A versatile multi-tone laser system for manipulating atomic qubits based on a fiber Mach-Zehnder modulator and second harmonic generation.

Stimulated Raman transition is a fundamental method to coherently manipulate quantum states in different physical systems. Phase-coherent dichromatic radiation fields matching the energy level splitting are the key to realizing stimulated Raman transition. Here we demonstrate a flexible-tuning, spectrum-clean and fiber-compatible method to generate a highly phase-coherent and high-power multi-tone laser. This method features the utilization of a broadband fiber Mach-Zehnder modulator working at carrier suppression condition and second harmonic generation. We generate a multi-tone continuous-wave 532 nm laser with a power of 1.5 Watts and utilize it to manipulate the spin and motional states of a trapped 171Yb+ ion via stimulated Raman transition. For spin state manipulation, we acquire an effective Rabi frequency of 2π × 662.3 kHz. Due to the broad bandwidth of the fiber modulator and nonlinear crystal, the frequency gap between tones can be flexibly tuned. Benefiting from the features above, this method can manipulate 171Yb+ and 137Ba+ simultaneously in the multi-species ion trap and has potential to be widely applied in atomic, molecular and optical physics.

High-sensitivity C-reactive protein could be a potential indicator of bone mineral density in adolescents aged 10-20 years.

There was very limited evidence linking high-sensitivity C-reactive protein (HS-CRP) and total bone mineral density (BMD) in adolescents. The aim of this population-based study was to investigate the relationship between HS-CRP and total BMD in adolescents aged 10-20 years. A cross-sectional study was performed in the normal U.S. population from the data of the National Health and Nutrition Examination Survey (NHANES). The correlation between HS-CRP and total BMD was evaluated by using weighted multivariate linear regression models. And further subgroup analysis was conducted. There were 1747 participants in this study, 47.1% were female, 29.4% were white, 19.5% were black, and 22.3% were Mexican-American. In the multi-regression model that after the potential confounders had been adjusted, HS-CRP was negatively associated with total BMD. The negative association was also observed in the subgroup analyses stratified by gender and age. Our results demonstrated that higher HS-CRP was negatively correlated with total BMD in 10-20 years old adolescents.

Quantum frequency conversion from ultraviolet to visible band through waveguides in a period-poled MgO:LiTaO3 crystal.

In research on hybrid quantum networks, visible or near-infrared frequency conversion has been realized. However, technical limitations mean that there have been few studies involving the ultraviolet band, and unfortunately the wavelengths of the rare-earth or alkaline-earth metal atoms or ions that are used widely in research on quantum information are often in the UV band. Therefore, frequency conversion of the ultraviolet band is very important. In this paper, we demonstrate a quantum frequency conversion between ultraviolet and visible wavelengths by fabricating waveguides in a period-poled MgO:LiTaO3 crystal with a laser writing system, which will be used to connect the wavelength of the dipole transition of 171Yb+ at 369.5 nm and the absorption wavelength of Eu3+ at 580 nm in a solid-state quantum memory system. An external conversion efficiency of 0.85% and a signal-to-noise ratio of greater than 500 are realized with a pumping power of 3.28 W at 1018 nm. Furthermore, we complete frequency conversion of the classical polarization state by means of a symmetric optical setup based on the fabricated waveguide, and the process fidelity of the conversion is (96.13 ± 0.021)%. This converter paves the way for constructing a hybrid quantum network and realizing a quantum router in the ultraviolet band in the future.

ROS-boosted photodynamic therapy against metastatic melanoma by inhibiting the activity of antioxidase and oxygen-producing nano-dopants.

The antioxidant effect weakens the ability of PDT to resist melanoma, and the hypoxic tumor environment further restricts the application of photosensitizers in tumors. Therefore, to enhance the ability of PDT to resist melanoma, we designed a sequential enhanced PDT theranostic platform (Au@MTM-HA). Firstly, the nanotherapeutic platform uses TiO2 as a photosensitizer, which is doped with MnO2 to form a mesoporous MTM. The MTM can continuously provide oxygen, thereby increasing the level of reactive oxygen species (ROS) and reducing the metastatic effect by alleviating tumor hypoxia. Furthermore, the released Au25Sv9 could inhibit the activity of antioxidant defense enzymes and reduce the scavenging of ROS and further enhance the PDT effect. Simultaneously, surface-modified HA could not only recognize CD44 receptor but also act as a sealing agent for carriers. Result: Au@MTM-HA could explosively produce a 3-fold higher ROS and improve the PDT effect. Therefore, this work may provide strong evidence for Au@MTM-HA as a new and promising PDT candidate for the treatment of metastatic melanoma.

