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Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that causes severe infections in humans and the swine industry. Acquisition and utilization of available carbon sources from challenging host environments is necessary for bacterial pathogens to ensure growth and proliferation. Glycogen is abundant in mammalian body and may support the growth of SS2 during infection in hosts. However, limited information is known about the mechanism between the glycogen utilization and host adaptation of SS2. Here, the pleiotropic effects of exogenous glycogen on SS2 were investigated through transcriptome sequencing. Analysis of transcriptome data showed that the main basic metabolic pathways, especially the core carbon metabolism pathways and virulence-associated factors, of SS2 responded actively to glycogen induction. Glycogen induction led to the perturbation of the glycolysis pathway and citrate cycle, but promoted the pentose phosphate pathway and carbohydrate transport systems. Extracellular glycogen utilization also promoted the mixed-acid fermentation in SS2 rather than homolactic fermentation. Subsequently, apuA, a gene encoding the unique bifunctional amylopullulanase for glycogen degradation, was deleted from the wild type and generated the mutant strain ΔapuA. The pathogenicity details of the wild type and ΔapuA cultured in glucose and glycogen were investigated and compared. Results revealed that the capsule synthesis or bacterial morphology were not affected by glycogen incubation or apuA deletion. However, extracellular glycogen utilization significantly enhanced the hemolytic activity, adhesion and invasion ability, and lethality of SS2. The deletion of apuA also impaired the pathogenicity of bacteria cultured in glucose, indicating that ApuA is indeed an important virulence factor. Our results revealed that exogenous glycogen utilization extensively influenced the expression profile of the S. suis genome. Based on the transcriptome response, exogenous glycogen utilization promoted the carbon adaption and pathogenicity of SS2.

EGFR signaling promotes ovarian cancer tumorigenesis, and high EGFR expression correlates with poor prognosis. However, EGFR inhibitors alone have demonstrated limited clinical benefit for ovarian cancer patients, owing partly to tumor resistance and the lack of predictive biomarkers. Cotargeting EGFR and the PI3K pathway has been previously shown to yield synergistic antitumor effects in ovarian cancer. Therefore, we reasoned that PI3K may affect cellular response to EGFR inhibition. In this study, we revealed PI3K isoform-specific effects on the sensitivity of ovarian cancer cells to the EGFR inhibitor erlotinib. Gene silencing of PIK3CA (p110α) and PIK3CB (p110β) rendered cells more susceptible to erlotinib. In contrast, low expression of PIK3R2 (p85β) was associated with erlotinib resistance. Depletion of PIK3R2, but not PIK3CA or PIK3CB, led to increased DNA damage and reduced level of the nonhomologous end joining DNA repair protein BRD4. Intriguingly, these defects in DNA repair were reversed upon erlotinib treatment, which caused activation and nuclear import of p38 MAPK to promote DNA repair with increased protein levels of 53BP1 and BRD4 and foci formation of 53BP1. Remarkably, inhibition of p38 MAPK or BRD4 re-sensitized PIK3R2-depleted cells to erlotinib. Collectively, these data suggest that p38 MAPK activation and the subsequent DNA repair serve as a resistance mechanism to EGFR inhibitor. Combined inhibition of EGFR and p38 MAPK or DNA repair may maximize the therapeutic potential of EGFR inhibitor in ovarian cancer.

Objective: To analyze the prescription rules of traditional Chinese medicine for patients with COVID-19 in Wuhan Third Hospital, and summarize the disease characteristics and clinical treatment ideas, in order to learn from the treatment of this disease by traditional Chinese medicine. Methods: This study established a cloud database based on the ancient and modern medical cases to mine the rules of medication with analyses of frequency of drug used, association analysis, cluster analysis, complex network and other methods. Results: Of 340 COVID-19 patients discharged from our hospital, 143 males and 197 females with male: female = 0.73: 1, and there were 167 patients over 60 years old, and the majority of clinical illnesses were mainly middle-aged and elderly people. Most of them had dry cough, anorexia, fatigue, etc. The traditional Chinese medicine for the treatment of COVID-19 involves a total of 204 flavors. The most frequent use is Fuling of 225 times. The treatment of traditional Chinese medicines is mainly involved with flavors such as warm, spicy and sweet. Mainly detoxification, dampness and phlegm, Qingfei Paidu Decoction is a common clinical prescription, of which the core drugs are Huoxiang, Fabanxia, Chenpi, Baizhu, Cangzhu, Fuling, Chaihu, Huangqin, Xingren, and Gancao.Conclusion: Through this study, the patients with COVID-19 in our hospital are mainly middle-aged and elderly people, and the etiology is characterized by "cold, wet, poisonous, and epidemic". Wetness is the most important core of the disease.

PIK3R2 encodes the p85β regulatory subunit of phosphatidylinositol 3-kinase and is frequently amplified in cancers. The signaling mechanism and therapeutic implication of p85β are poorly understood. Here we report that p85β upregulates the protein level of the receptor tyrosine kinase AXL to induce oncogenic signaling in ovarian cancer. p85β activates p110 activity and AKT-independent PDK1/SGK3 signaling to promote tumorigenic phenotypes, which are all abolished upon inhibition of AXL. At the molecular level, p85β alters the phosphorylation of TRIM2 (an E3 ligase) and optineurin (an autophagy receptor), which mediate the selective regulation of AXL by p85β, thereby disrupting the autophagic degradation of the AXL protein. Therapeutically, p85β expression renders ovarian cancer cells vulnerable to inhibitors of AXL, p110, or PDK1. Conversely, p85β-depleted cells are less sensitive to these inhibitors. Together, our findings provide a rationale for pharmacological blockade of the AXL signaling axis in PIK3R2-amplified ovarian cancer., p85β (PIK3R2), a regulatory subunit of PI3K, has oncogenic properties. Here the authors show that p85β promotes AXL protein stability, which in turn activates p110 to induce PDK1/SGK3 signaling, and therapeutically, p85β-expressing ovarian cancer cells are sensitive to AXL inhibition.

