Controlling single rare earth ion emission in an electro-optical nanocavity.

Rare earth emitters enable critical quantum resources including spin qubits, single photon sources, and quantum memories. Yet, probing of single ions remains challenging due to low emission rate of their intra-4f optical transitions. One feasible approach is through Purcell-enhanced emission in optical cavities. The ability to modulate cavity-ion coupling in real-time will further elevate the capacity of such systems. Here, we demonstrate direct control of single ion emission by embedding erbium dopants in an electro-optically active photonic crystal cavity patterned from thin-film lithium niobate. Purcell factor over 170 enables single ion detection, which is verified by second-order autocorrelation measurement. Dynamic control of emission rate is realized by leveraging electro-optic tuning of resonance frequency. Using this feature, storage, and retrieval of single ion excitation is further demonstrated, without perturbing the emission characteristics. These results promise new opportunities for controllable single-photon sources and efficient spin-photon interfaces.

Bidirectional interconversion of microwave and light with thin-film lithium niobate.

Superconducting cavity electro-optics presents a promising route to coherently convert microwave and optical photons and distribute quantum entanglement between superconducting circuits over long-distance. Strong Pockels nonlinearity and high-performance optical cavity are the prerequisites for high conversion efficiency. Thin-film lithium niobate (TFLN) offers these desired characteristics. Despite significant recent progresses, only unidirectional conversion with efficiencies on the order of 10-5 has been realized. In this article, we demonstrate the bidirectional electro-optic conversion in TFLN-superconductor hybrid system, with conversion efficiency improved by more than three orders of magnitude. Our air-clad device architecture boosts the sustainable intracavity pump power at cryogenic temperatures by suppressing the prominent photorefractive effect that limits cryogenic performance of TFLN, and reaches an efficiency of 1.02% (internal efficiency of 15.2%). This work firmly establishes the TFLN-superconductor hybrid EO system as a highly competitive transduction platform for future quantum network applications.

Photonic integration of Er3+:Y2SiO5 with thin-film lithium niobate by flip chip bonding.

Rare earth ions are known as promising candidates for building quantum light-matter interface. However, tunable photonic cavity access to rare earth ions in their desired host crystal remains challenging. Here, we demonstrate the integration of erbium doped yttrium orthosilicate (Er3+:Y2SiO5) with thin-film lithium niobate photonic circuit by plasma-activated direct flip chip bonding. Resonant coupling to erbium ions is realized by on-chip electro-optically tuned high Q lithium niobate micro-ring resonators. Fluorescence and absorption of erbium ions at 1536.48 nm are measured in the waveguides, while the collective ion-cavity cooperativity with micro-ring resonators is assessed to be 0.36. This work presents a versatile scheme for future rare earth ion integrated quantum devices.

Improvement of the C-glycosylation Step for the Synthesis of Remdesivir.

The bulk supply of the antiviral C-nucleoside analogue remdesivir is largely hampered by a low-yielding C-glycosylation step in which the base is coupled to the pentose unit. Here, we disclose a significantly improved methodology for this critical transformation. By utilizing diisopropylamine as a cost-effective additive, the addition reaction furnishes an optimal yield of 75% of the desired ribofuranoside adduct, representing the highest yield obtained thus far for this key step. The method proved suitable for hectogram scale synthesis without column chromatographic operations.

[CRISPR/Cas9-mediated foreign gene targeted knock-in into the chicken EAV-HP genome].

