Fluorescent perylene derivative functionalized titanium oxide gel for sensitive and portable ascorbic acid detection

An inorganic titanium oxide (TiO) gel sensor was demonstrated for convenient detection of ascorbic acid (AA). It is composed of TiO (PI–TiO) functionalized with a perylene diimide derivative containing carboxylic groups as a new soft dopant material. A traditional solvothermal reaction is adopted to prepare the PI–TiO composite, which exhibits a different spectrum according to the reaction time. The final gel possesses a strong chelating affinity with AA molecules, in which phenol hydroxyl groups are shown to compete with those already present in PI. We further utilize the functionalized gel to prepare a series of films with a simple and portable AA response. A visual colour variation can be recognized by the naked eye, together with obvious fluorescence changes for selective and sensitive AA detection. Finally, the as-prepared gel film displays good stability and reproducibility for real sample responses with satisfying results.

A fluorescent inorganic titanium oxide gel sensor was prepared from perylene diimide functionalized composite materials, and applied for sensitive and portable ascorbic acid detection.     

同期两镜或三镜下留置输尿管导管胆管引流207例

目的总结运用同期两镜或三镜术中留置输尿管导管胆管引流的治疗经验。方法从1992年10月-2014年8月,我们运用同期两镜或三镜术中留置输尿管导管胆管引流的手术方式,即腹腔镜术中经胆囊管残端输尿管导管胆管引流术（LUD）,对207例患者进行治疗。结果 181例胆管引流获得成功（87.4%）。输尿管导管插管失败12例（5.8%）,其中中转为鼻胆管引流7例,T管引流2例,放弃胆管引流3例。输尿管导管打折或堵塞导致无任何液体流出2例（1.0%）。输尿管导管早期滑脱导致胆汁性腹膜炎2例（1.0%）,再次腹腔镜下放置输尿管导管及腹腔引流管1例和放置T管及腹腔引流管1例而治愈。术后胆漏4例（1.9%）,经腹腔引流管引流自愈。乳头切开术后发生轻症胰腺炎3例（1.4%）。术后经输尿管导管胆管造影无残石,胆管切口一期缝合术后有轻度狭窄影像2例未处理,乳头区狭窄影像1例未处理。无其他严重并发症,无死亡。结论只要选择合适的病例,同期两镜或三镜术中留置输尿管导管胆管引流是可行、有效和安全的。     

Variants of COL3A1 Are Associated with the Risk of Stroke Recurrence and Prognosis in the Chinese Population: a Prospective Study

Type III collagen plays an important role in activating platelets, forming thrombus, and maintaining the mechanical properties of arteries. This study aimed to test the hypothesis that genetic variants of COL3A1 (gene encoding type III collagen) contribute to recurrence and prognosis of stroke. We investigated the associations of three variants (rs2138533, rs11887092, and rs1800255) in the COL3A1 gene with stroke recurrence and prognosis in 1,544 patients with three subtypes of stroke: lacunar infarction (n?=?442), atherothrombotic infarction (n?=?670), and hemorrhage (n?=?432). These associations were evaluated by Kaplan–Meier analysis and Cox regression models. Patients were followed up for 4.5 years. The A allele of rs1800255 in the COL3A1 gene coding region was significantly associated with a reduced risk of stroke recurrence in patients with lacunar infarction (adjusted hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36–0.93, P?=?0.024), but there was an increased risk of all-cause mortality of atherothrombotic patients (adjusted HR 1.43, 95 % CI 1.01–2.00, P?=?0.044). The TT genotype of rs2138533 showed a significantly increased risk of death caused by cardiovascular disease or stroke in lacunar infarct patients (adjusted HR 2.98, 95 % CI 1.27–6.98, P?=?0.012), but there was a reduced risk of all-cause mortality for patients with intracerebral hemorrhage (adjusted HR 0.34, 95 % CI 0.12–0.93, P?=?0.036). The G allele of rs11887092 increased the risk of stroke recurrence in patients with atherothrombotic stroke (adjusted HR 1.59, 95 % CI 1.04–2.44, P?=?0.035). In conclusion, variants of COL3A1 might play a vital role in determining the risk of recurrence and prognosis after stroke.     