The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is dysregulated in a broad spectrum of human cancers. Genomic alterations of the pathway members can cause cell transformation and tumorigenesis. The class IA PI3K is a dimeric enzyme composed of a catalytic subunit and a regulatory subunit to initiate AKT activation, with the two major regulatory subunits being p85α and p85β. Apart from sharing a canonical function in binding to and stabilizing p110α, we and the others have demonstrated that p85α and p85β carry distinct activities. We have recently reported an oncogenic role of p85β in ovarian cancer cells. In this study, we analyzed multiple omics data to further explore the oncogenic mechanism of p85β. BCL2 Associated Transcription Factor 1 (BCLAF1) was identified as a downstream effector of p85β. We found that the protein level of BCLAF1 was consistently decreased upon PIK3R2 silencing in ovarian cancer cell lines, and that the decrease could be reversed after PIK3R2 overexpression. Importantly, knockdown of BCLAF1 reduced the oncogenicity of p85β, whereas BCLAF1 overexpression promoted cell viability, cell invasion and migration. Accompanied with the increase in total protein level was enhanced phosphorylation of multiple serine residues of BCLAF1. Functional analysis of the serine residues by expressing the phosphorylation-defective mutants suggested that Ser161, Ser512 and Ser531 are critical for BCLAF1 oncogenic functions in ovarian cancer. Together, the findings reveal a new downstream effector by which p85β exerts its oncogenic effects in ovarian cancer. Citation Format: Panpan Wang, Ling Rao, Victor CY Mak, Lydia WT Cheung. Identifying BCLAF1 as a downstream effector of p85β in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2563.

The phosphatidylinositol 3-kinase (PI3K), which is composed of the p85 regulatory and p110 catalytic subunits, is known to be downstream of the receptor tyrosine kinase (RTK). Our recent findings revealed that p85β increases the protein level of AXL (an RTK) to activate p110, suggesting bidirectional regulation between PI3K and RTK.

In this paper, we report a self-sacrificing route for fabrication of the Ce/Tb co-doped GdPO

To investigate the association of clinical and histological characteristics and the development of ESRD in T2DM patients with renal involvement.We conducted a retrospective analysis of clinical and pathologic data from T2DM patients who underwent renal biopsy (n = 120).The mean age, duration of diabetes, and eGFR were 50.9 ± 11.2 years, 92.8 ± 41.3 months, 55.1 ± 42.3 mL/min/1.73 mThe prognosis of DN patients is significantly worse than that of NDRD patients. Compared with glomerular lesions, tubulointerstitial lesions were associated with higher risk for renal death in DN patients.

Small-sized BaLaF

Ammonia inhibition easily affects the performance of anaerobic digestion (AD) for municipal sludge and the oxidization of volatile fatty acids (VFAs) is the rate-limiting step of this process. Bioaugmentation is considered to be an effective method to alleviate ammonia inhibition of AD, but most study used the hydrogenotrophic methanogens as the bioaugmentation culture. In this study, bioaugmentation of mesophilic AD (MAD) and thermophilic AD (TAD) under ammonia inhibition with syntrophic acetate and propionate oxidizing consortia was investigated. The results showed that the bioaugmented reactors recovered earlier than control reactors with 20 (MAD) and 8 (TAD) days, respectively. The high-throughput 16S rRNA gene sequencing indicated that the relative abundance of carbohydrates fermenter (Lentimicrobium), syntrophic VFAs-oxidizing bacteria (Rikenellaceae_DMER64, Smithella and Syntrophobacter) and acetoclastic and hydrogenotrophic methanogens (Methanosaeta, Methanolinea and Methanospirillum) increased in MAD after bioaugmentation. However, part of the bioaugmentation culture could not adapt to the high free ammonia (FAN) concentration in MAD and the effect was weakened. In TAD, proteolytic bacteria (Keratinibaculum and Tepidimicrobium), syntrophic VFAs-oxidizing bacteria (Syntrophomonas) and hydrogenotrophic methanogen (Methanosarcina) were strengthened. The effect of bioaugmentation in TAD was durable even at higher organic loading rate (OLR), due to its positive influence on microbial community. These results suggested that the different bioaugmentation mechanism occurred in MAD and TAD, which are derived from the synergetic effects of ammonia tolerance and microbial interactions. Our study revealed the VFAs-oxidizing consortia as bioaugmented culture could be the potential strategy to alleviate the ammonia stress of AD.

Three 2-phenyl-1,3-diazaazulene derivatives were synthesized and their protonation behaviours were investigated systematically via UV–vis absorption titration and 1H NMR titration, as well as theoretical calculations. One of them exhibited a monoprotonation process while the others displayed prominent halochromic diprotonation responses. Interestingly, upon protonation of 2-phenyl-1,3-diazaazulene derivatives, the coplanarity and conjugation of the 16-π-conjugated backbones were well kept, while the electronic structures were controllably adjusted. The response mechanism of 1,3-diazaazulene derivatives towards acid is through the attachment of acid proton to the nitrogen atom in the diazaazulene ring, resulting in the change of the hybridization of protonated-N from sp2 to sp3, which differed from that of the well-known azulene (analogue of 1,3-diazaazulene, protonation at carbon atom). This work would provide a new insight into the protonation research of the organic functional molecules.

We present a numerical method based on genetic algorithm combined with a fictitious domain method for a shape optimization problem governed by an elliptic equation with Dirichlet boundary condition. The technique of the immersed boundary method is incorporated into the framework of the fictitious domain method for solving the state equations. Contrary to the conventional methods, our method does not make use of the finite element discretization with obstacle fitted meshes. It conduces to overcoming difficulties arising from re-meshing operations in the optimization process. The method can lead to a reduction in computational effort and is easily programmable. It is applied to a shape reconstruction problem in the airfoil design. Numerical experiments demonstrate the efficiency of the proposed approach.

