4.4 kW Nd:YAG slab amplifier with a high repetition frequency and high beam quality.

Using the self-developed fused indium wetting technology and planar waveguide, the uniform heat dissipation of the slab crystal and uniform pumping of the pump light were achieved, respectively. Based on the master oscillator power amplification (MOPA) scheme, the power was then amplified when the seed light source passed through the Nd:YAG slab crystal three times. Additionally, the image transfer system that we added to the amplified optical path achieved high beam quality. Finally, we obtained a rectangular pulsed laser with an output average power of 4461 W, a repetition frequency of 20 kHz, a pulse width of 62 ns, an optical-to-optical conversion efficiency of 26.8%, and a beam quality of ß x=7.0 and ß y=7.7.

Efficient characterizations of multiphoton states with an ultra-thin optical device.

Metasurface enables the generation and manipulation of multiphoton entanglement with flat optics, providing a more efficient platform for large-scale photonic quantum information processing. Here, we show that a single metasurface optical device would allow more efficient characterizations of multiphoton entangled states, such as shadow tomography, which generally requires fast and complicated control of optical setups to perform information-complete measurements, a demanding task using conventional optics. The compact and stable device here allows implementations of general positive operator valued measures with a reduced sample complexity and significantly alleviates the experimental complexity to implement shadow tomography. Integrating self-learning and calibration algorithms, we observe notable advantages in the reconstruction of multiphoton entanglement, including using fewer measurements, having higher accuracy, and being robust against experimental imperfections. Our work unveils the feasibility of metasurface as a favorable integrated optical device for efficient characterization of multiphoton entanglement, and sheds light on scalable photonic quantum technologies with ultra-thin optical devices.

Characterizing Foxp3+ and Foxp3- T cells in the homeostatic state and after allo-activation: resting CD4+Foxp3+ Tregs have molecular characteristics of activated T cells.

Due to the intracellular expression of Foxp3 it is impossible to purify viable Foxp3+ cells on the basis of Foxp3 staining. Consequently CD4+Foxp3+ regulatory T cells (Tregs) in mice have mostly been characterized using CD4+CD25+ T cells or GFP-Foxp3 reporter T cells. However, these two populations cannot faithfully represent Tregs as the expression of CD25 and Foxp3 does not completely overlap and GFP+Foxp3+ reporter T cells have been reported to be functionally altered. The aim of this study was to characterize normal Tregs without separating Foxp3+ and Foxp3- cells for the expression of the main functional molecules and proliferation behaviors by flow cytometry and to examine their gene expression characteristics through differential gene expression. Our data showed that the expressions of Foxp3, CD25, CTLA-4 (both intracellular and cell surface) and PD-1 was mostly confined to CD4+ T cells and the expression of Foxp3 did not completely overlap with the expression of CD25, CTLA-4 or PD-1. Despite higher levels of expression of the T cell inhibitory molecules CTLA-4 and PD-1, Tregs maintained higher levels of Ki-67 expression in the homeostatic state and had greater proliferation in vivo after allo-activation than Tconv. Differential gene expression analysis revealed that resting Tregs exhibited immune activation markers characteristic of activated Tconv. This is consistent with the flow data that the T cell activation markers CD25, CTLA-4, PD-1, and Ki-67 were much more strongly expressed by Tregs than Tconv in the homeostatic state.

Polarization-multiplexed metasurface enabled tri-functional imaging.

Diffraction-limited focusing imaging, edge-enhanced imaging, and long depth of focus imaging offer crucial technical capabilities for applications such as biological microscopy and surface topography detection. To conveniently and quickly realize the microscopy imaging of different functions, the multifunctional integrated system of microscopy imaging has become an increasingly important research direction. However, conventional microscopes necessitate bulky optical components to switch between these functionalities, suffering from the system's complexity and unstability. Hence, solving the problem of integrating multiple functions within an optical system is a pressing need. In this work, we present an approach using a polarization-multiplexed tri-functional metasurface, capable of realizing the aforementioned imaging functions simply by changing the polarization state of the input and output light, enhancing the system structure's compactness and flexibility. This work offers a new avenue for multifunctional imaging, with potential applications in biomedicine and microscopy imaging.

Experimental demonstration of optical trapping and manipulation with multifunctional metasurface.

Chip-scale optical tweezers, which are usually implemented in a planar format without using bulky diffractive optical elements, are recognized as a promising candidate to be integrated with a lab-on-a-chip system. However, traditional chip-scale optical tweezers are often static and allow for only one type of manipulation functionality since the geometrical parameters of the tweezers are fixed. Herein, we introduce a new, to the best of our knowledge, class of on-chip optical tweezers for diverse types of manipulation of micro-particles. Utilizing both the propagation phase and Pancharatnam-Berry phase, we experimentally demonstrate the spin-dependent trapping, moving, and circling of micro-particles with the transfer of optical gradient force and orbital angular momentum to particles. We further show that the spin angular momentum of the output beam provides an additional degree of freedom to control the spinning rotation of particles. This new type of optical tweezers paves the way for multifunctional and dynamical trapping and manipulation of particles with a lab-on-a-chip system.

Detecting Tumor Antigen-Specific T Cells via Interaction-Dependent Fucosyl-Biotinylation.