Extramedullary multiple myeloma involving the liver and periportal lymph node,diagnosed by EUS‐FNA in a patient with cirrhosis

Extramedullary multiple myeloma (EMM) involving the liver as a focal space‐occupying lesion is very rare, especially in the patients with cirrhosis. Here, we report a case of EMM in the liver and periportal lymph node, diagnosed by endoscopic ultrasound guided‐fine‐needle aspiration (EUS‐FNA). A 57‐year‐old male patient, with history of cirrhosis, presented with abdominal pain and pancytopenia. The abdominal magnetic resonance imaging (MRI) demonstrated a 6.5 cm left hepatic mass with a 1.1 cm malignant‐appearing periportal lymph node and diffuse osseous lesions. The cytology specimens from the hepatic mass and the periportal lymph node were obtained through EUS‐FNA without rapid on‐site evaluation (ROSE). The thin‐layer preparations (ThinPrep) showed abundant plasmacytoid cells, which were confirmed to be Kappa‐restricted neoplastic plasma cells by the cell block preparations. Later, his serum level of Kappa light chain was found significantly elevated by flow cytometry, which was identified as monoclonal IgA Kappa light chain by serum protein electrophoresis (SPEP) with immunofixation. The patient was diagnosed as IgA multiple myeloma with extramedullary involvement of the liver and periportal lymph node. This is the first case showing the ThinPrep cytomorphologic features of EMM in the liver and periportal lymph node. This case highlights the importance of distinguishing plasma cells from being hepatocytes and lymphocytes on the ThinPrep and also emphasizes the utility of the cell block in the diagnosis of plasma cell neoplasm.     

Prolongation of liver allograft survival by dendritic cells modified with NF-κB decoy oligodeoxynucleotides

AIM: To induce the tolerance of rat liver allograft by dendritic cells (DCs) modified with NF-κB decoy oligodeoxynucleotides (ODNs).METHODS: Bone marrow (BM)-derived DCs from SD rats were propagated in the presence of GM-CSF or GM-CSF+IL-4 to obtain immature DCs or mature DCs. GM-CSF+IL-4-propagated DCs were treated with double-strand NF-κB decoy ODNs containing two NF-κB binding sites or scrambled ODNs to ascertain whether NF-κB decoy ODNs might prevent DC maturation. GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were treated with LPS for 18 h to determine whether NF-κB decoy ODNs could prevent LPS-induced IL-12 production in DCs. NF-κB binding activities, costimulatory molecule (CD40, CD80, CD86) surface expression, IL-12 protein expression and allostimulatory capacity of DCs were measured with electrophoretic mobility shift assay (ENSA),flow cytometry, Western blotting, and mixed lymphocyte reaction (MLR), respectively. GM-CSF-propagated DCs, GM-CSF+IL-4 -propagated DCs, and GM-CSF+NF-κB decoy ODNs or scrambled ODNs-propagated DCs were injected intravenously into recipient LEW rats 7 d prior to liver transplantation and immediately after liver transplantation.Histological grading of liver graft rejection was determined 7 d after liver transplantation. Expression of IL-2, IL-4 and IFN-γ, mRNA in liver graft and in recipient spleen was analyzed by semiquantitative RT-PCR. Apoptosis of liver allograft-infiltrating cells was measured with TUNEL staining.RESULTS: GM-CSF-propagated DCs, GM-CSF+NF-κB decoy ODNs-propagated DCs and GM-CSF+ scrambled ODNs-propagated DCs exhibited features of immature DCs, with similar low level of costimulatory molecule(CD40, CD80,CD86) surface expression, absence of NF-κB activation,and few allocostimulatory activities. GM-CSF+IL-4-propagated DCs displayed features of mature DCs, with high levels of costimulatory molecule (CD40, CD80, CD86) surface expression, marked NF-κB activation, and significant allocostimulatory activity. NF-κB decoy ODNs completely abrogated IL-4-induced DC maturation and allocostimulatory activity as well as LPS-induced NF-κB activation and IL-12 protein expression in DCs. GM-CSF+NF-κB decoy ODNs-propagated DCs promoted apoptosis of liver allograft-infiltrating cells within portal areas, and significantly decreased the expression of IL-2 and IFN-γ mRNA but markedly elevated IL-4 mRNA expression both in liverallograft and in recipient spleen, and consequently suppressed liver allograft rejection, and promoted liverallograft survival.CONCLUSION: NF-κB decoy ODNs-rnodified DCs canprolong liver allograft survival by promoting apoptosis of graft-infiltrating cells within portal areas as well as down-regulating IL-2 and IFN-γ mRNA and up-regulating IL-4 rnRNA expression both in liver graft and in recipient spleen.     