In this paper, a series of Tb 3+ /Dy 3+ /Mn 2+ doped CePO 4 downconversion nanophosphors (DCNPs) were prepared by a one-pot hydrothermal process. The obtained DCNPs presented monoclinic and hexagonal phase structure with wire-like shape. The photoluminescence (PL) properties and the energy transfer (ET) mechanism of these DCNPs were investigated in detail. The ET mechanism of Ce 3+ /Tb 3+ in CePO 4 host was calculated by means of concentration quenching and spectral overlapping, and calculation results revealed that dipole–dipole interactions should be more responsible. The maximum value of ET efficiency was measured to 87.4% for Tb 3+ doped CePO 4 system. In addition, owing to the efficient ET between Ce 3+ and Tb 3+ /Dy 3+ /Mn 2+ , these as-prepared DCNPs exhibit tunable multi-color output under ultra-violet (UV) light excitation. More importantly, the intense cold and warm white emissions can be realized by singly doping 2%Dy 3+ and 20%Mn 2+ in CePO 4 host under UV irradiation, respectively. The corresponding CIE 1931 coordinates were calculated to be (0.30, 0.30) and (0.30, 0.32), respectively, which are closed to the standard white emission (0.33, 0.33). These findings demonstrate the efficient white light emission by singly doped Dy 3+ or Mn 2+ in CePO 4 system for the first time, which is different from commonly used co-doped or tri-doped system. The multicolor tuning and white emission make these Tb 3+ /Dy 3+ /Mn 2+ doped CePO 4 DCNPs potential phosphors in the fields of displays, lighting, and field-emission devices.

In this study, sub-10 nm BaLuF 5 nanocrystals with cubic phase structure were synthesized by a solvothermal method using oleic acid as the stabilizing agent. The as-prepared BaLuF 5 nanocrystals were characterized by transmission electron microscopy (TEM), X-ray diffraction (XRD), and analyzed by the upconversion (UC) spectra. The TEM results reveal that these samples present high uniformity. Compared with Gd-free samples, the size of BaLuF 5 :Yb/Er doped with 10% Gd 3+ decreased to 5.6 nm. In addition, BaLuF 5 :Yb/Tm/Gd upconversion nanoparticles (UCNPs) presented efficient near-infrared (NIR)-NIR UC luminescence. Therefore, it is expected that these ultra-small BaLuF 5 nanocrystals with well-controlled shape, size, and UC emission have potential applications in biomedical imaging fields.

In this paper, the monodispersed NaErF 4 :Yb, Mn nanoparticles (NPs) were successfully synthesized by a simple and mild solvothermal method. The as-prepared NPs were characterized by X-ray diffraction, transmission electron microscopy, and spectrophotometer. The crystal phase, size, morphology, and upconversion (UC) properties of these NPs can be readily tuned by doping Mn 2+ . With increasing Mn 2+ contents, the crystal phase of NaErF 4 :Yb NPs was transferred from hexagonal to cubic, and then a new orthorhombic phase NaMn 3 F 10 appeared. The morphology of NaErF 4 :Yb was tuned from nanodisks to nanocubes and then to large nanoflakes with increasing Mn 2+ dopant contents. Moreover, the UC luminescence (UCL) intensity can be enhanced by increasing Mn 2+ content. Interestingly, single-band red emission can be achieved when the Mn 2+ content reaches 20%. This is mainly ascribed to the efficient energy transfer between Er 3+ and Mn 2+ . The enhanced UCL intensity and single-band red UCL make these NaErF 4 :Yb/Mn NPs ideal probes for optical bioimaging owing to the low tissue absorption and deep tissue penetration of red light.

A strategy is demonstrated for simultaneous phase/size manipulation, multicolor tuning, and remarkably enhanced upconversion luminescence (UCL), particularly in red emission bands in fixed formulae of general lanthanide-doped upconverting nanoparticles (UCNPs), namely NaLnF4:Yb/Er (Ln: Lu, Gd, Yb), simply through transition metal Mn2+-doping. The addition of different Mn2+ dopant contents in NaLnF4:Yb/Er system favors the crystal structure changing from hexagonal (β) phase to cubic (α) phase, and the crystal size of UCNPs can be effectively controlled. Moreover, the UCL can be tuned from green through yellow and to dominant red emissions under the excitation of 980 nm laser. Interestingly, a large enhancement in overall UCL spectra of Mn2+ doped UCNPs (∼59.1 times for NaLuF4 host, ∼39.3 times for NaYbF4 host compared to the UCNPs without Mn2+ doping) is observed, mainly due to remarkably enhanced luminescence in the red band. The obtained result greatly benefits in vitro and in vivo upconversion bioimaging with highly sensitive and deeper tissue penetration. To prove the application, a select sample of nanocrystal is used as an optical probe for in vitro cell and in vivo bioimaging to verify the merits of high contrast, deeper tissue penetration, and the absence of autofluorescence. Furthermore, the blood vessel of lung of a nude mouse with the injection of Mn2+-doped NaLuF4: Yb/Er UCNPs can be readily visualized using X-ray imaging. Therefore, the Mn2+ doping method provides a new strategy for phase/size control, multicolor tuning, and remarkable enhancement of UCL dominated by red emission, which will impact on the field of bioimaging based on UCNP nanoprobes.

Visualization of blood vessel of lung can improve the detection of the lung and pulmonary vascular diseases. However, research on visualization of blood vessel of lung using the new generation upconversion nanoprobes is still scarce. Herein, high quality hexagonal phase NaLuF4:Gd/Yb/Er nanorods were synthesized by a simple hydrothermal method through doping Gd(3+). Doping Gd can not only promote the phase transformation from cubic to hexagonal and the shape evolution from microtube to rod-like, but also provide an additional magnetic properties for biomedical application. The as-prepared nanorods were further converted to water solubility by treating with HCl for eliminating the capped oleic acid. The ligand-free nanorods were successfully used for high-contrast upconversion fluorescent bioimaging of HeLa cells. Moreover, the in vivo synergistic upconversion fluorescent and X-ray imaging of nude mice were demonstrated by subcutaneously and intravenously administrated the ligand-free nanorods. The X-ray signals were matched well with the upconversion signal, indicating the successfully synergistic bioimaging. The ex-vivo X-ray and upconversion fluorescent imaging of various organs revealed that the nanorods were mainly accumulated in liver and lung. More importantly, the blood vessel of the lung can be readily visualized when these ligand-free nanorods are intravenously injected. Apart from the synergistic X-ray and upconversion bioimaging, the ligand-free nanorods can also possess excellent paramagnetic property for potential magnetic resonance imaging contrast agent. Our results have demonstrated the enhanced visualization of blood vessel of lung performed by dual-modal bioimaging of X-ray and upconversion fluorescence, revealing the great promise of these nanoprobes in angiography imaging. Such a new technique enables the integration of the two bioimaging techniques by combining their collective strengths and minimizing their shortcomings.