Re-activation and clonal expansion of tumor-specific antigen (TSA)-reactive T cells are critical to the success of checkpoint blockade and adoptive transfer of tumor-infiltrating lymphocyte (TIL)-based therapies. There are no reliable markers to specifically identify the repertoire of TSA-reactive T cells due to their heterogeneous composition. We introduce FucoID as a general platform to detect endogenous antigen-specific T cells for studying their biology. Through this interaction-dependent labeling approach, intratumoral TSA-reactive CD4+, CD8+ T cells, and TSA-suppressive CD4+ T cells can be detected and separated from bystander T cells based on their cell-surface enzymatic fucosyl-biotinylation. Compared to bystander TILs, TSA-reactive TILs possess a distinct T cell receptor (TCR) repertoire and unique gene features. Although exhibiting a dysfunctional phenotype, TSA-reactive CD8+ TILs possess substantial capabilities of proliferation and tumor-specific killing. Featuring genetic manipulation-free procedures and a quick turnover cycle, FucoID should have the potential of accelerating the pace of personalized cancer treatment.

d-Idose, d-Iduronic Acid, and d-Idonic Acid from d-Glucose via Seven-Carbon Sugars.

A practical synthesis of the very rare sugar d-idose and the stable building blocks for d-idose, d-iduronic, and d-idonic acids from ido-heptonic acid requires only isopropylidene protection, Shing silica gel-supported periodate cleavage of the C6-C7 bond of the heptonic acid, and selective reduction of C1 and/or C6. d-Idose is the most unstable of all the aldohexoses and a stable precursor which be stored and then converted under very mild conditions into d-idose is easily prepared.

Novel Approaches to Access Arylfluorosulfates and Sulfamoyl Fluorides Based on Sulfur (VI) Fluoride Exchange.

Sulfur (VI) fluoride exchange (SuFEx) is a new family of click chemistry reactions that relies on readily available sulfuryl fluoride (SO2 F2 ) and ethenesulfonyl fluoride to build diverse chemical structures bearing the SVI -F motif, such as fluorosulfate (-OSO2 F) and sulfonyl fluoride (-SO2 F). These motifs could be useful functional groups and connective linkers in organic synthesis. This unit describes two protocols for performing SuFEx. The first protocol describes an in situ method for rapid generation of arylfluorosulfates in 96-well plates for high-throughput screening. The second protocol outlines use of a shelf-stable fluorosulfuryl imidazolium salt for generating arylfluorosulfates and sulfamoyl fluorides. © 2019 by John Wiley & Sons, Inc.

SuFEx Click Chemistry Enabled Late-Stage Drug Functionalization.

Sulfur(VI) Fluoride Exchange (SuFEx) is a new family of click chemistry transformations which relies on readily available materials to produce compounds bearing the SVI-F motif. The potential of SuFEx in drug discovery has just started to be explored. We report the first method of SuFEx chemistry for the conversion of phenolic compounds to their respective arylfluorosulfate derivatives in situ in 96-well plates. This method is compatible with automated synthesis and screening to quickly assess the biological activities of the in situ generated, crude products. Using this method, we perform late-stage functionalization of a panel of known anticancer drugs to generate the corresponding arylfluorosulfates. These in situ generated arylfluorosulfates are directly tested in a cancer-cell growth inhibition assay in parallel with their phenolic precursors. We discover three arylfluorosulfates that exhibit improved anticancer cell proliferation activities compared to their phenol precursors. Among these three compounds, the fluorosulfate derivative of Fulvestrant possesses significantly enhanced activity to down-regulate estrogen receptor (ER) expression in ER+ breast cancer cell line MCF-7 and the fluorosulfate derivative of Combretastatin A4-a general anticancer drug currently being evaluated under clinical trials-exhibits a 70-fold increase in potency in the drug resistant colon cancer cell line HT-29.

A Single-Step Chemoenzymatic Reaction for the Construction of Antibody-Cell Conjugates.

Employing live cells as therapeutics is a direction of future drug discovery. An easy and robust method to modify the surfaces of cells directly to incorporate novel functionalities is highly desirable. However, genetic methods for cell-surface engineering are laborious and limited by low efficiency for primary cell modification. Here we report a chemoenzymatic approach that exploits a fucosyltransferase to transfer bio-macromolecules, such as an IgG antibody (MW∼ 150 KD), to the glycocalyx on the surfaces of live cells when the antibody is conjugated to the enzyme's natural donor substrate GDP-Fucose. Requiring no genetic modification, this method is fast and biocompatible with little interference to cells' endogenous functions. We applied this method to construct two antibody-cell conjugates (ACCs) using both cell lines and primary cells, and the modified cells exhibited specific tumor targeting and resistance to inhibitory signals produced by tumor cells, respectively. Remarkably, Herceptin-NK-92MI conjugates, a natural killer cell line modified with Herceptin, exhibit enhanced activities to induce the lysis of HER2+ cancer cells both ex vivo and in a human tumor xenograft model. Given the unprecedented substrate tolerance of the fucosyltransferase, this chemoenzymatic method offers a general approach to engineer cells as research tools and for therapeutic applications.