Construction and evaluation of tumor nucleus-targeting nanocomposite for cancer dual-mode imaging - Guiding photodynamic therapy/photothermal therapy.

To tackle the barrier of the insufficient intra-cellular delivery of reactive oxygen species (ROS) and heat, we designed a multifunctional nanoplatform to release ROS and heat directly in the cell nucleus for enhancing combined photodynamic therapy (PDT) and photothermal therapy (PTT) of tumors. As a photothermal agent, WS2 nanoparticles were adsorbed photosensitive Au25(Captopril)18- (Au25) nanoclusters via electrostatic interaction. And Dexamethasone (Dex), a glucocorticoid with nucleus targeting capability, played a key role in the intra-nuclear process of heat and ROS. PTT can increase intra-tumoral blood flow to promote Au25 produce more ROS for PDT. Under near infrared (NIR) laser irradiation at a single 808 nm, these nucleus targeting WS2 nanoplatforms showed a significant decreased cell viability of 18.2 ±â€¯1.7% and a high DNA damage degree of 59.6 ±â€¯8.3%. Furthermore, the WS2 nanoplatform could be further used for X-ray computed tomography (CT) images. Taken together, our study provided a new prospect for effectively diagnostic and enhancing PTT/PDT efficacy.

A sensitive detection assay based on signal amplification technology for Alzheimer's disease's early biomarker in exosome.

Alzheimer's disease (AD) considered as the third health "killer" has seriously threatened the health of the elderly. However, the modern diagnostic strategies of AD present several disadvantages: the low accuracy and specificity resulting in some false-negative diagnoses, and the poor sensitivity leading to a delayed treatment. In view of this situation, a enzyme-free and target-triggered signal amplification strategy, based on graphene oxide (GO) and entropy-driven strand displacement reaction (ESDR) principle, was proposed. In this strategy, when the hairpin structure probes (H)specially binds with beta-amyloid-(1-42) oligomers (Aß42 oligomers), it's structure will be opened, causing the bases complementary to FAM-labeled replacement probes R (R1 and R2) exposed. At this time, R1 and R2 will hybridize with H, resulting in the bound Aß42 oligomers released. The released Aß42 oligomers would participate in the next cycle reaction, making the signal amplified. As a quencher, GO could absorb the free single-stranded DNA R1 and R2 and quench their fluorescence; however, the DNA duplex still exists free and keeps its signal-on. Through the detection of Aß42 oligomers in exosomes, this ultrasensitive detection method with the advantages of low limit of detection (LOD, 20 pM), great accuracy, excellent precision and convenience provides an excellent prospect for AD's early diagnosis.

A "protective umbrella" nanoplatform for loading ICG and multi-modal imaging-guided phototherapy.

In order to prevent the aggregation of ICG and enhance its stability, a novel nanoplatform (TiO2:Yb,Ho,F-ß-CD@ICG/HA) was designed for NIR-induced phototherapy along with multi-mode imaging(UCL/MRI/Flu). In this nanosysytem: TiO2:Yb,Ho,F was used as upconversion materials and applied in vivo for the first time; ß-CD acted as a "protective umbrella" to load separated ICG and avoid the low phototherapy efficiency because of its aggregation; HA was the capping agent of ß-CD to prevent ICG unexpected leaking and a target to recognize CD44 receptor. The nanosystem exhibited excellent size (~200 nm) and photo- and thermal-stability, preferable reactive oxygen yield and temperature response (50.4 °C) under 808 nm laser. It could efficiently target and suppress tumor growth. The imaging ability (UCL/MRI) of TiO2:Yb,Ho,F could facilitate diagnosis of the tumor, especially for deep tissues. Altogether, our work successfully improved the phototherapy efficacy through incorporating the ICG into the cavity of ß-CD and applied TiO2:Yb,Ho,F for upconversion imaging in vivo.

A new PPARγ/DNA origami biochromatography and offline high performance liquid chromatography-mass spectrometry method for screening PPARγ receptor antagonists from ginsenosides.