In this paper, the lanthanide (Ln) doped fluorescent/magnetic NaYbF 4 microtubes with hexagonal phase were synthesized via a hydrothermal method using oleic acid as a capping ligand and surface modifier. The as-prepared samples were characterized by X-ray diffraction analysis (XRD), transmission electron microscopy (TEM), field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), upconversion luminescence (UCL) spectra, and vibrating sample magnetometer (VSM). The TEM and FE-SEM observations revealed that the NaYbF 4 microtubes present high quality hexagonal prism shape. Under the excitation of a 980 nm laser diode (LD) with a power density of 0.5 W cm −2 , the UCL colors can be tuned from purplish blue to blue, greenish white, and further to yellowish green by adjusting the Tm 3+ and Ho 3+ content in NaYbF 4 system. Moreover, the brighter greenish white light can be readily achieved via increasing excitation power. The UCL mechanisms for the white emission were proposed based on the spectral and pumping power dependence analyses. Moreover, these as-prepared NaYbF 4 microtubes exhibit excellent paramagnetic property at room temperature. The magnetic mass susceptibility and magnetization are measured to 4.17 × 10 −5 emu/gOe and ∼0.84 emu g −1 at 20 kOe, respectively. Therefore, these NaYbF 4 microtubes with hexagonal prism shape, tunable multicolor UCL and excellent paramagnetic property imply that NaYbF 4 is an excellent host material and may find applications in flat-panel displays, lasers photonics and dual-modal bioprobes.

Herein, a series of hexagonal phase lanthanide (Ln3+, Ln3+ = Eu3+, Dy3+, Tb3+) doped NaCeF4 nanorods (NRs) with uniform morphology and monodispersity have been successfully synthesized via a typical hydrothermal method using oleic acid as the capping agent. The crystal phase and microstructure of the obtained NRs were analyzed by X-ray diffraction (XRD) patterns and transmission electron microscopy (TEM). The down conversion (DC) luminescence properties and mechanisms of the as-prepared NaCeF4:Ln3+ NRs have been discussed in detail. The as-prepared samples show the characteristic f–f transition of Ln3+ (Ln3+ = Eu3+, Dy3+, Tb3+). The decay time and quantum yield of these obtained NRs are also studied. Moreover, tunable multicolor, especially white emissions, can be successfully achieved via varying the doping ions and doping concentration. By increasing the content of Eu3+, the emission colors vary from light green to white and finally to light red under the excitation of 395 nm. The calculated CIE coordinates of the obtained white emissions are (0.33, 0.31), which are very close to the standard white light located at (0.33, 0.33). This is the first time to demonstrate that white light emission is achieved via only singly-doping Eu3+ into the NaCeF4 system. In addition, the multicolor output changes from yellowish-green to yellow under the excitation at 261 nm, which was also obtained by only tuning the doped content of Dy3+ in the NaCeF4 host. As for Tb3+, bright yellowish green emissions were obtained under excitation at 261 nm. Moreover, the cathodoluminescence (CL) spectra demonstrate that these NRs can emerge as ideal nanophosphors under electron beam excitation. Therefore, the as-prepared NaCeF4:Ln3+ NRs with tunable multicolor output and bright white emissions might be applied in field-emission devices, multicolor displays and solid state lasers.

Polyethylene glycol (PEG) modified BaLuF5:Gd/Yb/Er upconversion nanoparticles (UCNPs) were synthesized by a facile one-pot hydrothermal method for simultaneous synthesis and surface functionalization. The novel, excellently biocompatible and water-soluble bioprobes were used for simultaneous upconversion (UC) luminescence and X-ray bioimaging for the first time. The as-prepared BaLuF5:Gd/Yb/Er UCNPs possess a face-centered cubic structure with an average size of 23.7 ± 2.7 nm. Under 980 nm laser excitation, these UCNPs emitted intense UC luminescence via a two-photon process. In vitro bioimaging and localized luminescence spectra detected from HeLa cells and the background reveal that these UCNPs are ideal candidates for optical bioimaging in the absence of autofluorescence. Furthermore, the synergistic in vivo UC luminescence and X-ray bioimaging reveal that these PEG-modified BaLuF5:Gd/Yb/Er UCNPs can be successfully used as ideal dual-modal bioprobes. These results demonstrate that these PEG modified UCNPs are ideal multi-modal nanoprobes for bioimaging.

Small-sized BaLaF5:Mn/Yb/Er upconversion nanoparticles (UCNPs) were successfully synthesized for dual-modal X-ray and upconversion (UC) luminescence bioimaging by a simple solvothermal method. The size, shape, and UC luminescence intensity of the as-prepared UCNPs can be readily modified by changing the contents of Mn2+. The size of BaLaF5 UCNPs doped with Mn2+ decreased largely compared with Mn-free UCNPs. When increasing the content of Mn2+ from 5% to 20%, the size of UCNPs was gradually increased from 6.5 nm to 9.7 nm. The as-prepared BaLaF5 UCNPs doped with 20% Mn2+ present intense UC luminescence. The in vitro UC luminescence imaging of HeLa cells and localized spectra detected from HeLa cells and the background based on these BaLaF5:Mn/Yb/Er (20/20/2%) UCNPs indicate that this sample can serve as an ideal bioprobe with the absence of autofluorescence under the excitation of 980 nm laser. Moreover, an obvious UC signal was observed in in vivo UC bioimaging, demonstrating that these BaLaF5:Mn/Yb/Er (20/20/2%) UCNPs can also be used as bioprobes for whole body optical bioimaging. In addition, owing to the high X-ray mass absorption coefficients of Ba2+, La3+ and the doped Yb3+, the simultaneous X-ray and UC in vivo bioimaging of a nude mouse further demonstrate that the as-prepared UCNPs can be successfully used as dual-modal bioprobes. Ex vivo UC bioimaging revealed that these UCNPs gathered at the lung of a mouse at the initial time, demonstrating that this sample was suitable for the detection of the lung diseases. In addition, the cytotoxicity test showed that the UCNPs possessed little toxicity. Therefore, the small-sized BaLaF5:Yb/Er/Mn UCNPs are ideal nanoprobes for dual-modal UC luminescence/X-ray bioimaging with non-autofluorescence, and enhanced detection of the lung diseases.

