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Couriers’ package pick-up route prediction is a fundamental task in the emerging intelligent logistics systems. It is beneficial for order dispatching and arrival-time estimation by leveraging the predicted routes to improve those downstream tasks. However, the package pick-up route prediction problem is challenging since couriers’ behaviors are affected by both strict Spatial–Temporal Constraints (STC) and personalized spatial-transfer patterns (STP). Specifically, couriers have to consider explicitly spatial-temporal requirements such as the locations of packages and the promised pick-up time when selecting future routes. In addition, couriers have personalized mobility patterns between different locations, which are implicit patterns hidden behind couriers’ historical trajectories and cannot be ignored to precisely depict their behaviors. This paper proposes a novel framework, named CP-Route, to predict a specific courier’s future package pick-up route under strict spatial-temporal constraints, and enhance the prediction performance by learning the spatial-transfer patterns (i.e., the routing patterns) of couriers. A sophisticated encoder is designed to capture the STC and STP, and a mixed-distribution-based decoder is designed to simultaneously consider the influence of spatial-temporal constraints and routing patterns on couriers’ final decisions. Extensive experiments conducted on an industry-scale logistics dataset demonstrate the superiority of our proposed framework against the existing baseline methods. The online A/B test shows our contribution to the improvement of arrival time prediction.

We report on the development and application of a novel, to the best of our knowledge, all-solid-state tunable narrow-linewidth 226 nm UV laser system. The laser system consists of three parts: a tunable single-frequency Ti:sapphire 787 nm laser, a single-frequency long-pulse-width flattop-shaped 532 nm laser, and a nonlinear frequency transformation system. The 532 nm laser is a sum-frequency mixed with the second harmonic of the 787 nm laser to produce the 226 nm laser. The maximum output pulse energy at 226 nm is 3 mJ. Nitric oxide planar laser-induced fluorescence velocimetry is demonstrated in the China Aerodynamics Research and Development Center’s FD14 hypersonic shock tunnel using this 226 nm laser system. It is proven that this laser is convenient for high-resolution molecular tagging fluorescence spectroscopy.

Efficient cancer vaccines not only require the co-delivery of potent antigens and highly immunostimulatory adjuvants to initiate robust tumor-specific host immune response but also solve the spatiotemporal consistency of host immunity and tumor microenvironment (TME) immunomodulation. Here, we designed a biomaterials-based strategy for converting tumor-derived antigenic microparticles (T-MPs) into a cancer vaccine to meet this conundrum and demonstrated its therapeutic potential in multiple murine tumor models. The internal cavity of T-MPs was employed to store nano-Fe3O4(Fe3O4/T-MPs), and then dense adjuvant CpG-loaded liposome arrays (CpG/Lipo) were tethered on the surface of Fe3O4/T-MP through mild surface engineering to get a vaccine (Fe3O4/T-MPs-CpG/Lipo), demonstrating that co-delivery of Fe3O4/T-MPs and CpG/Lipo to antigen presenting cells (APCs) could elicit strong tumor antigen-specific host immune response. Meanwhile, vaccines distributed in the TME could reverse infiltrated tumor-associated macrophages into a tumor-suppressive M1 phenotype by nano-Fe3O4, amazingly induce abundant infiltration of cytotoxic T lymphocytes, and transform a “cold” tumor into a “hot” tumor. Furthermore, amplified antitumor immunity was realized by the combination of an Fe3O4/T-MPs-CpG/Lipo vaccine and immune checkpoint PD-L1 blockade, specifically inhibiting ∼83% of the progression of B16F10-bearing mice and extending the median survival time to 3 months. Overall, this study synergistically modulates the tumor immunosuppressive network and host antitumor immunity in a spatiotemporal manner, which suggests a general cell-engineering strategy tailored to a personalized vaccine from autologous cancer cell materials of each individual patient.

With a resurgence of covalent drugs, there is an urgent need for the identification of new moieties capable of cysteine bond formation. Herein, we report on the N-acylamino saccharin moieties capable of novel covalent reactions with cysteine. Their utility as alternative electrophilic warheads was demonstrated through the covalent modification of fructose-1,6-bisphosphatase (FBPase), a promising target associated with cancer and type 2 diabetes. The cocrystal structure of title compound W8bound with FBPase unexpectedly revealed that the N-acylamino saccharin moiety worked as an electrophile warhead that covalently modified the noncatalytic C128 site in FBPase while releasing saccharin, suggesting a previously undiscovered covalent reaction mechanism of saccharin derivatives with cysteine. Treatment of title compound W8displayed potent inhibition of glucose production in vitro and in vivo. This newly discovered reactive warhead supplements the current repertoire of cysteine covalent modifiers while avoiding some of the limitations generally associated with established moieties.