The study aims to use CRISPR/Cas9 introducing foreign gene targeted knock-in into chicken EAV-HP genome. First, specific primers were designed for amplification of EAV-HP left, right homologous arms and enhanced green fluorescent protein (eGFP) expression cassette. PCR products of homologous arms were ligated to both sides of eGFP by overlap extension PCR, resulting in full-length donor DNA fragment designated as LER. Then LER fragments were cloned into pMD19-T to obtain donor vector pMDT-LER. Subsequently, the donor vector pMDT-LER was transfected into HEK293T cells to verify the expression of eGFP gene. Furthermore, co-transfection of CRISPR/Cas9 expression vector and pMDT-LER into chicken DF-1 cells was performed to achieve eGFP transgenic cells. Meanwhile, eGFP expression was observed in cells, and the event of eGFP integration into EAV-HP genome was detectable by amplification of target DNA. Finally, the transgenic DF-1 cells were passaged seven times, and the stable integration and expression of eGFP was checked by PCR and Western blotting. These results demonstrated that eGFP gene was knocked into the EAV-HP genome successfully, which provides a new integration site for research of transgenic chicken.

Specific expression pattern of IMP metabolism related-genes in chicken muscle between cage and free range conditions.

Inosine monophosphate (IMP) is a key factor affecting the fleshy flavor of meat; meanwhile, the free-range mode is an efficient strategy to improve muscular IMP content. To assess expression differences in IMP metabolism-related genes under different feeding patterns, Illumina Nextseq 500 sequencing was used to catalog the global gene expression profiles of muscle samples from Lueyang black-bone chicken under free-range and caging conditions. A total of 15510 unigenes were assembled, with 13423 (86.54%) and 6088 (39.25%) unigenes correctly annotated in the GO and KOG databases, respectively. Next, the "purine metabolism" pathway in the "nucleotide metabolism group" was assessed in depth. Through Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, we retrieved 172 nucleotide- and 5 purine- metabolism related genes that were differentially expressed in muscle samples from free-range and caged chickens. At 60-day-old, AMPD1, NT5C1A and ENTPD8 showed higher levels in the free-range group, while only ENTPD8 was upregulated in 120-day-old chickens. In addition, GART, GARS and ADSL in free-range chickens showed higher levels compared with caged animals. Furthermore, IMPDH levels in free-range chicken were lower than those of caged chicken. Real-time quantitative polymerase chain reaction (qPCR) was used to validate the above findings. These results revealed a set of differentially expressed genes potentially related to IMP metabolism in chicken under different breeding modes, providing novel insights into controlling IMP levels in chicken meat.

Ascorbic Palmitate as a Bifunctional Drug and Nanocarrier of Paclitaxel for Synergistic Anti-Tumor Therapy.

The in vivo application of ascorbate is currently limited by the very high blood concentrations that are required to achieve therapeutic levels in tumors, which needs to exploit a novel drug platform to improve the pharmacokinetics of vitamin C (Vc) and its antitumoral effects. In this study, ascorbyl palmitate (AP), an amphiphilic molecule, is the palmitate acid ester derivative of ascorbic acid, which can be formed a "bifunctional" nanoparticle in which the AP acts not only as an antitumor drug but also as a nanocarrier for encapsulating hydrophobic antitumor drugs such as paclitaxel (PTX). We developed a bifunctional nanocarrier based on AP, which loaded with PTX for synergistic cancer chemotherapy. The resulting PTX-AP nanoparticles (PTX-APNPs) were spherical and had an average size of 294.2 nm based on dynamic light scattering. The in vitro anti-B16F10 cells test of PTX-APNPs revealed an obvious synergistic effect of AP and PTX, and the PTX-APNPs strongly induced cell apoptosis and production of reactive oxygen species. In addition, PTX-APNPs formulation also effectively suppressed the tumorigenicity of B16F10 cells in female C57BL/6 mice without causing severe toxicity. These results suggest that AP-based nanoparticles formulated with paclitaxel are useful for synergistic chemotherapy.

Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System.

The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms.

Nano/microfibrous polymeric constructs loaded with bioactive agents and designed for tissue engineering applications: a review.