In this paper, we report a self-sacrificing route for fabrication of the Ce/Tb co-doped GdPO4 hollow spheres under hydrothermal conditions using the Gd(OH)CO3:Ce/Tb precursor as a template and NH4H2PO4 as a phosphorus source. The X-ray diffraction (XRD) patterns show the amorphous crystal nature of the precursor and pure hexagonal phase of the hollow spheres. The microstructures of the as-prepared precursor and hollow spheres were characterized by transmission electron microscopy (TEM) and scanning TEM (STEM) assays. The results reveal the urchin-like morphology of the solid precursor and hollow spheres. Bright green emissions of the spheres have been detected using an ultraviolet (UV) lamp at 288 nm and the calculated CIE coordinates are (0.289, 0.491). The energy transfer mechanism of Ce and Tb ions in the GdPO4 host has been investigated. The quantum efficiency of the hollow spheres was measured to be 61% and the lifetime calculated as 6.94 ms. In addition, the magnetic mass susceptibilities and magnetization of the spheres are found to be 6.39 × 10−5 emu gOe−1 and 1.27 emu g−1 at 20 kOe, respectively. Owing to their excellent downshift luminescence properties, the as-prepared GdPO4:Ce/Tb hollow spheres have been successfully applied in in vivo luminescence and X-ray bioimaging for the first time. Moreover, three-dimensional (3D) in vivo X-ray bioimaging of the mouse can provide the accurate location from multiple directions. The high contrast ratio makes the spheres a promising X-ray contrast agent. Due to the hollow structure, these GdPO4:Ce/Tb hollow spheres were also used as drug delivery systems for doxorubicin (DOX) loading and release. The drug loading efficiency was measured to be 17% at a pH value of 7.4, and the pH-dependent drug release was studied. 47% of the loaded DOX was released within 10 h when pH = 5, while there was only 30% during the same time at pH = 7.4 and it took nearly 48 h to reach a comparable level. The different release nature gives these spheres a promising application in targeted therapy of tumors.

The effect of chemotherapy drug Mitomycin C (MMC) in combination with recombinant adeno-associated virus II (rAAV2) in cancer therapy was investigated, and the mechanism of MMC affecting rAAV2’s bioactivity was also studied. The combination effect was evaluated by the level of GFP and TNF expression in a human glioma cell line, and the mechanism of MMC effects on rAAV mediated gene expression was investigated by AAV transduction related signal molecules. C57 and BALB/c nude mice were injected with rAAV-EGFP or rAAV-TNF alone, or mixed with MMC, to evaluate the effect of MMC on AAV-mediated gene expression and tumor suppression. MMC was shown to improve the infection activity of rAAV2 both in vitro and in vivo. Enhancement was found to be independent of initial rAAV2 receptor binding stage or subsequent second-strand synthesis of target DNA, but was related to cell cycle retardation followed by blocked genome degradation. In vivo injection of MMC combined with rAAV2 into the tumors of the animals resulted in significant suppression of tumor growth. It was thus demonstrated for the first time that MMC could enhance the expression level of the target gene mediated by rAAV2. The combination of rAAV2 and MMC may be a promising strategy in cancer therapy.

The purpose of this study was to evaluate the effect of cyclodextrins (CDs) on carotene content and quality of blended carrot-orange juice after enzymatic clarification. The blended carrot-orange juice was treated with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) and gamma cyclodextrin (γ-CD) in different concentrations (1–5 g/100 mL of juice) prior to enzymatic clarification. The results showed that in non-homogenized juice added with HP-β-CD, juice acidity was generally increased from 0.83 to 1.05 g/100 mL. In the homogenized juice added with 3% (w/v) HP-β-CD, the carotene content was also increased to 5.34 mg/mL, meaning two to six times compared to control samples. However, the addition of HP-β-CD prior to juice enzymatic clarification decreased the juice clarity more than that added with γ-CD; both CDs showed wider effect on the ascorbic acid content in non-homogenized than in homogenized, when compared to control samples. The non-enzymatic browning was significantly enhanced by the addition of CDs; though, the total polyphenol content increased with the addition of HP-β-CD from 32.59 to 37.09 and from 29.20 to 35.44 mg GAE/mL in non-homogenized and homogenized juice, respectively. The juice color turned red-yellow with increase in the carotene content of the juice. In conclusion, the addition of HP-β-CD in homogenized juice improved the nutritional and some physico-chemical parameters of the juice.

Ultrafiltration, silica gel and chitosan treatment methods were investigated to study the clarification effect on the green tea infusion. The results showed that ultrafiltration reduced the protein and polyphenol content, as well as color of the tea infusion. The silica gel and chitosan treatment were effective methods to clarify green tea infusion; they decreased the haze-active protein significantly, without much effect on the polyphenol. The silica gel and chitosan treatment also reduced the proline content by 18.65% and 23.79%, and histidine amino acid by 90.97%, and 90.31%, respectively. After the silica and chitosan treatment, the protein did not decrease significantly compared to the raw (untreated) infusion, while ultrafiltration treatment reduced the protein content significantly from 11.36 to 5.85 mg/100 mL with the 10 kDa membrane. Transmittance of silica gel and chitosan treated infusion was above 95.0% and 99.0%, respectively; and decreased slowly under prolonged storage time. The chitosan and silica treatment decreased the greenness and yellowness of the green tea infusion.