To rapidly identify novel PPARγ ligands, a robust binding assay amenable to high-efficiency screening toward PPARγ would be desirable. In this study, a new PPARγ assembled on DNA origami (PPARγ/DNA origami) biochromatography drug screening model was constructed and evaluated. The method was used to screen active ingredients acted on PPARγ from the total ginsenosides. The total ginsenosides were handled on this biochromatography column by HPLC. The collected retention fraction from the biochromatography column was analyzed by HPLC and HPLC/MS. The results showed that ginsenoside Re from the total ginsenosides was the targeted component which could act on PPARγ receptor in similar manner of rosiglitazone as a control drug. This method will be a useful method for drug screening with natural medicinal herbs as a leading compound resource, compared with previous drug screening, this method without the need for complex and time-consuming separation steps previously.

A Hollow NaGdF4 /AFn Nanosystem Based on "Relay Race" Release for Therapy.

To develop a multifunctional nanomaterial for dual-mode imaging and synergetic chemotherapy, curcumin (CUR) was physically entrapped into hollow upconversion NaGdF4 nanomaterial, then apoferritin (AFn) loaded with doxorubicin (DOX) was attached to the NaGdF4 surface. Subsequent modification with the targeting reagent folic acid (FA) led to generation of the CUR/NaGdF4 -DOX/AFn-FA conjugate for cancer treatment. X-ray diffraction, scanning (SEM) and transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy demonstrated the successful preparation of hexagonal-phase NaGdF4 and NaGdF4 -AFn-FA. Moreover, no toxicity was observed for NaGdF4 -AFn-FA. In vitro and in vivo experiments demonstrated that the two drugs are sequentially released from the nanocomposites. This two-drug system showed strong growth inhibitory effects on MCF-7 cells. Upconversion luminescence imaging and magnetic resonance (MR) imaging of NaGdF4 -AFn-FA were carried out. The results of this study show that NaGdF4 -AFn-FA can be used for targeted anticancer drug delivery as well as imaging, a novel multi-pronged theranostic system for tumor treatment.

Oxamate Enhances the Anti-Inflammatory and Insulin-Sensitizing Effects of Metformin in Diabetic Mice.

Metformin (MET) is the first-line drug for treating type 2 diabetes mellitus (T2DM). However, MET increases blood lactate levels in patients with T2DM. Lactate possesses proinflammatory properties and causes insulin resistance (IR). Oxamate (OXA), a lactate dehydrogenase inhibitor, can decrease tissue lactate production and blood lactate levels. This study was conducted to examine the effects of the combination of OXA and MET on inflammation, and IR in diabetic db/db mice. Supplementation of OXA to MET led to lowered tissue lactate production and serum lactate levels compared to MET alone, accompanied with further decreased tissue and blood levels of pro-inflammatory cytokines, along with better insulin sensitivity, beta-cell mass, and glycemic control in diabetic db/db mice. These results show that OXA enhances the anti-inflammatory and insulin-sensitizing effects of MET through the inhibition of tissue lactate production in db/db mice.

A "win-win" nanoplatform: TiO2:Yb,Ho,F for NIR light-induced synergistic therapy and imaging.

To avoid the defect of low energy transfer efficiency in core-shell UCNP-TiO2 NPs, doping rare earth into TiO2 and improving the photocatalytic activity of TiO2 itself under Vis-NIR light might be a more direct and efficient strategy for high 1O2 production. Here, we designed a TiO2:Yb,Ho,F-ß-CD@DTX/HA nanoplatform using TiO2:Yb,Ho,F as the core, ß-CD as the drug carrier, hyaluronic acid (HA) as the capping agent and target, and then applied it for 808 nm induced photodynamic-chemotherapy and 980 nm upconversion fluorescence/MR imaging. The results were as follows: (i) for TiO2 as a photosensitizer, after doping Yb, Ho, F into TiO2, it could directly generate reactive oxygen species under an 808 nm laser; the dopants enhanced the absorption under the UV-Vis-NIR region and increased the electron-hole pair separation. (ii) For TiO2 as the upconversion host, F and Ho also endowed TiO2:Yb,Ho,F with enhanced upconversion fluorescence under a 980 nm laser and T2-MRI contrast performance (r2 = 30.71 mM-1 s-1), respectively, thus, facilitating imaging for deep tissues. (iii) The HA shell outside of ß-CD prevented the unexpected leaking of DTX, which improved the target abilities and achieved the enzyme-responsive drug release. The in vitro and in vivo studies also demonstrated the nanosystem could efficiently suppress tumor growth by combination therapy and had excellent imaging (UCL/MR) ability. Particularly, our work was the first example that utilized TiO2 simultaneously as a photosensitizer and upconversion host, which simplified the core-shell UCNP-TiO2 nanocomposites and reached a "win-win" cooperation in NIR-induced photodynamic therapy and UCL imaging.