Augmented regeneration of partial liver allograft induced by nuclear factor-κB decoy oligodeoxynucleotides-modified dendritic cells

AIM: To investigate the effect of NF-κB decoy oligodeoxynuleotides (ODNs) - modified dendritic cells (DCs)on regeneration of partial liver allograft.METHODS: Bone marrow (BM)- derived DCs from SD rats were propagated in the presence of GM-CSF or GM-CSF+IL4 to obtain immature DCs or mature DCs, respectively. GMCSF-propagated DCs were treated with double-strand NF-κB decoy ODNs containing two NF-κB binding sites or scrambled ODNs. Allogeneic (SD rat to LEW rat) 50% partial liver transplantation was performed. Normal saline (group A),GM-CSF -propagated DCs (group B), GM-CSF+IL-4 -propagated DCs (group C), and GM-CSF+NF-κB decoy ODNs (group D) or scrambled ODNs -propagated DCs (group E)were injected intravenously into recipient LEW rats 7 days prior to liver transplantation and immediately after transplantation. DNA synthesis (BrdU labeling) and apoptosis of hepatocytes were detected with immunostaining and TUNEL staining postoperative 24 h, 48 h, 72 h and 84 h,respectively. Liver graft-resident NK cell activity, hepatic IFN-y mRNA expression and recipient serum IFN-γ level at the time of the maximal liver allograft regeneration were measured with 51Cr release assay, semiquantitative RT-PCR and ELISA, respectively.RESULTS: Regeneration of liver allograft was markedly promoted by NF-κB decoy ODNs-modified immature DCs but was significantly suppressed by mature DCs, the DNA synthesis of hepatocytes peaked at postoperative 72 h in group A, group B and group E rats, whereas the DNA synthesis of hepatocytes peaked at postoperative 84 h in group C rats and 48 h in group D rats, respectively. The maximal BrdU labeling index of hepatocytes in group D rats was significantly higher than that in the other groups rats.NF-κB decoy ODNs-modified immature DCs markedly suppressed but mature DCs markedly promoted apoptosis of hepatocytes, liver-resident NK cell activity, hepatic IFN-γmRNA expression and recipient serum IFN-γ production. At the time of the maximal regeneration of liver allograft, the minimal apoptosis of hepatocytes, the minimal activity of liver-resident NK cells, the minimal hepatic IFN-γ mRNA expression and serum IFN-γ production were detected in group D rats. The apoptotic index of hepatocytes, the activity of liver- resident NK cells, the hepatic IFN-γ mRNA expression level and the serum IFN-γlevel in group D rats were significantly lower than that in the other groups rats at the time of the maximal regeneration of liver allograft.CONCLUSION: The data suggest that the augmented regeneration of partial liver allograft induced by NF-κB decoy ODNs-modified DCs may be attributable to the reduced apoptotic hepatocytes, the suppressed activity of liverresident NK cells and the reduced IFN-γ production.     

Reversible dougong structured receptor–ligand recognition for building dynamic extracellular matrix mimics

Dynamic biomaterials excel at recapitulating the reversible interlocking and remoldable structure of the extracellular matrix (ECM), particularly in manipulating cell behaviors and adapting to tissue morphogenesis. While strategies based on dynamic chemistries have been extensively studied for ECM-mimicking dynamic biomaterials, biocompatible molecular means with biogenicity are still rare. Here, we report a nature-derived strategy for fabrication of dynamic biointerface as well as a three-dimensional (3D) hydrogel structure based on reversible receptor–ligand interaction between the glycopeptide antibiotic vancomycin and dipeptide d-Ala-d-Ala. We demonstrate the reversible regulation of multiple cell types with the dynamic biointerface and successfully implement the dynamic hydrogel as a functional antibacterial 3D scaffold to treat tissue repair. In view of the biogenicity and high applicability, this nature-derived reversible molecular strategy will bring opportunities for malleable biomaterial design with great potential in biomedicine.