A fictitious domain method, in which the Dirichlet boundary conditions are treated using boundary supported Lagrangian multipliers, is considered. The technique of the immersed boundary method is incorporated into the framework of the fictitious domain method. Contrary to conventional methods, it does not make use of the finite element discretization. It has a simpler structure and is easily programmable. The numerical simulation of two-dimensional incompressible inviscid uniform flows over a circular cylinder validates the methodology and the numerical procedure. The numerical simulation of propagation phenomena for time harmonic electromagnetic waves by methods combining controllability and fictitious domain techniques is also presented. Using distributed Lagrangian multipliers, the propagation of the wave can be simulated on an obstacle free computational region with regular finite element meshes essentially independent of the geometry of the obstacle and by a controllability formulation which leads to algorithms with good convergence properties for time-periodic solutions. The numerical results presented are in good agreement with those in the literature using obstacle fitted meshes.

This paper deals with the heat equation in which the source term involves a Dirac function and describes the elastic reaction of the immersed boundary. We analyze the existence of the approximate solution in two-dimensional case with Dirac function approximated by differentiable function. We obtain the result via finite element method, the Banach Fixed-Point Theorem and a theorem in nonlinear ordinary differential equations in abstract space.

We developed a coarse-grained force field and have extended it to polystyrene with longer chain length. A systematic method was introduced and was utilized to explain how the coarse-grained force field for polystyrene could be developed from the atomistic simulation in the paper. We elected to use polystyrene with different chain lengths of 20, 40 and 80 monomers in this study. In three cases, we utilized the same new mapping scheme. The coarsegrained force field does reproduce the bond, angle, and radial distribution of the atomistic model. The coarse-grained model proved successful, as shown by analyses of the static and dynamic properties of different chain lengths.

In this paper, we obtain an existence theorem of a connected set of solutions to a nonlinear variational inequality with explicit nonlinear constraints. This result follows in a constructive way by designing a simplicial algorithm. The algorithm operates on a triangulation of the unbounded regions and generates a piecewise linear path of parametrized stationary points. Each point on the path is an approximate solution.

Simultaneous in vivo luminescence and X-ray bioimaging in a tissue or animal integrates the advantages of each single-modal imaging technology, and will find widespread application in biological and clinical fields. However, synergistic dual-modal bioimaging that utilizes a new generation of upconversion nanoprobes is still limited. In addition, investigations concentrated on in vivo biodistribution of these nanoprobes may contribute to diagnosis and treatment, but long-term in vivo tracking based on these nanoprobes is rarely reported. In this work, water-soluble NaLuF4: Yb/Er nanophosphors were prepared through modified one-pot simultaneous synthesis and surface modification method. Owing to the outstanding upconverting emissions and large X-ray absorption coefficient/K-edge value of Lu and doped Yb ions, the obtained nanoprobes were successfully used as luminescent nanoprobes and X-ray contrast agents for in vivo synergistic upconversion luminescence and X-ray bioimaging. The in vivo biodistribution of these nanoprobes were observed, and the results based on long-term tracking reveal that the as-prepared nanoprobes first aggregated in the lung of the mouse, transferred to the liver, and finally moved to the spleen.

Polyethylene glycol (PEG) modified BaLuF5:Gd/Yb/Er upconversion nanoparticles (UCNPs) were synthesized by a facile one-pot hydrothermal method for simultaneous synthesis and surface functionalization. The novel, excellently biocompatible and water-soluble bioprobes were used for simultaneous upconversion (UC) luminescence and X-ray bioimaging for the first time. The as-prepared BaLuF5:Gd/Yb/Er UCNPs possess a face-centered cubic structure with an average size of 23.7 ± 2.7 nm. Under 980 nm laser excitation, these UCNPs emitted intense UC luminescence via a two-photon process. In vitro bioimaging and localized luminescence spectra detected from HeLa cells and the background reveal that these UCNPs are ideal candidates for optical bioimaging in the absence of autofluorescence. Furthermore, the synergistic in vivo UC luminescence and X-ray bioimaging reveal that these PEG-modified BaLuF5:Gd/Yb/Er UCNPs can be successfully used as ideal dual-modal bioprobes. These results demonstrate that these PEG modified UCNPs are ideal multi-modal nanoprobes for bioimaging.

In this work, the amine-functionalized NaYbF4:Er nanoparticles were developed as dual-modal nanoprobes for synergistic upconversion (UC) luminescence and X-ray imaging in a single system by a simple one-step method of simultaneous synthesis and surface modification. The water-soluble NaYbF4:Er nanoparticles present excellent green and dominant red UC emissions. The in vitro cell imaging shows that the high-contrast green and intense red UC emissions can be observed from HeLa cells treated with these nanoparticles, indicating the successful labeling of HeLa cells. Moreover, the localized spectra measured from HeLa cells and background presented significant green and dominant red UC emissions with the absence of any autofluorescence, further verifying that these nanoparticles can be successfully used as ideal probes for optical UC bioimaging with high contrast and non-autofluorescence. In addition, the amine-functionalized NaYbF4:Er nanoparticles maintained low cell toxicity in HeLa cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. More importantly, these amine-functionalized NaYbF4:Er nanoparticles can also be used as X-ray imaging, owing to the large X-ray absorption efficiency of the Yb ion. The synergistic in vivo UC and X-ray imaging present significant UC luminescence and X-ray signals in the same region of a nude mouse, and the two signals are matched very well, which provides direct evidence for simultaneous UC luminescence and X-ray imaging in a single compound of lanthanide-doped material. Moreover, ex vivo UC imaging shows that these nanoparticles are first accumulated in the lung and gradually translocated from the lung into the liver. These results demonstrate that the amine-functionalized NaYbF4:Er nanoparticles presented here are very attractive nanoprobes for dual-modal UC luminescence and X-ray imaging with low cytotoxicity, autofluorescence free, and synergistic combination of the advantages of the two imaging modalities.

We introduce the problems of differential inclusions for fuzzy maps, and study the existence of solutions to these problems by the continuous selection theorem and fixed point theorems, respectively.