Oxamate Improves Glycemic Control and Insulin Sensitivity via Inhibition of Tissue Lactate Production in db/db Mice.

Oxamate (OXA) is a pyruvate analogue that directly inhibits the lactate dehydrogenase (LDH)-catalyzed conversion process of pyruvate into lactate. Earlier and recent studies have shown elevated blood lactate levels among insulin-resistant and type 2 diabetes subjects and that blood lactate levels independently predicted the development of incident diabetes. To explore the potential of OXA in the treatment of diabetes, db/db mice were treated with OXA in vivo. Treatment of OXA (350-750 mg/kg of body weight) for 12 weeks was shown to decrease body weight gain and blood glucose and HbA1c levels and improve insulin secretion, the morphology of pancreatic islets, and insulin sensitivity in db/db mice. Meanwhile, OXA reduced the lactate production of adipose tissue and skeletal muscle and serum lactate levels and decreased serum levels of TG, FFA, CRP, IL-6, and TNF-α in db/db mice. The PCR array showed that OXA downregulated the expression of Tnf, Il6, leptin, Cxcr3, Map2k1, and Ikbkb, and upregulated the expression of Irs2, Nfkbia, and Pde3b in the skeletal muscle of db/db mice. Interestingly, LDH-A expression increased in the islet cells of db/db mice, and both treatment of OXA and pioglitazone decreased LDH-A expression, which might be related to the improvement of insulin secretion. Taken together, increased lactate production of adipose tissue and skeletal muscle may be at least partially responsible for insulin resistance and diabetes in db/db mice. OXA improved glycemic control and insulin sensitivity in db/db mice primarily via inhibition of tissue lactate production. Oxamic acid derivatives may be a potential drug for the treatment of type 2 diabetes.

A highly specific graphene platform for sensing collagen triple helix.

The construction of simple and efficient assays to detect collagen biomarkers plays a critical role in developing novel diagnosis and therapies for the highly prevalent chronic fibroproliferative diseases. Inspired by the successful development of various GO-based biosensors for DNA utilizing its well-known double helix structure, we have for the first time created a highly specific GO platform for sensing the collagen triple helix. We have designed a dye-labeled single stranded collagen (ssCOL) peptide probe to target a complementary single stranded collagen peptide sequence. We have revealed that GO binds with the ssCOL probe and quenches the fluorescence of the dye, while the hybridization of the ssCOL probe with its target collagen peptide GPO results in the retention of the fluorescence of the probe. We have demonstrated that this design provides a fluorescence-enhanced assay that is sensitive and selective to the target collagen peptide with little interferences from other proteins, and it can be applied for quantitative detection in complex biological fluids. These results indicate that this GO-based ssCOL platform has great potential in molecular diagnostics of fibroproliferative diseases. It may provide a novel strategy to construct efficient assays for the proteins containing triple helix motifs such as collectins, adiponectin, macrophage scavenger and C1q.

Paper-based FRET for the direct detection of collagen triple helix.

In order to develop improved diagnosis and therapies for the highly prevalent chronic fibroproliferative diseases, it is of utmost importance to construct efficient assays to detect collagen biomarkers. We have successfully created a paper-based FRET assay for the fast, inexpensive and direct detection of collagen triple helix. We have demonstrated that the adsorption of the dye-labeled probe peptide onto the GO-immobilized paper quenches the fluorescence of the dye, while the hybridization of the probe peptide with the target collagen peptide results in the desorption of the probe peptide from GO, thus restoring the fluorescence. We have also shown that this novel assay is highly specific to the target collagen peptide sequence with little interference from other proteins, and it can be applied for quantitative detection in complex biological fluids. Our integration of the GO-based FRET assay with a patterned paper provides a powerful new tool for the detection of collagen molecules with many superior features: tiny volumes of samples, multichannel detection mode, easy operation and low-cost equipment. This assay may have promising applications to fast screen multiple target collagen sequences for the discovery of new collagen biomarkers.