More than 2,500 y ago, the Chinese built their nail- and glue-less architectures (e.g., from Beijing''s Forbidden City to Sichuan Province''s Bao''en Temple) with a “dougong” structure, which is part of the network of wooden supports essential to the timber frame structure of the building. A typical dougong consists of a flat block of wood (dou), the top of which is fixed with an interlocking set of curved bows (gong), without the aid of nails or glue, to provide mechanical support to hold the three-dimensional (3D) network structure. Intriguingly, the microstructure of extracellular matrix (ECM) also demonstrates such reversible interlocking structure, which supports the integrity of tissues and organs. In natural ECM, the dougong structure occurs at the cell–ECM interfaces accompanied by a constant remodeling of the ECM network, giving rise to specific cell signaling, intracellular cascades, and subsequently, all relevant cell behaviors (1–3). Biomaterial designs based on the reversible interactions mimicking the cell–ECM interfaces are believed to boast distinct advantages, including the capability to modulate cell–biomaterial interactions, adapt to the development of cellular processes (1, 4–6), and facilitate the morphogenesis of tissues and organs (7, 8). Although the dynamic design of biomaterials is relatively complicated and challenging, this field attracts significant attention in building dynamic ECM mimics for regenerative medicine (1, 9–11).To faithfully reproduce the dynamics of ECM in artificial matrices, various strategies, including congenitally reversible noncovalent interactions (e.g., hydrogen bonds, coordinate bonds, hydrophobic forces, π–π interactions, van der Waals forces, and electrostatic effects) and dynamic covalent bonds (e.g., reversible boronic esters and benzoic–imine bonds and photosensitive nitrophenyl and azobenzene groups), have been exploited. Currently, biomaterial interfaces with dynamically functionalized bioligands are mainly designed through reversible covalent phenylboronic esters or benzoic–imine bonds (12–16), deformable azobenzene bonds (17), DNA and peptide molecular assemblies (18, 19), cyclodextrins/cucurbiturils-based macrocycle host–guest supermolecules (20–22), metal–ligand coordination (23, 24), and other multiple noncovalent interactions (25–29). They can elicit controllable and reversible cell behaviors (e.g., adhesion, migration, differentiation, and apoptosis) on the biomaterial interfaces (1, 4, 8). Unfortunately, these dynamic ECM-mimicking strategies carry critical problems (13). First, most dynamic strategies are based on nonbiogenic chemical molecules, which are usually nonbiocompatible and probably harmful. Second, the dynamics of these strategies commonly rely on the nonbiological stimuli (e.g., ultraviolet [UV] light or toxic chemicals), which are potentially invasive to cells. Third, current studies on mimicking dynamic ECM are usually limited to either reversible bioligand presentation or remoldable network fabrication; few works focus on both. In this context, the exploration of biocompatible molecular means for recapitulation of both dynamic bioactivity and dynamic structure in ECM is highly anticipated.Here, we present a nature-derived reversible strategy inspired by the receptor–ligand molecular recognition for design of dynamic ECM-mimicking biomaterial. The receptor–ligand molecular recognition relies on multi-noncovalent interaction between two or more molecules with exquisite complementarity in their chemical groups and geometries (30). With this in mind, we focus our attention on a typical simple yet elegant receptor–ligand system (i.e., the glycopeptide antibiotic vancomycin [Van] and the dipeptide d-Ala-d-Ala [AA]). Produced by a bacterial species named Amycolatopsis orientalis, Van exhibits strong bactericidal effect by inhibiting cell wall biosynthesis via the specific binding (K_d = 1.6 μM) (31) toward the terminal AA dipeptide of the bacterial cell wall precursors (Fig. 1A). As a proof of concept, we employ the reversible Van–AA interaction for building both a reversible dynamic biointerface and a 3D hydrogel network (Fig. 1 B and C). Due to the specific but reversible AA–Van molecular recognition, the dynamic biointerface demonstrates excellent reversibility in binding to cell-adhesive tripeptide arginylglycylaspartic acid (RGD) and modulating adhesion of multiple cells, demonstrating our strategy’s general applicability. In addition, the 3D hydrogel network based on the reversible AA–Van molecular recognition demonstrates self-recovery and injectability. The inherently antibacterial activity of the Van–AA hydrogel well equips the 3D hydrogel network for treating infected open skin wounds; the hydrogel could adapt to the shape of wound sites, resist self-fragmentation, and inhibit proliferation of pathogenic bacteria while continuously supporting wound healing. We believe that the specific but reversible Van–AA molecular recognition would be a strategy for dynamic biomaterial fabrication, and the easy-handling merit, ECM-like remoldability, and inherently antibacterial activity involved in this dynamic system will bring insights to biomaterial scaffold design in tissue engineering and regenerative medicine.Open in a separate windowFig. 1.Schematics showing the mechanism of dynamic biointerface and 3D ECM mimics based on a reversible dougong-structured natural receptor–ligand recognition. (A) The Van–AA molecular recognition on bacterial cell wall in nature. (B) Schematic illustration of the dynamic biointerface based on the reversible Van–AA interaction. Reversible bioligand presentation and controllable cell behaviors could be readily realized through the Van–AA interaction. (C) Schematic illustration of the dynamic hydrogels with remoldable network structure and its application in tissue repair.     