In this paper, multi-functional hexagonal phase NaErF4:Yb nanorods were synthesized by a facile hydrothermal method. The upconversion luminescence (UCL) intensity and red to green ratio of the multi-functional NaErF4 nanorods can be improved by Yb(3+) doping. More importantly, owing to the decreased distance of Er and Yb, the significant enhancement of red UCL can be obtained, which is different to the usual green UCL of Yb/Er doped NaYF4 host. In addition, the intensity of UCL is strongest when the Yb(3+)-doped concentration reached 30%. The in vitro cell imaging and localized UCL spectra taken from HeLa cells revealed that these NaErF4: 30% Yb(3+) nanorods are ideal nanoprobes with absence of autofluorescence for optical bioimaging. Moreover, these nanorods possess large X-ray absorption ions (Er(3+) and doped Yb(3+)), and were successfully used as contrast agents for in vivo X-ray bioimaging for the first time. In addition to the excellent UCL and X-ray absorption properties, these nanorods present significant paramagnetic properties and can be used as T2-weighted magnetic resonance imaging (MRI) agents. Therefore, these enhanced red UCL NaErF4 nanocrystals with excellent paramagnetic properties and X-ray absorption properties can be used as promising multi-modal nanoprobes for optical bioimaging, MRI, computed X-ray tomography (CT), and may have potential applications in bioseparation.

In this study, monodispersed and high-quality hexagonal phase LaF3 nanocrystals with different shapes and sizes were synthesized by a solvothermal method using oleic acid as the stabilizing agent. The as-prepared LaF3 nanocrystals were characterized by transmission electron microscopy (TEM), x-ray diffraction (XRD), and analysis of the upconversion spectra. The TEM results reveal that the samples present high uniformity and monodispersity and are self-assembled into a two-dimensional ordered array. Moreover, the shape, size and structure of the nanocrystals can be readily tuned by adjusting the NaF content. With increasing content of NaF, the shape of the LaF3 nanocrystals changed from particle to rod and the size gradually increased. More importantly, high NaF content favors the formation of one-dimensional nanorods. High Y b(3+) and Er(3+) content is beneficial to synthesizing the hexagonal phase of NaLaF4 nanocrystals. Furthermore, the TEM results show that the shape and size of the LaF3 nanocrystals can also be tuned by doping lanthanide ions, which provides a new route for size and shape control of nanocrystals. In addition, LaF3 nanocrystals co-doped with Y b(3+)/Tm(3+) present efficient near-infrared (NIR)-NIR upconversion luminescence. More importantly, the upconversion luminescent colors can be readily tuned from blue-white to blue by adjusting the excitation power. Therefore, it is expected that these LaF3 nanocrystals with well-controlled shape, size and NIR-NIR upconversion emission have potential applications in biomedical imaging fields.

Object To explore the effects of neutron-irradiation exposure on TRAIL/DR5 pathway in rat brain regions. Methods Fast neutron-irradiation was employed as the irradiated model. The expression changes of TRAIL and DR5 in cerebral cortex, hippocampus, cerebellum and corpus striatum were detected after 1, 7 and 14 d post-irradiation by RT-PCR, ELISA and western blotting. Cleaved caspase-8 was examined by western blotting. Results In protein expression level, TRAIL was increased in the four regions to different extents after 7 d and then recovered after 14 d; DR5 was detected to be up-regulated in cerebral cortex, hippocampus and corpus striatum but down-regulated in cerebellum after 14 d post-irradiation. No significant changes of TRAIL and DR5 were observed in RNA level by RT-PCR. The cleaved caspase-8 was up-expressed the greatest after 1 d in cerebral cortex, hippocampus and cerebellum but continually up-regulated in corpus striatum from 1 to 14 d after irradiation treatment. Conclusion TRAIL was induced in rat brain at early stage while the expression changes of DR5 were delayed by neutron-irradiation and vary in different brain regions. Moreover, caspase-8 was not activated in accord with the changes of TRAIL and DR5 in some brain regions. These indicate that the activation of TRAIL/DR5 pathway plays a role in irradiation-induced injury, which is regulated in a region-specific and time-dependent manner.

Yb/Er codoped Gd(OH)3was synthesized firstly via a simple hydrothermal treatment of the corresponding nitrate in the presence of alkali by tuning the pH values. The Gd2O3:Yb/Er nanocrystals were obtained via sintering the corresponding hydroxides precursors. The as-prepared samples were characterized by the typical X-ray diffraction, energy-dispersive X-ray spectroscopy, transmission electron microscopy (TEM), high-resolution TEM, and spectrophotometer. The results revealed that two shapes of the as-prepared Gd2O3:Yb/Er nanocrystals can be readily tuned from lemon-like particle to rod-like structure via tuning pH values from 7 to 14. Moreover, compared with the samples prepared at pH 7, the Gd2O3:Yb/Er nanocrystals prepared at pH 14 exhibit enhanced red upconversion emission and higher upconversion luminescence intensity under the excitation of 980 nm laser.

Highly crystalline body-centered cubic structure Y2O3with lanthanide (Ln) codopants (Ln = Yb3+/Er3+and Yb3+/Ho3+) has been synthesized via a moderate hydrothermal method in combination with a subsequent calcination. The structure and morphology of Y(OH)3precursors and Y2O3nanoparticles were characterized by X-ray diffraction and transmission electron microscopy. The results reveal that the Y2O3nanoparticles possess cubic phase and form the quasispherical structure. The upconversion luminescence properties of Y2O3nanoparticles doped with different Ln3+(Yb3+/ Er3+and Yb3+/ Ho3+) ions were well investigated under the 980 nm excitation. The results show that the Yb3+/Er3+and Yb3+/Ho3+codoped Y2O3nanoparticles exhibit strong red and light yellow upconversion emissions, respectively. It is expected that these Y2O3nanoparticles with tunable multicolor output and intense red upconversion emission may have potential application in color displays and biolabels.

The fictitious domain technique is coupled to the improved time-explicit asymptotic method for calculating time-periodic solution of wave equation. Conventionally, the practical implementation of fictitious domain method relies on finite difference time discretizations schemes and finite element approximation. Our new method applies finite difference approximations in space instead of conventional finite element approximation. We use the Dirac delta function to transport the variational forms of the wave equations to the differential form and then solve it by finite difference schemes. Our method is relatively easier to code and requires fewer computational operations than conventional finite element method. The numerical experiments show that the new method performs as well as the method using conventional finite element approximation.

