to explore the nonlinear optical (NLO) characteristics of the above crystals. In addition, the thermal properties of the title crystal were also evaluated with thermogravimetrical analysis.

The title cobalt complex, [Co(C9H7N2O2)2H2O]H2O, has been synthesized by the reaction of ligand, 9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one (HL), and cobalt nitrate. The synthesized complex was characterized by IR, elemental analysis (C, H and N), mass spectrometry and X-ray crystallography. The structure was solved in monoclinic, space group P21/c with a = 14.4584(13), b = 6.9385(8), c = 18.045(2) A, β = 94.8440(10), V = 1803.8(3) A3, Z = 4, and with R int = 0.034. The Co(II) complex, as shown by the single-crystal structure determination, existed as a mononuclear complex with distorted square-pyramidal geometry. The mental center was coordinated by two molecules from the bidentate ligand (HL) and an O atom from the coordinated water molecule. The intermolecular aromatic π–π stacking interactions generate discrete dimers. Furthermore, these discrete dimers were connected via O–H···O hydrogen bond in complex to form three-dimensional networks. At room temperature, the complex can emit blue luminescence at 430 nm in the solid state, while it about 42 nm blue-shifted in ethanol solution. Compared with free ligand, the luminescence was greatly intensified. A new cobalt complex [Co(L)2H2O]H2O (L=9-hydroxy-2-methyl-4H-pyrido[1,2-a]pyrimidine-4-one) was obtained. The synthesized complex was characterized by IR, elemental analysis (C, H and N), mass spectrometry and X-ray crystallography. The structure was solved in monoclinic, space group P21/c with a = 14.4584(13), b = 6.9385(8), c = 18.045(2) A, β = 94.8440(10), V = 1803.8(3) A3, Z = 4 and with R int=0.034. The Co(II) complex, as shown by the single-crystal structure determination, existed as a mononuclear complex with distorted square-pyramidal geometry. The mental center was coordinated by two molecules from the bidentate ligand and an O atom from the coordinated water molecule. At room temperature, the complex can emit blue luminescence at 430 nm in the solid state, while it about 42 nm blue-shifted in ethanol solution. Compared with free ligand, the luminescence was greatly intensified.

Synthesis of Core-shell Star Poly(methyl methacrylate) with Benzene Arborol Core by Atom Transfer Radical Polymerization

Hepatitis B virus (HBV) X protein (HBx) is implicated in the development of hepatocellular carcinoma (HCC). Yes-associated protein 1 (YAP) is an important proto-oncogene, which is a downstream effector molecule in the Hippo signaling pathway. The aim of the present study was to investigate the association between HBx expression in HCC samples and YAP expression in the Hippo pathway. A total of 20 pathologically confirmed HCC samples, 20 corresponding adjacent non-tumor liver tissues and 5 normal liver tissue samples were collected. The expression of HBx and YAP in the tissues was analyzed by quantitative reverse transcription-polymerase chain reaction and western blot analysis. The intensity and location of YAP expression were analyzed by immunohistochemistry. YAP mRNA and protein expression levels in HCC samples infected with HBV were significantly higher than those of normal liver tissues. Furthermore, YAP expression was positively correlated with HBx expression in HBV-positive HCC samples. Immunohistochemical staining revealed that YAP was predominantly expressed in the nuclei in HBV-positive HCC tissues. YAP expression was significantly decreased in the normal liver tissue and corresponding adjacent liver tissue when compared with the HCC tissues and by contrast to HCC tissues, YAP was predominantly located in the cytoplasm. In conclusion, these results indicate that the YAP gene is a key driver of HBx-induced liver cancer. Therefore, YAP may present a novel target in the treatment of HBV-associated HCC.

To enhance site-specific intracellular delivery against the folate receptor, a drug carrier was designed and synthesized by bioconjugation of folic acid (FA) to β-cyclodextrins (β-CD) through a poly(ethylene glycol) (PEG) spacer from "click chemistry" strategy. The resulted conjugates were confirmed by (1)H NMR and IR spectroscopy. Host-guest interactions between hydrophobic drug and β-CD are capable of entrapping a hydrophobic drug, like 5-Fluorouracil, to form drug-β-CD-PEG-FA nanoparticles (NPs) in aqueous solution. The morphology and size of β-CD-PEG-FA NPs were measured by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The targeting ability of the β-CD-PEG-FA NPs was investigated against two kinds of cell lines (HeLa and A549), which have different amounts of folate receptors on their surface. Confocal image analysis revealed that β-CD-PEG-FA conjugate-assembled nanoparticles exhibited a greater extent of cellular uptake against HeLa cells than A549 cells. This suggests folate-receptor-mediated endocytosis can affect the cellular uptake efficiency of drug-loaded β-CD-PEG-FA NPs. The β-CD-PEG-FA conjugates that are presented may be promising active tumor-targeting carrier candidates via folate mediation.