Cyclodextrin and its derivatives as effective excipients for amorphous ulipristal acetate systems

Many efforts have been devoted to screening new solid-state forms of poorly soluble drugs in the pharmaceutical industry, thus modulating the drug properties without changing the pharmacological nature. It is a wise strategy to prepare amorphous series with cyclodextrin (CD) and its derivatives as excipients to enhance the aqueous solubility, dissolution, and bioavailability of water-insoluble drugs. In this study, four binary amorphous mixtures of ulipristal acetate (UPA) with CDs (β-CD, γ-CD, dimethyl-β-CD, hydroxypropyl-β-CD) were prepared by the co-milling method and characterized in the solid-state. According to powder X-ray diffraction (PXRD) and differential scanning calorimetry (DSC), UPA existed in the noncrystalline form in the four binary amorphous mixtures. Fourier transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) indicated that UPA interacted with the four CDs, which was also verified by molecular docking. Compared with the crystalline and amorphous UPA, the solubility, dissolution, and stability of the drug in the four amorphous UPA systems were significantly improved, so they were considered potentially advantageous solid forms. Our research shows that CDs can be used as new effective excipients in amorphous systems for active pharmaceutical ingredients (API).

Probing into the amorphous mixtures of ulipristal acetate and cyclodextrins.     

Luminescence properties,energy transfer and thermal stability of white emitting phosphor Sr3(PO4)2:Ce3+/Tb3+/Mn2+ for white LEDs

A series of Sr₃(PO₄)₂:Ce³⁺/Mn²⁺/Tb³⁺ phosphors were synthesized by a high temperature solid phase method. After introducing Ce³⁺ as sensitizer in Sr₃(PO₄)₂:Ce³⁺/Mn²⁺, the efficient energy transfer from Ce³⁺ to Mn²⁺ was observed and analyzed in detail, and Sr₃(PO₄)₂:Ce³⁺/Mn²⁺ was demonstrated to be color tunable, changing from blue to orange red. In addition, Tb³⁺ ion, which mainly emits green light, was further added into the Sr₃(PO₄)₂:Ce³⁺/Mn²⁺. Due to the addition of this green emission, the white emitting phosphors with good quality were obtained. At the same time, the energy transfer mechanisms among Ce³⁺, Tb³⁺ and Mn²⁺ ions were also analyzed in detail. The results show that Sr₃(PO₄)₂:Ce³⁺/Mn²⁺/Tb³⁺ is a promising candidate for white light emitting diodes.

The tunable emission phosphor was realized by the energy transfer.