To observe the effect of DNA methyltransferase 1 (DNMT1) gene silencing by RNA interfering technology on the proliferation and apoptosis of HeLa cells.Recombinant plasmid pshRNA-DNMT1-A, B and C were respectively transfected into HeLa cells by lipofectamine 2000, while cells transfected plasmid vector pSilencer3. 1-H1 and cells untreated as control groups. RT-PCR was adopted to select the recombinant plasmid which showed the most optimal inhibition effect. RT-PCR and western blotting was used to detected the mRNA and protein expression of DNMT1 in HeLa cells transfected for 24, 48 and 72 hours. Cell counting kit-8 (CCK-8) assay was used to investigate the proliferation of the HeLa cells after transfection, while apoptosis was detected by flowcytometry (FCM) method.Three DNMT1-targeted short hairpin RNA (shRNA) A,B and C were successfully inserted into the plasmid vector pshRNA, and the coding sequences of the obtained shRNA were consistent with the designed fragments. The results indicated that both recombinant plasmid pshRNA-DNMT1-A and B could effectively knock down the expression of DNMT1 gene in human cervical cancer cells, of which pshRNA-DNMT1-B was the better choice. While no effect of pshRNA-DNMT1-C was seen. RT-PCR results showed that the relative mRNA expression of DNMT1 gene in HeLa cells transfected with pshRNA-DNMT1 for 24, 48 and 72 hours were 0.406 +/- 0.057, 0.191 +/- 0.036 and 0. 104 +/- 0.015, which were significantly lower than that in HeLa cells transfected by empty vector and non-transfected cells (0.520 +/- 0.020, 0.537 +/- 0.041, respectively, P0. 05). The western blotting analysis manifested that the relative expression of DNMT1 protein of HeLa cells transfected by pshRNA-DNMT1 for 24, 48 and 72 hours were 0.197 +/- 0.024, 0.075 +/- 0.015, 0.040 +/- 0. 013, which were significantly lower than that in transfected cells by empty vector and non-transfected cells (0.273 +/- 0.010, 0.283 +/- 0.016, respectively, P0.05). The CCK-8 results showed that the cell survival rates of HeLa cells transfected by pshRNA-DNMT1 for 24, 48, 72, 96 and 120 hours were 70.8%, 64.8%, 51.6%, 45.3% and 38.0%, there were statistically different compared with cells transfected by empty vector and non-transfected cells at different time-points (P0.01). The results of FCM indicated that the apoptosis rate of HeLa cells transfected with pshRNA-DNMT1 for 24, 48 and 72 hours were (17.7 +/- 1.3)%, (35.3 +/- 1.3)%, (47.6 +/- 1.6)%, which were significantly higher than empty vector transfected cells and non-transfected cells [(4.9 +/- 0.5)%, (5.1 +/- 0.7)%, respectively, P0.05].DNMT1 can be successfully silenced by RNA interfering in cervical HeLa cells. Downregulation of DNMT1 can inhibit cervical cancer cells proliferation and induce cell apoptosis.

In this work, we developed a novel and biocompatible dual-modal nanoprobe based on single-phase amine-functionalized BaYF5:Yb/Er nanoparticles (NPs) for upconversion (UC) fluorescence and in vivo computed X-ray tomography (CT) bioimaging for the first time. High-quality water-soluble amine-functionalized BaYF5:Yb/Er NPs with an average size of 24 nm were synthesized by a facile environmentally friendly hydrothermal method for simultaneous synthesis and surface functionalization. Structure investigation based on the Rietveld refinement method revealed that the as-synthesized BaYF5:Yb/Er NPs present a cubic phase structure, which differs from the previously reported tetragonal structure. Under 980 nm excitation, high-contrast green and red UC emissions were observed from HeLa cells incubated with these amine-functionalized NPs. The UC spectra measured from the NPs incubated with HeLa cells presented only green and red UC emissions without any autofluorescence, further revealing that these NPs are ideal candidates for fluorescent bioimaging. In addition, the cell cytotoxicity test showed low cell toxicity of these NPs. These amine-functionalized NPs were also successfully used as CT agents for in vivo CT imaging because of the efficient X-ray absorption efficiency of Ba and doped Yb ions. A prolonged (2 h) signal enhancement of the spleen in a mouse was observed in CT imaging, which can improve the detection of splenic diseases. More importantly, the simultaneous X-ray and UC in vivo bioimaging was demonstrated in a nude mouse for the first time, indicating the as-prepared UCNPs can be successfully used as dual-modal bioprobes. These results demonstrate that BaYF5:Yb/Er NPs are ideal nanoprobes for dual-modal fluorescent/CT bioimaging with low cytotoxicity, non-autofluorescence, and enhanced detection of the spleen.

In this paper, optical/magnetic multi-functional NaErF4 nanocrystals with high quality, different phases and shapes were synthesized by a simple hydrothermal method using oleic acid as the capping agent. The structure, upconversion luminescence and magnetic properties were characterized by various techniques. The transmission electron microscopy results reveal that the nanocrystals are of high quality and can be self-assembled into a two-dimensional ordered structure. Moreover, the crystal phase and shape can be readily controlled by adjusting the reaction temperature and F− content. The results reveal that high temperature can favor the formation of a hexagonal phase structure and promote the phase transformation from the cubic to hexagonal phase. The phase transformation mechanism based on the free energy theory was discussed in detail. In addition, the F− content plays a critical role in determining the morphology of the final products. A high F− content is beneficial for the formation of the one-dimensional rod-like shape. Interestingly, phase-induced upconversion luminescence color tuning from red to green was observed. All of the as-prepared NaErF4 nanocrystals possess paramagnetic properties at room temperature and the magnetizations of the nanocrystals with spherical-like cubic, cubic, and rod-like shapes were measured as 1.69 emu g−1, 2.53 emu g−1and 2.29 emu g−1 at 20 kOe, respectively, which are larger than most previously reported Gd-based nanocrystals. In addition, T2-weighted magnetic resonance imaging based on these NaErF4 nanocrystals was demonstrated for the first time. Therefore, these tunable upconversion fluorescent NaErF4 nanocrystals with excellent paramagnetic properties can be used as promising dual-modal nanoprobes for optical bioimaging and magnetic resonance imaging, and may have potential applications in bioseparation.