Nano/microfibrous polymeric constructs present various inherent advantages, such as highly porous architecture and high surface to volume ratio, making them attractive for tissue engineering purposes. Electrospinning is the most preferred technique for the fabrication of polymeric nanofibrous assemblies that can mimic the physical functions of native extracellular matrix greatly favoring cells attachment and thus influencing their morphology and activities. Different approaches have been developed to apply polymeric microfiber fabrication techniques (e.g. wet-spinning) for the obtainment of scaffolds with a three-dimensional network of micropores suitable for effective cells migration. Progress in additive manufacturing technology has led to the development of complex scaffold's shapes and microfibrous structures with a high degree of automation, good accuracy and reproducibility. Various loading methods, such as direct blending, coaxial electrospinning and microparticles incorporation, are enabling to develop customized strategies for the biofunctionalization of nano/microfibrous scaffolds with a tailored kinetics of release of different bioactive agents, ranging from small molecules, such as antibiotics, to protein drugs, such as growth factors, and even cells. Recent activities on the combination of different processing techniques and loading methods for the obtainment of biofunctionalized polymeric constructs with a complex multiscale structure open new possibilities for the development of biomimetic scaffolds endowed with a hierarchical architecture and a sophisticated release kinetics of different bioactive agents. This review is aimed at summarizing current advances in technologies and methods for manufacturing nano/microfibrous polymeric constructs suitable as tissue engineering scaffolds, and for their combination with different bioactive agents to promote tissue regeneration and therapeutic effects.

Development of a pulmonary peptide delivery system using porous nanoparticle-aggregate particles for systemic application.

As a non-invasive administration route, pulmonary peptide delivery for systemic application has shown great promise. However, many barriers exist that prevent effective peptide delivery. The use of porous nanoparticle-aggregate particles (PNAPs) is an excellent option because of their proper aerodynamic size and maximal deposition. However, in most cases, the spray drying heating process for PNAPs has been challenging in regard to maintaining peptide stability and activity. To overcome these issues, we developed a spray freeze-drying method for PNAP preparation. To solve the low entrapment efficiency problem of nanostructured lipid carriers, we used hydrophobic ion pair complexes to increase the lipophilicity of the peptide, thus increasing entrapment efficiency and drug loading. Here, we used a model peptide, octreotide acetate, for PNAP preparation, which has a high entrapment efficiency (>95%) and proper aerodynamic size (~3 µm). In addition, after intrapulmonary administration, we evaluated the pharmacokinetics and pharmacodynamics in a rat preventive hepatic ischemia-reperfusion injury model. Our in vivo data showed significantly increased area under the curve and improved plasma aspartate aminotransferase levels for our PNAP intrapulmonary delivery system vs. the clinically used octreotide acetate delivery via subcutaneous injection. Together, PNAPs may have great potential for carrying peptide drugs for pulmonary delivery.

In vitro evaluation of the genotoxicity of a family of novel MeO-PEG-poly(D,L-lactic-co-glycolic acid)-PEG-OMe triblock copolymer and PLGA nanoparticles.

Despite the booming development of nanoparticle materials for pharmaceutical applications, studies on their genotoxicity are few. In our previous efforts to develop an intravenous nanoparticle material, a family of novel monomethoxy(polyethylene glycol)-poly(D,L-lactic-co-glycolic acid)-monomethoxy (PELGE) polymers was synthesized. The cytotoxicity and genotoxicity of nine kinds of selected blank PELGE and PLGA (poly(D,L-lactic and glycolic acid)) nanoparticles were evaluated using methyl thiazolyl tetrazolium (MTT), micronucleus (MN) and sister chromatid exchange (SCE) assays with or without the addition of a metabolic activation system (S9 mix), using Chinese hamster ovary (CHO) cells. The cytotoxicity of nanoparticles exhibited a dose-dependent response, with a concentration of 5 mg ml(-1) being the turning point. The frequencies of MN observed in samples treated with various nanoparticles were not statistically different from those seen in the negative controls in the presence or absence of the S9 mix. Also, no cell cycle delay was observed. The numbers of SCE per cell observed in samples treated with five kinds of PELGE nanoparticles were significantly greater than those found in the negative controls with or without the S9 mix. The discrepancies found in the two assays suggest that the five kinds of nanoparticles may produce only a weakly clastogenic response.